5. Chest | Radiology Review Manual (Dahnert, Radiology Review Manual)

Authors: Dahnert, Wolfgang

Title: Radiology Review Manual, 6th Edition

> Table of Contents > Chest

Chest

Differential Diagnosis of Chest Disorders

Pulmonary hemorrhage

WITHOUT RENAL DISEASE
- Bleeding diathesis: leukemia, hemophilia, disseminated intravascular coagulation (DIC)
- Pulmonary embolism, thromboembolism
- Blunt trauma: contusion
- Idiopathic pulmonary hemosiderosis
- Limited Wegener granulomatosis
- Infectious diseases
- Drugs: amphotericin B, mitomycin, high-dose cyclophosphamide, cytarabine (ara-C), D-penicillamine, anticoagulants, lymphangiography
WITH RENAL DISEASE
- medium-sized vessel vasculitis
  - Polyarteritis nodosa
- ANCA -associated small-vessel vasculitis:
  - Wegener granulomatosis
  - Churg-Strauss syndrome
- immune-complex small vessel vasculitis:
  - Goodpasture syndrome = antibasement membrane antibody disease with a linear pattern on tissue stains
  - Henoch-Sch nlein purpura
  - Beh et disease
- Collagen vascular disease:
  - Systemic lupus erythematosus: granular pattern of immune complexes on tissue stains, noncaseating granulomas, malar rash
  - Rheumatoid arthritis
  - Seronegative juvenile rheumatoid arthritis
- others
  - Rapidly progressive glomerulonephritis immune complexes
  - Immunoglobulin A nephropathy
  - Idiopathic pulmonary hemorrhage
  - Idiopathic glomerulonephritis
HEMORRHAGIC PNEUMONIA
Bacteria:

Viruses:

Fungi:
Legionnaires' disease CMV, herpes, Rocky Mountain spotted fever, infectious mononucleosis
Aspergillosis, mucormycosis
BLEEDING METASTASIS, eg, choriocarcinoma

acute respiratory distress
hemoptysis (uncommon)

CXR:

bilateral heterogeneous + homogeneous opacities
multifocal patchy segmental/lobar consolidation

HRCT:

bilateral patchy/confluent ground-glass opacities/consolidation
ground-glass centrilobular nodules
may delineate underlying etiology (bronchiectasis, lung cancer, TB, pulmonary embolism)

NUC:

typically matched defect on V/Q scan in bronchial artery bleeding

Hemoptysis

frothy sputum, bright red blood, alkaline pH

Source:

bronchial a. (90%), pulmonary a. ( recruitment of intercostal, inferior phrenic, internal mammary, subclavian aa.)

enlarged tortuous bronchial arteries with bronchial-to-pulmonary-artery shunting, hypervascularity, parenchymal staining
normal bronchial arteries are usually not visible on thoracic angiography

TUMOR
- Carcinoma (35%)
- Bronchial adenoma
BRONCHIAL WALL INJURY
- Foreign body erosion
- Bronchoscopy/biopsy
VASCULAR
- COPD
- Pulmonary embolus with infarction
- Venous hypertension (most common): mitral stenosis
- Arteriovenous malformation
- Rupture of pulmonary artery aneurysm:
  
  TB, vasculitis, trauma, neoplasm, abscess, septic embolus, indwelling catheter
INFECTION (pneumonia)
- Chronic inflammation of lung can induce angiogenesis + hypertrophy of bronchial/systemic arteries that may rupture
- Chronic bronchitis
- Bronchiectasis, mouthful (15%)
- Tuberculosis (Rasmussen aneurysm)
- Aspergillosis
- Abscess
- Cystic fibrosis

In 5 10% of patients no cause is found!
The two most common identifiable causes are bronchial carcinoma + bronchiectasis (in adults) and cystic fibrosis + congenital heart disease (in children)!

Rx:	transcatheter particulate embolization of bronchial arteries using polyvinyl alcohol (PVA) + Gelfoam pledgets (effective in 70 95%, but recurrent bleeding in 20 30% of patients) N.B.: search for artery of Adamkiewicz at vertebral level of T8 to L2 prior to embolization
DDx:	hematemesis (containing food particles, dark blood, acid pH)

Aspiration

= intake of solid/liquid materials into the airways and lungs

Predisposing factors:

Alcoholism (most common in adults)
General anesthesia, loss of consciousness
Structural abnormalities of pharynx/esophagus (congenital/acquired tracheoesophageal + tracheopulmonary fistula), laryngectomy

P.406

Neuromuscular disorders
Deglutition abnormalities

Substrate:

foreign bodies
liquids
- gastric acid = Mendelson syndrome
- water = near drowning
- barium, water-soluble contrast material
- liquid paraffin/petroleum = acute exogenous lipoid pneumonia/fire-eater pneumonia
- mineral oil/cod liver oil = chronic exogenous lipoid pneumonia
contaminated substances from oropharynx/GI tract

Pulmonary disease associated with cigarette smoking

Bronchogenic carcinoma
Chronic bronchitis
Centrilobular emphysema
Panacinar emphysema with -1 antitrypsin deficiency
Respiratory bronchiolitis-associated interstitial lung disease (RB-ILD)
- upper lung centrilobular nodules
Pulmonary Langerhans cell histiocytosis (PLCH)

Age: 30 40 years
- nodules + cysts in upper + mid lung fields
Desquamative interstitial pneumonitis (DIP)

Age: 4th-5th decade of life

Hypersensitivity to organic dusts

TRACHEOBRONCHIAL HYPERSENSITIVITY

large particles reaching the tracheobronchial mucosa (pollens, certain fungi, some animal/insect epithelial emanations)
- Extrinsic asthma
- Hypersensitivity aspergillosis
- Bronchocentric granulomatosis
- Byssinosis in cotton-wool workers
ALVEOLAR HYPERSENSITIVITY
- = HYPERSENSITIVITY PNEUMONITIS
- = EXTRINSIC ALLERGIC ALVEOLITIS
  
  small particles of <5 m reaching alveoli

Drug-induced pulmonary damage

Histopathologic manifestations:

Diffuse alveolar damage

bleomycin, busulfan, carmustine, mitomycin, cyclophosphamide, melphalan, gold salts
Nonspecific interstitial pneumonia

amiodarone, methotrexate, carmustine, chlorambucil
Bronchiolitis obliterans organizing pneumonia

bleomycin, gold salts, methotrexate, amiodarone, nitrofurantoin, penicillamine, sulfasalazine, cyclophosphamide
Eosinophilic pneumonia

penicillamine, sulfasalazine, nitrofurantoin, nonsteroidal anti-inflammatory drugs, paraaminosalicylic acid
Pulmonary hemorrhage

anticoagulants, amphotericin B, cytarabine (ara-C), penicillamine, cyclophosphamide

CYTOTOXIC DRUGS (most important group)

Cyclophosphamide

Use:	variety of malignancies, Wegener granulomatosis, glomerulonephritis
Toxicity:	after 2 weeks - 13 years (mean, 3.5 years), no relationship to dose/duration of therapy
Prognosis:	good after discontinuation of therapy

diffuse alveolar damage (most common)
nonspecific interstitial pneumonia
BOOP (least common)

Busulfan = Myleran (for CML)

Toxicity: dose-dependent, after 3 4 years on the drug in 1 10%
- diffuse linear pattern (occasionally reticulonodular/nodular pattern)
- partial/complete clearing after withdrawal of drug
DDx: Pneumocystis pneumonia, interstitial leukemic infiltrate
Nitrosoureas = carmustine (BCNU), Iomustine (CCNU)

Use: CNS glioma, lymphoma, myeloma

Toxicity: in 50% after doses >1500 mg/m²; sensitivity increased after radiation Rx
- diffuse alveolar damage (most common)
- nonspecific interstitial pneumonia:
  - linear/finely nodular opacities (following treatment of 2 3 years)
- high incidence of pneumothorax

Bleomycin

Use:	squamous cell carcinoma of neck/cervix/vagina, Hodgkin lymphoma, testicular ca.
Toxicity:	at doses >300 mg (in 3 6%); increased risk with age + radiation therapy + high oxygen concentrations
Prognosis:	death from respiratory failure within 3 months of onset of symptoms

diffuse alveolar damage (most common)
nonspecific interstitial pneumonia/BOOP:
- subpleural linear/nodular opacities (5 30 mm) in lower lung zones occurring after 1 3 months following beginning of therapy
  
  DDx: metastases

Taxoid derivatives = paclitaxel, docetaxel, gemcitabine, topotecan, vinorelbine

Use: breast cancer, lung cancer, ovarian cancer

NONCYTOTOXIC DRUGS

Amiodarone
- = triiodinated benzofuran
Use: refractory ventricular tachyarrhythmia

Toxicity: in 5 10%; risk increased with daily dose > 400 mg + in elderly

Prognosis: good after discontinuation of drug
- pulmonary insufficiency after 1 12 months in 14 18% on long-term therapy
- nonspecific interstitial pneumonia (most common) + associated BOOP:
  - alveolar + interstitial infiltrates (chronic presentation)
- focal homogeneous peripheral consolidation (acute presentation):
  
  P.407
  - attenuation values of iodine (due to incorporation of amiodarone into type II pneumocytes)
- pleural thickening (inflammation) adjacent to consolidation
- associated high-attenuation of liver relative to spleen
Gold salts

Use: inflammatory arthritis

Toxicity: in 1% within 2 6 months
- mucocutaneous lesions (30%)
- diffuse alveolar damage (common)
- nonspecific interstitial pneumonia (common)
- BOOP (less common)

Methotrexate, procarbazine

Use:	lung cancer, breast cancer, head and neck epidermoid cancer, nonmetastatic osteosarcoma, advanced stage NHL, AML, recalcitrant psoriasis, severe rheumatoid arthritis, pemphigus)
Toxicity:	in 5 10%; not dose-related
Prognosis:	usually self-limited despite continuation of therapy

blood eosinophilia (common)
nonspecific interstitial pneumonia (most common)
BOOP (less frequent)
linear/reticulonodular process (time delay of 12 days to 5 years, usually early)
acinar filling pattern (later)
transient hilar adenopathy + pleural effusion (on occasion)

DDx:

Pneumocystis pneumonia

Nitrofurantoin (Macrodantin )

Use: urinary tract infection

Toxicity: rare
- positive for ANA + LE cells
- acute disorder within 2 weeks of administration:
  - fever, dyspnea, cough
  - peripheral eosinophilia (more common)
  Prognosis: prompt resolution after withdrawal from drug
  - diffuse bilateral predominantly basal heterogeneous opacities
- chronic reaction with interstitial fibrosis (less common)
  - insidious onset of dyspnea + cough
  - may not be associated with peripheral eosinophilia
  - nonspecific interstitial pneumonia (common)
    - bilateral basilar interstitial opacities

OTHERS
- Heroin, propoxyphene, methadone
  
  Toxicity: overdose followed by pulmonary edema in 30 40%
  - bilateral widespread airspace consolidation
  - aspiration pneumonia in 50 75%
- Salicylates
  - asthma
  - pulmonary edema (with chronic ingestion)
- Intravenous contrast material
  - pulmonary edema

Disorders with hepatic and pulmonary manifestations

Alpha-1-antitrypsin deficiency
Cystic fibrosis
Hereditary hemorrhagic telangiectasia
Autoimmune disease: primary biliary cirrhosis, rheumatoid arthritis, Hashimoto thyroiditis, Sj gren syndrome, scleroderma, sarcoidosis
Drugs with toxic effects on lung and liver: methotrexate, phenytoin, amiodarone

Pulmonary edema

= abnormal accumulation of fluid in the extravascular compartments of the lung

Pathophysiology (Starling equation):

transcapillary flow dependent on

hydrostatic pressure
oncotic (= colloid osmotic) pressure
capillary permeability (the endothelial cells are relatively impermeable to protein but remain permeable to water and solutes; the tight intercellular junctions of alveolar epithelium remain nearly impermeable to water and solutes)

Q_filt = K_filt (HP_iv - HP_ev) - t(OP_iv - OP_ev)

Q_filt	= amount of fluid filtered per unit area per unit time
HP_iv	= intravascular hydrostatic pressure
HP_ev	= extravascular hydrostatic pressure
OP_iv	= intravascular oncotic pressure
OP_ev	= extravascular oncotic pressure
K_filt	= conductance of capillary wall = water resistance of capillary endothelial cell junction
t	= oncotic reflection coefficient = permeability of capillary membrane to macromolecules
Cause:	disturbed equilibrium of net flow F_net between fluid transudation/exudation Q_filt and lymphatic absorption Q_lymph

F_net = Q_filt - Q_lymph

INCREASED HYDROSTATIC PRESSURE
- cardiogenic (most common)
  - = PULMONARY VENOUS HYPERTENSION
  - Heart disease: left ventricular failure, mitral valve disease, left atrial myxoma
  - Pulmonary venous disease: acute/chronic pulmonary embolism, primary venoocclusive disease, mediastinal fibrosis
  - Pericardial disease: pericardial effusion, constrictive pericarditis (extremely rare)
  - Drugs: antiarrhythmic drugs; drugs depressing myocardial contractility (beta-blocker)
- noncardiogenic
  - Renal failure
  - IV fluid overload
  - Hyperosmolar fluid (eg, contrast medium)
- neurogenic
  - ? sympathetic venoconstriction in cerebrovascular accident, head injury, CNS tumor, postictal state
DECREASED COLLOID OSMOTIC PRESSURE
- Hypoproteinemia
- Transfusion of crystalloid fluid
- Rapid reexpansion of lung
INCREASED CAPILLARY PERMEABILITY

Endothelial injury from
- physical trauma: parenchymal contusion, radiation therapy
- aspiration injury:
  - Mendelson syndrome (gastric contents)
  - Near drowning in sea water/fresh water
  - Aspiration of hypertonic contrast media
- inhalation injury:
  - Nitrogen dioxide = silo-filler's disease
  - Smoke (pulmonary edema may be delayed by 24 48 hours)
  - Sulfur dioxide, hydrocarbons, carbon monoxide, beryllium, cadmium, silica, dinitrogen tetroxide, oxygen, chlorine, phosgene, ammonia, organophosphates
- injury via bloodstream
  - Vessel occlusion: shock (trauma, sepsis, ARDS) or emboli (air, fat, amniotic fluid, thrombus)
  - Circulating toxins: snake venom, paraquat
  - Drugs: heroin, morphine, methadone, aspirin, phenylbutazone, nitrofurantoin, chlorothiazide
  - Anaphylaxis: transfusion reaction, contrast medium reaction, penicillin
  - Hypoxia: high altitude, acute large airway obstruction

mnemonic:

ABCDEFGHI - PRN

Aspiration
Burns
Chemicals
Drugs (heroin, nitrofurantoin, salicylates)
Exudative skin disorders
Fluid overload
Gram-negative shock
Heart failure
Intracranial condition
Polyarteritis nodosa
Renal disease
Near drowning

Atypical pulmonary edema = lung edema with an unusual radiologic appearance

Unusual form of pulmonary edema = lung edema from unusual causes

Increased Hydrostatic Pressure Edema

Pulmonary capillary wedge pressure (PCWP):
- = reflects left atrial pressure and correlates well with radiologic features of CHF + pulmonary venous HTN
- In acute CHF radiologic features are delayed in onset and resolution

flow inversion = cephalization of pulmonary vessels is only seen in longstanding left heart failure, NEVER in pulmonary edema of renal failure/overhydration/low oncotic pressure

HRCT:

smooth interlobular septal + peribronchovascular thickening
ground-glass opacities in a perihilar/dependent distribution, which may progress to consolidation
centrilobular ground-glass nodules

Radiographic Signs in Pressure Edema
PCWP [mm Hg]	Findings
5 12	normal
12 17	cephalization of pulmonary vessels (only in chronic conditions)
17 20	Kerley lines, subpleural effusions
>25	alveolar flooding edema

Interstitial Pulmonary Edema

= 1st phase of pressure edema with increase in quantity of extracellular fluid

Cause:

increase in mean transmural arterial pressure of 15 25 mm Hg

early loss of definition of subsegmental + segmental vessels
mild enlargement of peribronchovascular spaces
appearance of Kerley lines
subpleural effusions
progressive blurring of vessels due to central migration of edema at lobar + hilar levels
small peripheral vessels difficult to identify due to a decrease in lung radiolucency
Often marked dissociation between clinical signs + symptoms + roentgenographic evidence
Nothing differentiates it from other interstitial lesions
Does not necessarily develop before alveolar pulmonary edema
NOT typical for bacterial pneumonia

Alveolar Flooding Edema

= 2nd phase of pressure edema

Cause:

increase in mean transmural arterial pressure of >25 mm Hg pressure-induced damage to alveolar epithelium

tiny nodular/acinar areas of increased opacity
frank consolidation

Bat-Wing Edema (in <10%)

= central nongravitational distribution of alveolar edema

Cause:

rapidly developing severe cardiac failure (acute mitral insufficiency associated with papillary muscle rupture, massive MI, valve leaflet destruction by septic endocarditis) or renal failure

lung cortex spared from fluid (due to pumping effect of respiration/contractile property of alveolar septa/mucopolysaccharide-filled perivascular matrix)

Asymmetric Distribution of Pressure Edema

Cause:

morphologic lung changes in COPD, hemodynamics, patient position

lung apices spared (= lung emphysema in heavy smokers)
upper + middle portions of lung spared (= end-stage TB, sarcoidosis, asbestosis)
predominantly RUL involvement (= mitral regurgitation refluxes preferentially into right upper pulmonary vein)
anteroposterior gradient on CT in recumbent position

P.409

unilateral edema in lateral decubitus position

Pulmonary Edema with Acute Asthma

Cause:	air trapping maintains a positive intraalveolar pressure and thus decreases hydrostatic pressure gradient
Pathogenesis:	associated with severity of M ller maneuver

heterogeneous edema (due to nonuniform airway obstruction)
peribronchial cuffing
ill-defined vessels
enlarged ill-defined hila
patency of narrowed airways maintained (due to high negative pleural pressure in forced inspiration)

Postobstructive Pulmonary Edema

Cause:	following relief from an upper airway obstruction (impacted foreign body, laryngospasm, epiglottitis, strangulation)
Pathogenesis:	(a) forced inspiration causes a high negative intrathoracic pressure (M ller maneuver) and increases venous return (b) obstruction creates high positive intrathoracic pressure that impairs development of edema

septal lines, peribronchial cuffing
central alveolar edema
normal heart size

Prognosis:

resolution within 2 3 days

Edema with Pulmonary Embolism (<10%)

Cause:

occlusion of pulmonary arterial bed causes redirection of blood flow and hypertension in uninvolved areas

areas of ground-glass attenuation
sharply demarcated from areas of transparency distal to occluded arteries
associated with dilated pulmonary arteries (70%)

Pulmonary Edema with Pulmonary Venoocclusive Disease

Cause:

organized thrombi in small veins causes an increase in peripheral resistance and hydrostatic pressure

rapidly progressive dyspnea, orthopnea
hemoptysis
normal/low pulmonary capillary wedge pressure
enlarged pulmonary arteries
diffuse interstitial edema + numerous Kerley lines
peribronchial cuffing
dilated right ventricle

Permeability Edema

Heroin-induced Pulmonary Edema

Hx:	overdose of opiates (almost exclusively with heroin, rarely with cocaine/ crack )
Frequency:	15% of cases of heroin overdose
Pathophysiology:	depression of medullary respiratory center leading to hypoxia + acidosis

widespread patchy bilateral airspace consolidations
ill-defined vessels + peribronchial cuffing
markedly asymmetric gravity-dependent distribution of edema (motionless recumbent position for hours/days)
resolution within 1 or 2 days in uncomplicated cases

Cx:

extensive crush injuries with associated muscle damage and ensuing renal insufficiency (from motionless recumbency)
aspiration of gastric contents

Prognosis:

10% mortality rate

Pulmonary Edema following Administration of Cytokines

intravenous interleukin 2 (IL-2):

enhances tumoricidal activity of natural killer cells in metastatic melanoma + RCC
intraarterial tumor necrosis factor:

increases production + release of IL-2

Frequency:	in 75% of IL-2 therapy; in 20% of tumor necrosis factor therapy; in 25% of recombinant IL-2 therapy
Pathophysiology:	permeability disruption of capillary endothelial cells

12 mm Hg increase in pulmonary capillary wedge pressure (direct toxic effect on myocardium)
pulmonary edema 1 5 days after start of therapy:
bilateral symmetric interstitial edema with thickened septal lines
peribronchial cuffing (75%)
small pleural effusions (40%)
no alveolar edema (unless associated cardiac insufficiency)

High-altitude Pulmonary Edema

Predisposed:	young males after rapid ascent to >3,000 m
Cause:	prolonged exposure to low partial oxygen atmospheric pressure
Pathophysiology:	acute persistent hypoxia with endothelial leakage

prodromal acute mountain sickness
dyspnea at rest, cough with frothy pink sputum
neurologic disturbances (due to brain edema)
arterial oxygen levels as low as 38%
central interstitial pulmonary edema
peribronchial cuffing
ill-defined vessels
patchy airspace consolidation

Mixed Hydrostatic & Permeability Edema

Neurogenic Pulmonary Edema

Frequency:	in up to 50% of severe brain trauma, subarachnoid hemorrhage, stroke, status epilepticus
Pathophysiology:	modification in neurovegetative pathways causes sudden increase in pressure in pulmonary venules with reduced venous outflow

dyspnea, tachypnea, cyanosis shortly after brain insult + rapid disappearance
bilateral inhomogeneous/homogeneous airspace consolidations, in 50% affecting predominantly the apices, disappearing within 1 2 days

P.410

Dx:	by exclusion
DDx:	fluid overload, postextubation edema

Reperfusion Pulmonary Edema

Frequency:	in up to 90 100%
Cause:	pulmonary thrombendarterectomy for massive pulmonary embolism/for webs and segmental stenosis
Pathophysiology:	rapid increase in blood flow + pressure

dyspnea, tachypnea, cough during the first 24 48 hours after reperfusion
pulmonary edema within 2 days after surgery:
heterogeneous airspace consolidation, predominantly in areas distal to recanalized vessels
random distribution in up to 50%

Reexpansion Pulmonary Edema

Cause:	rapid reexpansion of a collapsed lung following evacuation of hydrothorax, hemothorax or pneumothorax
Pathophysiology:	prolonged local hypoxic event, abrupt restoration of blood flow, sudden marked increase in intrapleural pressure, diffuse alveolar damage

frank respiratory insufficiency: cough, dyspnea, tachypnea, tachycardia, frothy pink sputum
may be asymptomatic
pulmonary edema within reexpanded entire lung within 1 hour (in 64%)
increase in severity within 24 48 hours with slow resolution over next 5 7 days

Prognosis:

20% mortality

Pulmonary Edema due to Air Embolism

Cause:	usually iatrogenic complication (neurosurgical procedure in sitting position, placement/manipulation of central venous line), rare in open/closed chest trauma
Pathophysiology:	embolized air bubbles cause mechanical obstruction of pulmonary microvasculature

sudden onset of chest pain, tachypnea, dyspnea
hypotension
air bubbles in right-sided cardiac chambers on echocardiography
interstitial edema
bilateral peripheral alveolar areas of increased opacity, predominantly at lung bases

Postpneumonectomy Pulmonary Edema

= life-threatening complication in the early postoperative period after pneumonectomy (rare in lobectomy or lung reduction surgery)

Frequency:	2.5 5%; R > L pneumonectomy
Risk factors:	excessive administration of fluid during surgery, transfusion of fresh frozen plasma, arrhythmia, marked postsurgical diuresis, low serum colloidal osmotic pressure
Pathophysiology:	increased capillary hydrostatic pressure, altered capillary permeability

marked dyspnea during first 2 3 postop days
ARDS-like picture

Prognosis:

very high mortality rate

Pulmonary Edema after Lung Transplantation

Frequency:	in up to 97% during first 3 days after surgery
Pathophysiology:	tissue hypoxia, disruption of pulmonary lymphatic drainage, lung denervation

progressive diffuse confluent areas of increased opacity, most pronounced on postop day 5
return to normal 2 weeks after surgery

Unilateral Pulmonary Edema

IPSILATERAL = on side of preexisting abnormality
- filling of airways
  - Unilateral aspiration/pulmonary lavage
  - Bronchial obstruction (drowned lung)
  - Pulmonary contusion
- increased pulmonary venous pressure
  - Unilateral venous obstruction
  - Prolonged lateral decubitus position
- pulmonary arterial overload
  - Systemic artery-to-pulmonary artery shunt (Waterston, Blalock-Taussig, Pott procedure)
  - Rapid thoracentesis (rapid reexpansion)
CONTRALATERAL = opposite to side of abnormality
- pulmonary arterial obstruction
  - Congenital absence/hypoplasia of pulmonary artery
  - Unilateral arterial obstruction
  - Pulmonary thromboembolism
- loss of lung parenchyma
  - Swyer-James syndrome
  - Unilateral emphysema
  - Lobectomy
  - Pleural disease
RIGHT UPPER LOBE PATHOGNOMONIC for mitral valve regurgitation

Pulmonary Edema with Cardiomegaly

Cardiogenic
Uremic (with cardiomegaly from pericardial effusion/hypertension)

Pulmonary Edema without Cardiomegaly

mnemonic:

U DOPA

Uremia
Drugs
Overhydration
Pulmonary hemorrhage
Acute myocardial infarction, arrhythmia

Noncardiogenic Pulmonary Edema

mnemonic:

The alphabet

ARDS, Alveolar proteinosis, Aspiration, Anaphylaxis
Bleeding diathesis, Blood transfusion reaction
CNS (increased pressure, trauma, surgery, CVA, cancer)
Drowning (near), Drug reaction
Embolus (fat, thrombus)

P.411

Fluid overload, Foreign-body inhalation
Glomerulonephritis, Goodpasture syndrome, Gastrografin aspiration
High altitude, Heroin, Hypoproteinemia
Inhalation (SO₂, smoke, CO, cadmium, silica)
-
Narcotics, Nitrofurantoin
Oxygen toxicity
Pancreatitis
-
Rapid reexpansion of pneumothorax/removal of pleural effusion
-
Transfusion
Uremia

Pneumonia

Classic pneumonia pattern:

Lobar distribution:
Bulging fissure:
Pulmonary edema:
Pneumatocele:
Alveolar nodules:

Streptococcus pneumoniae
Klebsiella
Viral/Pneumocystis pneumonia
Staphylococcus
Varicella, bronchogenic spread of TB

Distribution:

SEGMENTAL/LOBAR
- Normal host: S. pneumoniae, Mycoplasma, virus
- Compromised host: S. pneumoniae
BRONCHOPNEUMONIA
- Normal host: Mycoplasma, virus, Streptococcus, Staphylococcus, S. pneumoniae
- Compromised host: gram-negative, Streptococcus, Staphylococcus
- Nosocomial: gram-negative, Pseudomonas, Klebsiella, Staphylococcus
- Immunosuppressed: gram-negative, Staphylococcus, Nocardia, Legionella, Aspergillus, Phycomycetes
EXTENSIVE BILATERAL PNEUMONIA
- Normal host: virus (eg, influenza), Legionella
- Compromised host: candidiasis, Pneumocystis, tuberculosis
BILATERAL LOWER LOBE PNEUMONIA
- Normal host: anaerobic (aspiration)
- Compromised host: anaerobic (aspiration)
PERIPHERAL PNEUMONIA
- Noninfectious eosinophilic pneumonia

Transmission:

COMMUNITY-ACQUIRED PNEUMONIA

Organism: viruses, S. pneumoniae, Mycoplasma

Mortality: 10%
NOSOCOMIAL PNEUMONIA
- gram-negative organism (>50%): Klebsiella pneumoniae, P. aeruginosa, E. coli, Enterobacter
- gram-positive organism (10%): S. aureus, S. pneumoniae, H. influenzae

Complications:

Empyema
Pulmonary abscess
Cavitary necrosis
Pneumatocele
Pneumothorax
Pyopneumothorax
Bronchopleural fistula

Bacterial Pneumonia

Lobar Pneumonia

= ALVEOLAR PNEUMONIA
= pathogens reach peripheral air space, incite exudation of watery edema into alveolar space, centrifugal spread via small airways, pores of Kohn + Lambert into adjacent lobules + segments
nonsegmental sublobar consolidation
round pneumonia (= uniform involvement of contiguous alveoli)
- Streptococcus pneumoniae
- Klebsiella pneumoniae (more aggressive); in immunocompromised + alcoholics
- any pneumonia in children
- atypical measles
expansion of lobe with bulging of fissures
lung necrosis with cavitation
lack of volume loss

DDx:

Aspiration, pulmonary embolus

Lobular Pneumonia

= BRONCHOPNEUMONIA
= combination of interstitial + alveolar disease (injury starts in airways, involves bronchovascular bundle, spills into alveoli, which may contain edema fluid, blood, leukocytes, hyaline membranes, organisms)

Organism:

Staphylococcus aureus, Pseudomonas pneumoniae: thrombosis of lobular artery branches with necrosis + cavitation
Streptococcus (pneumococcus), Klebsiella, Legionnaires' bacillus, Bacillus proteus, E. coli, anaerobes (Bacteroides + Clostridia), Nocardia, actinomycosis
Mycoplasma

small fluffy ill-defined acinar nodules, which enlarge with time
lobar + segmental densities with volume loss from airway obstruction secondary to bronchial narrowing + mucus plugging

Atypical Bacterial Pneumonia

= bacterial infection with radiographic appearance of viral pneumonia

Organism:

Mycoplasma
Pertussis
Chlamydia trachomatis

Gram-negative Pneumonia

In 50% cause of nosocomial necrotizing pneumonias (including staphylococcal pneumonia)

Predisposed:

elderly, debilitated, diabetes, alcoholism, COPD, malignancy, bronchitis, gram-positive pneumonia, treatment with antibiotics, respirator therapy

P.412

Organism:

Klebsiella
Pseudomonas
coli
Proteus
Haemophilus
Legionella

airspace consolidation (Klebsiella)
spongy appearance (Pseudomonas)
affecting dependent lobes (poor cough reflex without clearing of bronchial tree)
bilateral
cavitation common

Cx:

(1) Exudate/empyema
(2) Bronchopleural fistula

Mycotic Infections of Lung

IN HEALTHY SUBJECTS
- Histoplasmosis
- Coccidioidomycosis
- Blastomycosis
OPPORTUNISTIC INFECTION
- Aspergillosis
- Mucormycosis (phycomycosis)
- Candidiasis

Growth:

(a) mycelial form
(b) yeast form (depending on environment)

Source of contamination:

soil
growth in moist areas (apart from Coccidioides)
contaminated bird/bat excreta

Viral Pneumonia

= infection of bronchi + peribronchial tissues

Pathophysiology:

tracheitis; bronchitis; bronchiolitis; peribronchial + interstitial septal infiltrates; injury to alveolar cells with hyaline membranes; necrosis of alveolar walls with blood, edema, fibrin, macrophages in alveoli

Organism:

Influenza virus: cavitary lesion confirms superimposed infection
Coxsackie virus, echovirus, reovirus
Parainfluenzavirus
Adenovirus
RSV = respiratory syncytial virus (12%)
Rhinovirus (43%)
Cytomegalic inclusion virus: features suggestive of bronchopneumonia
Varicella/herpes zoster: 10% of adults; 2 5 days after rash
Rubeola (measles) = before/with onset of rash; following overt measles = giant cell pneumonia
Mycoplasma (10%)

Path:	necrosis of ciliated epithelial cells, goblet cells, bronchial mucous glands with frequent involvement of peribronchial tissues + interlobular septa
Age:	most common cause of pneumonia in children under 5 years of age
Distribution:	usually bilateral

dirty chest = peribronchial cuffing + opacification:
- parahilar peribronchial linear densities (bronchial wall thickening)
- interstitial pattern
hyperaeration + air trapping (due to bronchial + bronchiolar narrowing from edema + secretions)
segmental + subsegmental atelectasis (common)
airspace pattern (from hemorrhagic edema) in 50%
pleural effusion (20%)
hilar adenopathy (3%)
striking absence of pneumatoceles, lung abscess, pneumothorax
radiographic resolution lags 2 3 weeks behind clinical

Cx:

(1) Bacterial superinfection (child becomes toxic after a week of sickness, peripheral consolidations + pleural effusion)
(2) Bronchiectasis
(3) Unilateral hyperlucent lung, bronchiolitis obliterans

Atypical measles pneumonia does NOT show the typical radiographic findings of viral pneumonias!

Cavitating Pneumonia

Staphylococcus aureus
Haemophilus influenzae
pneumoniae

other gram-negative organisms (eg, Klebsiella)

Cavitating Opportunistic Infections

FUNGAL INFECTIONS
- Aspergillosis
- Nocardiosis
- Mucormycosis (= phycomycosis)
SEPTIC EMBOLI
- Anaerobic organisms
STAPHYLOCOCCAL ABSCESS
TUBERCULOSIS (nummular form)

Repeated infections in same patient are not necessarily due to same organism!

DDx:

Metastatic disease in carcinoma/Hodgkin lymphoma

Interstitial Pneumonia

Acute Interstitial Pneumonia

= NONBACTERIAL PNEUMONIA
Initially predominantly affecting interstitial tissues

Organism:

viruses, Mycoplasma, Pneumocystis

often subacute atypical pneumonia
diffuse interstitial process with peribronchial thickening
segmental/lobar densities (mucus plugging + damage of surfactant-producing type 2 alveolar cells)

Chronic Interstitial Pneumonia

= diverse group of inflammatory disorders that can progress to pulmonary fibrosis

Modified Liebow classification:

Usual interstitial pneumonia (UIP)
Desquamative interstitial pneumonia (DIP)
Bronchiolitis obliterans with organizing pneumonia (BOOP)

P.413

added:

Acute interstitial pneumonia = Hamman-Rich syndrome
Nonspecific interstitial pneumonitis
Respiratory bronchiolitis-associated interstitial lung disease

no longer included:

Lymphoid interstitial pneumonia (LIP)

= potentially malignant lymphoproliferative disorder
Giant cell interstitial pneumonia (GIP)

= manifestation of hard-metal pneumoconiosis

Recurrent Pneumonia in Childhood

IMMUNE PROBLEM
- Immune deficiency
- Chronic granulomatous disease of childhood (males)
- Alpha 1-antitrypsin deficiency
ASPIRATION
- Gastroesophageal reflux
- H-type tracheoesophageal fistula
- Disorder of swallowing mechanism
- Esophageal obstruction, impacted esophageal foreign body
UNDERLYING LUNG DISEASE
- Sequestration
- Bronchopulmonary dysplasia
- Cystic fibrosis
- Atopic asthma
- Bronchiolitis obliterans
- Sinusitis
- Bronchiectasis
- Ciliary dysmotility syndromes
- Pulmonary foreign body

Eosinophilic lung disease

= PULMONARY INFILTRATION WITH BLOOD/TISSUE EOSINOPHILIA (PIE)

Classification:

IDIOPATHIC EOSINOPHILIC LUNG DISEASE
- Transient pulmonary eosinophilia = L ffler syndrome
  - peripheral eosinophilia
- Acute/chronic eosinophilic pneumonia
  - no peripheral eosinophilia
EOSINOPHILIC LUNG DISEASE OF SPECIFIC ETIOLOGY
- drug induced:
  
  nitrofurantoin, penicillin, sulfonamides, ASA, tricyclic antidepressants, hydrochlorothiazide, cromolyn sodium, mephenesin
- parasite induced:
  
  tropical eosinophilia (ascariasis, schistosomiasis), strongyloidiasis, ancylostomiasis (hookworm), filariasis, Toxocara canis (visceral larva migrans), Dirofilaria immitis, amebiasis (occasionally in RLL + RML)
- fungus induced:
  
  allergic bronchopulmonary aspergillosis, bronchocentric granulomatosis
- Pulmonary eosinophilia with asthma
EOSINOPHILIC LUNG DISEASE ASSOCIATED WITH ANGITIS GRANULOMATOSIS
- Wegener granulomatosis
- Churg-Strauss syndrome
- Lymphomatoid granulomatosis
- Bronchocentric granulomatosis
- Necrotizing sarcoid granulomatosis
- Polyarteritis nodosa
- Rheumatoid disease
- Scleroderma
- Dermatomyositis
- Sj gren syndrome
- CREST

Neonatal lung disease

Parenchymal Lung Disease on 1st Day of Life

Radiographic findings overlap!

Transient tachypnea of newborn
Respiratory distress syndrome
Neonatal pneumonia
Meconium aspiration syndrome
Premature with accelerated lung maturity (PALM)

Air Leaks in Neonatal Chest

Pulmonary interstitial emphysema
Pneumomediastinum
Pneumothorax
Gas below visceral pleura
- gas at lung base/against fissure
Pneumopericardium
Gas embolus to cardiac chambers/blood vessels

Mediastinal Shift & Abnormal Aeration in Neonate

SHIFT TOWARD LUCENT LUNG
- Diaphragmatic hernia
- Chylothorax
- Cystic adenomatoid malformation
SHIFT AWAY FROM LUCENT LUNG
- Congenital lobar emphysema
- Persistent localized pulmonary interstitial emphysema
- Obstruction of mainstem bronchus (by anomalous or dilated vessel/cardiac chamber)

Pulmonary Infiltrates in Neonate

mnemonic:

I HEAR

Infection (pneumonia)
Hemorrhage
Edema
Aspiration
Respiratory distress syndrome

Reticulogranular Densities in Neonate

Respiratory distress syndrome (90%): premature infant, inadequate surfactant
Prematurity with accelerated lung maturity (PALM)
- = IMMATURE LUNG SYNDROME:
  
  premature infant, normal surfactant (due to maternal steroid therapy/intrauterine stress)
- lung granularity, almost clear
- small thymus (stress/steroids)

P.414

Transient tachypnea of the newborn
Neonatal group-B streptococcal pneumonia
Idiopathic hypoglycemia
Congestive heart failure
Early pulmonary hemorrhage
Infant of diabetic mother

Hyperinflation in Newborn

level of inflation beyond 8th rib posteriorly
depressed configuration of hemidiaphragms best judged on LAT view

Fetal aspiration syndrome
Neonatal pneumonia
Pulmonary hemorrhage
Congenital heart disease
Transient tachypnea (mild)

Hyperinflation in Child

mnemonic:

BUMP FAD

Bronchiectasis
Upper airway obstruction (vascular ring, laryngitis)
Mucoviscidosis (cystic fibrosis)
Pneumonia (esp. staph)
Foreign body inhalation/ingestion
Asthma/viral bronchiolitis
Dehydration (diarrhea, acidosis)

Congenital Pulmonary Malformation

= SEQUESTRATION SPECTRUM

Congenital lobar emphysema
Bronchogenic cyst
Cystic adenomatoid malformation
Bronchopulmonary sequestration
Hypogenetic lung syndrome
Pulmonary arteriovenous malformation

Abnormal Lung Patterns

Mass
- = any localized density not completely bordered by fissures/pleura
Consolidative (alveolar) pattern
- = commonly produced by filling of air spaces with fluid (transudate/exudate)/cells/other material, ALSO by alveolar collapse, airway obstruction, confluent interstitial thickening
  
  ground glass = hazy area of increased attenuation not obscuring bronchovascular structures
  
  consolidation = marked increase in attenuation with obliteration of underlying anatomic features
Interstitial pattern
Vascular pattern
- increased vessel size:
  
  CHF, pulmonary arterial hypertension, shunt vascularity, lymphangitic carcinomatosis
- decreased vessel size: emphysema, thromboembolism
Bronchial pattern
- wall thickening: bronchitis, asthma, bronchiectasis
- density without air bronchogram (= complete airway obstruction)
- lucency of air trapping (= partial airway obstruction with ball-valve mechanism)

Alveolar (Consolidative) Pattern

Classic appearance of airspace consolidation:

mnemonic:

A²BC³

Acinar rosettes: rounded poorly defined nodules in size of acini (6 10 mm), best seen at periphery of opacity
Air alveologram/bronchogram
Butterfly/bat-wing distribution: perihilar/bibasilar
Coalescent/confluent cloudlike ill-defined opacities
Consolidation in diffuse, perihilar/bibasilar, segmental/lobar, multifocal/lobular distribution
Changes occur rapidly (labile/fleeting)

HRCT:

poorly marginated densities within primary lobule (up to 1 cm in size)
rapid coalescence with neighboring lesions in segmental distribution
predominantly central location with sparing of subpleural zones
air bronchograms

Diffuse airspace Disease

INFLAMMATORY EXUDATE = PUS
- Lobar pneumonia
- Bronchopneumonia: especially gram-negative organisms
- Unusual pneumonias
  - viral: extensive hemorrhagic edema especially in immunocompromised patients with hematologic malignancies + transplants
  - Pneumocystis
  - fungal: Aspergillus, Candida, Cryptococcus, Phycomycetes
  - tuberculosis
- Aspiration
HEMORRHAGE = BLOOD
- Trauma: contusion
- Pulmonary embolism, thromboembolism
- Bleeding diathesis:
  
  leukemia, hemophilia, anticoagulants, DIC
- Vasculitis:
  
  Wegener granulomatosis, Goodpasture syndrome, SLE, mucormycosis, aspergillosis, Rocky Mountain spotted fever, infectious mononucleosis
- Idiopathic pulmonary hemosiderosis
- Bleeding metastases: eg, choriocarcinoma
TRANSUDATE = WATER
- Cardiac edema
- Neurogenic edema
- Hypoproteinemia
- Fluid overload
- Renal failure
- Radiotherapy
- Shock
- Toxic inhalation
- Drug reaction
- Adult respiratory distress syndrome

P.415

SECRETIONS = PROTEIN
- Alveolar proteinosis
- Mucus plugging
MALIGNANCY = CELLS
- Bronchioloalveolar cell carcinoma
- Lymphoma
INTERSTITIAL DISEASE simulating airspace disease, eg, alveolar sarcoid

mnemonic: AIRSPACED
- Aspiration
- Inhalation, Inflammatory
- Renal (uremia)
- Sarcoidosis
- Proteinosis (alveolar)
- Alveolar cell carcinoma
- Congestive (CHF)
- Emboli
- Drug reaction, Drowning

Air-space Opacification in Trauma

ACUTE PHASE
- Pulmonary contusion = hemorrhage into alveoli
- Pulmonary laceration = tear in lung parenchyma
  - spherical hematoma = filled with blood
  - traumatic pneumatocele = filled with air
- Aspiration pneumonia
- Atelectasis due to splinting/mucous plug
- Pulmonary edema: cardiogenic/noncardiogenic
SUBACUTE PHASE (>24 hours) add
- Fat embolism
- Adult respiratory distress syndrome

Localized Airspace Disease

mnemonic:

4P's & TAIL

Pneumonia
Pulmonary edema
Pulmonary contusion
Pulmonary interstitial edema
Tuberculosis
Alveolar cell carcinoma
Infant
Lymphoma

Acute Alveolar Infiltrate

mnemonic:

I 2 CHANGE FAST

Infarct
Infection
Contusion
Hemorrhage
Aspiration
Near drowning
Goodpasture syndrome
Edema
Fungus
Allergic sensitivity
Shock lung
Tuberculosis

Chronic Alveolar Infiltrate

mnemonic:

STALLAG

Sarcoidosis
Tuberculosis
Alveolar cell carcinoma
Lymphoma
Lipoid pneumonia
Alveolar proteinosis
Goodpasture syndrome

CT Angiogram Sign

= homogeneous low attenuation of lung consolidation, which allows vessels to be clearly seen

Lobar bronchioloalveolar cell carcinoma
Lobar pneumonia
Pulmonary lymphoma
Extrinsic lipid pneumonia
Pulmonary infarction
Pulmonary edema

Interstitial lung disease

= thickening of lung interstices (= interlobular septa)

MAJOR LYMPHATIC TRUNKS
- Lymphangitic carcinomatosis
- Congenital pulmonary lymphangiectasia
- Pulmonary edema
- Alveolar proteinosis
PULMONARY VEINS (increased pulmonary venous pressure)
- Left ventricular failure
- Venous obstructive disease
SUPPORTING CONNECTIVE TISSUE NETWORK
- Interstitial edema
- Chronic interstitial pneumonia
- Pneumoconioses
- Collagen-vascular disease
- Interstitial fibrosis
- Amyloid
- Tumor infiltration within connective tissue
- Desmoplastic reaction to tumor

Path:

stereotypical inflammatory response of alveolar wall to injury
(a) acute phase: fluid + inflammatory cells exude into alveolar space, mononuclear cells accumulate in edematous alveolar wall
(b) organizing phase: hyperplasia of type II pneumocytes attempt to regenerate alveolar epithelium, fibroblasts deposit collagen
(c) chronic stage: dense collagenous fibrous tissue remodels normal pulmonary architecture

Characterizing criteria:

zonal distribution:
- upper/lower lung zones
- axial (core)/parenchymal (middle)/peripheral
volume loss
time course
interstitial lung pattern

Classification scheme:

Interstitial pneumonias
- Usual interstitial pneumonia (UIP)
- Nonspecific interstitial pneumonia (NSIP)
- Acute interstitial pneumonia (AIP)
- Alveolar macrophage pneumonia (AMP)
  - = desquamative interstitial pneumonia (DIP)
- Bronchiolitis obliterans organizing pneumonia
Diffuse infiltrative disease with granulomas
- Sarcoidosis
- Hypersensitivity pneumonitis
Lymphocytic interstitial pneumonia (LIP)
Pneumoconioses
Interstitial lung disease with cysts
- Langerhans cell histiocytosis
- Lymphangioleiomyomatosis
Interstitial lung disease with interlobular septal thickening
- Lymphangitic carcinomatosis
- Interstitial pulmonary edema
- Alveolar proteinosis
Eosinophilic syndrome
Pulmonary hemorrhage
Vasculitis

Interstitial Lung Pattern on CXR

LINEAR PATTERN
- Kerley lines = septal lines
  - = thickened connective septa
    
    Path: accumulation of fluid/tissue
    - Kerley A lines = relatively long fine linear shadows in upper lungs, deep within lung parenchyma radiating from hila
    - Kerley B lines = short horizontally oriented peripheral lines extending + perpendicular to pleura in costophrenic angles + retrosternal clear space
- reticulations
  - = innumerable interlacing linear opacities suggesting a mesh/network
  - Kerley C lines = fine spider web/lacelike polygonal opacities distributed primarily in a peripheral/subpleural location
    
    Path: pulmonary fibrosis (lower lobes), hypersensitivity pneumonitis (upper lobes)
  - thick linear opacities in a central/perihilar distribution
    
    Path: (a) dilated thick-walled bronchi of bronchiectasis
    (b) cysts of lymphangioleiomyomatosis/tuberous sclerosis
NODULAR/MILIARY PATTERN
- = small well-defined innumerable uniform 3 5-mm nodules with even distribution
  
  Path: diffuse metastatic disease, infectious granulomatous disease (TB, fungal), noninfectious granulomatous disease (pneumoconioses, sarcoidosis, eosinophilic granuloma)
DESTRUCTIVE FORM = honeycomb lung

Signs of Acute Interstitial Disease

peribronchial cuffing = thickened bronchial wall + peribronchial sheath (when viewed end on)
thickening of interlobular fissures
Kerley lines
perihilar haze = blurring of hilar shadows
blurring of pulmonary vascular markings
increased density at lung bases
small pleural effusions

Signs of Chronic Interstitial Disease

irregular visceral pleural surface
reticulations:
- fine reticulations
  - = early potentially reversible/minimal irreversible alveolar septal abnormality
  - (1) idiopathic pulmonary fibrosis (basilar predominance)
- coarse reticulations
  
  in 75% related to environmental disease, sarcoidosis, collagen-vascular disorders, chronic interstitial pneumonia
nodularity:

in 90% related to infectious/noninfectious granulomatous process, metastatic malignancy, pneumoconioses, amyloidosis
linearity:
- cardiogenic/noncardiogenic interstitial pulmonary edema
  - symmetric linearity
- lymphangitic malignancy
  - asymmetric linearity
- diffuse bronchial wall disorders (cystic fibrosis, bronchiectasis, hypersensitivity asthma)
honeycombing
- = usually subpleural clustered cystic air spaces <1 cm in diameter with thick well-defined walls set off against a background of increased lung density (end-stage lung)

HRCT approximately 60% more sensitive than CXR

Distribution of Interstitial Disease

MIDLUNG/PERIHILAR DISEASE
- Acute rapidly changing
  - Pulmonary edema
  - Pneumocystis pneumonitis
  - Early extrinsic allergic alveolitis
- Chronic slowly progressive
  - Lymphangitic carcinomatosis often unilateral, associated with adenopathy, pleural effusion
PERIPHERAL LUNG DISEASE
- Acute rapidly changing
  - Interstitial pulmonary edema with Kerley B lines (most common)
  - Active fibrosing alveolitis
- Chronic slowly progressive
  - Secondary pulmonary hemosiderosis
UPPER LUNG DISEASE
- Chronic slowly progressive volume loss
  - Postprimary TB (common)
  - Silicosis (common)
- Chronic slowly progressive with volume loss
  - Sarcoidosis (common)
  - Ankylosing spondylitis (rare)
  - Sulfa drugs (rare)
- Chronic slowly progressive without volume loss
  - Extrinsic allergic alveolitis
  - Eosinophilic granuloma
  - Aspiration pneumonia
  - Postradiation pneumonitis
  - Recurrent Pneumocystis carinii pneumonia (PCP) in a patient receiving aerosolized pentamidine prophylaxis

mnemonic:

SHIRT CAP

Sarcoidosis
Histoplasmosis
Idiopathic
Radiation therapy
Tuberculosis (postprimary)
Chronic extrinsic alveolitis
Ankylosing spondylitis
Progressive massive fibrosis

Chronic Diffuse Infiltrative Lung Disease

= CHRONIC INTERSTITIAL LUNG DISEASE
- = GENERALIZED INTERSTITIAL LUNG DISEASE

Prevalence:	up to 15% of pulmonary conditions
Cause:	>200 described disorders; in only 25 30% known/established etiology; 15 20 diseases comprise >90% of cases

dyspnea (primary complaint)
dry basilar rales/crackles that fail to clear with coughing

CXR:

Difficult to characterize due to similar findings
Differentiation into alveolar + interstitial disease is unreliable as interstitial disease invariably involves alveoli + vice versa
nonspecific abnormality

mnemonic:

HIDE FACTS

Hamman-Rich, Hemosiderosis
Infection, Irradiation, Idiopathic
Dust, Drugs
Eosinophilic granuloma, Edema
Fungal, Farmer's lung
Aspiration (oil), Arthritis (rheumatoid, ankylosing spondylitis)
Collagen vascular disease
Tumor, TB, Tuberous sclerosis
Sarcoidosis, Scleroderma

Zonal Predilection of Chronic Diffuse Lung Disease

Chronic Diffuse Infiltrative Lung Disease of Upper Lung Zone

= zone with higher oxygen tension and pH, but less efficient lymphatic drainage

inhalational disease
- Silicosis
- Coal worker pneumoconiosis
- Extrinsic allergic alveolitis
- Aspiration pneumonia
granulomatous disease
- Sarcoidosis
- Langerhans cell histiocytosis (EG)
- Postprimary TB (common)
others
- Cystic fibrosis
- Ankylosing spondylitis
- Chronic interstitial pneumonia
- Sulfa drugs (rare)
- Postradiation pneumonitis
- Recurrent Pneumocystis carinii pneumonia (PCP) in a patient receiving aerosolized pentamidine prophylaxis

mnemonic:

CASSET

Cystic fibrosis
Ankylosing spondylitis
Silicosis
Sarcoidosis
Eosinophilic granuloma
Tuberculosis, fungus

CHRONIC DIFFUSE INFILTRATIVE LUNG DISEASE OF LOWER LUNG ZONE

= zone with greater ventilation, perfusion, and lymphatic drainage

Idiopathic pulmonary fibrosis: usual interstitial pneumonia (common)
Lymphangitic carcinomatosis
Collagen vascular disease: scleroderma (common)
Asbestosis (posterior aspect of lung base)
Lymphangioleiomyomatosis
Chronic aspiration pneumonia with fibrosis (often regional + unilateral)

mnemonic:

BAD LASS RIF

Bronchiectasis
Aspiration
Dermatomyositis
Lymphangitic spread
Asbestosis
Sarcoidosis
Scleroderma
Rheumatoid arthritis
Idiopathic pulmonary fibrosis
Furadantin

Compartmental Predilection of Chronic Diffuse Lung Disease

AXIAL COMPARTMENT
- = peribronchial vascular bundles + lymphatics
- Sarcoidosis
- Lymphangitic carcinomatosis
- Lymphoma
MIDDLE/PARENCHYMAL COMPARTMENT
- = formed by alveolar walls
- Sarcoidosis
- Lymphangitic carcinomatosis
- Chronic medications
- Neurofibromatosis
- Vasculitis
- Silicosis
PERIPHERAL COMPARTMENT
- = pleura with subpleural connective tissue, interlobular septa, pulmonary veins, lymphatics, walls of cortical alveoli
- Sarcoidosis
- Lymphangitic carcinomatosis
- Idiopathic pulmonary fibrosis
- Collagen vascular disease
- Rheumatoid arthritis

Lung Volumes in Chronic Diffuse Lung Disease

CHRONIC DIFFUSE INFILTRATIVE LUNG DISEASE WITH NORMAL LUNG VOLUME

Sarcoidosis
Langerhans cell histiocytosis (in 66%)
Early stage

CHRONIC DIFFUSE INFILTRATIVE LUNG DISEASE WITH INCREASED LUNG VOLUME

mnemonic:

ELECT

Emphysema with interstitial lung disease
Lymphangioleiomyomatosis
Eosinophilic granuloma (Langerhans) in 33%
Cystic fibrosis
Tuberous sclerosis

CHRONIC DIFFUSE INFILTRATIVE LUNG DISEASE WITH REDUCED LUNG VOLUME

due to fibrotic process

Systemic lupus erythematosus
Collagen vascular disease (eg, scleroderma, dermatomyositis, polymyositis)
Idiopathic pulmonary fibrosis
Chronic interstitial pneumonias
Asbestosis

Pleural Disease in Chronic Diffuse Lung Disease

CHRONIC DIFFUSE INFILTRATIVE LUNG DISEASE WITH PNEUMOTHORAX

Lymphangioleiomyomatosis
Langerhans cell histiocytosis
End-stage lung disease

CHRONIC DIFFUSE INFILTRATIVE LUNG DISEASE WITH PLEURAL EFFUSION

Lymphangioleiomyomatosis
Rheumatoid arthritis
Systemic lupus erythematosus
Mixed connective tissue disorder
Wegener granulomatosis
Lymphangitic carcinomatosis
Pulmonary edema

CHRONIC DIFFUSE INFILTRATIVE LUNG DISEASE WITH PLEURAL THICKENING

Asbestosis
Collagen vascular disease

Lymphadenopathy in Chronic Diffuse Lung Disease

Silicosis
Sarcoidosis
Lymphoma
Lymphangitic carcinomatosis

Diffuse Fine Reticulations

Acute Diffuse Fine Reticulations

ACUTE INTERSTITIAL EDEMA
- Congestive heart failure
- Fluid overload
- Uremia
- Hypersensitivity
ACUTE INTERSTITIAL PNEUMONIA
- Viral pneumonia (Hantavirus, CMV)
- Mycoplasma pneumonia
- Pneumocystis carinii pneumonia

mnemonic:

HELP

Hypersensitivity
Edema
Lymphoproliferative
Pneumonitis (viral)

Chronic Diffuse Fine Reticulations

VENOUS OBSTRUCTION
- Atherosclerotic heart disease
- Mitral stenosis
- Left atrial myxoma
- Pulmonary venoocclusive disease
- Sclerosing mediastinitis
LYMPHATIC OBSTRUCTION
- Lymphangiectasia (pediatric patient)
- Mediastinal mass (lymphoma)
- Lymphoma/leukemia
- Lymphangitic carcinomatosis:
  
  predominantly basilar distribution
  - bilateral (breast, stomach, colon, pancreas)
  - unilateral (lung tumor)
- Lymphocytic interstitial pneumonitis
INHALATIONAL DISEASE
- Silicosis: small nodules + reticulations
- Asbestosis: basilar distribution, pleural thickening + calcifications
- Hard metals
- Allergic alveolitis
GRANULOMATOUS DISEASE

from a nodular to a reticular pattern if
- nodules line up along bronchovascular bundles
- interlobular septa show fibrotic changes
- Sarcoidosis:
  - hilar + mediastinal adenopathy (may have disappeared)
- Eosinophilic granuloma: upper lobe distribution
CONNECTIVE-TISSUE DISEASE
- reticulations in late stages
- Rheumatoid lung
- Scleroderma
- Systemic lupus erythematosus
DRUG REACTIONS
IDIOPATHIC
- Usual interstitial pneumonitis (UIP)
- Desquamative interstitial pneumonitis (DIP)
- Tuberous sclerosis: smooth muscle proliferation
- Lymphangiomyomatosis
- Idiopathic pulmonary hemosiderosis
- Alveolar proteinosis (late complication)
- Amyloidosis
- Interstitial calcification (chronic renal failure)

mnemonic:

LIFE lines

Lymphangitic spread
Inflammation/infection
Fibrosis

P.419

Edema

Coarse Reticulations

= architectural destruction of interstitium = end-stage scarring of lung = interstitial pulmonary fibrosis = honeycomb lung
coarse reticular interstitial densities with intervening cystic spaces
rounded radiolucencies <1 cm in areas of increased lung density
small lung volume (decreased compliance)

Cx:

(1) Intercurrent pneumothoraces
(2) Bronchogenic carcinoma = scar carcinoma

Cause:

INHALATIONAL DISEASE
- Pneumoconioses
  - Asbestosis: basilar distribution, shaggy heart, pleural thickening + calcifications
  - Silicosis: upper lobe predominance, pleural thickening, hilar and mediastinal lymphadenopathy
  - Berylliosis
- Chemical inhalation (late)
  - Silo-filler's disease (nitrogen dioxide)
  - Sulfur dioxide, chlorine, phosgene, cadmium
- Extrinsic allergic alveolitis
  - (= hypersensitivity to organic dusts)
- Oxygen toxicity
  - sequelae of RDS therapy with oxygen
- Chronic aspiration
  - eg, mineral oil: localized process in medial basal segments/middle lobe
GRANULOMATOUS DISEASE
- Sarcoidosis
- Eosinophilic granuloma
COLLAGEN-VASCULAR DISEASE
- Rheumatoid lung
- Scleroderma
- Ankylosing spondylitis: upper lobes
- SLE: rarely produces honeycombing
IATROGENIC
- Drug hypersensitivity
- Radiotherapy
IDIOPATHIC
- Usual interstitial pneumonitis (UIP)
  - honeycombing in 50%
  - severe volume loss in 45%
- Desquamative interstitial pneumonitis (DIP)
  - honeycombing in 12.5%
  - severe volume loss in 23%
- Lymphangiomyomatosis
- Tuberous sclerosis (rare)
- Neurofibromatosis (rare)
- Pulmonary capillary hemangiomatosis (rare)

DDx:

bronchiectasis, cavitary metastases (rare)

Reticulations & Pleural Effusion

ACUTE
- Edema
- Infection: viral, Mycoplasma (very rare)
CHRONIC
- Congestive heart failure
- Lymphangitic carcinomatosis
- Lymphoma/leukemia
- SLE
- Rheumatoid disease
- Lymphangiectasia
- Lymphangiomyomatosis
- Asbestosis

Reticulations & Hilar Adenopathy

Sarcoidosis
Silicosis
Lymphoma/leukemia
Lung primary: particularly oat cell carcinoma
Metastases: lymphatic obstruction/spread
Fungal disease
Tuberculosis
Viral pneumonia (rare combination)

Chronic Interstitial Disease Simulating Airspace Disease

Thoracic manifestations of Collagen vascular Disease
	Ankylosing Spondylitis	Dermatomyositis Polymyositis	Progressive Systemic Sclerosis	Rheumatoid Arthritis	Sj gren Syndrome	Systemic Lupus Erythematosus (SLE)
Pulmonary fibrosis	occasional	common	frequen	frequent	occasional	occasional
Pleural disease				frequent		frequent
Diaphragm weakness		frequent				frequent
Aspiration pneumonia		frequent	frequent
Bronchiectasis				occasional	common
Apical fibrosis	frequent
Bronchiolitis obliterans				common
BOOP		common		common

REPLACEMENT OF LUNG ARCHITECTURE BY AN INTERSTITIAL PROCESS
- neoplastic:
  - Hodgkin disease, histiocytic lymphoma
- benign cellular infiltrate:
  - lymphocytic interstitial pneumonia, pseudolymphoma
- granulomatous disease:
  - alveolar sarcoidosis
- fibrosis
EXUDATIVE PHASE OF INTERSTITIAL PNEUMONIA
- UIP
- Adult respiratory distress syndrome
- Radiation pneumonitis
- Drug reaction
- Reaction to noxious gases
CELLULAR FILLING OF AIR SPACE
- Desquamative interstitial pneumonia
- Pneumocystis carinii pneumonia

Reticulonodular Lung Disease

mnemonic:

Please Don't Eat Stale Tuna Fish Sandwiches Every Morning

Pneumoconiosis
Drugs
Eosinophilic granuloma
Sarcoidosis
Tuberculosis
Fungal disease
Schistosomiasis
Exanthem (measles, chickenpox)
Metastases (thyroid)

Reticulonodular Pattern & Lower Lobe Predominance

mnemonic:

CIA

Collagen vascular disease
Idiopathic
Asbestosis

Nodular Lung Disease

= round moderately well marginated opacity <3 cm in maximum diameter

GRANULOMATOUS LUNG DISEASE
- infections: eg, tuberculosis
- fungal disease: eg, histoplasmosis
- silicosis
- vasculitis: eg, Wegener granulomatosis
NEOPLASM
- metastatic lung diseases: eg, thyroid cancer
- lymphoma
- bronchioloalveolar cell carcinoma
OTHER DISEASE
- drug-induced: methotrexate
- nongranulomatous vasculitis
- sarcoidosis

Macronodular Lung Disease

nodules >5 mm in diameter

mnemonic:

GAMMA WARPS

Granuloma (eosinophilic granuloma, fungus)
Abscess
Metastases
Multiple myeloma
AVM
Wegener granulomatosis
Amyloidosis
Rheumatoid lung
Parasites (Echinococcus, paragonimiasis)
Sarcoidosis

Micronodular Lung Disease

= discrete 3 5-7-mm small round focal opacity of at least soft-tissue attenuation

Granulomatous disease (miliary tuberculosis, histoplasmosis)
Hypersensitivity (organic dust)
Pneumoconiosis (inorganic dust, thesaurosis = prolonged hair spray exposure)
Sarcoidosis
Metastases (thyroid, melanoma)
Histiocytosis X
Chickenpox

Diffuse Fine Nodular Disease & Miliary Nodules

very small 1 4-mm sharply defined nodules of interstitial disease

Inhalational disease
- Silicosis + coal worker's pneumoconiosis
- Berylliosis
- Siderosis
- Extrinsic allergic alveolitis (chronic phase)
Granulomatous disease
- Eosinophilic granuloma
- Sarcoidosis (with current/previous adenopathy)

Infectious disease

1. Bacteria:	salmonella, nocardiosis
2. Tuberculosis
3. Fungus:	histoplasmosis, coccidioidomycosis, blastomycosis, aspergillosis (rare), cryptococcosis (rare)
4. Virus:	varicella (more common in adults), Mycoplasma pneumonia

Metastases:
- thyroid carcinoma, melanoma, adenocarcinoma of breast, stomach, colon, pancreas
Alveolar microlithiasis (rare)
Bronchiolitis obliterans
Gaucher disease

mnemonic: TEMPEST

Tuberculosis + fungal disease
Eosinophilic granuloma
Metastases (thyroid, lymphangitic carcinomatosis)
Pneumoconiosis, Parasites
Embolism of oily contrast
Sarcoidosis
Tuberous sclerosis

FINE NODULAR DISEASE IN AFEBRILE PATIENT

Inhalational disease
Eosinophilic granuloma
Sarcoidosis
Metastases
Fungal infection (late stage)
Miliary tuberculosis (rare)

P.421

FINE NODULAR DISEASE IN FEBRILE PATIENT

Tuberculosis
Fungal infection (early stage)
Pneumocystis
Viral pneumonia

End-stage Lung Disease

= evidence of honeycombing/cystic change/conglomerate fibrosis

DISTRIBUTION
- Usual interstitial pneumonia
  - subpleural distribution + lower lobe predominance
- Asbestosis
  - subpleural distribution + lower lobe predominance + pleural thickening
- Sarcoidosis
  - subpleural honeycombing
  - central cystic bronchiectasis
  - conglomerate fibrosis
  - peribronchovascular distribution
  - upper lobe predominance
- Extrinsic allergic alveolitis
  - diffuse random distribution + patchy areas of ground-glass attenuation
CYSTIC SPACES WITH WELL-DEFINED WALLS
- Langerhans cell histiocytosis
  - upper lobe predominance
- Lymphangioleiomyomatosis
  - no zonal predominance
CONGLOMERATE FIBROTIC MASSES
- Sarcoidosis
  - peribronchovascular distribution
- Silicosis
  - bronchi splayed around masses
- Talcosis
  - areas of high attenuation (= talc deposits)

Honeycomb Lung

mnemonic:

SHIPS BOATS

Sarcoidosis
Histiocytosis X
Idiopathic (UIP)
Pneumoconiosis
Scleroderma
Bleomycin, Busulfan
Oxygen toxicity
Arthritis (rheumatoid), Amyloidosis, Allergic alveolitis
Tuberous sclerosis, TB
Storage disease (Gaucher)

Diffuse Lung Disease on HRCT

Patterns of Diffuse lung Disease on HRCT

maximum resolution = 300 m

linear densities
- = thickening of interlobular septa + bronchovascular interstitium
Cause: interstitial fluid/fibrosis/cellular infiltrates
- smooth septal thickening:
  - pulmonary edema, lymphangitic carcinomatosis
- beaded septa/septal nodules:
  - lymphangitic carcinomatosis
- irregular septa imply fibrosis
  - distorted lobules: fibrosis
  - no architectural distortion of lobules: edema/infiltration
reticular densities
- intricate network of criss-cross lines in subpleural location
- predominantly subpleural small reticular elements of 6 10 mm in diameter with small cystic changes ( honeycombing )
  
  Associated with: interstitial fibrosis, lymphangio-leiomyomatosis, amyloidosis
- fine diffusely distributed network of 2 3-mm basic elements
  
  Associated with: miliary TB, reactions to methotrexate
Distribution:
- lower lung zones in subpleural areas:
  - idiopathic pulmonary fibrosis, collagen vascular disease, asbestosis
- mid lung zone/all lung zones:
  - chronic extrinsic allergic alveolitis
- mid + upper lung zones: sarcoidosis
nodules
- interstitial nodules
  
  lymphangitic carcinomatosis, sarcoidosis, histiocytosis X, silicosis, coal worker pneumoconiosis, tuberculosis, hypersensitivity pneumonitis, metastatic tumor, amyloidosis
  - perihilar, peribronchovascular, centrilobular, interlobular septa, subpleural nodules
- airspace nodules
  
  lobular pneumonia, transbronchial spread of TB, bronchiolitis obliterans organizing pneumonia (BOOP), pulmonary edema
  - ill-defined nodules, a few mm to 1 cm in size
  - peribronchiolar + centrilobular
- Distribution:
  - along bronchoarterial bundles + interlobular septa + subpleural: sarcoidosis
  - upper zone: silicosis, coal-worker's pneumoconiosis
  - centrilobular: extrinsic allergic alveolitis
- DDx: vessel on cross section
Ground-glass attenuation
- = hazy increase in lung opacity without obscuration of underlying vessels secondary to parenchymal abnormalities below spatial resolution of HRCT
- Often indicative of an acute, active, and potentially treatable process!
- Histo:
  - alveolar wall inflammation/thickening
  - partial filling of air-spaces
  - combination of both
- Cause:
  - early interstitial lung disease = minimal alveolar wall thickening
  - alveolitis = minimal airspace filling as in ARDS, viral/mycoplasmal/pneumocystis pneumonia
    
    P.422
    - areas of higher attenuation with nodular/centrilobular distribution
    - pulmonary vessels uniform in size in areas of differing attenuation
    - increase in lung attenuation in low- and high-attenuation areas on expiratory HRCT
  - edema = increased capillary blood volume
  - hypersensitivity pneumonia
  - pulmonary hemorrhage
  - partial atelectasis = partial collapse of alveoli
  - normal during expiration
- Distribution:
  - peripheral in lower lung zones: DIP, UIP
  - mid + upper lung zones: sarcoidosis
  - crazy paving appearance: alveolar proteinosis
  - mosaic perfusion: chronic thromboembolism, bronchiolitis obliterans
Consolidation
- = increase in lung opacity with obscuration of underlying vessels
- air-bronchogram
- sharp border at major fissure
- advancing margin of ground-glass opacity
- vessels visible only on enhanced CT
- Cause:
  - any process filling airspaces with blood, fluid, inflammatory cells, tumor cells
  - alveolar collapse = atelectasis
- subpleural in mid + upper lung zones:
  - chronic eosinophilic pneumonia
- subpleural + peribronchial: BOOP
- focal:
  - bronchioloalveolar cell carcinoma, lymphoma
- random: infectious pneumonia
Cystic airspaces
- = circumscribed round structure filled with air
  - with well-defined walls:
    - lymphangioleiomyomatosis, pulmonary Langerhans-cell granulomatosis, honeycomb lung, cystic bronchiectasis
  - without well-defined walls:
    - centrilobular, panlobular (panacinar), paraseptal emphysema
- Cause:
  - focally clustered:
    - cystic bronchiectasis
  - subpleural location:
    - honeycombing, Langerhans cell histiocytosis, lymphangioleiomyomatosis

Centrilobular Nodules

Acute/chronic bronchiolar infection
- Bacterial infection
- Viral infection
- Fungal infection
Inflammation
- Hypersensitivity pneumonia
- Respiratory bronchiolitis
- Bronchiolitis obliterans organizing pneumonia
- Bronchiolitis obliterans
- Pneumoconiosis
- Sarcoidosis
- Asthma
- Autoimmune/immunodeficiency disease

PERIBRONCHIAL/PERIBRONCHIOLAR NODULES

Metastatic calcifications
Endobronchial spread of infection
Hypersensitivity pneumonia
Sarcoidosis
Silicosis
Langerhans cell histiocytosis
Respiratory bronchiolitis

CENTRILOBULAR NODULES WITHOUT GROUND-GLASS OPACITIES

Endobronchial TB
Chronic bronchiolitis
Silicosis
Langerhans cell histiocytosis

CENTRILOBULAR NODULES WITH GROUND-GLASS OPACITIES

Hypersensitivity pneumonia
Bronchiolitis obliterans organizing pneumonia

Random Nodules

Hematogenous metastases: thyroid, kidney, breast
Miliary infection
Langerhans cell histiocytosis
Sarcoidosis
Silicosis

Thickened Bronchovascular, Interlobular Septal & Pleural Interstitium

Uni-/bilateral
- Lymphangitic tumor
- Lymphoma
Bilateral
- Kaposi sarcoma
- Edema

Parenchymal Bands & Architectural Distortion

Asbestos-related lung disease
Atelectasis
Tuberculosis
Sarcoidosis
Diffuse pulmonary fibrosis

Smooth Thickening of Interstitium

Lymphangitic tumor
Edema
Lymphoma
Kaposi sarcoma
Sarcoidosis (uncommon)

HRCT of Bronchiolitis

[CT findings are nonspecific and must be interpreted in the appropriate clinical context]

Cause:

infection via endobronchial spread:
- bacterial (most common)
- mycobacterial: classic TB, nonclassic M. avium-intracellulare ( Lady Windermere syndrome commonly in RML + lingula)
- viral: acute infectious bronchiolitis in infants and young children due to RSV, adenovirus, mycoplasma
- parasitic
- fungal
- Most common cause of tree-in-bud appearance
aspiration of infected oral secretions/other irritant material/inert barium: mineral dust airway disease, extrinsic allergic alveolitis, chronic bronchitis
immunologic deficiency or impaired host defense: cystic fibrosis, dyskinetic cilia syndrome
cigarette smoking
- Respiratory bronchiolitis
idiopathic
- Diffuse panbronchiolitis in Orientals
- Follicular bronchiolitis: rheumatoid arthritis, Sj gren syndrome
- Asthma
- Bronchiolitis obliterans
- Bronchiolitis obliterans with organizing pneumonia

DIRECT SIGNS
- ringlike tubular structures in lung periphery
  
  Cause: wall thickening
- dilatation of bronchioles
  
  Cause: bronchiolectasis
- 2- to 4-mm nodules/branching linear structures in lung periphery
  
  Cause: bronchiolar luminal impaction with pus, mucus, granulomas, inflammatory exudate, fibrosis
INDIRECT SIGNS
- subsegmental atelectasis = wedge-shaped area of ground-glass attenuation
- air trapping = area of decreased attenuation from collateral air drift/ball-valve effect distal to occluded/stenotic airway more prominent on expiration:
  
  DDx: physiologic air trapping with a few lucent secondary pulmonary lobules
  - mosaic perfusion = scattered areas of air trapping
  - centrilobular emphysema = destruction of small airways + surrounding parenchyma in the center of the pulmonary lobule
- centrilobular airspace nodule = acinar nodule = <1 cm ill-defined nodule of ground-glass attenuation (from inflammation within alveolar space) less prominent on expiration
  
  Cause: extrinsic allergic alveolitis, sarcoidosis (perivenular nodules), pneumoconiosis (asbestosis, silicosis)
DDx: (1) Cystic lung disease (thin septum surrounds area of air attenuation, central vessel not present)
(2) Panlobular emphysema (distortion of vascular + septal architecture, bullae)

Pattern of Bronchiolar Disease

Tree-in-bud appearance

= peripheral (within 5 mm of pleural surface) small (2 4 mm) centrilobular well-defined nodules connected to linear branching opacities with more than one contiguous branching sites

Histo:

bronchiolar luminal impaction with mucus, pus or fluid
+ dilatation of distal bronchioles
+ bronchiolar wall thickening
+ peribronchiolar inflammation
(analogous to gloved finger appearance)

depiction of the normally invisible branching course of the intralobular bronchiole on HRCT
air trapping subsegmental consolidation

INFECTION (most common)
- Bacterial: Mycobacterium tuberculosis (endobronchial spread of active TB), M. avium-intracellulare complex, Staphylococcus aureus, Haemophilus influenzae
- Viral: CMV, Respiratory syncytial virus
- Fungal: invasive aspergillosis
IMMUNOLOGIC DISORDER
- Allergic bronchopulmonary aspergillosis
- Congenital immunodeficiencies
CONGENITAL
- Cystic fibrosis
- Dyskinetic cilia syndrome (Kartagener syndrome)
- Yellow nail syndrome
CONNECTIVE TISSUE DISORDER
- Rheumatoid arthritis
- Sj gren syndrome
IDIOPATHIC
- Obliterative bronchiolitis
- Diffuse panbronchiolitis
NEOPLASM
- Primary pulmonary lymphoma
- Laryngotracheal papillomatosis
TUMOR EMBOLI
- Gastric cancer
- Breast cancer
- Ewing sarcoma
- Renal cancer
ASPIRATION of irritant substance
- Aspiration pneumonitis
INHALATION of toxic fumes + gases

Mosaic Perfusion

= patchwork of normal and air-attenuated segments
vessels in areas of low attenuation are smaller in 94% (due to differential blood flow)
normal/dilated arteries in areas of hyperattenuation in 77%
Pathophysiology:
- Air trapping
  - due to any obstructive lung disease
    - Chronic bronchitis/bronchiolitis
    - Bronchiectasis
    - Emphysema
    - Asthma
    - also: sarcoidosis, hypersensitivity pneumonia
  - attenuation differences are accentuated on expiratory HRCT
- Vascular obstruction
  - due to
    - Precapillary pulmonary hypertension
    - Pulmonary veno-occlusive disease
  - increase in lung attenuation in low- and high-attenuation areas on expiratory HRCT

Focal Air-trapping on HRCT

Asthma
Bronchiolitis obliterans
Bronchiectasis

Ground-glass Attenuation

Desquamative interstitial pneumonia
Extrinsic allergic alveolitis
Sarcoidosis
Usual interstitial pneumonia
Alveolar proteinosis
Cryptogenic organizing pneumonia

Large Symmetric Regions of Ground-glass Opacities

WATER
- Pulmonary edema
- Uremic lung
- Acute interstitial pneumonia
- Adult respiratory distress syndrome
PROTEIN
- Alveolar proteinosis
- Nonspecific interstitial pneumonia
RBCs
- Pulmonary hemorrhage
WBCs
- Hypersensitivity pneumonia
- Acute/chronic eosinophilic pneumonia
- Desquamative interstitial pneumonia
- Churg-Strauss syndrome
- Atypical pneumonia (viral, pneumocystis, mycoplasma)
TUMOR
- Bronchioloalveolar cell carcinoma

Focal Area of Ground-glass Attenuation

Bronchioloalveolar cell carcinoma
Pulmonary infiltrate with eosinophilia syndrome
- simple pulmonary eosinophilia
- idiopathic hypereosinophilic syndrome
- parasitic infection
Lymphoma
Hemorrhagic nodule

Ground-glass Opacities & Interlobular Septal Lines

ACUTE/SUBACUTE
- Hypersensitivity pneumonia
- Pulmonary edema
- Diffuse alveolar hemorrhage
- Viral, pneumocystis, mycoplasmal pneumonia
CHRONIC
- Hypersensitivity pneumonia
- Pulmonary alveolar proteinosis
- Usual interstitial pneumonia
- Bronchioloalveolar cell carcinoma

Ground-glass Opacity & Reticular Change

Nonspecific interstitial pneumonia
Desquamative interstitial pneumonia
Acute interstitial pneumonia
BOOP
Chronic eosinophilic pneumonia
Churg-Strauss syndrome

Crazy-paving Pattern

= combination of patchy ground-glass opacities + smooth interlobular septal thickening in geographic distribution

Pulmonary alveolar proteinosis
Pneumocystic carinii pneumonia
Mucinous bronchioloalveolar cell carcinoma
Sarcoidosis
Nonspecific interstitial pneumonia
Organizing pneumonia
Exogenous lipoid pneumonia
ARDS
Pulmonary hemorrhage syndromes

Pulmonary nodule/mass

Solitary Nodule/Mass

Definition:

any pulmonary/pleural sharply defined discrete nearly circular opacity

2 30 mm in diameter

nodule

>30 mm in diameter

mass (>90% prevalence of malignancy)

Incidence: 150,000 annually in USA on CXR

roentgenographic survey of low-risk population: <5% of nodules are cancerous
on surgical resection: 40% malignant tumors (lung primar + metastases), 40% granulomas

Early Lung Cancer Action Project:

233 noncalcified nodules in 1000 participants by CT;

P.425

2244 noncalcified nodules in 1000 of 1520 participants (Mayo Clinic) by CT

INFLAMMATION/INFECTION
- infectious
  - Granuloma (most common lung mass): sarcoidosis (1/3), tuberculosis, histoplasmosis, coccidioidomycosis, nocardiosis, cryptococcosis, talc, Dirofilaria immitis (dog heartworm), gumma, atypical measles infection
  - Fluid-filled cavity: abscess, hydatid cyst, bronchiectatic cyst, bronchocele
  - Mass in preformed cavity: fungus ball, mucoid impaction
  - Rounded atelectasis
  - Inflammatory pseudotumor: fibroxanthoma, histiocytoma, plasma cell granuloma, sclerosing hemangioma
  - Paraffinoma = lipoid granuloma
  - Focal organizing pneumonia
  - Round pneumonia
- noninfectious
- Rheumatoid arthritis
- Wegener granulomatosis
MALIGNANT TUMORS (<30%)
- A solitary pulmonary nodule is the initial radiographic finding in 20 30% of patients with lung cancer!
- Malignant primaries of lung:
  - Bronchogenic carcinoma (66%, 2nd most common mass)
  - Primary pulmonary lymphoma
  - Primary sarcoma of lung
  - Plasmacytoma (primary/secondary)
  - Clear cell carcinoma, carcinoid, giant cell ca.
- Metastases (4th most common cause) in adults: kidney, colon, ovary, testes in children: Wilms tumor, osteogenic sarcoma, Ewing sarcoma, rhabdomyosarcoma

BENIGN TUMORS

lung tissue
fat tissue
fibrous tissue
muscle tissue
neural tissue
lymph tissue
deposits

: hamartoma (6%, 3rd most common lung mass), chondroma
: lipoma (usually pleural lesion)
: fibroma
: leiomyoma
: schwannoma, neurofibroma, paraganglioma
: intrapulmonary lymph node
: amyloid, splenosis, endometrioma, extramedullary hematopoiesis

VASCULAR
- Arteriovenous malformation (AVM), hemangioma
- Hematoma
- Organizing infarct
- Pulmonary venous varix
- Pseudoaneurysm of pulmonary artery
DEVELOPMENTAL/CONGENITAL
- Bronchogenic cyst (fluid-filled)
- Pulmonary sequestration
- Bronchial atresia
INHALATIONAL
- Silicosis (conglomerate mass)
- Mucoid impaction (allergic aspergillosis)
MIMICKING DENSITIES (20%)
- Pseudotumor
  - Fluid in fissure
  - Composite area of increased opacity
- Mediastinal mass
- Chest wall lesion
  - Nipple
  - Skin tumor: mole, neurofibroma, lipoma, keloid
  - Bone island, rib osteochondroma
  - Rib fracture/osteophyte
  - Pleural plaque/mass (mesothelioma)
- External object
  - Electrocardiographic lead attachment
  - Buttons, snaps

mnemonic:

Big Solitary Pulmonary Masses Commonly Appear Hopeless And Lonely

Bronchogenic carcinoma
Solitary metastasis, Sequestration
Pseudotumor
Mesothelioma
Cyst (bronchogenic, neurenteric, echinococcal)
Adenoma, Arteriovenous malformation
Hamartoma, Histoplasmosis
Abscess, Actinomycosis
Lymphoma

Morphologic Evaluation of Solitary Pulmonary Nodule

SIZE
- The smaller the nodule the more likely it is benign!
- <20 mm nodule: in 80% benign
- >30 mm nodule: in >93% malignant
- N.B.:
  - 15% of malignant nodules are <10 mm
  - 42% of malignant nodules are <20 mm
  - nodule >3 cm is suspect for malignancy
MARGIN/EDGE
- smooth well-defined margin = likely benign
- Mostly benign, in 21% malignant
- corona radiata = irregular spiculated margin
- In 89% malignant, in 10% benign
- pleural tag
- In 25% malignant, in 9% benign
- halo sign (= nodule surrounded by ground-glass opacity)
- In neutropenic patient suggests aspergillosis
- vessels feeding a smooth/lobulated nodule
- in arteriovenous malformation
CONTOUR
- sharply marginated lesions are benign in 79%
- lobulated nodule implies
  - organizing mass
  - tumor with multiple cell types growing at different rates (malignancy, hamartoma)
- A lobulated contour implies malignancy in 58%, but occurs in 25% of benign nodules!
- vessel leading to mass: pulmonary varix, AVM

P.426

INTERNAL ATTENUATION
- homogeneous attenuation in 55% of benign + 20% of malignant nodules
- pseudocavitation (= small focal hypodense region) with air bronchogram suggest bronchioloalveolar cell carcinoma/lymphoma/resolving pneumonia
- Air bronchogram in nodules of <2 cm: in 65% malignant, in 5% benign
- bubblelike areas of low attenuation: bronchioloalveolar cell carcinoma (in 50%)
CAVITATION
- a thin ( 4 mm) smooth wall is benign in 94%
- a thick (>16 mm) irregular wall suggests a malignant nodule
INTRANODULAR FAT (-40 to -120 HU)
- Fat is a reliable indicator of a hamartoma!
- fat density in up to 50% of hamartomas
CALCIFICATION
- 22 36% of nodules considered noncalcified on CXR contain calcium on thin-section CT!
- HRCT detects more calcium by 24% compared to standard CT!
- HRCT is 10 20 times more sensitive than CXR!
- >200 HU at CT densitometry indicates calcification within a nodule (66% sensitive, 98% specific for benign disease)
- 38 63% of benign nodules are not calcified!
- diffuse amorphous, eccentric, stippled = malignant pattern
- central, completely solid, laminated: granuloma of prior infection (TB/histoplasmosis)
- popcornlike = chondroid calcification in a hamartoma in 5 50%
- peripheral calcification: granuloma, tumor
Calcifying malignant lung tumors:
- carcinoid (up to 33%), lung cancer (up to 6%), osteosarcoma, chondrosarcoma, metastatic mucinous adenocarcinoma
SATELLITE LESION
- = nodule(s) in association with larger peripheral nodule
- in 99% due to inflammatory disease (often TB)
- in 1% due to primary lung cancer
ENHANCEMENT PATTERN
- see next section

Growth Rate Assessment of Indeterminate Solitary Pulmonary Nodule

= comparing size of nodule on current image with that on prior image

General recommendation:

3-month intervals for up to 1 year and 6-month intervals for another year

Best method (quite imprecise):

early repeat HRCT (resolution in and y planes of 0.3 mm) in 1 4 weeks for nodules >5 mm measuring volume/area/diameter of nodule

Doubling time (= time required to double in volume):

for most malignant nodules: 30 400 days
- = 26% increase in diameter
- 30 days: aggressive small cell cancer
- 90 days: squamous cell carcinoma
- 120 days: large cell carcinoma
- 150 days: aggressive adenocarcinoma
- 180 days: average adenocarcinoma
for benign nodules: <30 and > 400 days
- Absence of growth over a 2-year period implies a doubling time of >730 days

Disadvantage:

only 65% positive predictive value
- very slow growth:
  - hamartoma, bronchial carcinoid, inflammatory pseudotumor, granuloma, low-grade adenoca., metastases from renal cell carcinoma
- very rapid growth:
  - osteosarcoma, choriocarcinoma, testicular neoplasm, organizing infectious process, infarct (thromboembolism, Wegener granulomatosis)
unreliable growth perception in nodules <10 mm:
- eg, a nodule with a doubling time of 6 months increases its diameter from 5 mm to only 6.25 mm remaining radiologically stable
better: volumetric growth assessment
delay can worsen the prognosis
- decrease in size with time: benign lesion
- Bronchogenic carcinoma may show temporary decrease in size due to infarction - necrosis - fibrosis - retraction sequence!

Clinical Assessment of Indeterminate Solitary Pulmonary Nodule

by patient age (prevalence of cancer <30 years is low), history of prior malignancy, presenting symptoms, smoking history

Management Strategies of Indeterminate Solitary Pulmonary Nodule

Bayesian Analysis
- Analysis of patient characteristics + selected radiologic features is superior to evaluation by experienced radiologist in stratification of benign and malignant nodules!
- Likelihood ratio (LR) = probability of malignancy = LR of 1.0 means a 50% chance of malignancy
- Odds of malignancy (Odds_ca) = sum of LR of radiologic features or patient characteristics
- Probability of malignancy:
  - (pCa) = Odds_ca/(1 + Odds_ca)
Decision Analysis
- = cost-effective strategy for management decision determined by pCa
pCa <0.05 observation

pCa >0.05 and <0.6 biopsy

pCa 0.60 immediate surgical resection
Contrast-enhanced thin-section CT
- = degree of enhancement directly related to vascularity + likelihood of malignancy
- Technique:
  - 300 mg/mL iodine at 2 mL/sec (total dose 420 mg/kg)
  - delay of 20 seconds from onset of injection
  - contiguous sections through the nodule obtained at 1, 2, 3, and 4 minutes after onset of injection
  - scan of chest and upper abdomen obtained between 1 and 2 minutes after onset of injection
- nodule enhancement of
  - <15 HU suggests benign lesion
  - >20 HU indicates malignancy
  - (98% sensitive, 73% specific, 75 85% accurate)

F-18-FDG Positron Emission Tomography (PET)

= increased glucose metabolism in tumors resulting in increased accumulation (= uptake and trapping of FDG-6-phosphate)
no uptake = benign nodule (92 100% sensitive, 52 100% specific, 94% accurate)
intensity greater than mediastinum/SUV (standardized uptake value) >2.5 indicates malignancy (95 100% sensitive, 80 89% specific, 92% accurate for nodules >15 mm)
SUV of 0.4 - 2.0 indicates a benign lesion
continually increasing FDG uptake over time is indicative of malignancy
gradual washout of FDG after initial increase suggests benign inflammatory lesion

FN:	elevated serum glucose level >250 mg/dL, low-grade malignancy (bronchioloalveolar carcinoma), carcinoid tumor, mucinous neoplasm; malignant lesion <7 mm
FP:	sarcoidosis, active TB, fungal infection (histoplasmosis, aspergillosis, coccidiomycosis), silicoanthracosis, lipoid pneumonia, rheumatoid nodule, Wegener, radiation pneumonitis

Transthoracic Needle Aspiration Biopsy
- 95 100% sensitive for 10 15-mm malignancies;
- up to 91% sensitive for establishing a benign diagnosis
Cx: pneumothorax (5 30%) with chest tube placement in 15%; self-limiting hemorrhage
Bronchoscopy
- 10% diagnostic yield for nodules <20 mm;
- 40 60% diagnostic yield for nodules 20 40 mm
Cx: lower than transthoracic needle biopsy

Probability of malignancy for indeterminate Solitary Pulmonary nodule
Characteristic/Feature	Likelihood Ratio
spiculated margin	5.54
size >3 cm	5.23
>70 years of age	4.16
malignant growth rate	3.40
smoker	2.27
upper lobe location	1.22
size <10 mm	0.52
smooth margin	0.30
30 39 years of age	0.24
never smoked	0.19
20 29 years of age	0.05
benign calcification	0.01
benign growth rate	0.01

CT Halo Sign

central area of soft-tissue attenuation surrounded by a halo of ground-glass attenuation

Hemorrhagic Pulmonary Nodule
- HEMORRHAGIC INFARCTION (angioinvasion)
  - Early invasive aspergillosis
  - Mucormycosis
  - Hematogenous candidiasis
  - Coccidioidomycosis
- NECROTIZING VASCULITIS
  - Wegener granulomatosis
- FRAGILITY OF NEOVASCULAR TISSUE
  - Metastatic angiosarcoma
  - Metastatic choriocarcinoma
  - Metastatic osteosarcoma
  - Kaposi sarcoma
- TRAUMA
  - Following lung biopsy
  - Lung transplant
LEPEDIC TUMOR GROWTH
- Bronchioloalveolar carcinoma
- Metastatic extrapulmonary adenocarcinoma
- Lymphoma
OTHERS
- Eosinophilic pneumonia
- Bronchiolitis obliterans organizing pneumonia
- Tuberculoma associated with hemoptysis
- Mycobacterium avium complex
- Herpes simplex, CMV, varicella-zoster virus

Benign Lung Tumor

CENTRAL LOCATION
- Bronchial polyp
- Bronchial papilloma
- Granular cell myoblastoma
  - = cell of origin from neural crest
  Age: middle-aged, esp. Black women
  - endobronchial lesion in major bronchi
PERIPHERAL LOCATION
- Hamartoma
- Leiomyoma:
  - benign metastasizing leiomyoma, history of hysterectomy
- Amyloid tumor:
  - not associated with amyloid of other organs/rheumatoid arthritis/myeloma
- Intrapulmonary lymph node
- Arteriovenous malformation
- Endometrioma, fibroma, neural tumor, chemodectoma
CENTRAL/PERIPHERAL
- Lipoma:
  - subpleural
  - endobronchial
PSEUDOTUMOR
- Fibroxanthoma/xanthogranuloma
- Plasma cell granuloma
- Sclerosing hemangioma:
  - middle-aged woman, RML/RLL (most commonly), may be multiple
- Pseudolymphoma
- Round atelectasis
- Pleural pseudotumor = accumulation of pleural fluid within interlobar fissure

Lung Tumor in Childhood

Metastatic (common)
Blastoma
Mucoepidermoid carcinoma
Bronchogenic carcinoma
Hemangiopericytoma
Rhabdomyosarcoma

Large Pulmonary Mass

mnemonic:

CAT PIES

Carcinoma (large cell, squamous cell, cannon ball metastasis
Abscess
Toruloma (Cryptococcus)
Pseudotumor, Plasmacytoma
Inflammatory
Echinococcal disease
Sarcoma, Sequestration

Cavitating Lung Nodule

NEOPLASM
- Lung primary:
  - Squamous cell carcinoma (10%)
  - Adenocarcinoma (9.5%)
  - Bronchioloalveolar carcinoma (rare)
  - Hodgkin disease (rare)
- Metastases (4% cavitate):
  - Squamous cell carcinoma (2/3):
    - nasopharynx (males), cervix (females), esophagus
  - Adenocarcinoma (colorectal)
  - Sarcoma: Ewing sarcoma, osteo-, myxo-, angiosarcoma
  - Melanoma
  - Seminoma, teratocarcinoma
  - Wilms tumor
COLLAGEN-VASCULAR DISEASE
- Pulmonary angitis + granulomatosis - Wegener granulomatosis + Wegener variant
- Rheumatoid nodules + Caplan syndrome
- SLE
- Periarteritis nodosa (rare)
GRANULOMATOUS DISEASE
- Histiocytosis X
- Sarcoidosis (rare)
VASCULAR DISEASE
- Pulmonary embolus with infarction
- Septic emboli (Staphylococcus aureus)
INFECTION
- Bacterial: pneumatoceles from staphylococcal/gramnegative pneumonia
- Mycobacterial: TB
- Fungal: nocardiosis, cryptococcosis, coccidioidomycosis (in 10%), aspergillosis
- Parasitic: echinococcosis (multiple in 20 30%), paragonimiasis
TRAUMA
- Traumatic lung cyst (after hemorrhage)
- Hydrocarbon ingestion (lower lobes)
BRONCHOPULMONARY DISEASE
- Infected bulla
- Cystic bronchiectasis
- Communicating bronchogenic cyst
mnemonic: CAVITY
- Carcinoma (squamous cell), Cystic bronchiectasis
- Autoimmune disease (Wegener granulomatosis, rheumatoid lung)
- Vascular (bland/septic emboli)
- Infection (abscess, fungal disease, TB, Echinococcus)
- Trauma
- Young = congenital (sequestration, diaphragmatic hernia, bronchogenic cyst)

Pulmonary Mass with Air Bronchogram

Bronchioloalveolar carcinoma
Lymphoma
Pseudolymphoma
Kaposi sarcoma
Blastomycosis

Air-crescent Sign

= air in a crescentic shape separating the outer wall of a nodule/mass from an inner sequestrum
- INFECTION
  - Invasive pulmonary aspergillosis
  - Noninvasive mycetoma
  - Echinococcal lung cyst
  - Tuberculoma
  - Rasmussen aneurysms (most are too small to be identified on CXR)
  - Bacterial lung abscess pulmonary gangrene
- CAVITATING NEOPLASM
  - Primary/metastatic carcinoma/sarcoma
  - Bronchial adenoma
  - Cystic hamartoma
- TRAUMA
  - Pulmonary hematoma
- THROMBOEMBOLISM

Shaggy Pulmonary nodule

mnemonic:

Shaggy Sue Made Loving A Really Wild Fantasy Today

Sarcoidosis, alveolar type
Septic emboli
Metastasis
Lymphoma, Lung primary, Lymphomatoid granulomatosis
Alveolar cell carcinoma
Rheumatoid lung
Wegener granulomatosis
Fungus
Tuberculosis

Multiple Pulmonary Nodules and Masses

homogeneous masses with sharp border
no air alveolo-/bronchogram

TUMORS
- malignant
  
  P.429
  - Metastases:
    - from breast, kidney, GI tract, uterus, ovary, testes, malignant melanoma, sarcoma, Wilms tumor
  - Lymphoma (rare)
  - Multiple primary bronchogenic carcinomas (synchronous in 1% of all lung cancers)
- benign
  - Hamartoma (rarely multiple)
  - Benign metastasizing leiomyoma
  - AV malformations
  - Amyloidosis
VASCULAR LESIONS
- Thromboemboli with organizing infarcts
- Septic emboli with organized infarcts
COLLAGEN-VASCULAR DISEASE
- Wegener granulomatosis: vasculitis with organizing infarcts
- Wegener variants
- Rheumatoid nodules: tendency for periphery, occasionally cavitating
INFLAMMATORY GRANULOMAS
- Fungal: coccidioidomycosis, histoplasmosis, cryptococcosis
- Bacterial: nocardiosis, tuberculosis
- Viral: atypical measles
- Parasites: hydatid cysts, paragonimiasis
- Sarcoidosis: large accumulation of interstitial granulomas
- Inflammatory pseudotumors: fibrous histiocytoma, plasma cell granuloma, hyalinizing pulmonary nodules, pseudolymphoma

mnemonic:

SLAM DA PIG

Sarcoidosis
Lymphoma
Alveolar proteinosis
Metastases
Drugs
Alveolar cell carcinoma
Pneumonias
Infarcts
Goodpasture syndrome

Multiple Cavitating Nodules/Masses

Pulmonary vasculitis
- Wegener granulomatosis
- Necrotizing sarcoid granulomatosis
- Bronchocentric granulomatosis
Metastatic disease
- particularly squamous histologic type
Multifocal infection
- Pseudomonas
- Tuberculosis
- Septic abscesses
Multiple pulmonary infarcts
Bronchiectasis
Neoplasms
- Lymphoma
- Multicentric bronchioloalveolar carcinoma
Collagen-vascular disease
- Rheumatoid nodules
Granulomatous disease
- Cystic form of sarcoidosis
- Langerhans cell histiocytosis

Small Pulmonary Nodules

mnemonic:

MALTS

Metastases (esp. thyroid)
Alveolar cell carcinoma
Lymphoma, Leukemia
TB
Sarcoid

Pulmonary Nodules & Pneumothorax

Osteosarcoma
Wilms tumor
Histiocytosis

Pleura-based Lung Nodule

ill-defined/sharply defined lesion mimicking a true pleural mass
associated linear densities in lung parenchyma
- Granuloma (fungus, tuberculosis)
- Inflammatory pseudotumor
- Metastasis
- Rheumatoid nodule
- Pancoast tumor
- Lymphoma
- Infarct: Hampton hump
- Atelectatic pseudotumor

Intrathoracic Mass of Low Attenuation

CYSTS
- Bronchogenic/neurenteric/pericardial cyst
- Hydatid disease
FATTY SUBSTRATE
- Hamartoma
- Lipoma
- Tuberculous lymph node
- Lymphadenopathy in Whipple disease
NECROTIC MASSES
- Resolving hematoma
- Treated lymphoma
- Metastases from ovary, stomach, testes

Pneumoconiosis

= tissue reaction to the presence of an accumulation of dust in the lungs

Path:

Fibrosis
- focal/nodular (silicosis)
- diffuse fibrosis (asbestosis)
Aggregates of particle-laden macrophages in inert dusts (iron, tin, barium)

Types:

Silicosis
Coal worker pneumoconiosis
Siderosis
Carbon black pneumoconiosis
- = burning of natural gas + petroleum products (filler in rubber, plastics, phonograph records, inks, carbon paper, carbon electrodes)
- fine reticulonodular pattern with lower zone predominance
Hard metal pneumoconiosis
- = alloy of tungsten, carbon and cobalt (occasionally adding titanium, tantalum, nickel, chromium)
- giant cell interstitial pneumonia, desquamative interstitial pneumonia, interstitial pneumonia
Asbestos-related disease

Pneumoconiosis classification

according to ILO (International Labour Office)

TYPE OF OPACITIES
- Silicosis, coal worker's pneumoconiosis
  
  nodular opacities:
  - p = <1.5 mm
  - q = 1.5 3 mm
  - r = 3 10 mm
- Asbestosis
  
  linear opacities:
  - s = fine
  - t = medium
  - u = coarse/blotchy
PROFUSION/SEVERITY
- 0 = normal
- 1 = slight
- 2 = moderate
- 3 = advanced
- intermediate grading:
- 2/2 = definitely moderate profusion
- 2/3 = moderate, possibly advanced profusion

Pneumoconiosis with Mass

Anthracosilicosis with:

Granuloma (histoplasmosis, TB, sarcoidosis)
Bronchogenic carcinoma (incidence same as in general population)
Metastasis
Progressive massive fibrosis
Caplan syndrome (rheumatoid nodules)

Pulmonary calcifications

Multiple Pulmonary Calcifications

INFECTION
- Histoplasmosis
- Tuberculosis
- Chickenpox pneumonia
INHALATIONAL DISEASE
- Silicosis
MISCELLANEOUS
- Hypercalcemia
- Mitral stenosis
- Alveolar microlithiasis

Calcified Pulmonary Nodules

mnemonic:

HAM TV Station

Histoplasmosis, Hamartoma
Amyloid, Alveolar microlithiasis
Mitral stenosis, Metastasis (thyroid, osteosarcoma, mucinous carcinoma)
Tuberculosis
Varicella
Silicosis
Central/laminated/popcorn/diffuse calcifications are characteristic of benign solitary lung nodules!

Dense lung lesions

Opacification of Hemithorax

mnemonic:

FAT CHANCE

Fibrothorax
Adenomatoid malformation
Trauma (ie, hematoma)
Collapse, Cardiomegaly
Hernia
Agenesis of lung
Neoplasm (ie, mesothelioma)
Consolidation
Effusion

Atelectasis

TUMOR
- Bronchogenic carcinoma (2/3 of squamous cell carcinoma occur as endobronchial mass with persistent/recurrent atelectasis or recurrent pneumonia)
- Bronchial carcinoid
- Metastases: primary tumor of kidney, colon, rectum, breast, melanoma
- Lymphoma (usually as a late presentation)
- Lipoma, granular cell myoblastoma, amyloid tumor, fibroepithelial polyp
INFLAMMATION
- Tuberculosis (endobronchial granuloma, broncholith, bronchial stenosis)
- Right middle lobe syndrome (chronic right middle lobe atelectasis)
- Sarcoidosis (endobronchial granuloma rare)
MUCUS PLUG
- Severe chest/abdominal pain (postoperative patient)
- Respiratory depressant drug (morphine; CNS illness)
- Chronic bronchitis/bronchiolitis obliterans
- Asthma
- Cystic fibrosis
- Bronchopneumonia (peribronchial inflammation)
OTHER
- Large left atrium (mitral stenosis + left lower lobe atelectasis)
- Foreign body (aspiration of food, endotracheal intubation)
- Broncholithiasis
- Amyloidosis
- Wegener granulomatosis
- Bronchial transection

Signs:

local increase in lung density
crowding of pulmonary vessels
bronchial rearrangement
displacement of fissures
displacement of hilus
mediastinal shift
elevation of hemidiaphragm

P.431

cardiac rotation
approximation of ribs
compensatory overinflation of normal lung

Obstructive Atelectasis

Resorptive Atelectasis

Pathophysiology:

sum of partial gas pressures in venous blood perfusing atelectatic region is less than atmospheric pressure, which is responsible for gradual resorption of air trapped distal to site of obstruction; continuing secretion into small airways leads to consolidation (postobstructive pneumonitis/bacterial infection)

Cause:

bronchiolar obstruction by

Tumor
Stricture
Foreign body
Mucus plug
Bronchial rupture

airless collapse within minutes to hours
MR:
high signal intensity on T2WI in atelectatic area

Nonobstructive Atelectasis

Pathophysiology:

pathway between bronchial system + alveoli is maintained because bronchi are less compliant than lung parenchyma + remain patent; secretions can be eliminated + convective airflow to distal bronchioles remains
collapsed lung not completely airless (up to 40% residual air)
MR:
low-signal intensity on T2WI in atelectatic area

Passive Atelectasis

= pleural space-occupying process
- Pneumothorax
- Hydrothorax/hemothorax
- Diaphragmatic hernia
- Pleural masses: metastases, mesothelioma

Adhesive Atelectasis

= decrease in surfactant production
- Respiratory distress syndrome of the newborn (hyaline membrane disease)
- Pulmonary embolism: edema, hemorrhage, atelectasis
- Intravenous injection of hydrocarbon

Cicatrizing Atelectasis

= parenchymal fibrosis causing decreased lung volume
- Tuberculosis/histoplasmosis (upper lobes)
- Silicosis (upper lobes)
- Scleroderma (lower lobes)
- Radiation pneumonitis (nonanatomical distribution)
- Idiopathic pulmonary fibrosis

Discoid Atelectasis

mnemonic:

EPIC

Embolus
Pneumonia
Inadequate inspiration
Carcinoma, obstructing

Rounded Atelectasis

Cause:

any type of pleural inflammatory reaction (asbestos as leading cause)

Pathomechanism:

thickening of visceral pleura with progressive wrinkling + folding of subpleural lung

Cause:

posterobasal subpleural

round/lentiform mass incompletely surrounded by lung
increased attenuation in periphery of mass
pleural thickening in vicinity of mass
curving of vessels + bronchi toward mass
air bronchogram within mass
lesion may be stable/enlarge

Left Upper Lobe Collapse

PA view:
Luftsichel sign = sharply marginated paraaortic crescent of hyperlucency (= hyperexpanded superior segment of LLL extending toward lung apex + between aortic arch and atelectatic LUL)
hazy opacification of left hilum + cardiac border
elevation of left hilum
near horizontal course of left main bronchus
posterior + leftward rotation of heart
Lateral view:
retrosternal opacity
major fissure displaced anteriorly paralleling anterior chest wall

DDx:

Herniation of right lung across midline (leftward displacement of anterior junction line)
Medial pneumothorax

Multifocal Ill-defined Densities

= densities 5 30 mm resulting in airspace filling

INFECTION
- Bacterial bronchopneumonia
- Fungal pneumonia:
  - histoplasmosis, blastomycosis, actinomycosis, coccidioidomycosis, aspergillosis, cryptococcosis, mucormycosis, sporotrichosis
- Viral pneumonia
- Tuberculosis (primary infection)
- Rocky Mountain spotted fever
- Pneumocystis carinii
GRANULOMATOUS DISEASE
- Sarcoidosis (alveolar form secondary to peribronchial granulomas)
- Eosinophilic granuloma
VASCULAR
- thromboembolic disease
- septic emboli
- vasculitis
  - Wegener granulomatosis
  - Wegener variants: limited Wegener, lymphomatoid granulomatosis
  - Infectious vasculitis = invasion of pulmonary arteries: mucormycosis, invasive form of aspegillosis, Rocky Mountain spotted fever
  - Goodpasture syndrome
  - Scleroderma
NEOPLASTIC
- Bronchioloalveolar cell carcinoma
  - = only primary lung tumor to produce multifocal illdefined densities with air bronchograms
- Alveolar type of lymphoma
  - = massive accumulation of tumor cells in interstitium with compression atelectasis + obstructive pneumonia
- Metastases
  - Choriocarcinoma: hemorrhage (however rare)
  - Vascular tumors: malignant hemangiomas
- Waldenstr m macroglobulinemia
- Angioblastic lymphadenopathy
- Mycosis fungoides
- Amyloid tumor
IDIOPATHIC INTERSTITIAL DISEASE
- Lymphocytic interstitial pneumonitis (LIP)
- Desquamative interstitial pneumonitis (DIP)
- Pseudolymphoma = localized form of LIP
- Usual interstitial pneumonitis (UIP)
INHALATIONAL DISEASE
- Allergic alveolitis: acute stage (eg, farmer's lung)
- Silicosis
- Eosinophilic pneumonia
DRUG REACTIONS

Diffuse Infiltrates in Immunocompromised Cancer Patient

mnemonic:

FOLD

Failure (CHF)
Opportunistic infection
Lymphangitic tumor spread
Drug reaction

Segmental & lobar Densities

PNEUMONIA
- Lobar pneumonia
- Lobular pneumonia
- Acute interstitial pneumonia
- Aspiration pneumonia
- Primary tuberculosis
PULMONARY EMBOLISM

(rarely multiple/larger than subsegmental)
NEOPLASM
- Obstructive pneumonia
- Bronchioloalveolar cell carcinoma
ATELECTASIS

Chronic infiltrates

Chronic Infiltrates in Childhood

mnemonic:

ABC'S

Asthma, Agammaglobulinemia, Aspiration
Bronchiectasis
Cystic fibrosis
Sequestration, intralobar

Chronic Multifocal Ill-defined Opacities

Organizing pneumonia
Granulomatous disease
Allergic alveolitis
Bronchioloalveolar cell carcinoma
Lymphoma

SUBACUTE/CHRONIC CONSOLIDATION & GROUND-GLASS OPACITIES
- BOOP
- Chronic eosinophilic pneumonia
- Churg-Strauss syndrome
- Desquamative interstitial pneumonia
- Nonspecific interstitial pneumonia
- Chronic hypersensitivity pneumonia
- Mycoplasma pneumonia
- Lymphoma
- Lipoid pneumonia

Chronic Diffuse Confluent Opacities

Alveolar proteinosis
Hemosiderosis
Sarcoidosis

Ill-defined Opacities with Holes

INFECTION
- Necrotizing pneumonias:
  - Staphylococcus aureus, -hemolytic streptococcus, Klebsiella pneumoniae, E. coli, Proteus, Pseudomonas, anaerobes
- Aspiration pneumonia:
  - mixed gram-negative organisms
- Septic emboli
- Fungus:
  - histoplasmosis, blastomycosis, coccidioidomycosis, cryptococcosis
- Tuberculosis
NEOPLASM
- Primary lung carcinoma
- Lymphoma (cavitates very rarely)
VASCULAR + COLLAGEN-VASCULAR DISEASE
- Emboli with infarction
- Wegener granulomatosis
- Necrobiotic rheumatoid nodules
TRAUMA
- Contusion with pneumatoceles

Recurrent Fleeting Infiltrates

L ffler disease
Bronchopulmonary aspergillosis/bronchocentric granulomatosis
Asthma
Subacute bacterial endocarditis with pulmonary emboli

Tubular Density

Mucoid impaction
Vascular malformation
- Arteriovenous malformation
- Pulmonary varix

Mucoid Impaction

= V-/Y-shaped branching tubular opacities of dilated bronchi filled with inspissated mucus surrounded by aerated lung (collateral air drift circumvents obstructed bronchi)

P.433

gloved finger sign

bronchiectasis due to bronchial obstruction
- CONGENITAL
  - Congenital bronchial atresia
  - Interlobar sequestration
  - Intrapulmonary bronchogenic cyst
- BRONCHIAL TUMOR
  - Bronchial hamartoma
  - Bronchial lipoma
  - Bronchogenic carcinoma
  - Carcinoid
- OTHERS
  - Tuberculous stricture
  - Broncholithiasis
  - Foreign body aspiration
bronchiectasis without bronchial obstruction
- Allergic bronchopulmonary aspergillosis
- Asthma
- Cystic fibrosis

Perihilar Bat-wing Infiltrates

mnemonic:

Please, Please, Please, Study Light, Don't Get All Uptight

Pulmonary edema
Proteinosis
Periarteritis
Sarcoidosis
Lymphoma
Drugs
Goodpasture syndrome
Alveolar cell carcinoma
Uremia

Peripheral Reverse Bat-wing Infiltrates

mnemonic:

REDS

Resolving pulmonary edema
Eosinophilic pneumonia
Desquamative interstitial pneumonia
Sarcoidosis

Lucent Lung Lesions

Pulmonary Oligemia

Generalized Oligemia

= reduction in pulmonary blood volume

Aortic valve disease
- indicative of markedly diminished stroke volume + cardiac output
- LV enlargement
Overpenetration of film = artifact
Deep inspiration + Valsalva maneuver
Positive pressure ventilation

Regional Oligemia

DECREASE IN BLOOD VOLUME
- Pulmonary arterial hypoplasia
- Mitral valve disease
- Pulmonary embolism
- Flow inversion (= oligemic bases + hyperemic upper lobes in longstanding elevation of left heart pressure)
INCREASE IN AIR SPACES
- Swyer-James syndrome
- Regional emphysema
- Valvular air trapping

Hyperlucent Lung

Bilateral Hyperlucent Lung

FAULTY RADIOLOGIC TECHNIQUE
- Overpenetrated film
DECREASED SOFT TISSUES
- Thin body habitus
- Bilateral mastectomy
CARDIAC CAUSE of decreased pulmonary blood flow
- Right-to-left shunt:
  - Tetralogy of Fallot (small proximal pulmonary vessels), pseudotruncus, truncus type IV, Ebstein malformation, tricuspid atresia
- Eisenmenger physiology of left-to-right shunt:
  - ASD, VSD, PDA (dilated proximal pulmonary vessels)
PULMONARY CAUSE of decreased pulmonary blood flow
- Decrease of vascular bed:
  - Pulmonary embolism:
    - bilaterality is rare; localized areas of hyperlucency (Westermark sign)
- Increase in air space:
  - Air trapping (reversible changes):
    - acute asthmatic attack, acute bronchiolitis (pediatric patient)
  - Emphysema
  - Bulla
  - Bleb
  - Interstitial emphysema

Unilateral Hyperlucent Lung

FAULTY RADIOLOGIC TECHNIQUE
- Rotation of patient
CHEST WALL DEFECT
- Mastectomy
- Absent pectoralis muscle (Poland syndrome)
INCREASED PULMONARY AIR SPACE with decreased pulmonary blood flow
- Large airway obstruction with air trapping
  - @ Bronchial compression:
    - Hilar mass (rare)
    - Cardiomegaly compressing LLL bronchus
  - @ Endobronchial obstruction with air trapping (collateral air drift):
    - Foreign body
    - Broncholith
    - Bronchogenic carcinoma
    - Carcinoid
    - Bronchial mucocele
- Small airway obstruction
  - Bronchiolitis obliterans
  - Swyer-James/MacLeod syndrome
  - Emphysema (particularly bullous emphysema)
  - Emphysema + unilateral lung transplant
- Pneumothorax (in supine patient)
PULMONARY VASCULAR CAUSE of decreased pulmonary blood flow
- Pulmonary artery hypoplasia
- Pulmonary embolism
- Congenital lobar emphysema
- Compensatory overaeration

Localized Lucent Lung Defect

Lung Cavity

= tissue necrosis with bronchial drainage

Infection
- BACTERIAL PNEUMONIA
  - Pyogenic infection = abscess = necrotizing pneumonia:
    - Staphylococcus, Klebsiella, Pseudomonas, anaerobes, -hemolytic streptococcus, E. coli, mixed gram-negative organisms
  - Aspiration pneumonia = gravitational pneumonia:
    - mixed gram-negative organisms, anaerobes
- GRANULOMATOUS INFECTION
  - Tuberculosis:
    - cavitation indicates active infectious disease with risk for hematogenous/bronchogenic dissemination
  - Fungal infection:
    - nocardiosis (in immunocompromised), coccidioidomycosis (any lobe, desert Southwest), histoplasmosis, blastomycosis, mucormycosis, sporotrichosis, aspergillosis, cryptococcosis
    - very thin-walled cavities less likely to follow apical distribution of TB/histoplasmosis
  - Sarcoidosis (stage IV, upper lobe predominance)
  - Angioinvasive organism (septic lung infarction followed by cavity formation):
    - Aspergillus, Mucorales, Candida, Torulosis, P. aeruginosa
- PARASITIC INFESTATION: hydatid disease
Neoplasm
- Primary lung tumor:
  - 16% of peripheral lung cancers (in particular in squamous cell carcinoma (30%); also in bronchioloalveolar cell carcinoma
- Metastasis (usually multiple)
  - Squamous cell carcinoma (nasopharynx, esophagus, cervix) in 2/3
  - Adenocarcinoma (lung, breast, GI)
  - Osteosarcoma (rare)
  - Melanoma
  - Lymphoma (rare): with adenopathy; cavities often secondary to opportunistic infection with nocardiosis + cryptococcosis
Vascular occlusion
- Infarct (thromboembolic, septic)
- Wegener granulomatosis
- Rheumatoid arthritis
Inhalation
- Silicosis with coal worker's pneumoconiosis
  - complicating tuberculosis
  - ischemic necrosis of center of conglomerate mass (rare)

MASS WITHIN CAVITY
- Mycetoma = aspergilloma
- Tissue fragment within carcinoma
- Necrotic lung within abscess
- Disintegrating hydatid cyst
- Intracavitary blood clot

Lung cyst

= round circumscribed space surrounded by an epithelial/fibrous wall of uniform/varied thickness containing air/liquid/semisolid/solid material

CONGENITAL CYST (rare)
- Bronchogenic cyst
- Intralobar sequestration: multicystic structure in lower lobes
- Congenital cystic adenomatoid malformation (CCAM) type I
- Congenital lobar emphysema
- Diaphragmatic hernia (congenital/traumatic)
- Bronchial atresia
ACQUIRED CYST
- Centrilobular/bullous emphysema
  - Bleb = cystic air collection within visceral pleura; mostly apical with narrow neck; associated with spontaneous pneumothorax
  - Bulla = sharply demarcated dilated air space within lung parenchyma >1 cm in diameter with epithelialized wall <1 mm thick due to destruction of alveoli (= air cyst in localized/centrilobular/panlobular emphysema)
    - usually asymptomatic
    - typically at lung apex
    - slow progressive enlargement
    - Cx:
      - Spontaneous pneumothorax
      - Vanishing lung = large area of localized emphysema causing atelectasis + dyspnea
      Rx: surgical resection if bulla >33% of hemithorax
- Pneumatocele
  - Postinfectious pneumatocele
  - Traumatic pneumatocele: lung hematoma/hydrocarbon inhalation
- Cystic bronchiectasis
  - Cystic fibrosis (more obvious in upper lobes)
  - Agammaglobulinemia (predisposed to recurrent bacterial infections)
  - Recurrent bacterial pneumonias
    - multiple thin-walled lucencies with air-fluid levels in lower lobes
  - Childhood infection: tuberculosis, pertussis
  - Allergic bronchopulmonary aspergillosis (in asthmatic patients)
    - involvement of proximal perihilar bronchi
  - Kartagener syndrome (ciliary dysmotility)
- Infection
  - Hydatid disease
- Interstitial emphysema
  - Pseudocyst

Multiple Lucent Lung Lesions

Multiple Lung Cavities

Infection
- Bacterial pneumonia: cavitating pneumonia, lung abscess
- Granulomatous infection: TB, sarcoidosis
- Fungal infection: coccidioidomycosis
- Parasitic infection: echinococcosis
- Protozoan infection: pneumocystosis
Neoplasm
Vascular
- Thromboembolic + septic infarcts
- Wegener granulomatosis
- Rheumatoid arthritis
- Angioinvasive organism (septic lung infarction followed by cavity formation): Aspergillus, Mucorales, Candida, torulosis, P. aeruginosa

MULTIPLE THIN-WALLED CAVITIES

mnemonic:

BITCH

Bullae + pneumatoceles
Infection (TB, cocci, staph)
Tumor (squamous cell carcinoma)
Cysts (traumatic, bronchogenic)
Hydrocarbon ingestion

Multiple Lung Cysts

CONGENITAL
- Multiple bronchogenic cysts
- Intralobar sequestration:
  - multicystic structure in lower lobes
- Congenital cystic adenomatoid malformation (CCAM) type I
- Diaphragmatic hernia (congenital/traumatic)
INFECTION
- Tuberculosis
- Pneumocystis carinii pneumonia in AIDS
VASCULAR-EMBOLIC
- Cavitating septic emboli
  - often seen at end of feeding vessel
- Angioinvasive infection (invasive pulmonary aspergillosis, candida, P. aeruginosa)
- Pulmonary vasculitis (Wegener granulomatosis)
DILATATION OF BRONCHI = cystic bronchiectasis
- bronchial wall thickening
- Cystic fibrosis (more obvious in upper lobes)
- Agammaglobulinemia (predisposed to recurrent bacterial infections)
- Recurrent bacterial pneumonias
- Tuberculosis
- Allergic bronchopulmonary aspergillosis (in asthmatic patients)
DISRUPTION OF ELASTIC FIBER NETWORK
- Centrilobular emphysema
  - imperceptible walls
  - chiefly in upper lung zones
- Panlobular emphysema
  - lobular architecture preserved with bronchovascular bundle in central position, areas of lung destruction without arcuate contour
- Paraseptal emphysema
  - cysts with walls arrayed in a single subpleural tier
- Lymphangioleiomyomatosis
  - randomly scattered cysts surrounded by normal lung
  - normal/increased lung volumes
- Tuberous sclerosis
  - associated skin abnormalities, mental retardation, epilepsy
- Air-block disease (adult respiratory distress syndrome, asthma, bronchiolitis, viral/bacterial pneumonia)
REMODELING OF LUNG ARCHITECTURE
- = honeycombing of idiopathic pulmonary fibrosis (= fibrosing alveolitis)
- 3 10-mm small irregular thick-walled cystic air spaces usually of comparable diameter surrounded by abnormal + distorted lung parenchyma
- predominantly peripheral + basilar distribution
- bibasilar reticular opacities
- progressive reduction in lung volumes
MULTIFACTORIAL/UNKNOWN
- Langerhans cell histiocytosis
  - cysts with walls of variable thickness + irregular shape
  - in combination with nodules cavitation
  - septal thickening
  - predilection for upper lung zones with relative sparing of lung bases
- Lymphocytic interstitial pneumonia
  - thickening of interlobular septa + bronchovascular bundles
  - enlarged mediastinal nodes
- Klippel-Trenaunay syndrome
- Juvenile tracheolaryngeal papillomatosis
- Neurofibromatosis
  - cystic air spaces predominantly apical
- Pneumatoceles

Cystlike Pulmonary Lesions

mnemonic:

C.C., I BAN WHIPS

Coccidioidomycosis
Cystic adenomatoid malformation
Infection
Bronchogenic cyst, Bronchiectasis, Bowel
Abscess
Neoplasm
Wegener granulomatosis
Hydatid cyst, Histiocytosis X
Infarction
Pneumatocele
Sequestration

Pleura

Pneumothorax

= accumulation of air in the pleural space

P.436

Pathophysiology: disruption of visceral pleura/trauma to parietal pleura
pleuritic back/shoulder pain, dyspnea (in 80 90%)
Etiology:
- TRAUMATIC PNEUMOTHORAX
  - penetrating trauma
  - blunt trauma
    - Rib fracture
    - Increased intrathoracic pressure against closed glottis: lung contusion/laceration
    - Bronchial fracture
      - fallen lung sign = hilum of lung below expected level within chest cavity
      - persistent pneumothorax with functioning chest tube
      - mediastinal pneumothorax
  - iatrogenic:
    - tracheostomy, central venous catheter, PEEP ventilator (3 16%), thoracic irradiation
- SPONTANEOUS PNEUMOTHORAX
  - Primary/idiopathic spontaneous pneumothorax (80%)
    
    Cause: rupture of subpleural blebs in apical region of lung
    
    Age: 20 40 years; M:F = 8:1; esp. in patients with tall asthenic stature; mostly in smokers
    - chest pain (69%)
    - dyspnea
    Prognosis: recurrence in 30% on same side, in 10% on contralateral side
    
    Rx: simple aspiration (in >50% success)/tube thoracostomy (in 90% effective)
  - Secondary spontaneous pneumothorax (20%):
    - Air-trapping disease: spasmodic asthma, diffuse emphysema, Langerhans cell histiocytosis, lymphangiomyomatosis, tuberous sclerosis, cystic fibrosis
      - Chronic obstructive pulmonary disease is the most common predisposing disorder of secondary spontaneous pneumothorax
    - Pulmonary infections: lung abscess, necrotizing pneumonia, hydatid disease, pertussis, acute bacterial pneumonia, Staphylococcus aureus, Pneumocystis carinii pneumonia
    - Granulomatous disease: tuberculosis, coccidioidomycosis, sarcoidosis, berylliosis
    - Malignancy: primary lung cancer, lung metastases (esp. osteosarcoma, pancreas, adrenal, Wilms tumor)
    - Connective tissue disorder: scleroderma, rheumatoid disease, Marfan syndrome, Ehlers-Danlos syndrome
    - Pneumoconiosis: silicosis, berylliosis
    - Vascular disease: pulmonary infarction
    - Catamenial [kata, Greek = according to; men, Greek = month] pneumothorax
      - = recurrent spontaneous pneumothorax during menstruation associated with endometriosis of the diaphragm; R >> L
    - Neonatal disease: meconium aspiration, respirator therapy for hyaline membrane disease
    - Cx of honeycomb lung: pulmonary fibrosis, cystic fibrosis, sarcoidosis, scleroderma, eosinophilic granuloma, interstitial pneumonitis, Langerhans cell histiocytosis, rheumatoid lung, idiopathic pulmonary hemosiderosis, pulmonary alveolar proteinosis, biliary cirrhosis

mnemonic:

THE CHEST SET

Trauma
Honeycomb lung, Hamman-Rich syndrome
Emphysema, Esophageal rupture
Chronic obstructive pulmonary disease
Hyaline membrane disease
Endometriosis
Spontaneous, Scleroderma
Tuberous sclerosis
Sarcoma (osteo-), Sarcoidosis
Eosinophilic granuloma
Tuberculosis + fungus

Types:
- Closed pneumothorax = intact thoracic cage
- Open pneumothorax = sucking chest wound
- Tension pneumothorax
  - = accumulation of air within pleural space due to free ingress + limited egress of air
  Pathophysiology:
  - intrapleural pressure exceeds atmospheric pressure in lung during expiration (check-valve mechanism)
    
    P.437
    
    Frequency: in 3 5% of patients with spontaneous pneumothorax, higher in barotrauma
  - displacement of mediastinum/anterior junction line
  - deep sulcus sign = on frontal view larger lateral costodiaphragmatic recess than on opposite side
  - diaphragmatic inversion
  - total/subtotal lung collapse
  - collapse of SVC/IVC/right heart border (decreased systemic venous return + decreased cardiac output)
  - N.B.: Medical emergency!
- Tension hydropneumothorax
  - sharp delineation of visceral pleural by dense pleural space
  - mediastinal shift to opposite side
  - air-fluid level in pleural space on erect CXR
Pneumothorax size:
- Average Interpleural Distance (AID) = (A + B + C) 3 [in cm] converts to percentage of pneumothorax see nomogram in drawing
Radiographic signs in upright position:
- white margin of visceral pleura separated from parietal pleura
  
  DDx: skin fold, air trapped between chest wall soft tissues, hair braid, overlying tubing/dressing/line, prior chest tube track
- absence of vascular markings beyond visceral pleural margin

Radiographic signs in supine position:

30% of pneumothoraces go undetected on supine radiographs!

Anteromedial pneumothorax (earliest location)
- outline of medial diaphragm under cardiac silhouette
- sharp delineation of mediastinal contours (SVC, azygos vein, left subclavian artery, anterior junction line, superior pulmonary vein, heart border, IVC, pericardial fat-pad)
- relative lucency of entire lung
- depression of ipsilateral diaphragm
- band of air in minor fissure bounded by two visceral pleural lines
- outline of anterior junction line (in bilateral pneumothoraces)
- figure 8 / pseudomass = compression of malleable lobes of thymus (in bilateral pneumothoraces)
Subpulmonic/anterolateral pneumothorax (second most common location)
- deep sulcus sign = lucency of abnormally deep lateral costophrenic angle extending toward hypochondrium (DDx: COPD)
- hyperlucent upper abdominal quadrant/hypochondrial region
- sharply outlined diaphragm/inferior surface of lung in spite of parenchymal disease/collapsed lower lobe
- double-diaphragm sign = air outlining anterior costophrenic sulcus + aerated lung outlining diaphragmatic dome
- visible lateral edge of right middle lobe due to medial retraction
Apicolateral pneumothorax (least common location)
- visualization of visceral pleural line
- displacement of minor fissure from chest wall
Posteromedial pneumothorax (in presence of lower lobe collapse)
- lucent triangle with vertex at hilum
- V-shaped base delineating costovertebral sulcus

Pneumothorax outlines pulmonary ligament

Prognosis:	resorption of pneumothorax occurs at a rate of 1.25% per day (accelerated by increasing inspired oxygen concentrations)
Rx:	A pneumothorax >35% usually requires management with a chest tube!

Pleural effusion

TRANSUDATE (protein level of 1.5 2.5 g/dL)

Pathophysiology: result of systemic abnormalities causing an outpouring of low-protein fluid
- Increased hydrostatic pressure
  - Congestive heart failure (in 65%):
    - bilateral (88%); right-sided (8%); left-sided (4%); least amount on left side due to cardiac movement, which stimulates lymphatic resorption
  - Constrictive pericarditis (in 60%)
- Decreased colloid-oncotic pressure
  - decreased protein production
    - Cirrhosis with ascites (in 6%):
      - right-sided (67%)
  - protein loss/hypervolemia
    - Nephrotic syndrome (21%), overhydration, glomerulonephritis (55%), peritoneal dialysis
    - Hypothyroidism
- Chylous effusion
  - Most frequent cause of isolated pleural effusion in newborn with 15 25% mortality!
  - chylomicrons + lymphocytes in fluid

EXUDATE

Pathophysiology:

increased permeability of abnormal pleural capillaries with release of high-protein fluid into pleural space

Criteria:
- pleural fluid total protein/serum total protein ratio of >0.5
- pleural fluid LDH/serum LDH ratio of >0.6
- pleural fluid LDH >2/3 of upper limit of normal for serum LDH (upper limit for LDH ~200 IU)
- pleural fluid specific gravity >1.016
- protein level >3 g/dL
effusion with septation/low-level echoes
split pleura sign on CECT = thickened enhancing visceral + parietal pleura separated by fluid
extrapleural fat thickening of >2 mm + increased attenuation (edema/inflammation)

Infection
- Empyema
  - empyema necessitatis = chronic empyema attempting to decompress through chest wall (in TB, actinomycosis, aspergillosis, blastomycosis, nocardiosis)
- Parapneumonic effusion (in 40%)
  - = any effusion associated with pneumonia/lung abscess/bronchiectasis without criteria for an empyema
- Tuberculosis (in 1%):
  - high protein content (75 g/dL), lymphocytes >70%, positive culture (only in 20 25%)
- Fungi: Actinomyces, Nocardia
- Parasites: amebiasis (secondary to liver abscess in 15 20%), Echinococcus
- Mycoplasma, rickettsia (in 20%)

Malignant disease (in 60%)

positive cytologic results

Pathogenesis:

pleural metastases (increased pleural permeability)
lymphatic obstruction (pleural vessels, mediastinal nodes, thoracic duct disruption)
bronchial obstruction (loss of volume + resorptive surface)
hypoproteinemia (secondary to tumor cachexia)

Cause:	lung cancer (26 49%), breast cancer (8 24%), lymphoma (10 28%, in 2/3 chylothorax), ovarian cancer (10%), malignant mesothelioma containing hyaluronic acid (5%)
Rx:	sclerosing agents: doxycycline, bleomycin, talc

Vascular
- Pulmonary emboli (in 15 30% of all embolic events): often serosanguinous
Abdominal disease
- Pancreatitis/pancreatic pseudocyst/pancreaticopleural fistula (in 2/3):
  - usually left-sided pleural effusion
  - high amylase levels
- Boerhaave syndrome:
  - left-sided esophageal perforation
- Subphrenic abscess
  - pleural effusion (79%)
  - elevation + restriction of diaphragmatic motion (95%)
  - basilar platelike atelectasis/pneumonitis (79%)
- Abdominal tumor with ascites
- Meigs-Salmon syndrome
  - = primary pelvic neoplasms (ovarian fibroma, thecoma, granulosa cell tumor, Brenner tumor, cystadenoma, adenocarcinoma, fibromyoma of uterus) cause pleural effusion in 2 3%; ascites + hydrothorax resolve with tumor removal
- Endometriosis
- Bile fistula
Collagen-vascular disease
- Rheumatoid arthritis (in 3%):
  - unilateral; R > L (in 75%), recurrent alternating sides; pleural effusion relatively unchanged in size for months; predominantly in men; LOW GLUCOSE content of 20 50 mg/dL (in 70 80%) without increase following IV infusion of glucose (DDx: TB, metastatic disease, parapneumonic effusion)
- SLE (in 15 74%)
  - most common collagenosis to give pleural effusion, bilateral in 50%; L > R
  - enlargement of cardiovascular silhouette (in 35 50%)
- Wegener granulomatosis (in 50%)
- Sj gren syndrome
- Mixed connective tissue disease
- Periarteritis nodosa
- Postmyocardial infarct syndrome
Traumatic
- hemorrhagic, chylous, esophageal rupture, thoracic/abdominal surgery, intrapleural infusion = infusothorax (0.5%), radiation pneumonitis
Miscellaneous
- Sarcoidosis
- Uremic pleuritis (in 20% of uremic patients)
- Drug-induced effusion

CXR:
- first 300 mL not visualized on PA view (collect in subpulmonic region first, then spill into posterior costophrenic sinus)
- lateral decubitus views may detect as little as 25 mL
- hemidiaphragm + costophrenic sinuses obscured
- extension upward around posterior > lateral > anterior thoracic wall (mediastinal portion fixed by pulmonary ligament + hilum)
- meniscus-shaped semicircular upper surface with lowest point in midaxillary line
- associated collapse of ipsilateral lung
- Massive pleural effusion:
  - enlargement of ipsilateral hemithorax
  - displacement of mediastinum to contralateral side
  - severe depression/flattening/inversion of ipsilateral hemidiaphragm
  - visible air bronchogram
- Subpulmonic/subdiaphragmatic/infrapulmonary pleural effusion:
  - peak of dome of pseudodiaphragm laterally positioned
  - acutely angulated costophrenic angle
  - increased distance between stomach bubble and lung
  - blunted posterior costophrenic sulcus
  - thin triangular paramediastinal opacity (mediastinal extension of pleural effusion)
  - flattened pseudodiaphragmatic contour anterior to major fissure (on lateral CXR)
CT:
- fluid outside diaphragm
- fluid elevating crus of diaphragm
- indistinct fluid-liver interface
- fluid posteromedial to liver (= bare area of liver)
  
  CAVE: central oval sign of ascites may be seen in subpulmonic effusion with inverted diaphragm

Unilateral Pleural Effusion

The majority of massive unilateral pleural effusions are malignant (lymphoma, metastatic disease, primary lung cancer)!

Neoplasm
Infection: TB

P.439

Collagen vascular disease
Subdiaphragmatic disease
Pulmonary emboli
Trauma: fractured rib
Chylothorax

LEFT-SIDED PLEURAL EFFUSION
- Spontaneous rupture of the esophagus
- Dissecting aneurysm of the aorta
- Traumatic rupture of aorta distal to left subclavian artery
- Transection of distal thoracic duct
- Pancreatitis: left-sided (68%), right-sided (10%), bilateral (22%)
- Pancreatic + gastric neoplasm
RIGHT-SIDED PLEURAL EFFUSION
- Congestive heart failure
- Transection of proximal thoracic duct
- Pancreatitis

Pleural Effusion & Large Cardiac Silhouette

Congestive heart failure (most common)
- cardiomegaly
- prominence of upper lobe vessels + constriction of lower lobe vessels
- prominent hilar vessels
- interstitial edema (fine reticular pattern, Kerley lines, perihilar haze, peribronchial thickening)
- alveolar edema (perihilar confluent ill-defined densities, air bronchogram)
- phantom tumor = fluid localized to interlobar pleural fissure (in 78% in right horizontal fissure)
Pulmonary embolus + right heart enlargement
Myocarditis/pericarditis with pleuritis
- viral infection
- tuberculosis
- rheumatic fever (poststreptococcal infection)
Tumor: metastatic, mesothelioma
Collagen-vascular disease
- SLE (pleural + pericardial effusion)
- rheumatoid arthritis

Pleural Effusion & Hilar Enlargement

Pulmonary embolus
Tumor
- bronchogenic carcinoma
- lymphoma
- metastasis
Tuberculosis
Fungal infection (rare)
Sarcoidosis (very rare)

Pleural Effusion & Subsegmental Atelectasis

Postoperative (thoracotomy, splenectomy, renal surgery) secondary to thoracic splinting + mucous plugging of small airway
Pulmonary embolus
Abdominal mass
Ascites
Rib fractures

Pleural Effusion & Lobar Densities

Pneumonia with empyema
Pulmonary embolism
Neoplasm
- bronchogenic carcinoma (common)
- lymphoma
Tuberculosis

Hemothorax

rapidly enlarging high-attenuation pleural effusion
heterogeneous attenuation
hyperattenuating areas of debris
fluid-hematocrit level

TRAUMA
- Closed/penetrating injury
- Surgery
- Interventional procedures: thoracentesis, pleural biopsy, catheter placement
BLEEDING DIATHESIS
- Anticoagulant therapy
- Thrombocytopenia
- Factor deficiency
VASCULAR
- Pulmonary infarct
- Arteriovenous malformation
- Aortic dissection
- Leaking atherosclerotic aneurysm
MALIGNANCY
- Mesothelioma
- Lung cancer
- Metastasis
- Leukemia
OTHER
- Catamenial hemorrhage
- Extramedullary hematopoiesis

Solitary Pleural Mass

= density with incomplete margins and tapered superior + inferior borders

Loculated pleural effusion ( vanishing tumor )
Organized empyema
Metastasis
Local benign mesothelioma
Subpleural lipoma: may erode adjacent rib
Hematoma
Mesothelial cyst
Neural tumor: schwannoma, neurofibroma
Localized fibrous tumor of pleura
Fibrin bodies
- = 3 4 cm large tumorlike concentrations of fibrin forming in serofibrinous pleural effusions; usually near lung base
DDx: chest wall mass (rib destruction reliable sign of chest wall mass)

Multiple Pleural Densities

diffuse pleural thickening with lobulated borders

Loculated pleural effusion:
- infectious, hemorrhagic, neoplastic
Pleural plaques

P.440

Metastasis (most common cause)

Origin: lung (40%), breast (20%), lymphoma (10%), melanoma, ovary, uterus, GI tract, pancreas, sarcoma
- Metastatic adenocarcinoma histologically similar to malignant mesothelioma!
Diffuse malignant mesothelioma:
- almost always unilateral, associated with asbestos exposure
Invasive thymoma (rare)
- contiguous spread, invasion of pleura, spreads around lung
- NO pleural effusion
Thoracic splenosis
- = autotransplantation of splenic tissue to pleural space following thoracoabdominal trauma; discovered 10 30 years later
- asymptomatic/recurrent hemoptysis
- one or several nodules in left pleura/fissures measuring several mm to 6 cm
- positive Tc-99m sulfur colloid scan, indium-111 labeled platelets, Tc-99m labeled heat-damaged RBCs

mnemonic:

Mary Tyler Moore Likes Lemon

Metastases (especially adenocarcinoma)
Thymoma (malignant)
Malignant mesothelioma
Loculated pleural effusion
Lymphoma

Pleural Thickening

TRAUMA
- Fibrothorax (most common cause)
  - = organizing effusion/hemothorax/pyothorax
  - dense fibrous layer of approx. 2 cm thickness; almost always on visceral pleura
  - frequent calcification on inner aspect of pleural peel
INFECTION
- Chronic empyema: over bases; history of pneumonia; parenchymal scars
- Tuberculosis/histoplasmosis: lung apex; associated with apical cavity
- Aspergilloma: in preexisting cavity concomitant with pleural thickening
COLLAGEN-VASCULAR DISEASE
- Rheumatoid arthritis: pleural effusion fails to resolve
INHALATIONAL DISORDER
- Asbestos exposure: lower lateral chest wall; basilar interstitial disease (<25%); thickening of parietal pleura with sparing of visceral pleura
- Talcosis
NEOPLASM
- Metastases: often nodular appearance; may be obscured by effusion
- Diffuse malignant mesothelioma
- Pancoast tumor
OTHER
- Pleural hyaloserositis
  
  Path: hyaline sclerotic tissue = cartilagelike whitish sugar icing appearance (Zuckerguss) with occasional calcification
- Mimicked by extrathoracic musculature, 1st + 2nd rib companion shadow, subpleural fat, focal scarring around old rib fractures

mnemonic:

TRINI

Trauma (healed hemothorax)
Rheumatoid arthritis (collagen vascular disease)
Inhalation disease (asbestosis, talcosis)
Neoplasm
Infection

Apical Cap

Inflammatory process: TB, healed empyema
Postradiation fibrosis
Neoplasm
Vascular abnormality
Mediastinal hemorrhage
Mediastinal lipomatosis
Peripheral upper lobe collapse

Pleural calcification

INFECTION
- Healed empyema
- Tuberculosis (and Rx for TB: pneumothorax/oleothorax), histoplasmosis
TRAUMA
- Healed hemothorax = fibrothorax:
  - Hx of significant chest trauma
  - irregular plaques of calcium usually in visceral pleura
  - healed rib fracture
- Radiation therapy
PNEUMOCONIOSIS
- Asbestos-related pleural disease (most common):
  - combination of basilar reticular interstitial disease (<1/3) + pleural thickening
  - calcifications of parietal pleura frequently diagnostic (diaphragmatic surface of pleura, bilateral but asymmetric)
- Talcosis: similar to asbestos-related disease
- Bakelite
- Muscovite mica
HYPERCALCEMIA
- Pancreatitis
- Secondary hyperparathyroidism of chronic renal failure/scleroderma
MISCELLANEOUS
- Mineral oil aspiration
- Pulmonary infarction

mnemonic:

TAFT

Tuberculosis
Asbestosis
Fluid (effusion, empyema, hematoma)
Talc

Mediastinum

Acute Mediastinal Widening

Rupture of aorta/brachiocephalic arteries
Venous hemorrhage: traumatic/iatrogenic (malpositioning of central venous line)

P.441

Congestive heart failure (venous dilatation)
Rupture of esophagus
Rupture of thoracic duct
Atelectasis abutting the mediastinum
Magnification + geometric distortion on supine radiograph (attempt at suspended full inspiration, no rotation, 10 15 caudal angulation of central beam)

Mediastinal Shift

= displacement of heart, trachea, aorta, hilar vessels
Expiration film, lateral decubitus film (expanded lung down), fluoroscopy help to determine side of abnormality

DECREASED LUNG VOLUME
- Atelectasis
- Postoperative (lobectomy, pneumothorax)
- Hypoplastic lung/lobe
  - small pulmonary artery + small hilum
  - decreased peripheral pulmonary vasculature
  - irregular reticular vascular pattern (bronchial origin) without converging on the hilum
- Bronchiolitis obliterans = Swyer-James syndrome
INCREASED LUNG VOLUME
- = air trapping = retention of excess gas in all/part of the lung, especially during expiration, as a result of
  - complete/partial airway obstruction, or
  - local abnormalities in pulmonary compliance
- @ Major bronchus
  - Foreign body obstructing main-stem bronchus (common in children) with ball-valve mechanism + collateral air drift
    - contralateral mediastinal shift increasing with expiration
- @ Emphysema
  - Bullous emphysema (localized form)
    - large avascular areas with thin lines
  - Congenital lobar emphysema: only in infants
  - Interstitial emphysema
    
    Cause: Cx of positive pressure ventilation therapy
    - pattern of diffuse coarse lines;
- @ Cysts/masses
  - Bronchogenic cyst: with bronchial connection + check-valve mechanism
  - Cystic adenomatoid malformation
  - Large mass (pulmonary, mediastinal)
PLEURAL SPACE ABNORMALITY
- Large unilateral pleural effusion:
  - opaque hemithorax through empyema, congestive failure, metastases
- Tension pneumothorax:
  - not always complete collapse of lung
- Large diaphragmatic hernia:
  - usually detected in neonatal period
- Large pleural mass
Partial absence of pericardium/pectus excavatum
- shift of heart without shift of trachea, aorta, or mediastinal border

Pneumomediastinum

Frequency:

in 1% of patients with pneumothorax

Source of air:

INTRATHORACIC
- Trachea, major bronchi: blunt chest trauma
- Esophagus
- Lung
  - narrowed/plugged airways (most common) = air trapping in small airways as in asthma
  - straining against closed glottis: vomiting, parturition, weight-lifting
  - blunt chest trauma
  - alveolar rupture
- Pleural space
EXTRATHORACIC
- Head and neck: sinus fracture, dental extraction
- Intra- and retroperitoneum: perforation of hollow viscus

Pathophysiology:

after alveolar rupture air tracks along bronchovascular sheath + ruptures through fascial sheath at lung root into mediastinum and facial planes of the neck producing subcutaneous emphysema

NOT a life-threatening condition!
subcutaneous emphysema
streaky lucencies of air in mediastinum (look at thoracic inlet on PA + retrosternal space on LAT film)
ring around artery sign = air surrounding intramediastinal segment of right pulmonary artery (LAT view)
tubular artery sign = air adjacent to major aortic branches, eg, left subclavian + left common carotid aa.
continuous diaphragm sign = air trapped posterior to pericardium produces lucency connecting both domes of hemidiaphragms (frontal view)
double bronchial wall sign = clear depiction of bronchial wall by air next to and within a bronchus
V sign of Naclerio / extrapleural sign = mediastinal air extending laterally between mediastinal pleura/lower thoracic aorta + diaphragm
spinnaker sail / thymic sail / angel wing sign in children = air outlining the thymus
air in azygoesophageal recess
air in pulmonary ligament = triangular gas collection in low mid chest

DDx:

other collections:
- medial/subpulmonary pneumothorax (simulating extrapleural sign); pneumoperitoneum (simulating extrapleural sign); pneumopericardium
mistaken normal anatomic structures:
- superior aspect of major fissure (on lordotic view); anterior junction line; Mach band effect

Spontaneous Pneumomediastinum

Age:

neonates (0.05 1%), 2nd 3rd decade

Cause:

Rupture of marginally situated alveoli from sudden/prolonged rise in intraalveolar pressure with subsequent dissection of air centrally along bronchovascular bundles to hila (interstitial emphysema) + rupture into mediastinum:
- Valsalva maneuver, status asthmaticus, aspiration
  P.442
  
  pneumonia, hyaline membrane disease, measles, giant cell pneumonia, coughing, vomiting, strenuous exercise, parturition, diabetic acidosis, crack cocaine inhalation = free-basing (mixing solid cocaine salt with a solvent to render it smokeable )
Tumor erosion of trachea/esophagus
Pneumoperitoneum/retropneumoperitoneum
- = extension from peritoneal/retroperitoneal/deep fascial planes of the neck

Traumatic Pneumomediastinum (rare)

Cause:

Pulmonary interstitial emphysema
- = disruption of marginal alveoli with gas traveling toward mediastinum due to positive pressure ventilation
Bronchial/tracheal rupture
- commonly associated with pneumothorax
Esophageal rupture: diabetic acidosis, alcoholic, Boerhaave syndrome
Iatrogenic - accidental:
- neck/chest/abdominal surgery, subclavian vein catheterization, mediastinoscopy, bronchoscopy, gastroscopy, recto-sigmoido-colonoscopy, electrosurgery with intestinal gas explosion, positive pressure ventilation, intubation, barium enema

Mediastinal Fat

MEDIASTINAL LIPOMATOSIS
FAT HERNIATION
- = omental fat herniating into chest
- Foramen of Morgagni
  - = cardiophrenic-angle mass, R >> L side
- Foramen of Bochdalek
  - = costophrenic-angle mass, almost always on left
- Paraesophageal hernia
  - = perigastric fat through phrenicoesophageal membrane
- CT:
  - fat with fine linear densities (= omental vessels)
LIPOMA
- = un-/encapsulated fatty tissue with variable amount of fibrous septa
- smooth + sharply defined boundaries
DDx: Liposarcoma, lipoblastoma (infancy), fat-containing teratoma, thymolipoma (inhomogeneous, higher CT numbers, poor demarcation, invasion of surrounding structures)
MULTIPLE SYMMETRIC LIPOMATOSIS
- rare entity without involvement of anterior mediastinal/cardiophrenic/paraspinal areas
- compression of trachea
- periscapular lipomatous masses

Low-attenuation Mediastinal Mass

FLUID
- Foregut cyst
- Lymphocele
- Seroma
- Hematoma
- Abscess
- Hydatid disease
LYMPH NODE
- Tuberculous lymph nodes
- Metastasis from thyroid/testicular tumor
- Lymphoma: treated/untreated
PRIMARY NEOPLASM
- Neurogenic tumor
- Fat-containing neoplasm

Mediastinal Cyst

= 21% of all primary mediastinal tumors
@ Anterior mediastinum
- Thymic cyst
- Dermoid cyst
- Parathyroid cyst (uncommon as mediastinal mass)
@ Middle mediastinum
- Pericardial cyst
- Bronchogenic cyst
@ Posterior mediastinum
- Esophageal duplication cyst
- Neurenteric cyst
- Thoracic duct cyst rare, filled with chyle
  
  Etiology: degenerative/lymphangiomatous
- Transdiaphragmatic jejunal duplication
- Cystic hygroma
- lateral meningocele
  - = outpouching of leptomeninges through intervertebral foramen
    
    Etiology: in 75% neurofibromatosis
  - spinal abnormalities (kyphoscoliosis, scalloping of dorsal vertebrae, enlargement of intervertebral foramen, pedicle erosion, thinning of ribs)
- Posttraumatic lymphocele
  - = contained pleural/mediastinal lymph collection
  - history of prolonged chylous chest tube drainage
  Time of onset: several months after injury
- Hydatid cyst
  
  Location: paravertebral gutter
  - erosion of ribs + vertebrae

Frequency of Developmental Mediastinal Cyst

Enterogenous cyst = Foregut cyst (45%):
- Bronchogenic cyst (35%)
- Esophageal duplication cyst (15%)
- Neurenteric cyst (least common)
Pericardial cyst (30%)
Thymic cyst (10%)
Nonspecific mesothelial cyst (10%)
Cystic hygroma (5%)

Mediastinal Mass

(excluding hyperplastic thymus glands, granulomas, lymphoma, metastases)

1. Neurogenic tumors	(28%)	: malignant in 16%
2. Teratoid lesions	(19%)	: malignant in 15%
3. Enterogenous cysts	(16%)
4. Thymomas	(13%)	: malignant in 46%
5. Pericardial cysts	(7%)

BENIGN MEDIASTINAL MASS
- 66 75% of all mediastinal tumors are benign (in all age groups)
- 88% discovered incidentally on routine chest x-ray
MALIGNANT MEDIASTINAL MASS
- 57% found in association with symptoms (pain, cough, shortness of breath)
- 80% of malignant tumors are symptomatic
Cervicothoracic sign:
- posterior superior mediastinal masses are sharply outlined by apical lung
- anterior superior mediastinal masses extending into neck have unsharp borders

Thoracic Inlet Lesions

Thyroid mass
- 1 3% of all thyroidectomies have a mediastinal component; 1/3 of goiters are intrathoracic
  
  Location: anterior (80%)/posterior (20%) mediastinum
- displacement of trachea posteriorly + laterally(anterior goiter)
- displacement of trachea anteriorly + esophagus posteriorly + laterally (posterior goiter)
- inhomogeneous density (cystic spaces, high-density iodine contents of >100 HU)
- focal calcifications (common)
- marked + prolonged contrast enhancement
- connection to thyroid gland
- vascular displacement + compression
- NUC (rarely helpful as thyroid tissue may be nonfunctioning):
  - uptake on I-123/I-131 scan (pertechnetate sufficient with modern gamma cameras, SPECT imaging may be helpful)
Cystic hygroma 3 10% involve mediastinum; childhood
Lymphoma
Other tumors: adenoma, carcinoma, ectopic thymoma

MASS RAIDER TRIANGLE

Raider triangle = on LAT CXR formed by posterior wall of trachea + thoracic vertebrae + aortic arch

Aberrant right subclavian artery
Aberrant left subclavian a. with right aortic arch
Aneurysms
Posterior descending goiter
Enlarged lymph node
Esophageal mass/duplication cyst

Anterior Mediastinal Mass

mnemonic:

4 T's

Thymoma
Teratoma
Thyroid tumor/goiter
Terrible lymphoma

SOLID THYMIC LESIONS
- Thymoma (benign, malignant): most common
- Normal thymus (neonate)
- Thymic hyperplasia (child)
- Thymic carcinoma
- Thymic carcinoid
- Thymolipoma
- Lymphoma
SOLID TERATOID LESIONS
- Teratoma
- Embryonal cell carcinoma
- Choriocarcinoma
- Seminoma
THYROID/PARATHYROID
- Substernal thyroid/intrathoracic goiter (10% of all mediastinal masses)
- Thyroid adenoma/carcinoma
- Ectopic parathyroid adenoma: ectopia in 1 3% (62 81% in anterior mediastinum/thymus, 30% within thyroid tissue, 8% in posterior superior mediastinum)
LYMPH NODES
- Lymphoma (Hodgkin, NHL): may arise in thymus, more common in young adults
- Metastases
- Benign lymph node hyperplasia
- Angioblastic lymphadenopathy
- Mediastinal lymphadenitis: sarcoidosis/granulomatous infection
CARDIOVASCULAR
- Tortuous brachiocephalic artery
- Aneurysm of ascending aorta
- Aneurysm of sinus of Valsalva
- Dilated SVC
- Cardiac tumor
- Epicardial fat-pad
CYSTS
- Cystic hygroma
- Bronchogenic cyst
- Extralobar sequestration
- Thymic cysts/dermoid cysts
- Pericardial cyst:
  - true cyst
  - pericardial diverticulum
- Pancreatic pseudocyst
OTHERS
- Neural tumor (vagus, phrenic nerve)
- Paraganglioma
- Hemangioma/lymphangioma
- Mesenchymal tumor (fibroma, lipoma)
- Sternal tumors
  - metastases from breast, bronchus, kidney, thyroid
  - malignant primary (chondrosarcoma, myeloma, lymphoma)
  - benign primary (chondroma, aneurysmal bone cyst, giant cell tumor)
- Primary lung/pleural tumor(invading mediastinum)
- Mediastinal lipomatosis:
  - Cushing disease
  - Corticosteroid therapy
- Morgagni hernia/localized eventration
- Abscess

Middle Mediastinal Mass

mnemonic: HABIT5

Hernia, Hematoma
Aneurysm

P.444

Bronchogenic cyst/duplication cyst
Inflammation (sarcoidosis, histoplasmosis, coccidioidomycosis, primary TB in children)
Tumors - remember the 5 L's:
- Lung, especially oat cell carcinoma
- Lymphoma
- Leukemia
- Leiomyoma
- Lymph node hyperplasia

LYMPH NODES
- 90% of masses in the middle mediastinum are malignant
- Neoplastic adenopathy
  - Lymphoma (Hodgkin:NHL = 2:1)
  - Leukemia (in 25%): lymphocytic > granulocytic
  - Metastasis (bronchus, lung, upper GI, prostate, kidney)
  - Angioimmunoblastic lymphadenopathy
- Inflammatory adenopathy
  - Tuberculosis/histoplasmosis (may lead to fibrosing mediastinitis)
  - Blastomycosis (rare)/coccidioidomycosis
  - Sarcoidosis (predominant involvement of paratracheal nodes)
  - Viral pneumonia (particularly measles + cat-scratch fever)
  - Infectious mononucleosis/pertussis pneumonia
  - Amyloidosis
  - Plague/tularemia
  - Drug reaction
  - Giant lymph node hyperplasia
    - = Castleman disease
  - Connective tissue disease (rheumatoid, SLE)
  - Bacterial lung abscess
- Inhalational disease adenopathy
  - Silicosis (eggshell calcification also in sarcoidosis + tuberculosis)
  - Coal worker's pneumoconiosis
  - Berylliosis
FOREGUT CYST
- Bronchogenic/respiratory cyst: cartilage, respiratory epithelium
- Enteric cyst = esophageal duplication cyst
- Extralobar sequestration (anomalous feeding vessel)
- Hiatal hernia
- Esophageal diverticula: Zenker, traction, epiphrenic
PRIMARY TUMORS (infrequent)
- Carcinoma of trachea
- Bronchogenic carcinoma
- Esophageal tumor: leiomyoma, carcinoma, leiomyosarcoma
- Mesothelioma
- Granular cell myoblastoma of trachea (rare)
VASCULAR LESIONS
- Aneurysm of transverse aorta
- Distended veins (SVC, azygos vein)
- Hematoma

Subcarinal Space Lesion

Enlarged lymph nodes
Bronchogenic cyst
Pericardial effusion
Enlarged left atrium
Esophageal mass
Aortic aneurysm

AORTICOPULMONARY WINDOW MASS

Adenopathy
Aneurysms: traumatic aortic pseudoaneurysm, pulmonary artery aneurysm, ductus Botalli aneurysm, bronchial artery aneurysm
Bronchogenic cyst
Tumor of tracheobronchial tree
Esophageal tumor
Neurogenic tumor
Mediastinal abscess

Widening of Paratracheal Space

Normal width:

<5 mm

Dilated tortuous vessels (brachiocephalic artery, SVC, azygos vein)
Enlarged lymph node
Bronchogenic carcinoma
Mediastinal lipomatosis
Mediastinal hematoma
Bronchogenic cyst

RETROCARDIAC SPACE OF HOLZKNECHT LESION

Hiatal hernia
Esophageal lesion
Left ventricular aneurysm
Pericardial cyst
Bronchogenic cyst
Aortic aneurysm
Vagal/phrenic nerve neurofibroma

Posterior Mediastinal Mass

NEOPLASM
- Neurogenic tumor (largest group): 30% malignant
  - Tumor of peripheral nerve origin
    - more common in adulthood
    - 80% appear as round masses with sulcus
    - lower attenuation than muscle (in 73%)
    - Schwannoma = neurilemoma (32%): derived from sheath of Schwann without nerve cells
    - Neurofibroma (10%): contains Schwann cells + nerve cells, 3rd + 4th decade
    - Malignant schwannoma
  - Tumor of sympathetic ganglia origin
    - more common in childhood
    - 80% are elongated with tapered borders
    - Ganglioneuroma (23 38%):
      - second most common tumor of posterior mediastinum after neurofibroma
    - Neuroblastoma (15%):
      - highly malignant undifferentiated small round cell tumor originating in sympathetic ganglia, <10 years of age
    - Ganglioneuroblastoma (14%):
      - both features, spontaneous maturation possible
  - Tumors of paraganglia origin (rare)
    - Chemodectoma = paraganglioma (4%)
    - Pheochromocytoma
    - rib spreading, erosion, destruction
    - enlargement of neural foramina (dumbbell lesion)
    - scalloping of posterior aspect of vertebral body
    - scoliosis
    - CT:
      - low-density soft-tissue mass (lipid contents)
- Spine tumor: metastases (eg, bronchogenic carcinoma, multiple myeloma), ABC, chordoma, chondrosarcoma, Ewing sarcoma
- Lymphoma
- Invasive thymoma
- Mesenchymal tumor (fibroma, lipoma, leiomyoma)
- Hemangioma
- Lymphangioma
- Thyroid tumor
INFLAMMATION/INFECTION
- Infectious spondylitis: pyogenic, tuberculous, fungal
  - destruction of endplates + disk space
  - paravertebral soft-tissue mass
- Mediastinitis
- Pancreatic pseudocyst
- Lymphoid hyperplasia
- Sarcoidosis (in 2%, typically asymptomatic patient)
VASCULAR MASS
- Aneurysm of descending aorta (curvilinear calcification; elderly)
- Enlarged azygos + accessory hemiazygos vein
- Esophageal varices
- Congenital vascular anomalies: aberrant subclavian artery, double aortic arch, pulmonary sling, interruption of IVC with azygos/hemiazygos continuation
TRAUMA
- Aortic aneurysm/pseudoaneurysm
- Hematoma
- Loculated hemothorax
- Traumatic pseudomeningocele
FOREGUT CYST
- cysts may demonstrate peripheral rimlike calcifications
- Bronchogenic cyst
- Enteric cyst
- Neurenteric cyst
- Extralobar sequestration
FATTY MASS
- Bochdalek hernia
- Mediastinal lipomatosis
- Fat-containing tumors: lipoma, liposarcoma, teratoma (rare)
OTHER
- Loculated pleural effusion
- Pancreatic pseudocyst
- Lateral meningocele (neurofibromatosis; enlarged neural foramen)
- Extramedullary hematopoiesis: in chronic bone marrow deficiency; paraspinal area rich in RES-elements
  - splenomegaly; widening of ribs
- Pseudomass of the newborn

mnemonic:

BELLMAN

Bochdalek hernia
Extramedullary hematopoiesis
Lymphadenopathy
Lymphangioma
Meningocele (lateral)
Aneurysm
Neurogenic tumor

Cardiophrenic-angle Mass

Lesion of pericardium
- Pericardial cyst
- Intrapericardiac bronchogenic cyst
- Benign intrapericardiac neoplasm: teratoma, leiomyoma, hemangioma, lipoma
- Malignant neoplasm: mesothelioma, metastasis (lung, breast, lymphoma, melanoma)
Cardiac lesion: aneurysm
Others: masses arising from lung, pleura, diaphragm, abdomen

Right Cardiophrenic-angle Mass

Heart
- Aneurysm (cardiac ventricle, sinus of Valsalva)
- Dilated right atrium
Peri-/epicardium
- Epicardial fat-pad/lipoma (most common cause)
  - triangular opacity in cardiophrenic angle less dense than heart
  - increase in size under corticosteroid treatment
- Pericardial cyst
Diaphragm
- Diaphragmatic hernia of Morgagni
- Diaphragmatic lymph node (esp. in Hodgkin disease + breast cancer)
Anterior mediastinal mass: thymolipoma
Primary lung mass
Paracardiac varices
Enlarged lymph node: lymphoma, metastasis (lung, breast, colon, ovary, melanoma)

Hypervascular Mediastinal Mass

Paraganglioma
Metastasis: typically renal cell carcinoma
Castleman disease
Hemangioma
Sarcoma
Tuberculosis
Sarcoidosis

Hilar mass

LARGE PULMONARY ARTERIES
- enlargement of main pulmonary artery
- abrupt change in vessel caliber
- enlarged pulmonary artery compared with bronchus (in same bronchovascular bundle)
- cephalization
- enlargement of right ventricle (RAO 45 , LAO 60 )
- Cause:
  - Chronic obstructive disease (emphysema)
  - Chronic restrictive interstitial lung disease (idiopathic fibrosis, cystic fibrosis, rheumatoid arthritis, sarcoidosis)
  - Pulmonary embolic disease (acute massive/chronic)
  - Idiopathic pulmonary hypertension
  - Left-sided heart failure + mitral stenosis
  - Congenital heart disease with left-to-right shunt
    - acyanotic: ASD, VSD, PDA
    - cyanotic (admixture lesions): transposition of great vessels, truncus arteriosus
DUPLICATION CYST
UNILATERAL HILAR ADENOPATHY
- NEOPLASTIC
  - Bronchogenic carcinoma (most common)
  - Metastases (lack of mediastinal involvement exceptional)
  - Lymphoma
- INFLAMMATORY
  - Tuberculosis (primary) in 80%
  - Fungal infection: histoplasmosis, coccidioidomycosis, blastomycosis
  - Viral infections: atypical measles
  - Infectious mononucleosis
  - Drug reaction
  - Sarcoidosis (in 1 3%)
  - Bilateral lung abscess
mnemonic: Fat Hila Suck
- fungus
- Hodgkin disease
- Squamous/oat cell carcinoma
BILATERAL HILAR ADENOPATHY
- NEOPLASTIC
  - Lymphoma (50% in Hodgkin disease)
  - Metastases
  - Leukemia
  - Primary bronchogenic carcinoma
  - Plasmacytoma
- INFLAMMATORY
  - Sarcoidosis (in 70 90%)
  - Silicosis
  - Histiocytosis X
  - Idiopathic pulmonary hemosiderosis
  - Chronic berylliosis
- INFECTIOUS
  - Rubella, ECHOvirus, varicella, mononucleosis
mnemonic: Please Helen Lick My Popsicle Stick
- Primary TB
- Histoplasmosis
- lymphoma
- metastases
- Pneumoconiosis
- Sarcoidosis

Eggshell Calcification of Nodes

PNEUMOCONIOSIS
- Silicosis (5%)
- Coal worker's pneumoconiosis (1.3 6%) not seen in: asbestosis, berylliosis, talcosis, baritosis
SARCOIDOSIS (5%)
FUNGAL + BACTERIAL INFECTION (rare)
- Tuberculosis
- Histoplasmosis
- Coccidioidomycosis
FIBROSING MEDIASTINITIS
LYMPHOMA FOLLOWING RADIATION THERAPY

Enlargement of azygos vein

Normal azygos vein (on upright CXR): 7 mm

COLLATERAL CIRCULATION
- Portal hypertension
- SVC obstruction/compression below azygos vein
- IVC obstruction/compression
- Interrupted IVC with azygos continuation
- Partial anomalous venous return (rare)
- Pregnancy
- Hepatic vein occlusion
RIGHT ATRIAL HYPERTENSION
- Right-sided heart failure
- Constrictive pericarditis
- Large pericardial effusion

Thymus

Thymic Mass

Thymoma
Thymolipoma
Thymic cyst
Thymic carcinoid

Diffuse Thymic Enlargement

BENIGN
- Thymic hyperplasia
- Intrathymic hemorrhage
- Hemangioma
- Lymphangioma
MALIGNANT THYMIC INFILTRATION
- presence of adenopathy elsewhere
- no pleural implants

Leukemia
Hodgkin/non-Hodgkin lymphoma
Langerhans cell histiocytosis

Trachea amp; Bronchi

Tracheal Narrowing

ANTERIOR COMPRESSION
- Congenital
  - Congenital goiter
  - Innominate artery syndrome
    - ablation of right radial pulse by rigid endoscopic pressure
    - posterior tracheal displacement
    - focal collapse of trachea at fluoroscopy
    - pulsatile indentation of anterior tracheal wall by innominate artery on MRI
    Rx: surgical attachment of innominate artery to manubrium
- Inflammatory
  - Cervical/mediastinal abscess
- Neoplastic
  - Cervical/intrathoracic teratoma
    - amorphous calcifications + ossifications
  - Thymoma
  - Thyroid tumors
  - Lymphoma
- Traumatic: hematoma
POSTERIOR TRACHEAL COMPRESSION
- Congenital
  - Vascular ring
    - complete: double aortic arch, right aortic arch
    - incomplete: anomalous right subclavian a.
    - posterior indentation of esophagus + trachea
  - Pulmonary sling
    - = anomalous left pulmonary artery arising from right pulmonary artery, passing between trachea + esophagus en route to left lung
  - Bronchogenic cyst
    - most common between esophagus + trachea at level of carina
- inflammatory: abscess
- neoplastic: neurofibroma
- traumatic: esophageal foreign body, esophageal stricture, hematoma
INTRINSIC TRACHEAL CAUSES
- Congenital:
  - Congenital tracheal stenosis:
    - generalized/segmental
    - = complete cartilaginous ring (instead of horseshoe shape)
  - Congenital tracheomalacia = immaturity of tracheal cartilage = chondromalacia
    - expiratory stridor
    - tracheal collapse on expiration
- Neoplastic: papilloma, fibroma, hemangioma
- Traumatic: acquired stenosis (endotracheal + tracheostomy tubes), granuloma, acquired tracheomalacia (cartilage degeneration after inflammation, extrinsic pressure, bronchial neoplasia, TE fistula, foreign body)

Tracheal Tumor

asthma symptomatology
hoarseness, cough
wheeze (inspiratory with extrathoracic lesion, expiratory with intrathoracic lesion)
hemoptysis

MALIGNANT
- Squamous-cell carcinoma (commonest primary)
  - 50% of all malignant tracheal lesions
- Adenoid cystic carcinoma = cylindroma
- Carcinoid
- Mucoepidermoid carcinoma
- Metastasis from renal cell carcinoma, colon cancer, malignant melanoma
- Lymphoma
- Plasmacytoma
BENIGN TUMOR
- Cartilaginous tumor (hamartoma)
- Squamous cell papilloma
- Fibroma/lipoma
- Hemangioma
- Granular cell myoblastoma
INFLAMMATION
- Granulomatous disease:
  - TB, sarcoidosis, Wegener granulomatosis
- Inflammatory myoblastic pseudotumor
- Amyloid tumor
- Pseudotumor: inspissated mucus, foreign body

Endobronchial Tumor

Neuroendocrine tumor (typical/atypical carcinoid)
Mucoepidermoid carcinoma
Adenoid cystic carcinoma
Hamartoma
Leiomyoma
Myoblastoma
Mucous gland adenoma
Squamous cell carcinoma

Bronchial Obstruction

Foreign body: most commonly in young children
Granulomatous disease: due to granuloma formation in bronchial wall/extrinsic compression by adenopathy
Broncholiths = erosion of calcified nodes into bronchial lumen
Stenosis/atresia
Neoplasm
- Bronchogenic carcinoma
- Adenoid cystic carcinoma
- Mucoepidermoid tumor
- Hamartoma

mnemonic:

MEATFACE

Mucus plug
Endobronchial granulomatous disease
Adenoma
Tuberculosis
Foreign body
Amyloid, Atresia (bronchial)
Cancer (primary)
Endobronchial metastasis

Mucoid Impaction

= BRONCHIAL MUCOCELE = BRONCHOCELE
= accumulation of inspissated secretions (mucus/pus/inflammatory products) within bronchial lumen; usually associated with bronchial dilatation

WITH BRONCHIAL OBSTRUCTION in the presence of collateral air drift
- Bronchial obstruction by neoplasm:
  - bronchogenic carcinoma/adenoma
- Bronchial atresia

P.448

WITHOUT BRONCHIAL OBSTRUCTION
- Asthma (most frequent cause): esp. during acute attack or convalescent phase
- Fluid-filled bronchiectasis: history of childhood pneumonia; peripheral distribution
- Bronchopulmonary aspergillosis: central perihilar bronchiectasis
- Cystic fibrosis
- Chronic bronchitis

Bronchial Wall Thickening

Apparent thickness of bronchial wall varies with lung window chosen on CT: a mean window that is too low can make the bronchial wall appear abnormal!

PERIBRONCHOVASCULAR
- Sarcoidosis
- Lymphangitic carcinomatosis
- Kaposi sarcoma
- Lymphoma
- Pulmonary edema
BRONCHIAL WALL
- Airway disease
- Relapsing polychondritis
- Wegener granulomatosis
- Amyloidosis
MUCOSAL INFECTION
- Croup
- Tuberculosis
- Fungal disease
- Aspergillosis

Circumferential Tracheobronchial Wall Thickening

Wegener granulomatosis
Sarcoidosis
Inflammatory bowel disease
Post-intubation stenosis
Amyloidosis
Infection: Klebsiella rhinoscleromatis, fungal infection, TB

Signet-ring Sign

= cross section of usually thick-walled and dilated ringlike bronchus + branch of pulmonary artery as adjacent round soft-tissue opacity

Bronchiectasis
Multifocal bronchioloalveolar carcinoma
Metastatic adenocarcinoma

Broncholithiasis

Histoplasmosis
Tuberculosis
Cryptococcosis
Actinomycosis
Coccidioidomycosis

calcified lymph node within/adjacent to affected bronchus
bronchial obstruction: atelectasis, airspace disease, bronchiectasis, air trapping
absence of associated soft-tissue mass

Diaphragm

Bilateral Diaphragmatic Elevation

Shallow inspiration (most frequent)
Abdominal causes
- Obesity, pregnancy, ascites, large abdominal mass
Pulmonary causes
- Bilateral atelectasis
- Restrictive pulmonary disease (SLE)
Neuromuscular disease
- Myasthenia gravis
- Amyotrophic lateral sclerosis

Unilateral Diaphragmatic Elevation

Subpulmonic pleural effusion
- dome of pseudodiaphragm migrates toward the costophrenic angle and flattens
Altered pulmonary volume
- Atelectasis
  - associated pulmonary density
- Postoperative lobectomy/pneumonectomy
  - rib defects, metallic sutures
- Hypoplastic lung
  - small hemithorax (more often on the right), crowding of ribs, mediastinal shift, absent/small pulmonary artery, frequently associated with dextrocardia + anomalous pulmonary venous return
Phrenic nerve paralysis
- Primary lung tumor
- Malignant mediastinal tumor
- Iatrogenic
- Idiopathic
  - paradoxic motion on fluoroscopy (patient in lateral position sniffing)
Abdominal disease
- Subphrenic abscess: history of surgery, accompanied by pleural effusion
- Distended stomach/colon
- Interposition of colon
- Liver mass (tumor, echinococcal cyst, abscess)
Diaphragmatic hernia
Eventration of diaphragm
Traumatic rupture of diaphragm:
- associated with rib fractures, pulmonary contusion, hemothorax
Diaphragmatic tumor:
- Mesothelioma, fibroma, lipoma, lymphoma, metastases

Chest wall

Chest Wall Lesions

incomplete border sign (due to obtuse angle)
smooth tapering borders (tangential views)
tumor pedicle suggests a benign tumor

EXTERNAL
- Cutaneous lesion: moles, neurofibroma
- Nipples
- Artifact
NEOPLASTIC
- Mesenchymal tumor
  
  P.449
  - Lipoma (common): growing between ribs presenting as intrathoracic + subcutaneous mass; CT diagnostic)
  - Muscle tumor, fibroma
- Neural tumor
  - Schwannoma, neurofibroma (may erode ribs inferiorly with sclerotic bone reaction), neuroma, neuroblastoma
- Vascular tumor
  - Hemangioma, lymphangioma, hemangiopericytoma, aneurysm, false aneurysm
- Bone tumor (see also Rib lesion)
TRAUMATIC
- Hematoma
- Rib fracture
INFECTIOUS
- cellulitis, pyomyositis, abscess, necrotizing fasciitis
- Actinomycosis (parenchymal infiltrate, pleural effusion, chest wall mass, rib destruction, cutaneous fistulas)
- Aspergillosis, nocardiosis, blastomycosis, tuberculosis (rare)
- Pyogenic: Staphylococcus, Klebsiella
CHEST WALL INVASION
- Peripheral lung cancer (eg, Pancoast tumor)
- Recurrent breast cancer
- Lymphomatous nodes

Pancoast Syndrome

= superior sulcus tumor invading brachial plexus + sympathetic stellate ganglion
CLINICAL TRIAD:
- Ipsilateral arm pain
- Muscle wasting of hand
- Horner syndrome = enophthalmos, ptosis, miosis, anhidrosis

Cause:

lung cancer (most common), breast cancer, multiple myeloma, metastases, lymphoma, mesothelioma

Lung Disease with Chest Wall Extension

Infectious
- Actinomycosis
- Nocardia
- Blastomycosis
- Tuberculosis
Malignant tumor
- Bronchogenic carcinoma
- Lymphoma
- Metastases
- Mesothelioma
- Breast carcinoma
- Internal mammary node
Benign tumor
- Capillary hemangioma of infancy
- Cavernous hemangioma
- Extrapleural lipoma
- Abscess
- Hematoma

Chest Wall Tumors in Children

Malignant Tumors of Chest Wall in Children

More common than benign primary chest wall tumors!

Ewing sarcoma of rib (most common)
- older child: rib involvement in 7%, predominant involvement of pelvis + lower extremity
- child <10 years: rib involvement in 30%
DDx: osteomyelitis, unusual-appearing fracture, callus, direct spread of lung infection
Rhabdomyosarcoma
relatively common in children + adolescents
- sclerosis/destruction/scalloping of cortex (local extension to contiguous bone)
- may calcify
Metastases to: lung, occasionally lymph nodes

Prognosis: infiltrative growth with high risk of local recurrence
Metastasis
- Neuroblastoma
  - 10% present as chest wall mass
  - may calcify
- Leukemia
Askin tumor
- = PRIMITIVE NEUROECTODERMAL TUMOR
- = uncommon tumor probably arising from intercostal nerves in young Caucasian females
Path: neuroectodermal small cell tumor containing neuron-specific enolase (may also be found in neuroblastoma)
- rib destruction (occasionally arising from rib) in 25 63%
- malignant pleural effusion
Metastases to: bone, CNS, liver, adrenal

DDx: Ewing sarcoma, lymphoma, chest wall hamartoma in infancy
Chondro-/osteosarcoma
- quite rare in pediatric patients

Benign Tumors of Chest Wall in Children

OSSEOUS
- Aneurysmal bone cyst
- Chondroblastoma
- Enchondroma
- Osteoblastoma
- Osteochondroma
- Osteoid osteoma
- Often associated with systemic syndrome: neurofibromatosis, histiocytosis, osteochondromatosis
- cortical rib destruction + soft-tissue mass
SOFT TISSUE
- Lipoma
- Hemangioma
- Lymphangioma
- Teratoma

Bedside Chest Radiography

Benefit:

Unexpected findings:	in 37 43 65%
Change in diagnostic approach/therapy:	in 27%

P.450

Indications:

Apparatus position + complications
- Malposition of tracheal tube (12%)
  - tip of tube 4 6 cm above carina with neck in neutral position:
    - migration by 2 cm inferiorly with flexion
    - migration by 2 cm superiorly with extension
  - tube diameter should be 1/2 to 2/3 of tracheal lumen
  - diameter of inflated balloon should be less than diameter of trachea
  - Cx:
    - Tracheal damage (stenosis/rupture) if ratio of cuff to tracheal lumen >1.5
    - Aspiration (in 8%)
    - Dislodging of teeth/fillings
- Malposition of central venous line (9%) into internal jugular vein, azygous arch, internal mammary vein, congenital anomaly (eg, persistent left SVC), artery
  - ideal position = origin of SVC = between RA and most proximal venous valve (= beyond upper margin of 1st rib) = 2.5 cm distal to junction of subclavian + jugular veins
  Cx: placement into branch vein/anomalous vein (eg, persistent left SVC), intraarterial placement, extravascular placement
- Malposition of nasogastric tube
  - esophageal malposition
  - bronchial intubation
  - esophageal perforation
  - may not be on film if coiled in hypopharynx
- Swan-Ganz line (= balloon-directed line)
  - 25% of catheters malpositioned on initial CXR
  - tip should be in main/right/left pulmonary artery (NOT distal to proximal interlobar pulmonary artery)
  Cx: pulmonary infarction, pulmonary artery rupture, hemorrhage, cardiac perforation, pseudoaneurysm formation, malposition, intracardiac knot, arrhythmia
- Thoracostomy tube
  - break in radiopaque material (= most proximal side hole) should be intrathoracic
  - intrafissural placement makes tube ineffective
- Tracheostomy
  - Position NOT affected by flexion/extension of neck!
  - tube diameter should be 2/3 of tracheal lumen
  - tip should be at level of T3
- Intraaortic balloon pump (IABP)
  - tip of pump should be just distal to left subclavian artery in proximal descending aorta = 1 2 cm below top of aortic arch
  - balloon inflates in diastole, deflates in systole
Cardiopulmonary disease
- Atelectasis
  - most common CXR abnormality in ICU
  - Incidence increased:
    - after general anesthesia, thoracic/upper abdominal surgery, pre-existing lung disease, smoking, obesity, elderly
    Location: left lung base (most frequent)
  - linear/platelike subsegmental
  - lobar/segmental:
    - air bronchogram present = collapse of small airways bronchoscopy not beneficial
    - air bronchogram absent = central mucoid impaction bronchoscopy therapeutic
  - patchy mimicking pneumonia
  - rapid temporal change possible
- Pulmonary edema
  - cardiac (hydrostatic)
    - including CHF, overhydration, renal failure
      
      N.B.: cephalization of vasculature not helpful in supine position
    - usually cardiomegaly (cardiothoracic ratio 55%)
    - enlarged vascular pedicle (mediastinal width at SVC 70 mm)
    - Kerley lines
    - pleural effusion frequent
    - central/diffuse lung opacity
    - rapid onset + resolution
    Accuracy: 70% for pulmonary wedge pressure >18 mm Hg using both CT ratio + vascular pedicle width
  - noncardiac (permeability)
    - including ARDS, sepsis, drug reaction, near drowning, smoke inhalation, neurogenic edema, aspiration, fat embolism
    - cardiomegaly rare
    - Kerley lines absent
    - pleural effusions unusual + small
    - decreased lung volumes frequent
    - diffuse/peripheral lung opacity
    - Patchy peripheral distribution in 58% of permeability edema vs. in 13% of hydrostatic edema
    - delayed onset + resolution
    - barotrauma common
- Pleural effusion (due to CHF)
  
  Location: bilateral/right-sided
  A solely left-sided effusion suggests a superimposed process/gravity!
  - homogeneous density over lower lung
  - fluid over apex/in fissures
  - intrafissural pseudotumor
  - not visible in 30%
  DDx: atelectasis, empyema (loculated nonmobile effusion), postpericardiotomy syndrome (increasing effusion beyond 3rd postoperative day)
- Alveolar disease = pneumonia
  - in 10% of ICU patients, 60% with ARDS
  - commonly related to aspiration
  - slowly progressing, often multifocal patchy areas of consolidation/poorly defined opacities
  - air bronchograms
  - cavitation (most specific finding)
  Impossible DDx: ARDS, lobar atelectasis
- Interstitial disease
  
  DDx:
  - interstitial pulmonary edema daily changes
  - pneumonia (CMV, pneumocystis)
- Barotrauma (in 4 15% of ventilated patients)
  
  Increased risk: underlying lung disease (ARDS, pneumonia), peak inspiratory pressure >40 cm H²O, use of PEEP, large tidal volume
  - pulmonary interstitial edema (initially)
  - anteromedial/subpulmonic location
  - tension pneumothorax (in 60 96%) with mediastinal shift masked by PEEP
- Aspiration
  
  Increased risk: general anesthesia, depressed consciousness, neuromuscular disorder, esophageal disease, presence of NG/ET tube
  
  Location: posterior aspect of upper lobes, superior segments + posterior basilar segments of lower lobes
  - focal/multifocal consolidation in dependent location with central predominance
  - aspiration pneumonitis (may progress over first day but clearing within a few days)
  - aspiration pneumonia (lack of clearing/progression)
- Thoracic bleeding
- Mediastinal disease

P.452

Function and Anatomy of Lung

Bronchopulmonary Anatomy

Airways

Embryology of Airways

first 5 weeks GA	lung buds grow from ventral aspect of primitive foregut (from caudal end of laryngotracheal groove of primitive pharyngeal floor); pulmonary agenesis
5th week	GA trachea + esophagus separate
5 16 weeks	formation of tracheobronchial tree with bronchi, bronchioles, alveolar ducts, alveoli; bronchogenic cyst (= abnormal budding); pulmonary hypoplasia (= fewer than expected bronchi)
16 24 weeks	dramatic increase in number + complexity of airspaces and blood vessels; small airways + reduction in number and size of acini

Anomalous Bronchial Division

Tracheal Bronchus

= bronchus of variable length arising from lower trachea
blind-ending pouch/aeration of a portion or all of the RUL
early origin of apicoposterior LUL bronchus (less common)

Accessory Cardiac Bronchus

= true supernumerary anomalous bronchus M:F = 2.8:1
arises from medial wall of bronchus intermedius prior to origin of apical segmental RLL bronchus
caudal course toward pericardium
blind-ending pouch/ventilation of an accessory lobe

P.453

Paracardiac Bronchus

= normal bronchus arising from medial aspect of lower lobe

Prevalence: 5% of patients

Bronchial Tree in Lateral Projection

Airway

= conducting branches for the transport of air; ~300,000 branching airways from trachea to bronchiole with an average of 23 airway generations

Definition:

bronchus	=	cartilage in wall
bronchiole	=	absence of cartilage (after 6 to 12 divisions of segmental bronchus)

membranous bronchiole = purely air conducting
respiratory bronchiole = contains alveoli in its wall
lobular bronchiole = supplies secondary pulmonary lobule; may branch into 3 or more terminal bronchioles
terminal bronchiole = last generation of purely conducting bronchioles; each supplying one acinus

small airways	=	diameter <2 mm = small cartilaginous bronchi + membranous and respiratory bronchioles; account for 25% of airway resistance
large airways	=	diameter >2 mm; account for 75% of airway resistance

HRCT of normal lung (window level 700 HU, window width 1,000 1,500):

875 18 HU at inspiration;
620 43 HU at expiration
8th order bronchi visible = bronchi >2 mm in diameter
Normal lobular bronchioles not visible!

Acinus

= functionally most important subunit of lung = all parenchymal tissue distal to one terminal bronchiole comprising 2 5 generations of respiratory bronchioles + alveolar ducts + alveolar sacs + alveoli
gas exchange
radiologically not visible

[Primary Pulmonary Lobule]

= alveolar duct + air spaces connected with it

Secondary Pulmonary Lobule

= REID LOBULE
= smallest portion of lung surrounded by connective tissue septa = basic anatomic + functional pulmonary unit appearing as an irregular polyhedron; separated from each other by thin fibrous interlobular septa (100 m); supplied by 3 5 terminal bronchioles; contains 3 24 acini

Size:

10 25 mm in diameter

P.454

visible on surface of lung

Contents:
- centrally = lobular core: branches of terminal bronchioles (0.1 mm wall thickness is below the resolution of HRCT) + pulmonary arterioles (1 mm)
- peripherally (in interlobular septa): pulmonary vein + lymph vessels
HRCT:
barely visible fine lines of increased attenuation in contact with pleura (= interlobular septa); best developed in subpleural areas of

UL + ML: anterior + lateral + juxtamediastinal

LL: anterior + diaphragmatic regions
dotlike/linear/branching structures (= pulmonary arterioles) near center of secondary pulmonary lobule 3 5 mm from pleura

Interstitial Anatomy

Bronchovascular interstitium
- surrounding bronchovascular bundle
Centrilobular interstitium
- surrounds distal bronchiolovascular bundle
- line extending to the center of a lobule
Interlobular septal interstitium
- lines perpendicular to pleura surrounding a lobule
Pleural interstitium

Criss-sectional Anatomy of Bronchovascular Divisions

Lung Development

lung bud
- derived from primitive foregut; pulmonary arteries arise from 6^th aortic arch
Time: 26 days to 6 weeks EGA
pseudoglandular phase
- development of airways to terminal bronchioles
Time: 6 16 weeks EGA
canalicular/acinar phase
- multiple alveolar ducts arise from respiratory bronchioles lined by type II alveolar cells capable of surfactant synthesis
Time: 16 28 weeks EGA

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saccular phase
- increase in number of terminal sacs + thinning of interstitium + early development of true alveoli
Time: 28 34 weeks EGA
alveolar phase

Time: 36 weeks EGA 18^th postnatal month

Surfactant

= surface-active material essential for normal pulmonary function

lung interstitium
Division	Components
Axial	bronchovascular sheaths, lymphatics
Middle (parenchymal)	alveolar wall (interalveolar septum)
Peripheral	pleura subpleural connective tissue, interlobular septa (enclosing pulmonary veins, lymphatics, walls of cortical alveoli)

Substrate:
- phospholipids (dipalmitoylphosphatidylcholine, phosphatidylglycerol), other lipids, cholesterol, lung-specific proteins

Production:

type II pulmonary alveoli synthesize + transport + secrete lung surfactant; earliest production around 18th week of gestation (in amniotic fluid by 22nd week of gestation)

Action:

increases lung compliance, stabilizes alveoli, enhances alveolar fluid clearance, reverses surface tension, protects against alveolar collapse during respiration, protects epithelial cell surface, reduces opening pressure + precapillary tone

Cross-sectional Anatomy of Lung Segments

Pulmonary Circulation

Primary pulmonary circulation (98% of cardiac output) pulmonary arteries travel along lobar + segmental bronchi down to subsegmental level matching caliber of airways
- large elastic pulmonary arteries (500 > 1,000 m) accompany lobar + segmental bronchi matching caliber of airways
  - main pulmonary artery/trunk: <28 mm
  - right/left pulmonary artery
  - lobar pulmonary artery
  - segmental pulmonary artery
- muscular arteries (50 1,000 m)
  - accompany subsegmental airways + terminal bronchioles
  - provide active vasodilatation + constriction
- arterioles (15 150 m)
  - accompany respiratory bronchioles + alveolar ducts
- capillary network in alveolar walls
- venules
- pulmonary veins
  - course through interlobular fibrous septa

Bronchial circulation (1 2% of cardiac output)

Origin:	proximal to mid-descending thoracic aorta between 4th + 7th thoracic vertebra at level of left main bronchus, intercostal arteries (usually 2 vessels for each lung)
Pressure:	6 that of normal pulmonary circulation

Variants:

40% have 2 left bronchial aa. + 1 right intercostal bronchial trunk artery (ICBT)
20% have 1 left bronchial a. + 1 right ICBT
20% have 1 left bronchial a. + 1 common bronchial trunk + 1 right ICBT
10% have 2 left bronchial aa. + 1 right bronchial a. + 1 right ICBT

Supply:	esophagus, trachea, visceral pleura, lymph nodes, extra- and intrapulmonary airways, bronchovascular + neural bundles, vasa vasorum of pulmonary circulation
Course:	tortuous path along peribronchial sheath of mainstem airway to terminal bronchioles

Anastomoses: through microvascular connections
- bronchial blood flow may increase by 300% in the weeks following pulmonary artery embolization
The Secondary Pulmonary Nodule

Lung function

Lung Volumes & Capacities

Tidal volume (TV)
- = amount of gas moving in and out with each respiratory cycle
Residual volume (RV)
- = amount of gas remaining in the lung after a maximal expiration
Total lung capacity (TLC)
- = gas contained in lung at the end of a maximal inspiration
Vital capacity (VC)
- = amount of gas that can be expired after a maximal inspiration without force
Functional residual capacity (FRC)
- = volume of gas remaining in lungs at the end of a quiet expiration

Terminal Airways within the Secondary Pulmonary lobule

Changes In Lung Volumes

DECREASED VC:
- Reduction in functioning lung tissue due to
  - space-occupying process (eg, pneumonia, infarction)
  - surgical removal of lung tissue
- Process reducing overall volume of the lungs (eg, diffuse pulmonary fibrosis)
- Inability to expand lungs due to
  - muscular weakness (eg, poliomyelitis)
  - increase in abdominal volume (eg, pregnancy)
  - pleural effusion
INCREASED FRC and RV:
- characteristic of air trapping and overinflation (eg, asthma, emphysema)
  
  Associated with: increased TLC
- normal level of inflation to 8 posterior ribs
DECREASED FRC and RV:
- Process reducing overall volume of lungs (eg, diffuse pulmonary fibrosis)
- Process that occupies volume within alveoli eg, alveolar microlithiasis)
- Process that elevates diaphragm (eg, ascites, pregnancy), usually associated with decreased TLC

P.457

Lung Volumes and Capacities

Flow Rates

Spirometric measurements:
- Forced expiratory volume (FEV)
  - = amount of air expired during a certain period (usually 1 + 3 sec)
  Normal values: FEV₁ = 83% FEV₃ =97%
- Maximal midexpiratory flow rate(MMFR)
  - = amount of gas expired during the middle half of forced expiratory volume curve (largely effort independent)
  - Indicator of small airway resistance
- Flow-volume loop
  - = gas flow is plotted against the actual volume of lung at which this flow is occurring
  - Useful in identifying obstruction in large airways
Resistance in small airways
- Closing volume = lung volume at which dependent lung zones cease to ventilate because of airway closure in small airway disease or loss of lung elastic recoil
- decrease in FEV, MMFR, MBC:
  - expiratory airway obstruction (reversible as in spasmodic asthma/irreversible as in emphysema)
  - respiratory muscle weakness

Diffusing Capacity

= rate of gas transfer across the alveolocapillary membrane in relation to a constant pressure difference across it; measured by the carbon monoxide diffusion method DL_CO.
Technique:
- patient inspires maximally a gas with a known small concentration of CO
- holds his/her breath for 10 seconds and then slowly expires to residual volume (RV)
- an aliquot of the end-expired (alveolar) gas is analyzed for amount of CO absorbed during breath
Measurement: in mL of CO absorbed/min/mm Hg
Reduction:
- Ventilation/perfusion inequality: less CO is taken up by poorly ventilated or poorly perfused areas (eg, emphysema)
- Reduction of total surface area (eg, emphysema, surgical resection)
- Reduction in permeability from thickening of alveolar membrane (eg, cellular infiltration, edema, interstitial fibrosis)
- Anemia with lack of hemoglobin

Arterial Blood Gas Abnormalities

decreased pulmonary arterial O2:
- Alveolar hypoventilation
- Impaired diffusion
- Abnormal ventilation/perfusion ratios
- Anatomic shunting
elevated pulmonary arterial CO₂:
- Alveolar hypoventilation
- Impaired ventilation/perfusion ratios

V/Q Inequality

NORMAL
- blood flow decreases rapidly from base to apex
- ventilation decreases less rapidly from base to apex
  - V/Q is low at base and high at apex
  - Pulmonary arterial O2 is substantially higher at apex
  - Pulmonary arterial CO2 is substantially higher at base
ABNORMAL
- chiefly resulting from non-/underventilated lung regions (non- /underperfused regions do not result in blood gas disturbances)

Compliance

= relationship of the change in intrapleural pressure to the volume of gas that moves into the lungs

DECREASED COMPLIANCE
- edema, fibrosis, granulomatous infiltration
INCREASED COMPLIANCE
- emphysema (faulty elastic architecture)
- height of diaphragm at TLC can provide some indication of lung compliance, particularly valuable in sequential roentgenograms for comparison in:
  - Diffuse interstitial pulmonary edema
  - Diffuse interstitial pulmonary fibrosis

Mediastinum

Terminology:

Spigelius (1578 1626): Quod per medium stat = what sits in the middle

SUPERIOR MEDIASTINAL COMPARTMENT
- = thoracic inlet
INFERIOR MEDIASTINAL COMPARTMENT
- anterior mediastinum = retrosternal region
- middle mediastinum = visceral region
- posterior mediastinum = contains esophagus, descending aorta, paraspinal region

Thymus

[thymos, Greek = warty excrescence, soul, spirit]

Embryogenesis:

dorsal + ventral wings of 3rd (and possibly 4th) branchial/pharyngeal pouch begin to form the primordia of the inferior parathyroid and thymic glands at 4th-5th week of gestation; both glands separate from pharyngeal wall + migrate caudally and medially with the thymus pulling the inferior parathyroid glands along the thymopharyngeal tract; thymic primordium fuses with its contralateral counterpart inferior to thyroid
P.458

gland; thymic tail thins + disappears by 8th week of GA

Residual thymic tissue in neck in 1.8 21%

Histo:	contains elements of all 3 germinal layers; until 9th week EGA purely epithelial; lymphoid cells migrate from fetal liver + bone marrow by 10th week EGA; differentiation into cortex + medulla completed by 16th week EGA
Cortex:	primarily lymphocytes = thymocytes
Medulla:	more epithelial cells = nurse cells (essential for maturation of T lymphocytes); Hassall corpuscles (round keratinized formations with mature epithelial cells)
Function:	T-cell differentiation + maturation throughout life

Thymic weight:
- increases from birth to age 11 12 years (22 13 g in neonate, 34 15 g at puberty); ratio of thymic weight to body weight decreases with age (largest during infancy, involution after puberty, total fatty replacement after age 60)
- Atrophies under stress (due to increase in endogenous steroids)
Extent: from manubrium to 4th costal cartilage; may bulge into neck/extend down to diaphragm

CXR:
- prominent normal thymus visible in 50% of neonates + infants 0 2 years of age
- notch sign = indentation at junction of thymus + heart
- sail sign = triangular density extending from superior mediastinum, usually on right side
- wave sign = rippled undulated lateral border due to indentation by ribs
- shape changes with respiration + position
DDx: mediastinal mass, upper lobe pneumonia, atelectasis
CT:
- measurement (perpendicular to axis of aorticarch):
  - mean thickness of 11 mm before age 20 and 5mm over age 50;
  - maximal thickness < 18 mm before age 20 and < 13 mm after age 20
- triangular shape like an arrowhead (62%), bilobed (32%), single lobe (6%)
- muscular density of 30 HU (before puberty)
- flat/concave borders with abundant fat (after puberty)
- detected in 83% of subjects <50 years of age; in 17% of subjects > 50 years of age
US (supra-, trans-, parasternal approach in infants):
- homogeneous finely granular echotexture with some echogenic strands
- mildly hypoechoic relative to liver, spleen, thyroid
- smooth well-defined margin (due to fibrous capsule)
- hypo-/avascular

Ectopic Thymus

Unilateral failure of thymic primordium to descend
- neck mass of thymic tissue on one side of neck
- ipsilateral absence of normal thymic lobe
- parathyroid tissue within ectopic thymus
Small rest of thymus left behind within thymopharyngeal tract during migration
- neck mass
- normally positioned bilobed thymus
Atypical location: trachea, skull base, intrathyroidal
- widened superior mediastinum
- solid mass of identical attenuation/signal as normal thymus
- often connected to normal thymus
- cystic mass (= endodermal-lined cavity of thymopharyngeal duct/cystic degeneration of Hassall corpuscles or glandular epithelium)
Rx: no treatment unless symptomatic

Medical Devices on CXR

Cardiac Devices

Coronary Artery Bypass Surgery (CABG)

median sternotomy wires
vascular clips
anastomotic markers

Coronary Artery Stent

with self/balloon/thermally expandable stents

Cardiac Pacemaker

consists of (1) pulse generator and (2) lead wires with electrodes
temporary epicardial electrode
single-lead intramyocardial electrode
right atrial-biventricular synchronous pervenous device
cardiac resynchronization therapy (CRT) with lead placed in a tributary of coronary sinus combined with implantable defibrillator into appendage of RA
automatic implantable cardioverter defibrillator (AICD)

Circulatory Assist Devices

Intraaortic Counterpulsation Balloon Pump (IACB) inflated with CO₂ during ventricular diastole to augment perfusion of coronary arteries
Ventricular Assist Device (VAD)

Heart Valve Replacement

mechanical: Starr-Edwards, Bjork-Shiley, Medtronic Hall, St. Jude Medical, Sorin Bicarbon, Carbomedics
biologic: homograft (from human cadaver), xenograft from porcine aortic cusps, bovine pericardium, Carpentier-Edwards, Tissue Med, Hancock

Vascular Devices

Central Venous Pressure Catheter

= CVP = CENTRAL CATHETER = CENTRAL LINE

Types: Hickman, Broviac, Leonard, Hohn, Cordis Sheath, Swan-Ganz (= pulmonary artery catheter), Groshong

Implantable Access Devices

= SUBCUTANEOUS PORT

Types: Port-A-Cath, Slimport, Dialock, Lifesite

Peripheral Inserted Central Catheter (PICC)

P.459

Chest Disorders

Aids

= Acquired immune deficiency syndrome
= ultimately fatal disease characterized by HIV seropositivity, specific opportunistic infections, specific malignant neoplasms (Kaposi Sarcoma, Burkitt lymphoma, primary lymphoma of brain)
= patient with CD4 cell count <200 cells/ L (normal range, 800 1,200 cells/ L)

Incidence:	2 million Americans are infected with HIV + 270,000 have AIDS (estimate in 1993); >50% develop pulmonary disease
Organism:	human immunodeficiency virus (HIV) = human T-cell lymphotropic virus type III (HTLV III) = lymphadenopathy-associated virus (LAV)

Pathomechanism:

HIV retrovirus attaches to CD4 molecule on surface of T-helper lymphocytes + macrophages + microglial cells; after cellular invasion HIV genetic information is incorporated into cell's chromosomal DNA; virus remains dormant for weeks to years; after an unknown stimulus for viral replication CD4 lymphocytes are destroyed (normal range of 800 1,000 cells/mm³) and others become infected leading to impairment of the immune system; CD4 lymphocyte number and function decreases (at an approximate rate of 50 80 cells/year)

AIDS-defining illness related to CD4 T-lymphocyte count [cells/ L]:

<400	extrapulmonary Mycobacterium tuberculosis, Kaposi sarcoma
<200	Candida albicans (thrush, hairy leukoplakia), Histoplasma capsulatum, Cryptosporidium species, Pneumocystis carinii pneumonia, non-Hodgkin lymphoma
<150	cerebral toxoplasmosis
<100	Cytomegalovirus, Herpes simplex virus, Mycobacterium avium complex (intestinal CMV + MAI infection)
<50	AIDS-related lymphoma
Prognosis:	median survival with CD4 lymphocyte count <50 cells/mm3 is 12 months
Transmission by:	intimate sexual contact, exposure to contaminated blood/bloody body secretions

Groups at risk:

Homosexual males (74%)
IV drug abusers (16%)
Recipients of contaminated blood products (3%)
Sexual partner of drug abuser + bisexual man
Infants born to woman infected with AIDS virus

HIV antibodies present in >50% of homosexuals + 90% of IV drug abusers!
Rate of heterosexual transmission is increasing!

Clinical classification:

group I	acute HIV infection with seroconversion
group II	asymptomatic HIV infection
group III	persistent generalized lymphadenopathy
group IV	other HIV disease
subgroup A	constitutional disease
subgroup B	neurologic disease
subgroup C	secondary infectious disease
subgroup D	secondary cancers
subgroup E	other conditions

AIDS-defining pulmonary conditions (CDC, 1987):

Tracheal/bronchial/pulmonary candidiasis
Pulmonary CMV infection
Herpes simplex bronchitis/pneumonitis
Kaposi sarcoma
Immunoblastic/Burkitt lymphoma
Pneumocystis carinii pneumonia

LYMPHADENOPATHY

Cause:
- reactive follicular hyperplasia = HIV adenopathy (50%), AIDS-related lymphoma (20%), mycobacterial infection (17%), Kaposi sarcoma (10%), metastatic tumor, opportunistic infection with multiple organisms, drug reaction
Location: mediastinum, axilla, retrocrural
OPPORTUNISTIC INFECTION
- accounts for majority of pulmonary disease
- Pulmonary infection is often the first AIDS-defining illness!
- Pneumocystis carinii pneumonia (60 80%)
  
  20 40% develop >1 episode during disease
  - CD4+ T helper lymphocyte cell count 200/mm3
  - subacute insidious onset with malaise, minimal cough
  - bilateral ground-glass infiltrates without effusion/adenopathy
  - bilateral perihilar interstitial infiltrates
  - diffuse bilateral alveolar infiltrates
  - frequently associated with pneumatoceles
  - apical predominance (in patients on prophylactic aerosolized pentamidine)
  Mortality: in 25% fatal
  
  CD4 Lymphocyte Count versus Pulmonary Disease
- Fungal disease (<5%)
  - Cryptococcus neoformans pneumonia (2 15%) usually associated with brain/meningeal disease
    - segmental infiltrate + superimposed pulmonary nodules lymphadenopathy pleural effusion
  - Histoplasma capsulatum
    - typically diffuse nodular/miliary pattern at time of diagnosis
    - normal CXR in up to 35%
  - Coccidioides immitis
    - diffuse infiltrates + thin-walled cavities
  - Candida albicans
  - Aspergillus: less common + less invasive due to relative preservation of neutrophilic function
    - invasive pulmonary aspergillosis
    - chronic necrotizing aspergillosis
    - necrotizing tracheobronchitis
    - obstructing bronchopulmonary aspergillosis
- Mycobacterial infection (10% per year)
  - M. tuberculosis (increasing frequency)
    - AIDS patients are 500 times more likely to become infected than general population!
    - postprimary TB pattern with upper-lobe cavitating infiltrate (CD4 lymphocyte count of 200 500 cells/mm3
    - primary TB pattern with lung infiltrate/lung masses + hilar/mediastinal lymphadenopathy + pleural effusion (CD4 lymphocyte count of 50 200 cells/mm3)
    - atypical TB pattern with diffuse reticular/nodular infiltrates (CD4 lymphocyte count of <50 cells/mm3)
    - adenopathy of low attenuation with rim enhancement on CECT
  - M. avium-intracellulare (5%)
    - in patients with low CD4 lymphocyte count only
    - diffuse bilateral reticulonodular infiltrates
    - adenopathy, miliary disease
  - M. kansasii and others
- Bacterial pneumonia (5 30%):
  - Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus
    - frequently multilobar distribution
    - bacteremia (common)
  - Nocardia pneumonia (<5%)
    - usually occurs in cavitating pneumonia
    - segmental/lobar alveolar infiltrate cavitation ipsilateral pleural effusion
  - Rhodococcus equii (aerobic, gram negative)
    - cavitary pneumonia
  - Bartonella henselae (Gram negative)
    - = bacillary angiomatosis
    - cutaneous lesions
    - highly vascular small pulmonary nodules
    - dramatic enhancement of enlarged lymph nodes
- CMV pneumonia
  - most frequent infection found at autopsy (49 81%), diagnosed before death in only 13 24%;
  - high combined prevalence with Kaposi sarcoma
  - bilateral hazy infiltrates, focal nodules, masses
  - bronchiectasis/bronchial wall thickening
- Toxoplasmosis
  - coarse interstitial/nodular pattern
  - focal areas of consolidation cavities
  DDx: indistinguishable from PCP
TUMOR
- Kaposi sarcoma (15%)
  
  Location: lung involvement (20%) preceded by widespread skin + organ involvement
  
  Site: peribronchovascular distribution (best appreciated on CT)
  - numerous fluffy ill-defined nodules/asymmetric clusters in a vague perihilar distribution
  - interlobular septal thickening
  - pleural effusion (30%)
  - lymphadenopathy (10 35%), late in disease
- AIDS-related lymphoma of B-cell origin (2 5%)
  
  primarily immunoblastic NHL/Burkitt lymphoma/non-Burkitt lymphoma; occasionally Hodgkin disease
  
  Location: pulmonary involvement (8 15%), CNS, GI tract, liver, spleen, bone marrow
  
  Site: primarily extranodal
  - pleural effusion (50%)
  - hilar/mediastinal adenopathy (25%); axillary/supraclavicular/cervical adenopathy
  - solitary/multiple well-defined pulmonary nodules (occasionally with doubling time of 4 6 weeks)
  - diffuse bilateral reticulonodular heterogeneous opacities
  - alveolar infiltrates
  - paraspinal masses
LYMPHOID INTERSTITIAL PNEUMONITIS

Age: in children <13 years of age
SEPTIC EMBOLI
PREMATURE DEVELOPMENT OF BULLAE (40%) with disposition to spontaneous pneumothorax

AIDS-related Complex (ARC)

= GENERALIZED LYMPHADENOPATHY SYNDROME
= prodromal phase of HIV seropositivity, generalized lymphadenopathy, CNS diseases other than those associated with AIDS

Time interval:

approximately 10 years between seroconversion + clinical AIDS

weight loss, malaise, diarrhea
fever, night sweats, lymphadenopathy
lymphopenia with selective decrease in helper T-cells

Adult Respiratory Distress Syndrome

= SHOCK LUNG = POSTTRAUMATIC PULMONARY INSUFFICIENCY = HEMORRHAGIC LUNG SYNDROME
= RESPIRATOR LUNG = STIFF LUNG SYNDROME = PUMP LUNG = CONGESTIVE ATELECTASIS = OXYGEN TOXICITY
= severe unexpected life-threatening acute respiratory distress characterized by abrupt onset of marked dyspnea, increased respiratory effort, severe hypoxemia associated with widespread airspace consolidation

Etiology:

ARDS is the most severe form of permeability edema associated with diffuse alveolar damage

PRIMARY = DIRECT INJURY
- = ARDS due to underlying pulmonary disease
- = exposure to chemical agents, infectious pathogens, gastric fluid, toxic gas
Associated with: pulmonary consolidation

SYSTEMIC CONDITION

= ARDS due to extrapulmonary disease
= systemic biochemical cascade creating oxidating agents, inflammatory mediators, enzymes during sepsis, pancreatitis, severe trauma, blood transfusion

Associated with:

interstitial edema, alveolar collapse

Histo:

(a) up to 12 hours:	fibrin + platelet microemboli
(b) 12 24 hours:	interstitial edema
(c) 24 48 hours:	capillary congestion, extensive interstitial + alveolar proteinaceous edema + hemorrhage, widespread microatelectasis, destruction of type I alveolar epithelial cells
(d) 5 7 days:	extensive hyaline membrane formation, hypertrophy + hyperplasia of type II alveolar lining cells
(e) 7 14 days:	extensive fibroblastic proliferation in interstitium + within alveoli, rapidly progressing collagen deposition + fibrosis; almost invariably associated with infection

Predisposed:

hemorrhagic/septic shock, massive trauma (pulmonary/general body), acute pancreatitis, aspiration of liquid gastric contents, heroine/methadone intoxication, massive viral pneumonia, traumatic fat embolism, near-drowning, conditions leading to pulmonary edema

mnemonic:

DICTIONARIES

Disseminated intravascular coagulation
Infection
Caught drowning
Trauma
Inhalants: smoke, phosgene, NO₂
O₂ toxicity
Narcotics + other drugs
Aspiration
Radiation
Includes pancreatitis
Emboli: amniotic fluid, fat
Shock: septic, hemorrhagic, cardiogenic, anaphylactic

initially few/no symptoms
rapidly progressive dyspnea, tachypnea, cyanosis
hypoxia unresponsive to oxygen therapy (due to arteriovenous shunting)
no increase in pulmonary capillary pressure

Stages (often overlapping):

1st (exudative) stage

interstitial edema with high protein content rapidly filling the alveolar spaces
associated with hemorrhage + ensuing hyaline membrane formation
interstitial edema (with high protein content) initially
perihilar areas of increased opacity following rapidly
widespread alveolar consolidation with predominantly peripheral cortical distribution
air bronchogram
gravitational gradient (best seen on CT) due to dependent atelectasis

DDx: cardiogenic edema (cardiomegaly, apical vascular distribution, Kerley lines)

2nd (proliferative) stage

organization of fibrinous exudate
subsequent regeneration of alveolar lining + thickening of alveolar septa
inhomogeneous areas of ground-glass opacities

3rd (fibrotic) stage

varying degrees of scarring
subpleural and intrapulmonary cysts

: pneumothorax

CXR:

NO cardiomegaly/pleural effusion
- up to 12 hours:
  - characteristic 12-hour delay between clinical onset of respiratory failure and CXR abnormalities
- 12 24 hours:
  - patchy ill-defined opacities throughout both lungs
- 24 48 hours:
  - massive airspace consolidation of both lungs
- 5 7 days:
  - consolidation becomes inhomogeneous (resolution of alveolar edema)
  - local areas of consolidation (pneumonia)
- >7 days:
  - reticular/bubbly lung pattern (diffuse interstitial + airspace fibrosis)

Alpha-1 Antitrypsin Deficiency

= rare autosomal recessive disorder

Source:	alpha-1 antitrypsin (glycoprotein) is to >90% synthesized in hepatocytes + released into serum
Gene:	codominant gene expression on chromosome 14 with >100 genetic variants of the protein; most severe hepatopulmonary manifestations result from homozygous Pizz phenotype
Action:	proteolytic inhibitor of neutrophil elastase, trypsin, chymotrypsin, plasmin, thrombin, kallikrein, leukocytic + bacterial proteases; neutralizes circulating proteolytic enzymes

Mode of injury from deficiency:

PMNs + alveolar macrophages sequester into lung during recurrent bacterial infections + release neutrophil elastase, which acts unopposed + digests basement membrane

Age:

early age of onset (20 30 years); m:f = 1:1

rapid + progressive deterioration of lung function:
dyspnea in 4th and 5th decade

20% of homozygotic individuals never develop clinically
apparent emphysema

chronic sputum production (50%)

severe panacinar emphysema with basilar predominance (due to gravitational distribution of pulmonary blood flow):
severe reduction in size + number of pulmonary vessels in lower lobes
redistribution of blood flow to unaffected upper lung zones
bullae at both lung bases
marked flattening of diaphragm
minimal diaphragmatic excursion

P.462

multilobar cystic bronchiectasis (40%)
hepatopulmonary syndrome

Cx:

hepatic cirrhosis (in homozygotic individuals)

most common metabolic liver disease in children

Prognosis:

15 20-year decrease in longevity in smokers relative to nonsmokers

Alveolar Microlithiasis

= very rare disease of unknown etiology characterized by
myriad of calcospherites (= tiny calculi) within alveoli

Age peak:

30 50 years; begins in early life; has been identified in utero; m:f = 1:1; in 50% familial (restricted to siblings)

usually asymptomatic (70%)
dyspnea on exertion (reduction in residual volume)
cyanosis, clubbing of fingers
striking discrepancy between striking radiographic findings and mild clinical symptoms
NORMAL serum calcium + phosphorus levels

very fine, sharply defined, sandlike micronodulations
(<1 mm)
diffuse involvement of both lungs
intense uptake on bone scan

Prognosis:

late development of pulmonary insufficiency secondary to interstitial fibrosis
disease may become arrested
microliths may continue to form/enlarge

DDx:

mainline pulmonary granulomatosis = IV abuse of talc-containing drugs such as methadone (rarely as numerous + scarring + loss of volume)

Alveolar Proteinosis

= PULMONARY ALVEOLAR PROTEINOSIS (PAP)
= rare disorder characterized by accumulation of lipoproteinaceous material in alveoli (due to altered surfactant homeostasis)

Forms:

Congenital PAP
Primary Acquired PAP (90%)

Age: median 39 years; M>>F

Predisposed: smoking in 72%

Secondary PAP

Cause:	hematologic cancers, pharmacologic immunosuppression, inhalation of inorganic dust (eg, silica), toxic fumes, certain infections
Pathophysiology:	functional impairment/reduced number of alveolar macrophages
Etiology:	?; associated with dust exposure (eg, silicoproteinosis is histologically identical to PAP), immunodeficiency, hematologic + lymphatic malignancies, AIDS, chemotherapy

Pathophysiology:

overproduction of surfactant by granular pneumocytes
defective clearance of surfactant by alveolar macrophages

Histo:	alveoli filled with proteinaceous material (the ONLY pure airspace disease), normal interstitium
Age peak:	39 years (range, 2 70 years); M:F = 3:1

asymptomatic (10 20%)
gradual onset of dyspnea + cough
weight loss, weakness, hemoptysis
defect in diffusing capacity

bilateral air-space disease with ill-defined nodular/confluent ground-glass pattern:
- perihilar predominance of bat-wing configuration WITHOUT signs of left-side heart failure
small acinar nodules + coalescence + consolidation
patchy peripheral/primarily unilateral infiltrates (rare)
reticular/reticulonodular/linear interstitial pattern with Kerley B lines (late stage)
slow clearing over weeks or months
slow progression (1/3), remaining stable (2/3)
NO adenopathy, NO cardiomegaly, NO pleural effusion

HRCT:

crazy-paving pattern = combination of patchy ground-glass opacities + smooth interlobular septal thickening often in geographic distribution
sharp demarcation between normal + abnormal lung
consolidation

Cx:

susceptible to pulmonary infections (secondary to poorly functioning macrophages + excellent culture medium): opportunistic pathogens (esp. Nocardia asteroides), other common respiratory pathogens

Prognosis:

highly variable course with clinical and radiologic episodes of exacerbation + remissions

50% improvement/recovery
30% death within several years under progression

Dx:

bronchoalveolar lavage, transbronchial/open lung biopsy

Rx:

bronchopulmonary lavage

DDx:

during acute phase: pulmonary edema, diffuse pneumonia, ARDS
in chronic stage:
- Idiopathic pulmonary hemosiderosis (boys, symmetric involvement of mid + lower zones, progression to nodular + linear pattern)
- Hemosiderosis (bleeding diathesis)
- Pneumoconiosis
- Hypersensitivity pneumonitis
- Goodpasture syndrome (more rapid changes, renal disease)
- Desquamative interstitial pneumonia ( ground-glass appearance, primarily basilar + peripheral)
- Pulmonary alveolar microlithiasis (widespread discrete intraalveolar calcifications primarily in lung bases, rare familial disease)
- Sarcoidosis (usually with lymphadenopathy)
- Lymphoma
- Bronchioloalveolar cell carcinoma (more focal, slowly enlarging with time)

Amniotic Fluid Embolism

most common cause of maternal peripartum death

dyspnea
shock during/after labor + delivery

Pathogenesis:

amniotic debris enters maternal circulation resulting in:
(1) pulmonary embolization
(2) anaphylactoid reaction
(3) DIC

P.463

usually fatal before radiographs obtained
may demonstrate pulmonary edema

Amyloidosis

= disease characterized by an extracellular deposit of proteinaceous twisted -pleated sheet fibrils of great chemical diversity

Histo:

protein (immunoglobulin)/polysaccharide complex; affinity for Congo red stain

@ Lung involvement

Incidence: 1 amyloidosis (in up to 70%),
2 amyloidosis (rare)
- TRACHEOBRONCHIAL TYPE (most common)
  - hemoptysis (most frequent complaint)
  - stridor, cough, dyspnea, hoarseness, wheezing
  - multiple nodules protruding from wall of trachea/large bronchi
  - diffuse rigid narrowing of a long tracheal segment
  - prominent bronchovascular markings
  - destructive pneumonitis
- NODULAR TYPE
  
  Age: >60 years of age; M:F = 1:1
  - usually asymptomatic
  - mediastinal/hilar adenopathy
  - solitary/multiple parenchymal nodules in a peripheral/subpleural location central calcification/ossification; slow growth over years
  - pleural effusion
  DDx: metastatic disease, granulomatous disease, rheumatoid lung, sarcoidosis, mucoid impaction
- DIFFUSE PARENCHYMAL TYPE (least common)
  
  Age: >60 years of age
  - usually asymptomatic with normal CXR
  - cough + dyspnea with abnormal CXR
  - widespread small irregular densities (exclusively interstitial involvement) calcification
  - may become confluent honeycombing
  DDx: idiopathic interstitial fibrosis, pneumoconiosis (especially asbestosis), rheumatoid lung, Langerhans cell histiocytosis, scleroderma

Asbestos-Related Disease

[asbestos, Greek = inextinguishable = several fibrous silicate minerals sharing the property of heat resistance]

Substances:

aspect (length-to-diameter) ratio effects carcinogenicity: eg, aspect ratio of 32 = 8 m long, 0.25 m wide
- commercial amphiboles: straight, rigid, needlelike
  - crocidolite = blue/black asbestos
  - amosite = brown asbestos
- commercial serpentines (= nonamphiboles):
  - chrysotile = white asbestos (the only mineral in the serpentine group accounting for >90% of asbestos used in the United States)
- noncommercial contaminating amphiboles
  - actinolite
  - anthophyllite
  - tremolite
  - relatively benign:
    - chrysotile in Canada
    - anthophyllite in Finland, North America
    - tremolite
  - relatively malignant:
    - crocidolite in South Africa, Australia
    - amosite
  - Very fine fibers (crocidolite) associated with largest number of pleural disease!
  - Asbestos fibers up to 100 m in length

Occupational exposure:

asbestos mining, milling, and processing
insulation manufacturing, textile manufacturing, construction and demolition, pipe fitting, shipbuilding, gaskets, brake linings

Pathophysiology:

asbestos-activated macrophages produce a variety of growth factors that interact to induce fibroblast proliferation; oxygen-free radicles released by macrophages damage proteins + lipid membranes sustaining the inflammatory process

Asbestos-related Pleural Disease

Pleural Effusion (21%)
- = earliest asbestos-related pleural abnormality, frequently followed by diffuse pleural thickening + rounded atelectasis
Prevalence: 3% (increases with increasing levels of asbestos exposure)

Latency period: 8 10 years after exposure
- benign asbestos pleurisy:
  - may be associated with chest pain (1/3)
  - usually small sterile, serous/hemorrhagic exudate
- recurrent bilateral effusions
- plaque formation
DDx: TB, mesothelioma

Focal Pleural Plaques (65%)

= hyalinized collagen in submesothelial layer of parietal pleura

Incidence:	most common manifestation of exposure; 6% of general population will show plaques
Latency period:	in 10% after 20 years; in 50% after 40 years
Histo:	dense hypocellular undulating collagen fibers often arranged in a basket weave pattern focal/massive calcifications; may contain large numbers of asbestos fibers (almost exclusively chrysotile)
Location:	bilateral + multifocal; posterolateral midportion of chest wall between 7 10th rib; aponeurotic portion of diaphragm; mediastinum; following rib contours; apices + costophrenic angles typically spared
Site:	parietal pleura (visceral pleura typically spared)

asymptomatic, no functional impairment
usually focal area of pleural thickening (<1 cm thick) with edges thicker than central portions of plaque; in 48% only finding; in 41% with parenchymal changes; stable over time
no hilar adenopathy
usually not calcified

P.464

DDx:

chest wall fat, rib fractures, rib companion shadows

Pleural Calcification (21 25 60%)
- HALLMARK of asbestos exposure!
- detected by radiography in 25%, by CT in 60%
Overall incidence: 20%

Latency period: >20 years to become visible; in 40% after 40 years

Histo: calcification starts in parietal pleura; calcium deposits may form within center of plaques
- dense lines paralleling the chest wall, mediastinum, pericardium, diaphragm
  - bilateral diaphragmatic calcifications with clear costophrenic angles are PATHOGNOMONIC
- advanced calcifications are leaflike with thick-rolled edges
DDx: talc exposure, hemothorax, empyema, therapeutic pneumothorax for TB (often unilateral, extensive sheetlike, on visceral pleura)
Diffuse Pleural Thickening (17%)
- = smooth uninterrupted diffuse thickening of parietal pleura extending over at least 1/4 of chest wall (visceral pleura involved in 90%, but difficult to demonstrate)
- may cause restriction of pulmonary function
May be associated with: rounded atelectasis
- bilateral process with shaggy heart appearance (20%)
- smooth; difficult to assess when viewed en face
- thickening of interlobar fissures
- focally thickened diaphragm
- obliterated costophrenic angles (minority of cases)
DDx: pleural thickening from parapneumonic effusion, hemothorax, connective tissue disease

Pulmonary Asbestosis

= (term asbestosis reserved for) chronic progressive diffuse interstitial fibrosis

Incidence:	in 49 52% of industrial asbestos exposure
Latency period:	40 45 years; dose-effect relationship
Histo:	interstitial fibrosis begins around respiratory bronchioles, then progresses to involve adjacent alveoli

Diagnostic criteria:

Reliable history of exposure
Appropriate time interval between exposure + detection
CXR evidence
Restrictive pattern of lung impairment
Abnormal diffusing capacity
Bilateral crackles at posterior lung bases, not cleared by cough

dyspnea
restrictive pulmonary function tests: progressive reduction of vital capacity + diffusing capacity
asbestos bodies in bronchoalveolar lavage fluid

Location:	lower posterior bases > apices
Site:	most severe in subpleural zones (asbestos fibers concentrate beneath visceral pleura)

small irregular linear opacities (NOT rounded as in coal/silica) progress from fine to coarse reticulation
confined to lung bases, progressing superiorly
septal lines (= fibrous thickening around secondary lobules)
shaggy heart border = obscuration secondary to parenchymal + pleural changes
ill-defined outline of diaphragm
honeycombing (uncommon)
rarely massive fibrosis, predominantly at lung bases without migration toward hilum (ddx from silicosis/cWP)
ABsence of hilar/mediastinal adenopathy (if present consider other diagnosis)
Ga-67 uptake gives a quantitative index of inflammatory activity

HRCT:

Obtain scan in prone position to differentiate from gravity-related physiologic phenomena
thickened intralobular lines as initial finding (due to centrilobular peribronchiolar fibrosis):
- multiple subpleural curvilinear branching lines ( subpleural pulmonary arcades ) = dotlike reticulonodularities connected to the most peripheral branch of pulmonary artery
Site: most prominent posteriorly parallel to and within 1 cm of pleura
thickened interlobular septal lines (= interlobular fibrotic/edematous thickening):
- reticulation = network of linear densities, usually posteriorly at lung bases
- architectural distortion of lobule
parenchymal band = linear <5 cm long + several mm wide opacity, often extending to pleura, which may be thickened + retracted at site of contact
subpleural lines
patchy areas of ground-glass attenuation
- (= alveolar wall thickening due to fibrosis/edema)
honeycombing = multiple cystic spaces <1 cm in diameter with thickened walls

DDx:

idiopathic pulmonary fibrosis

Atelectatic Asbestos Pseudotumor

= ROUND ATELECTASIS = FOlDED LUNG
= infolding of redundant pleura accompanied by segmental /subsegmental atelectasis

The most common of benign masses caused by asbestos exposure!

Location:

posteromedial/posterolateral basal region of lower lobes (most common); frequently bilateral

2.5 8 cm focal subpleural mass abutting a region of thickened pleura
size + shape show little progression, occasionally decrease in size

CT:

rounded/lentiform/wedge-shaped peripheral mass
pleural thickening calcification always present and frequently greatest near mass
crow's feet = linear bands radiating from mass into lung parenchyma (54%)
vacuum cleaner / comet sign
- = bronchovascular markings emanating from nodular subpleural mass + coursing toward ipsilateral hilum
swiss cheese air bronchogram (18%)
partial interposition of lung between pleura + mass

P.465

volume loss of affected lobe hyperlucency of adjacent lung

Asbestos-related Malignancy

Lung Cancer

Incidence:

180,000 new cases per year in united states; 20 25% of workers heavily exposed to asbestos

Occurrence related to:

cumulated dose of asbestos fibers
smoking (synergistic carcinogenic effect)
- 100-fold increased risk in smokers versus a 7-fold increased risk in nonsmokers!
preexisting interstitial disease
occupational exposure to known carcinogen

Latency period:	25 35 years
Associated with:	increased incidence of gastric carcinoma
Histo:	bronchioloalveolar cell carcinoma (most common); bronchogenic carcinoma (adenocarcinoma + squamous cell)
Location:	at lung base/in any location if associated with smoking

Malignant Mesothelioma

Incidence:	2,000 new cases per year in United States; 7,000-fold increase in incidence
Risk:	10% over lifetime of an asbestos worker; household members of asbestos worker; residents near asbestos mines and plants
Latency period:	20 40 years

Gastrointestinal Neoplasm

Incidence:

3-fold increase

Aspergillosis

Organism:

Aspergillus fumigatus = intensely antigenic ubiquitous fungus in soil, water, decaying vegetable and animal matter existing as

conidiophores = reproductive form releasing thousands of spores
hyphae (= matured spores) characterized by 45 dichotomous branching pattern

Occurrence:

commonly in sputum of normal persons, ability to invade arteries + veins facilitating hematogenous dissemination
M:F = 3:1

Predisposed:

preexisting lung disease (tuberculosis, bronchiectasis)
impairment of immune system (alcoholism, advanced age, malnutrition, concurrent malignancy, poorly controlled diabetes, cirrhosis, sepsis)

positive precipitin test to Aspergillus antigen
elevated Aspergillus-specific IgE, IgG-ELISA, polymerase chain reaction identification

Cx:

dissemination to heart, brain, kidney, GI tract, liver, thyroid, spleen

Sputum cultures are diagnostically unreliable because of normal (saprophytic) colonization of upper airways!

Noninvasive Aspergillosis

= SAPROPHYTIC ASPERGILLOSIS
= noninvasive colonization of preexisting cavity/cyst in immunologically normal patients with cavitary disease [remote tuberculosis, atypical mycobacterial infection, sarcoidosis (common), bronchiectasis, cystic fibrosis, abscess, lung trauma/surgery, ankylosing spondylitis, neurofibromatosis type 1, bullous emphysema, carcinoma]

sputum blood-streaked/severe hemoptysis (45 95%)
elevated serum precipitins level for Aspergillus (50%)

solid round gravity-dependent mass within preexisting spherical/ovoid thin-walled cavity (= Monad sign):

Histo:

mycetoma = aspergilloma = fungus ball = masslike collection of intertwined hyphae matted together with fibrin, mucus, cellular debris colonizing a pulmonary cavity

air-crescent sign = crescent-shaped air space separating fungus ball from nondependent cavity wall
fungus ball may calcify in scattered/rimlike fashion
pleural thickening adjacent to preexisting cyst/cavity, commonly first sign before visualizing mycetoma

Cx:	life-threatening hemoptysis
Dx:	transthoracic needle biopsy/bronchial washings

DDx of other organisms causing fungus ball:

Candida albicans, Pseudallescheria boydii, Coccioides immitis, Nocardia, Actinomyces

Semiinvasive Aspergillosis

= CHRONIC NECROTIZING ASPERGILLOSIS
= chronic cavitary slowly progressive disease in patients with preexisting lung injury (COPD, radiation therapy), mild immune suppression, or debilitation (alcohol, diabetes)

symptoms mimicking pulmonary tuberculosis

progressive consolidation (usually upper lobe)
development of air crescent and fungus ball over a period of months

Dx:

pathologic examination demonstrating local tissue invasion

Invasive Pulmonary Aspergillosis

= often fatal form in severely immunocompromised patients with absolute neutrophil count of <500

Predisposed:	most commonly in lymphoma/leukemia patients with prolonged granulocytopenia, after organ transplantation
Path:	endobronchial fungal proliferation followed by transbronchial vascular invasion eventually causes widespread hemorrhage + thrombosis of pulmonary arterioles + ischemic tissue necrosis + systemic dissemination; fungus ball = devitalized sequestrum of lung infiltrated by fungi

Type of Aspergillosis relative to Immune Status

P.466

Hx of series of bacterial infections + unremitting fever
pleuritic chest pain (mimicking emboli)
dyspnea, nonproductive cough
progression of pulmonary infiltrates not responding to broad-spectrum antibiotics

early signs

Frequency: 96% at day 0, 19% at day 14
- single/multiple ill-defined peripheral opacities abutting the pleural surface
- CT halo sign = single/multiple 1 3-cm peripheral nodules (= necrotic lung) with halo of ground-glass attenuation (= hemorrhagic edema)
- patchy localized bronchopneumonia
later signs of progression
- enlargement of nodules into diffuse bilateral consolidation
- development into large wedge-shaped pleural-based lesions
- air-crescent sign (in up to 50%) = cavitation of existing nodule (air crescent between retracting sequestered necrotic tissue and surrounding rim of hemorrhagic lung parenchyma) 1 3 weeks after recovery from neutropenia
  - has better prognosis than consolidation without cavitation (feature of resolution phase)

Prognosis:	mortality rate of 50 90%
Dx:	: biopsy showing branching hyphae at tissue examination; sputum culture positive in only 10%
Rx:	amphotericin B

Allergic Bronchopulmonary Aspergillosis

= hypersensitivity toward aspergilli in patients with long-standing asthma
Most common + clinically important form of aspergillosis!

Incidence:

in 1 2% of patients with asthma;in 1 15% of patients with cystic fibrosis

Age:

mostly young patients (begins in childhood); may be undiagnosed for 10 20 years

Pathophysiology:

inhaled spores are trapped in segmental bronchi of individuals with asthma, germinate, and form hyphae; immunologic response coupled with proteolytic enzymes causes pulmonary infiltrates + tissue damage + central bronchiectasis

ACUTE ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS
- Type I reaction = immediate hypersensitivity (IgE-mediated mast cell degranulation)
Histo: alveoli filled with eosinophils
- bronchoconstriction, mucus production
- bronchial wall edema (due to increased vascular permeability)
CHRONIC ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS
- Type III reaction = delayed immune complex response = Arthus reaction (IgG-mediated)
Histo: bronchial damage secondary to Aspergillus antigen reacting with IgG antibodies, immune complexes activate complement leading to tissue injury

Criteria:

Major diagnostic criteria:

acronym: ARTEPICS
- Asthma (84 96%)
- Roentgenographic transient or fixed pulmonary infiltrates
- Test for A. fumigatus positive: immediate skin reaction
- Eosinophilia in blood (8 40%)
- Precipitating antibodies to A. fumigatus (70%)
- IgE in serum elevated
- Central bronchiectasis (late manifestation that proves diagnosis)
- Serum-specific IgE and IgG A. fumigatus levels elevated
Minor diagnostic criteria (less common):
- Aspergillus fumigatus mycelia in sputum
- Expectoration of brown sputum plugs (54%)
- Arthus reaction (= late skin reactivity with erythema + induration) to Aspergillus antigen

Staging:

I acute phase with all primary diagnostic criteria
II clearing of pulmonary infiltrates with declining IgE levels
III all criteria of stage I reappear after emission
IV corticosteroid dependency
V irreversible lung fibrosis

flulike symptoms: fever, headache, malaise, weight loss, fleeting chest pain
migratory pneumonitis = transient recurrent fleeting alveolar patchy subsegmental/lobar infiltrates in upper lobes (50%), lower lobes (20%), middle lobe (7%), both lungs (65%); may persist for >6 months
central varicose/cystic bronchiectasis:
- tramlike bronchial walls (edema)
- 1 2-cm ring shadows (= bronchus on end) around hilum + upper lobes (HALLMARK)
- gloved finger/toothpaste shadow = V- or Y-shaped central mucus plugs in 2nd order bronchi of 2.5 6 cm in length remaining for months + growing in size
lobar consolidation (in 32%)
atelectasis (in 14%) with collateral air drift
cavitation (in 14%) secondary to postobstructive abscess
hyperinflation (due to bronchospasm)
pulmonary fibrosis + retraction
hilar elevation due to lobar shrinkage
emphysema
NORMAL peripheral bronchi
UNUSUAL are aspergilloma in cavity (7%), empyema, pneumothorax

DDx:

hypersensitivity pneumonitis or allergic asthma (no hyphae in sputum, normal levels of IgE + IgG to A. fumigatus), tuberculosis, lipoid pneumonia, L ffler syndrome, bronchogenic carcinoma

Pleural Aspergillosis

= Aspergillus empyema in patients with pulmonary tuberculosis, bacterial empyema, bronchopleural fistula
pleural thickening

P.467

Aspiration of Solid Foreign Body

@ Childhood

Age:	in 50% <3 years
Delay of diagnosis:	within 2 3 days (usual); weeks to months (rare)
Source:	in 85% vegetable origin (lentil, beans, peas, peanut, barley grass), broken fragments of teeth
Location:	almost exclusively in lower lobes; R:L = 2:1

varying degrees of cough
obstructive overinflation (68%) + reflex vasoconstriction
atelectasis (14 53%)
infiltrate (11%)
radiopaque foreign body (9%)
air trapping (expiratory/lateral decubitus film):
lobar/segmental overinflation
CT:
- low-attenuation intrabronchial material (SUGGESTIVE)
NUC:
- ventilation defect (initial breath) + retention (washout)
Cx: bronchiectasis (from long retention)

DDx: impacted esophageal foreign body

@ Adulthood (unusual)
- often clinically silent
- massive life-threatening hemoptysis
- chronic volume loss of affected lobe
- recurrent pneumonia
- bronchiectasis
- intrabronchial mass formation (= chronic inflammatory reaction around inhaled material)
- centrally located mass + lobar/segmental collapse

Aspiration Bronchiolitis

= chronic inflammatory reaction to repeatedly aspirated foreign particles in the bronchioles

Predisposed:	achalasia, Zenker diverticulum, esophageal carcinoma
Histo:	resembling diffuse panbronchiolitis

dysphagia, regurgitation, aspiration

moderate/marked dilatation of esophagus
lobar/segmental/disseminated small nodules

CT:

uni-/bilateral foci of branching areas of increased attenuation:
tree-in-bud appearance
mottled poorly defined opacified acinar areas

Aspiration Pneumonia

Predisposing conditions:

CNS disorders/intoxication: alcoholism, mental retardation, seizure disorders, recent anesthesia
Swallowing disorders: esophageal motility disturbances, head + neck surgery

low-grade fever
productive cough
choking on swallowing

Location:

gravity-dependent portions of lung, posterior segments of upper lobes + lower lobes in bedridden patients, frequently bilateral, right middle + lower lobe with sparing of left lung is common

Acute Aspiration Pneumonia

Cause:	gastric acid, food particles, anaerobic bacteria from GI tract provoke edema, hemorrhage, inflammatory cellular response, foreign-body reaction
Organism:	gram-negative bacteria; Pseudomonas aeruginosa, Actinomyces israelii

patchy bronchopneumonic pattern
lobar/segmental consolidation in dependent portion
necrotizing pneumonia
abscess formation

Chronic Aspiration Pneumonia

Cause:	repeated aspiration of foreign material from GI tract over long time/mineral oil (eg, in laxatives)
Associated with:	Zenker diverticulum, esophageal stenosis, achalasia, TE fistula, neuromuscular disturbances in swallowing

recurring segmental consolidation
progression to interstitial scarring (= localized honeycomb appearance)
bronchopneumonic infiltrates of variable location over months/years
residual peribronchial scarring

upper Gi:

abnormal swallowing/aspiration

Mendelson Syndrome

= aspiration of gastric acid with a pH <2.5

Associated with:	vomiting, gastroesophageal reflux, achalasia, hiatal hernia
Pathophysiology:	acid rapidly disseminates throughout bronchial tree + lung parenchyma, incites a chemical pneumonitis within minutes; extent of injury from mild bronchiolitis to hemorrhagic pulmonary edema depends on pH + aspirated volume
Location:	with patient in recumbent position: posterior segments of upper lobes + superior segments of lower lobes

bilateral perihilar ill-defined alveolar consolidations
multifocal patchy infiltrates
segmental/lobar consolidation localized to one/both lung bases

Prognosis:

30% mortality with massive aspiration; >50% with initial shock, apnea, secondary pneumonia, or ARDS

Asthma

= episodic reversible bronchoconstriction secondary to hypersensitivity to a variety of stimuli

INTRINSIC ASTHMA

Age: middle age

Pathogenesis: probably autoimmune phenomenon caused by viral respiratory infection and often provoked by infection, exercise, pharmaceuticals; no environmental antigen

P.468

EXTRINSIC ASTHMA = ATOPIC ASTHMA
- Pathogenesis:
  - secondary to antigens producing an immediate hypersensitivity response (type i); reagin sensitizes mast cells to release histamine followed by increased vascular permeability, edema, small muscle contraction; effects primarily bronchi causing airway obstruction
- Nonoccupational allergens:
  - pollens, dog + cat fur, tamarind seed powder, castor bean, fungal spores, grain weevil
- Occupational allergens:
  - natural substances: wood dust, flour, grain, beans
  - pharmaceuticals: antibiotics, ASA
  - inorganic chemicals: nickel, platinum

Path:

bronchial plugging with large amounts of viscid tenacious mucus (eosinophils, charcot-Leyden crystals), edematous bronchial walls, hypertrophy of mucous glands + smooth muscle

ACUTE SIGNS:

during asthmatic attack low values for FEV + MMFR and abnormal V/q ratios
increased resistance to airflow due to
- smooth muscle contraction in airway walls
- edema of airway wall caused by inflammation
- mucus hypersecretion with airway plugging
normal diffusing capacity
hyperexpansion of lungs = severe overinflation + air trapping:
- flattened diaphragmatic dome
- deepened retrosternal air space
- peribronchial cuffing (inflammation of airway wall)
- bronchial dilatation
- localized areas of hypoattenuation

CHRONIC CHANGES:

Normal chest x-ray in 73%, findings of abnormalities depend on
- age of onset (<15 years of age in 31%; >30 years of age in none)
- severity of asthma
central ring shadows = bronchiectasis
scars (from recurrent infections)

Cx:

Pneumonia (2 as frequent as in nonasthmatics)
- peripheral pneumonic infiltrates (secondary to blocked airways)
Atelectasis (5 15%) from mucoid impaction
Pneumomediastinum (5%), pneumothorax, subcutaneous emphysema; predominantly in children
Emphysema
Allergic bronchopulmonary aspergillosis with central bronchiectasis

Atypical Measles Pneumonia

= clinical syndrome in patients who have been previously inadequately immunized with killed rubeola vaccine and are subsequently exposed to the measles virus (= type III immune complex hypersensitivity); noted in children who have received live vaccine before 13 months of age
2- to 3-day prodrome of headache, fever, cough, malaise
maculopapular rash beginning on wrists + ankles (sometimes absent)
postinfectious migratory arthralgias
history of exposure to measles
extensive nonsegmental consolidation, usually bilateral
hilar adenopathy (100%)
pleural effusion (0 70%)
nodular densities of 0.5 10 cm in diameter in peripheral location, may calcify and persist up to 30 months

Baritosis

= inhalation of nonfibrogenic barium sulfate
asymptomatic
normal pulmonary function (benign course)
bilateral nodular/patchy opacities, denser than bone (high atomic number)
similar to calcified nodules
NO cor pulmonale, NO hilar adenopathy
regression if patient removed from exposure

Beh et Syndrome

= rare chronic inflammatory systemic vasculitis of veins + arteries of unknown origin characterized by recurrent
- aphthous stomatitis
- genital ulceration
- iritis
positive pathergy test = unusual hypersensitivity to pricking with formation of pustules at site of needle prick within 24 48 hours
skin changes: erythema nodosum, folliculitis, papulopustular lesions
arthritis, encephalitis
epididymitis
@ Chest (5%)
- multiple peripheral subpleural opacities (due to hemorrhage, necrotic pulmonary infarctions)
- increased perihilar radiopacity (pulmonary artery aneurysm)
@ Veins (25%)
- large vein occlusion; may cause SVC syndrome
- subcutaneous thrombophlebitis
@ Arteries
- arterial occlusion/pulseless disease
- aneurysm of large arteries (in 2%)

Berylliosis

= chronic granulomatous disorder as a result of beryllium-specific cell-mediated immune response (= delayed hypersensitivity reaction after exposure to acid salts from extraction of beryllium oxide)

Substance:	one of the lightest metals (atomic weight 9), marked heat resistance, great hardness, fatigue resistance, no corrosion
Occupational exposure:	fluorescent light bulb factories
Histo:	noncaseating granulomas within interstitium + along vessels + in bronchial submucosa

positive beryllium lymphocyte transformation test (blood test of T-lymphocyte response to beryllium)

Acute Berylliosis (25%)

pulmonary edema following an overwhelming exposure

P.469

Chronic Berylliosis

= widespread systemic disease of liver, spleen, lymph nodes, kidney, myocardium, skin, skeletal muscle; removed from lungs + excreted via kidneys

Latent period:

5 15 years

fine nodularity (granulomas similar to sarcoidosis)
irregular opacities, particularly sparing apices + bases
hilar + mediastinal adenopathy (may calcify)
emphysema in upper lobes + interstitial fibrosis
pneumothorax in 10%
HRCT:
- diffuse small parenchymal nodules (57%)
- septal lines (50%)
- patches of ground-glass attenuation (32%)
- hilar adenopathy (21 35%), only in the presence of parenchymal abnormalities
- bronchial wall thickening (46%)
- pleural irregularities (25%)
DDx: (1) Nodular pulmonary sarcoidosis (indistinguishable)
(2) Asbestosis without hilar adenopathy

Blastomycosis

=NORTH AMERICAN BLASTOMYCOSIS = Gilchrist DISEASE = CHICAGO DISEASE
= rare systemic mixed pyogenic + granulomatous fungal infection

Organism:

soil-born saprophytic dimorphic fungus Blastomyces dermatitidis, mycelial phase in soil + round thick-walled yeast form with broad-based budding in mammals

Geographic distribution:

worldwide; endemic in central + southeastern United States (Ohio + Mississippi river valleys, vicinity of Great Lakes), Africa, Canada (northern Ontario), Central + South America (acquired through activities in woods)

Age:

several months of age to 80 years (peak between 25 and 50 years of age)

Mode of infection:

inhalation of fungal conidia (primary portal of entry); spread to extrapulmonary sites, eg, skin, bone (often direct extension from skin lesion resembling actinomycosis), joints

Predisposed:

elderly, immunocompromised

Histo:

exudative phase: accumulation of numerous neutrophils with infecting organism
proliferative phase: proliferation of epithelioid granulomas + giant cells with central microabscesses containing neutrophils and yeast forms

mouth ulcers
fever, cough, weight loss, chest pain (majority)
crusted verrucous lesions on exposed body areas
@ Lung
- Clinical patterns following pulmonary infection:
  - severe pulmonary symptoms
  - asymptomatic pulmonary infection with spontaneous resolution
  - disseminated disease to single/multiple organs indolent for several years
  - extrapulmonary manifestation involving male GU system, skeleton, skin
- segmental/lobar airspace disease in lower lobes in acute illness (26 61%)
- solitary/multiple irregular nodular masses/satellite lesions in paramediastinal location
- air bronchogram in area of consolidation/mass (87%)
- interstitial disease
- cavitation if communicating with airway (13%)
- hilar/mediastinal lymph node enlargement (<25%)
@ Bone
- marked destruction surrounding sclerosis
- periosteal reaction in long bones, but not in short bones
- multiple osseous lesions are frequent
- vertebral bodies + intervertebral disks are destroyed (similar to tuberculosis)
- psoas abscess
- lytic skull lesions + soft-tissue abscess
- usually monoarticular arthritis: knee > ankle > elbow > wrist > hand
@ GU tract (20%): prostate, epididymis

Dx:	(1) Culture of organism (2) Silver stain microscopy of tissues
Prognosis:	spontaneous resolution of acute disease in up to 4 weeks; disease may reactivate for up to 3 years
Rx:	(1) Amphotericin B IV: 8 10 weeks for noncavitary + 10 12 weeks for cavitary lesions (2) Ketoconazole
DDx:	other pneumonias (ie, bacterial, tuberculous, fungal), pseudolymphoma, malignant neoplasm (ie, alveolar cell carcinoma, lymphoma, Kaposi sarcoma)

Blunt Chest Trauma

Incidence:	100,000 hospital admissions/year (in USA)
Cause:	high-speed motor vehicle accidents (70%)

Type of injury:

Pneumothorax
Lung contusion
Rib fracture
Hemothorax
Flail chest
Thoracic spine fracture
Clavicle fracture
Scapula fracture
Sternal fracture
Diaphragmatic injury
Tracheobronchial tear
Vascular injury
Esophageal rupture

69%
67%
66%
28%
14%
13%
13%
8%
5%
5%
2%
2%
1%

Bone Marrow Transplantation

= intravenous infusion of hematopoietic progenitor cells from patient's own marrow (autologous transplant)/HLA-matched donor (allogenic transplant) to reestablish marrow function after high-dose chemotherapy and total body irradiation for lymphoma, leukemia, anemia, multiple myeloma, congenital immunologic defects, solid tumors

Cx:

pulmonary complications in 40 60%

Neutropenic Phase Pulmonary Complications

Time:

2 3 weeks after transplantation

P.470

Angioinvasive aspergillosis
- nodule surrounded by halo of ground-glass attenuation
  - (= fungal infection spreading into lung parenchyma and surrounding area of hemorrhagic infarction)
- segmental/subsegmental consolidation
  - (= pulmonary infarction)
- cavitation of nodule with air-crescent sign (during recovery phase with resolving neutropenia)
- <5-mm centrilobular nodules to 5-cm peribronchial consolidation (= airway invasion with surrounding zone of hemorrhage/organizing pneumonia)
Diffuse alveolar hemorrhage (20%)
- hemosiderin-laden macrophages on lavage
- bilateral areas of ground-glass attenuation/consolidation
Pulmonary edema

Cause: infusion of large volumes of fluid combined with cardiac + renal dysfunction
- prominent pulmonary vessels, interlobar septal thickening, ground-glass attenuation, pleural effusions
Drug toxicity

Cause: bleomycin, busulfan, bischloronitrosurea (carmustine), methotrexate
- bilateral areas of ground-glass attenuation/consolidation/reticular attenuation (= fibrosis)

Early Phase Pulmonary Complications

Time:

up to 100 days after transplantation

CMV pneumonia (23%)
- multiple small nodules + associated areas of consolidation + ground-glass attenuation (= hemorrhagic nodules)
Pneumocystis carinii pneumonia
- diffuse/predominantly perihilar/mosaic pattern of ground-glass attenuation with sparing of some secondary pulmonary lobules
Idiopathic interstitial pneumonia (12%)
- nonspecific findings (diagnosis of exclusion)

Late Phase Pulmonary Complications

Time:

after 100 days post transplantation

Bronchiolitis obliterans (in up to 10%)
BOOP
Chronic graft-versus-host disease:
- infections, chronic aspiration, bronchiolitis obliterans, lymphoid interstitial pneumonia

Bronchial Adenoma

= misnomer secondary to locally invasive features, tendency for recurrence, and occasional metastasis to extrathoracic sites (10%) = low-grade malignancy

Path:	arises from duct epithelium of bronchial mucous glands (predominant distribution of Kulchitsky cells at bifurcations of lobar bronchi)
Incidence:	6 10% of all primary lung tumors
Age:	mean age of 35 45 years (range 12 60 years);90% occur <50 years of age;most common primary lung tumor under age 16;M:F = 1:1; Whites:Blacks = 25:1

Types:

mnemonic:

CAMP

Carcinoid	90%
Adenoid cystic carcinoma = Cylindroma	6%
Mucoepidermoid carcinoma	3%
Pleomorphic carcinoma	1%

Location:	most commonly near/at bifurcation of lobar/segmental bronchi; central:peripheral = 4:1
48% on right:	RLL (20%), RML (10%), RUL (7%), main right bronchus (8%), intermediate bronchus (3%)
32% on left:	LLL (13%), LUL (12%), main left bronchus (6%), lingular bronchus (1%)

hemoptysis (40 50%)
atypical asthma
persistent cough
recurrent obstructive pneumonia
asymptomatic (10%)

complete obstruction/air trapping in partial obstruction (rare)/nonobstructive (10 15%)
obstructive emphysema
recurrent postobstructive infection: pneumonitis, bronchiectasis, abscess
atelectasis/consolidation of a lung/lobe/segment (78%)
collateral air drift may prevent atelectasis
solitary round/oval slightly lobulated pulmonary nodule (19%) of 1 10 cm in size
hilar enlargement/mediastinal widening = central endo-/exobronchial mass

CT:

well-marginated sharply defined mass
in close proximity to an adjacent bifurcation with splaying of bronchus
coarse peripheral calcifications in 1/3 (cartilaginous/bony transformation)
may exhibit marked homogeneous enhancement

Biopsy	risky secondary to high vascularity of tumor
Prognosis:	95% 5-year survival rate, 75% 15-year survival rate after resection

Carcinoid

= NEUROENDOCRINE CARCINOMA
= slow-growing low-grade malignant tumor

Incidence:	12 15% of all carcinoid tumors in the body; 1 4% of all bronchial neoplasms
Age peak:	5th decade (range of 2nd 9th decade); 4% occur in children + adolescents; m:f = 2:1; very uncommon in Blacks
Associated with:	MEN 1 in <4% (almost all hormonally inactive)

Path:

originates from neurosecretory cells of bronchial mucosa (= Kulchitsky cells = argentaffine cells) just as small cell cancer; part of APud (amine precursor uptake and decarboxylation) system = chromaffin paraganglioma, which produces serotonin, AcTH, norepinephrine, bombesin, calcitonin, AdH, bradykinin

Pathologic classification:

(Kcc = Kulchitsky cell carcinoma)

P.471

KCC I =	classic carcinoid (least aggressive low-grade tumor) = bronchial adenoma (misnomer) = central location with endobronchial growth; usually <2.5 cm in size + well-defined; younger patient; m:f = 1:10; lymph node metastases in 3%; rarely metastasize
KCC II =	atypical carcinoid (25% of carcinoid tumors); central + peripheral location; mass usually >2.5 cm with well-defined margins; older patient; m:f = 3:1; lymph node metastases in 40 50%; metastases to brain, liver, bone (in 30%)
KCC III =	small cell carcinoma (most aggressive); mediastinal lymphadenopathy; ill-defined tumor margins

rarely cause for carcinoid syndrome or cushing syndrome!
recurrent unifocal pneumonitis, hemoptysis
wheezing, persistent cough, dyspnea, chest pain
carcinoid syndrome (rare)
endobronchial exophytic mass at endoscopy

Location:

58 90% central in lobar/segmental bronchi, 10 42% peripheral; located in submucosa; endobronchial/along bronchial wall/exobronchial

polypoid tumor with average size of 2.2 cm
most extend through bronchial wall thus involving bronchial lumen + parenchyma (= collar button lesion)
calcification/ossification (26 33%): central carcinoid (43%), peripheral carcinoid (10%)
vascular tumor supplied by bronchial circulation
cavitation (rare)
segmental/lobar atelectasis
obstructive pneumonitis
bronchiectasis + pulmonary abscess

CT:

dense ossification
scattered calcifications
intraluminal location

PET:

no uptake (most often)

Malignant potential:

low

Metastases:

regional lymph nodes in 25%
distantly in 5% (adrenal, liver, brain, skin, osteoblastic bone metastases)

Prognosis:	90% 10-year survival rate for classic carcinoids; 25 69% 5-year survival rate for atypical carcinoids
Rx:	endobronchial resection, bronchial sleeve resection, segmentectomy, lobectomy, pneumonectomy

Cylindroma

= ADENOID CYSTIC CARCINOMA (7%)
Second most common primary tumor of trachea

Path:

mixed serous + mucous glands; resembles salivary gland tumor

Histo:

Grade 1:	tubular + cribriform; no solid subtype entirely intraluminal
Grade 2:	tubular + cribriform; <20% solid subtype predominantly intraluminal
Grade 3:	solid subtype >20% predominantly extraluminal
Age peak:	4th 5th decade

typical Hx of refractory asthma
hemoptysis, cough, stridor, wheezing
dysphagia, hoarseness

endotracheal mass with extratracheal extension

Malignant potential:

more aggressive than carcinoid with propensity for local invasion + distant metastases (lung, bone, brain, liver) in 25%

Rx:	tracheal resection + adjunctive radiotherapy
Prognosis:	8.3 years mean survival

Mucoepidermoid Carcinoma

Path:

squamous cells + mucus-secreting columnar cells; resembles salivary gland tumor

may involve trachea = locally invasive tumor
sessile/polypoid endobronchial lesion

Pleomorphic Adenoma

= MIXED TYPE (extremely rare)

Bronchial Atresia

= local obliteration of proximal lumen of a segmental bronchus

Proposed causes:

local interruption of bronchial arterial perfusion >15 weeks GA (when bronchial branching is complete)
tip of primitive bronchial bud separates from bud and continues to develop

Path:	normal bronchial tree distal to obstruction patent and containing mucus plugs; alveoli distal to obstruction airfilled through collateral air drift
Associated with:	lobar emphysema, cystic adenomatoid malformation

minimal symptoms, apparent later in childhood (most by age 15)/adult life

Location:

apicoposterior segment of LUL (>>RUL/ML)

decreased perfusion
overexpanded segment (collateral air drift with expiratory air-trapping)
gloved finger sign = tubular opacity lateral to hilum (= mucus plug distal to atretic lumen) is CHARACTERISTIC
OB-US (detected >24 weeks MA):
- large echogenic fetal lung mass = fluid-filled lung distal to obstruction
- dilated fluid-filled bronchus

Rx:	no treatment because mostly asymptomatic
DDx:	Congenital lobar emphysema (no mucus plug)

Bronchiectasis

= localized mostly irreversible dilatation of bronchi often with thickening of the bronchial wall

Etiology:

Congenital
- Structural defect of bronchi: bronchial atresia, Williams-Campbell syndrome
- Abnormal mucociliary transport: Kartagener syndrome
- Abnormal secretions: cystic fibrosis
Congenital/acquired immune deficiency (usually IgG deficiency): chronic granulomatous disease of childhood, alpha-1 antitrypsin deficiency
Postinfectious childhood pneumonias (after necrotizing viral/bacterial bronchitis): measles, whooping cough, Swyer-James syndrome, allergic bronchopulmonary aspergillosis, chronic granulomatous infection (TB)
Distal to bronchial obstruction (due to accumulation of secretions): neoplasm, inflammatory nodes, foreign body
Aspiration/inhalation: gastric contents/inhaled fumes (late complication)
Traction bronchiectasis (due to increased elastic recoil with bronchial dilatation + mechanical distortion of bronchi): advanced pulmonary fibrosis/radiation-induced lung injury
Increased inflationary pressure

Classification:

Cylindrical/tubular/fusiform bronchiectasis
- = mildly and uniformly dilated bronchi (least severe type)
- reversible if associated with pulmonary collapse
Path: 16 subdivisions of bronchi
- square abrupt ending with lumen of uniform diameter and same width as parent bronchus
- HRCT:
  - tram lines of nontapering air ways (horizontal course)
  - signet-ring sign (vertical course) = cross section of dilated bronchus + branch of pulmonary artery
  - Y- or V-shaped areas of attenuation = mucous plugs filling bronchiectatic segments
Varicose bronchiectasis
- = moderately dilated and beaded bronchi (rare)
Associated with: Swyer-James syndrome

Path: 4 8 subdivisions of bronchi
- beaded contour with normal pattern distally
Saccular/cystic bronchiectasis
- = marked cystic dilatation (most severe type)
Associated with: severe bronchial infection

Path: <5 subdivisions of bronchi
- progressive ballooning dilatation toward periphery with diameter of saccules >1 cm
- irregular constrictions may be present
- dilatation of bronchi on inspiration, collapse on expiration
- contains variable amounts of pooled secretions
- HRCT:
  - string of cysts = string of pearls (horizontal course)/cluster of cysts = cluster of grapes
  - air-fluid level (frequent)

Age:

predominantly pediatric disease

chronic cough, excess sputum production
recurrent infection with expectoration of purulent sputum
shortness of breath
hemoptysis (50%)
frequent exacerbations + resolutions (due to superimposed infections)

Associated with:	obliterative + inflammatory bronchiolitis (in 85%)
Location:	posterior basal segments of lower lobes, bilateral (50%), middle lobe/lingula (10%), central bronchiectasis in bronchopulmonary aspergillosis

CXR (37% sensitive):

dilated air-filled bronchi
bronchial wall thickening
increased background density
parenchymal volume loss:
- crowding of lung markings (if associated with atelectasis)
- increase in size of lung markings (retained secretions)
- loss of definition of lung markings (peribronchial fibrosis)
cystic spaces air-fluid levels <2 cm in diameter (dilated bronchi)
honeycomb pattern (in severe cases)
compensatory hyperinflation of uninvolved ipsilateral lung

HRCT (87 97% sensitive, 93 100% specific):

lack of bronchial tapering (in 80% = most sensitive finding)
bronchial wall thickening
signet ring sign = internal diameter of bronchus larger than adjacent pulmonary artery (in 60%)
bronchi visible within 1 cm of pleura (in 45%)
mucus-filled dilated bronchi (in 6%)

Cx:

frequent respiratory infections

DDx of CT appearance:

Emphysematous blebs (no definable wall thickness, subpleural location)
Reversible bronchiectasis = temporary dilatation during pneumonia with return to normal within 4 6 months

Bronchiolitis Obliterans

= CONSTRICTIVE BRONCHIOLITIS = OBLITERATIVE BRONCHIOLITIS
= inflammation of bronchioles leading to (sometimes reversible) obstruction of bronchiolar lumen

Etiology:

Inhalation: 1 3 weeks after exposure to toxic fumes (isocyanates, phosgene, ammonia, sulfur dioxide, chlorine)
Postinfectious: Mycoplasma (children), virus (older individual); see Swyer-James syndrome
Drugs: bleomycin, gold salts, cyclophosphamide, methotrexate, penicillamine
Connective tissue disorder: rheumatoid arthritis, scleroderma, systemic lupus erythematosus
Chronic rejection: lung transplant, heart-lung transplant (30 50%)
Chronic graft-versus-host disease: bone marrow transplant
Cystic fibrosis (as a complication of repeated episodes of pulmonary infection)
Idiopathic (in immunocompetent patients)

Path:	submucosal and peribronchiolar fibrosis = irreversible fibrosis of small airway walls with narrowing/obliteration of airway lumina (respiratory bronchiole, alveolar duct, alveoli) by granulation tissue of immature fibroblastic plugs (Masson bodies)
Peak age:	40 60 years; M:F = 1:1

P.473

insidious onset of dyspnea over many months
obstructive pulmonary function tests
no response to antibiotics
persistent nonproductive cough, fever
normal CXR (in up to 40%)
hyperinflated lungs = limited disease with connective tissue plugs in airways
bilateral scattered heterogeneous + homogeneous opacities (typically peripheral in distribution; equally distributed between upper + lower lobes)
bronchiectasis
decreased vascularity (reflex vasoconstriction)
HRCT (paired expiration-inspiration images:
- mosaic perfusion of lobular air trapping (85 100%)
  - = patchy areas of decreased lung attenuation alternating with areas of normal attenuation:
  - areas of decreased attenuation containing vessels of decreased caliber (due to alveolar hypoventilation + secondary vasoconstriction of alveoli distal to bronchiolar obstruction)
  - areas of increased attenuation containing vessels of increased caliber (uninvolved areas with compensatory increased perfusion)
bronchial wall thickening (87%)
bronchiectasis (66 80%)
patchy air trapping on expiratory scans (due to collateral air drift into postobstructive alveoli) = failure of volume/attenuation change between expiratory + inspiratory images
poorly defined nodular areas of consolidation
tree-in-bud appearance of bronchioles
- = centrilobular branching structures and nodules caused by peribronchiolar thickening + bronchiolectasis with secretions (the only direct, but uncommon sign)
centrilobular ground-glass opacities

Rx:	steroids may stop progression
DDx:	(1) Bacterial/fungal pneumonia (response to antibiotics, positive cultures) (2) Chronic eosinophilic pneumonia (young female, eosinophilia in 2/3) (3) Usual interstitial pneumonia (irregular opacities, decreased lung volume)

Bronchiolitis obliterans with organizing pneumonia (BOOP)

= PROLIFERATIVE BRONCHIOLITIS = CRYPTOGENIC ORGANIZING PNEUMONITIS (COP)

Prevalence:	20 30% of all chronic infiltrative lung disease
Cause:	postobstructive pneumonia, organizing adult respiratory distress syndrome, lung cancer, extrinsic allergic alveolitis, pulmonary manifestation of collagen vascular disease, pulmonary drug toxicity, silo filler disease, idiopathic (50%)
Path:	granulation tissue polyps filling the lumina of alveolar ducts and respiratory bronchioles (bronchiolitis obliterans) + variable degree of infiltration of interstitium and alveoli with macrophages (organizing pneumonia)

Bronchiolitis obliterans component not present in up to 1/3!

Histo:	plugs of immature fibroblasts (Masson bodies) covered with low cuboidal epithelium, which may spread through collateral air drift pathways
Age:	40 70 years; M:F = 1:1

clinical + functional + radiographic manifestation of organizing pneumonia
nonproductive cough, dyspnea (1 4-month history), preceded by a brief flulike illness with sore throat (40%), low-grade fever, malaise (in 33%)
late respiratory crackles
restrictive pulmonary function tests + diminished diffusing capacity on pulmonary function tests
unresponsive to broad-spectrum antibiotics
no organism identified

Location:

mainly mid + lower lung zones; often subpleural (50%) and peribronchiolar distribution (30 50%)

CXR:
- frequently mixture of:
- uni-/bilateral patchy alveolar airspace consolidation (25 73%), often subpleural
- 3 5 mm nodules (up to 50%)
- irregular linear opacities (15 42%)
- unilateral focal/lobar consolidation (5 31%)
- pleural thickening (13%)
- cavitation/pleural effusion (<5%)
HRCT:
- patchy airspace consolidation (80%)
  - bilateral in 90% involving all lung zones
  - subpleural/peribronchial distribution in 50 60%
- patchy ground-glass opacities (due to alveolitis) in 60%
- 3 5 mm centrilobular nodules (30 50%) due to organized pneumonia
- air bronchograms = cylindrical bronchial dilatation in areas of airspace consolidation (36 70%)
- pleural effusion (28 35%)
- adenopathy (27%)

Rx:	improvement with corticosteroid therapy (in 84% of patients with idiopathic form)
Prognosis:	persistent abnormalities (30%); 10% mortality due to progressive/recurrent disease
Dx:	tissue examination from open lung biopsy

Bronchioloalveolar Carcinoma

= ALVEOLAR CELL CARCINOMA = BRONCHIOLAR CARCINOMA

Incidence:	1.5 6% of all primary lung cancers (increasing incidence to? 20 25%)
Etiology:	development from type ii alveolar epithelial cells
Age:	40 70 years; m:f = 1:1 (strikingly high in women)
Path:	peripheral neoplasm arising beyond a recognizable bronchus with tendency to spread locally using lung structure as a stroma (= lepedic growth)
Histo:	subtype of well-differentiated adenocarcinoma; cuboidal/columnar cells grow along alveolar walls + septa without disrupting the lung architecture or pulmonary interstitium (serving as scaffolding for tumor growth)

Subtypes:

mucinous (80%): mucin-secreting tall columnar peglike bronchiolar cells; more likely multicentric; 26% 5-year survival rate

P.474

nonmucinous (20%): cuboidal type ii alveolar pneumocytes with production of surfactant/nonciliated bronchiolar (clara) cells; more localized + solitary; 72% 5-year survival rate

Risk factors:

localized pulmonary fibrosis (tuberculous scarring, pulmonary infarct) in 27%, diffuse fibrotic disease (scleroderma), previous exogenous lipid pneumonia

history of heavy smoking (25 50%)
often asymptomatic (even with disseminated disease) with insidious onset
pleuritic chest pain (due to peripheral location)
cough (35 60%), hemoptysis (11%)
bronchorrhea = abundant white mucoid/watery expectoration (5 27%); can produce hypovolemia + electrolyte depletion; unusual + late manifestation only with diffuse bronchioloalveolar carcinoma
shortness of breath (15%)
weight loss (13%), fever (8%)

Location:	peripherally, beyond a recognizable bronchus
Spread:	tracheobronchial dissemination = cells detach from primary tumor + attach to alveolar septa elsewhere in ipsi-/contralateral lung; lymphogenous + hematogenous dissemination
Metastases:	involving almost any organ (in 50 60%); 33% of skeletal metastases are osteoblastic

LOCAL FORM (60 90%)
- Ground-glass attenuation
  - = early stage (due to lepedic growth pattern along alveolar septa with relative lack of acinar filling)
  - ground-glass haziness
  - bubblelike hyperlucencies/pseudocavitation
  - airway dilatation
  - lesion persists/progresses within 6 8 weeks
- Single mass (43%)
  - well-circumscribed focal mass in peripheral/subpleural location arising beyond a recognizable bronchus
  - open bronchus sign = air bronchogram = tumor/mucus surrounding aerated bronchus narrowing/stretching/spreading of bronchi
  - rabbit ears /pleural tags/triangular strand/ tail sign (55%) = linear strands extending from nodule to pleura (desmoplastic reaction/scarring granulomatous disease/pleural indrawing)
  - spiculated margin = sunburst appearance (73%)
  - solitary cavity due to central necrosis (7%)
    - 2nd most common cell type associated with cavitation after squamous cell carcinoma
  - pseudocavitation (= dilatation of intact air spaces from desmoplastic reaction/bronchiectasis/focal emphysema) in 50 60%
  - heterogeneous attenuation (57%)
  - confined to single lobe
  - rarely evolving into diffuse form
  - slowly progressive growth on serial radiographs
  - NO atelectasis
  - negative FDG PET results in 55%
Prognosis: 70% surgical cure rate for tumor <3 cm; 4 15 years' survival time with single nodule
DIFFUSE FORM = Pneumonic form (10 40%)
- Diffuse consolidation (30%)
  - acinar airspace consolidation + air bronchogram + poorly marginated borders
  - airspace consolidation may affect both lungs (mucus secretion)
  - cavitation within consolidation
  - CT angiogram sign = low-attenuation consolidation does not obscure vessels (mucin-producing subtype)
- Lobar form
  - expansion of a lobe with bulging of interlobar fissures
- Multinodular form (27%)
  - multiple bilateral poorly/well-defined nodules similar to metastatic disease
  - multiple poorly defined areas of ground-glass attenuation/consolidation
  - pleural effusion (8 10%)

Prognosis:

worse with extensive consolidation/multifocal/bilateral disease; death within 3 years with diffuse disease

Bronchocentric Granulomatosis

Age:

4th 7th decade

asthma with underlying allergic bronchopulmonary aspergillosis (33 50%)
fever, night sweats, cough, dyspnea, pleuritic chest pain
seropositive arthritis (rare)
ocular scleritis (rare)

Path:	thick-walled ectatic bronchi + bronchioles containing viscous material of mucopurulent/caseous character
Histo:	necrotizing granulomas surrounding small airways; pulmonary arteritis as a secondary phenomenon (1) large masses of eosinophils in necrotic zones, associated with endobronchial mucus plugs, eosinophilic pneumonia, Charcot-Leyden crystals, fungal hyphae in granulomas (with asthma) (2) polymorphonuclear cell infiltrate in necrotic zones (without asthma)
Location:	unilateral (75%); upper lobe predominance

branching opacities/atelectasis (from mucoid impaction)
multiple/solitary nodules/masses
ill-defined parenchymal consolidation
cavitation

Rx:

corticosteroid therapy

Bronchogenic Carcinoma

= LUNG CANCER = LUNG CARCINOMA
Most frequent cause of cancer deaths in males (35% of all cancer deaths) and females (21% of all cancer deaths); most common malignancy of men in the world; 6th leading cancer in women worldwide

Prevalence:	in 1991 161,000 new cases; 143,000 deaths
Age at diagnosis:	55 60 years (range 40 80 years); M:F = 1.4:1

asymptomatic (10 50%) usually with peripheral tumors
symptoms of central tumors:
- cough (75%), wheezing, pneumonia
- hemoptysis (50%), dysphagia (2%)
symptoms of peripheral tumors:
- pleuritic/local chest pain, dyspnea, cough
- Pancoast syndrome, superior vena cava syndrome
- hoarseness
symptoms of metastatic disease (CNS, bone, liver, adrenal gland)
paraneoplastic syndromes:
- cachexia of malignancy
- clubbing + hypertrophic osteoarthropathy
- nonbacterial thrombotic endocarditis
- migratory thrombophlebitis
- ectopic hormone production: hypercalcemia, syndrome of inappropriate secretion of antidiuretic hormone, Cushing syndrome, gynecomastia, acromegaly

Risk factors:

Cigarette smoking (squamous cell carcinoma + small cell carcinoma)
- related to number of cigarettes smoked, depth of inhalation, age at which smoking began
- 85% of lung cancer deaths are attributable to cigarette smoking!
- Passive smoking may account for 25% of lung cancers in nonsmokers!
Radon gas: may be the 2nd leading cause for lung cancer with up to 20,000 deaths per year
Industrial exposure: asbestos, uranium, arsenic, chlormethyl ether

Concomitant disease:

chronic pulmonary scar + pulmonary fibrosis
Scar carcinoma
- 45% of all peripheral cancers originate in scars!

Incidence:	7% of lung tumors; 1% of autopsies
Origin:	related to infarcts (>50%), tuberculosis scar (<25%)
Histo:	adenocarcinoma (72%), squamous cell carcinoma (18%)
Location:	upper lobes (75%)

Types:

Adenocarcinoma (50%)

Most common cell type seen in women + nonsmokers!
Intermediate malignant potential (slow growth, high incidence of early metastases)

Doubling time:	~150 180 days
Histo:	formation of glands/intracellular mucin
Subtype:	bronchioloalveolar carcinoma
Location:	almost invariably develops in periphery; frequently found in scars (tuberculosis, infarction, scleroderma, bronchiectasis) + in close relation to preexisting bullae

solitary peripheral subpleural mass (52%)/alveolar infiltrate/multiple nodules
may invade pleura + grow circumferentially around lung mimicking malignant mesothelioma
upper lobe distribution (69%)
air broncho-/bronchiologram on HRCT (65%)
calcification in periphery of mass (1%)
smooth margin/spiculated margin due to desmoplastic reaction with retraction of pleura

Squamous cell carcinoma = epidermoid carcinoma (30 35%)

Strongly associated with cigarette smoking

Histo:	mimics differentiation of the epidermis by producing keratin ( epidermoid carcinoma ); central necrosis is common
Histogenesis:	chronic inflammation with squamous metaplasia, progression to dysplasia + carcinoma in situ

positive sputum cytology
- Most common cell type diagnosed that is radiologically occult!
hypercalcemia from tumor-elaborated parathyroid hormonelike substance
- Slowest growth rate, lowest incidence of distant metastases

Doubling time:

~90 days

Central location within main/lobar/segmental bronchus (2/3)
- large central mass cavitation
- distal atelectasis bulging fissure (due to mass)
- postobstructive pneumonia
  - All cases of pneumonia in adults should be followed to complete radiologic resolution!
- airway obstruction with atelectasis (37%)
Solitary peripheral nodule (1/3)
- characteristic cavitation (in 7 10%)
  - Squamous cell carcinoma is the most common cell type to cavitate!
- invasion of chest wall
  - Squamous cell carcinoma is the most common cell type to cause Pancoast tumor!

Small cell undifferentiated carcinoma (15%)

Strongly associated with cigarette smoking
Rapid growth + high metastatic potential (early metastases in 60 80% at time of diagnosis); should be regarded as systemic disease regardless of stage; virtually never resectable

Doubling time:	~30 days
Path:	arises from bronchial mucosa with growth in submucosa + subsequent invasion of peribronchial connective tissue
Histo:	small uniform oval cells with scant cytoplasm; nuclei with stippled chromatin; numerous mitoses + large areas of necrosis; in 20% coexistent with non-small cell histologic types (most frequently squamous cell)
Subtype:	oat cell cancer with hyperchromatic nuclei;? related to Kulchitsky cell carcinomas

smooth-appearing mucosal surface endoscopically
ectopic hormone production: Cushing syndrome, inappropriate secretion of ADH
Most common primary lung cancer causing superior vena caval obstruction (due to extrinsic compression/endoluminal thrombosis/invasion)!

Location:

90% central within lobar/mainstem bronchus (primary tumor rarely visualized)

typically large hilar/perihilar mass often associated with mediastinal widening (from adenopathy)
extensive necrosis + hemorrhage
small lung lesion (rare)

P.476

Staging evaluation:
- CT of abdomen + head, bone scintigraphy, bilateral bone marrow biopsies

Large undifferentiated cell carcinoma (<5%)

Strongly associated with smoking
Intermediate malignant potential; rapid growth + early distant metastases

Doubling time:	~120 days
Histo:	tumor cells with abundant cytoplasm + large nuclei + prominent nucleoli; diagnosed per exclusion due to lack of squamous/glandular/small cell differentiation
Subtype:	giant cell carcinoma with very aggressive behavior + poor prognosis

large bulky usually peripheral mass >6 cm (50%)
large area of necrosis
pleural involvement
large bronchus involved in central lesion (50%)

Location:

60 80% arise in segmental bronchi
central: small cell carcinoma, squamous cell carcinoma (sputum cytology positive in 70%); arises in central airway often at points of bronchial bifurcation, infiltrates circumferentially, extends along bronchial tree

mnemonic: Small cell and Squamous are Sentral
peripheral: adenocarcinoma, large cell carcinoma
upper lobe: lower lobe = right lung:left lung = 3:2
most common site: anterior segment of RUL
Pancoast tumor (3%) = Superior sulcus tumor, frequently squamous cell carcinoma
- atrophy of muscles of ipsilateral upper extremity due to lower brachial plexus involvement
- Horner syndrome (enophthalmos, miosis, ptosis, anhidrosis) due to sympathetic chain + stellate ganglion involvement
- apical pleural thickening/mass
- soft-tissue invasion/bone destruction
- coronal + sagittal MR images improve evaluation
SVC obstruction (5%): often in small cell carcinoma

Presentation:

solitary peripheral mass with corona radiata/pleural tail sign/satellite lesion
cavitation (16%): usually thick-walled with irregular inner surface; in 4/5 secondary to squamous cell carcinoma, followed by bronchioloalveolar carcinoma
central mass (38%): common in small cell carcinoma
unilateral hilar enlargement (secondary to primary tumor/enlarged lymph nodes)
- calcified enlarged nodes frequently benign
- nodes in short axis diameter:
  - 0 10 mm normal (CAVE: micrometastases)
  - >10 mm (65% sensitive + specific for tumor)
  - 20 40 mm (37% not involved by tumor)
- PET (89% sensitive, 99% specific)
anterior + middle mediastinal widening (suggests small cell carcinoma)
segmental/lobar/lung atelectasis (37%) secondary to airway obstruction (particularly in squamous cell carcinoma):
- postobstructive lung enhances to a greater extent than tumor on CECT
- distal lung atelectasis has a higher signal intensity than the central mass in 77% on T2WI (due to accumulation of secretions in obstructed lung)
(reverse) S sign of Golden on PA CXR = combination of RUL collapse (inferiorly concave margin of lateral portion of minor fissure, which moved superiorly and medially with compensatory expansion of RML) + bulge of central tumor (inferiorly convex margin of medial portion of minor fissure)
rat tail termination of bronchus
bronchial cuff sign = focal/circumferential thickening of bronchial wall imaged end-on (early sign)
local hyperaeration (due to check-valve type endobronchial obstruction, best on expiratory view)
mucoid impaction of segmental/lobar bronchus (due to endobronchial obstruction)
persistent peripheral infiltrate (30%) = postobstructive pneumonitis
No air bronchogram
pleural effusion (8 15%): most commonly due to adenocarcinoma
chest wall invasion:
- localized chest wall pain = most sensitive predictor
- tumor interdigitation with chest wall musculature on T2Wi
- obliteration of high-intensity extrathoracic fat on T1Wi
- bone erosion of ribs/spine (9%)
involvement of main pulmonary artery (18%); lobar + segmental arteries (53%) may result in additional peripheral radiopacity (due to lung infarct)
calcification in 7% on cT (histologically in 14%) usually eccentric/finely stippled
- preexisting focus of calcium engulfed by tumor
- dystrophic calcium within tumor necrosis
- calcium deposit from secretory function of carcinoma (eg, mucinous adenocarcinoma)
Angio:
- bronchogenic carcinoma supplied by bronchial arteries
- distortion/stenosis/occlusion of pulmonary arterial circulation

Cx:

diaphragmatic elevation (phrenic nerve paralysis)
Hoarseness (laryngeal nerve involvement, left > right)
SVC obstruction (5%): lung cancer is cause of all SVC obstructions in 90%
Pleural effusion (10%): malignant, parapneumonic, lymphoobstructive
dysphagia: enlarged nodes, esophageal invasion
Pericardial invasion: pericardial effusion, localized pericardial thickening/nodular masses

Prognosis:

mean survival time <6 months; 10 13 15% overall 5-year survival; survival at 40 months: squamous cell 30% > large cell 16% > adenocarcinoma 15% > oat cell 1%

Rx:

Surgical resection for non-small cell histologic types unresectable: involvement of heart, great vessels, trachea, esophagus, vertebral body, malignant pleural effusion

P.477

Adjuvant chemotherapy + radiation therapy in extensive resectable disease
chemotherapy for small cell carcinoma + radiation therapy for bulky disease, cns metastases, spinal cord compression, SVC obstruction

Staging for small cell lung cancer:

Limited disease:
- Primary in one hemithorax
- ipsilateral hilar adenopathy
- ipsilateral supraclavicular adenopathy
- ipsi- and contralateral mediastinal adenopathy
- Atelectasis
- Paralysis of phrenic + laryngeal nerve
- small effusion without malignant cells
extensive disease (60 80%):
- contralateral hilar adenopathy
- contralateral supraclavicular adenopathy
- chest wall infiltration
- carcinomatous pleural effusion
- Lymphangitic carcinomatosis
- superior vena cava syndrome
- metastasis to contralateral lung
- extrathoracic metastases to bone (38%), liver (22 28%), bone marrow (17 23%), cns (8 15%), retroperitoneum (11%), other lymph nodes

Prognosis:

7 11 months median survival; 15 20% 2-year disease-free survival rate

MULTIPLE PRIMARY LUNG CANCERS

Incidence:

0.72 3.5%; in 1/3 synchronous, in 2/3 metachronous

10 32% of patients surviving resection of a lung cancer will develop a second primary!

Dx:

biopsy mandatory for proper therapy because the tumor may have a different cell type

PARANEOPLASTIC MANIFESTATIONS

Carcinomatous neuromyopathy (4 15%)
Migratory thrombophlebitis
Hypertrophic pulmonary osteoarthropathy (3 5%)
Endocrine manifestations (15%) usually with small cell carcinoma: Cushing syndrome, inappropriate secretion of ADH, HPT, excessive gonadotropin secretion

International System for Staging of Lung Cancer

Stage	Description
IA	T1 tumor in the absence of nodal/extrathoracic metastases
IB	T2 tumor in the absence of nodal/extrathoracic metastases
IIA	T1n1m0
IIB	T2n1m0 + T3n0m0
IIIA	T3 other than T3n0m0/n2
IIIB	T4/n3 disease
IV	metastatic disease

TNM Staging of Lung Cancer

Stage	Description
T1	<3 cm in diameter, surrounded by lung/visceral pleura
T2	3 cm in diameter/invasion of visceral pleura/lobar atelectasis/obstructive pneumonitis/at least 2 cm from carina
T3	tumor of any size; less than 2 cm from carina/invasion of parietal pleura, chest wall, diaphragm, mediastinal pleura, pericardium; pleural effusion; satellite nodule in same lobe
T4	invasion of heart, great vessels, trachea, esophagus, vertebral body, carina/malignant pleural effusion
N1	peribronchial/ipsilateral hilar nodes
N2	ipsilateral mediastinal nodes
N3	contralateral hilar/mediastinal nodes; scalene/supraclavicular nodes

SPREAD

Direct local extension
Hematogenous (small cell carcinoma)
Lymphatic spread (squamous cell carcinoma); tumor in 10% of normal-sized lymph nodes
Transbronchial spread least common

DISTANT METASTASES

Likelihood:	small cell > adeno > large cell > squamous
Location:	vertebrae (70%), pelvis (40%), femora (25%)

@ Bone
- Marrow: in 40% at time of presentation
- Gross lesions in 10 35%:
- osteolytic metastases (3/4)
- osteoblastic metastases (1/4):
- in small cell carcinoma/adenocarcinoma
- occult metastases in 36% of bone scans
@ Adrenals: in 37% at time of presentation
- 50% of adrenal masses in patients with lung cancer are benign!
@ Brain: asymptomatic metastases on brain scan in 7% (30% at autopsy), in 2/3 multiple
@ Kidney, GI tract, liver, abdominal lymph nodes
@ Lung-to-lung metastases (in up to 10%, usually in late stage)

Bronchogenic Cyst

= budding/branching abnormality of ventral diverticulum of primitive foregut (ventral segment = tracheobronchial tree; dorsal segment = esophagus) between 26 and 40 days of embryogenesis

Incidence:	most common intrathoracic foregut cyst (54 63% in surgical series)
Histo:	thin-walled cyst filled with mucoid material, lined with columnar respiratory epithelium, mucous glands, cartilage, elastic tissue, smooth muscle

P.478

contains mucus/clear or turbid fluid
sharply outlined round/oval mass
may contain air-fluid level
CT:
- cyst contents of water density (50%)/higher density (50%)
OB-US:
- single unilocular pulmonary cyst
- echogenic distended lung obstructed by bronchogenic cyst

Mediastinal Bronchogenic Cyst (86%)

Associated with:

spinal abnormalities

M:F = 1:1

usually asymptomatic
stridor, dysphagia

Location:

pericarinal (52%), paratracheal (19%), esophageal wall (14%), retrocardiac (9%); usually on right

rarely communicate with tracheal lumen
may show esophageal compression

Intrapulmonary Bronchogenic Cyst (14%)

M > F
infection (75%)
dyspnea, hemoptysis (most common)

Location:

lower:upper lobe = 2:1; usually medial third

36% will eventually contain air

DDx:

solitary pulmonary nodule, cavitated neoplasm, cavitated pneumonia, lung abscess

Bronchopulmonary Dysplasia

= Respirator lung
= complication of respirator therapy (PPV or nasal CPAP) treated with >21% oxygen for >28 days

Cause:

oxygen toxicity (lung damage by oxygen radicals) + barotrauma (bronchopulmonary injury from assisted ventilation)

chronic oxygen dependency in premature neonates:
mild BPD = breathing room air
moderate BPD = need for <30% oxygen
severe BPD = need for 30% oxygen PPV or nasal CPAP

Pathogenesis:

hypoxia + oxygen toxicity

capillary wall damage, leakage of fluid into interstitium and pulmonary edema
Stage I (0 3 days):

Path:

loss of ciliated cells + necrosis of bronchiolar mucosa

RDS pattern of hyaline membrane disease
Stage II (4 10 days):

Path:	hyaline membranes, eosinophilic exudate, squamous metaplasia, interstitial edema
Associated with:	congestive failure from PDA

complete opacification with air bronchogram
fibrosis of interstitium + groups of emphysematous alveoli
Stage III (10 20 days):

Path:

fewer hyaline membranes, persistent injury of alveolar epithelium, exudation of macrophages

small round cystic lucencies alternating with regions of irregular opacity
Stage IV (after 1 month):

Path:

septal wall thickening, dilated + tortuous lymphatics

spongy / bubbly coarse linear densities, esp. in upper lobes
hyperaeration of lung
lower lobe emphysema

CT:

regional air trapping
thickened interlobular septa
subsegmental atelectasis
reduced bronchoarterial diameter ratios
bronchial wall thickening
bullae + pneumatoceles

Prognosis:

40% mortality if not resolved by 1 month

Cx:

Increased airway reactivity = increased frequency of lower respiratory tract infections
Obstructive airway disease = asthmalike clinical picture
Focal atelectasis
Cor pulmonale
Rib fractures, rickets, renal calcifications (from chronic furosemide therapy
Cholelithiasis (hyperalimentation ? furosemide)
Focal areas of tracheomalacia, tracheal stenosis, acquired lobar emphysema

Rx	: supportive
Prognosis:	(1) Complete clearing over months/years (1/3)	(2) Retained linear densities in upper lobe emphysema (29%)

DDx:

(a) conditions present at birth:
- Diffuse neonatal pneumonia
- Meconium aspiration
- Total anomalous pulmonary venous return
- Congenital pulmonary lymphangiectasia
(b) conditions developing over time:
- Recurrent pneumonias with scarring (gastroesophageal reflux, TE fistula, immune deficiency, etc)
- Cystic fibrosis
- Idiopathic pulmonary fibrosis
(c) conditions not apparent at birth:
- Wilson-Mikity syndrome
- Pulmonary interstitial emphysema
- Patent ductus arteriosus (uncommon appearance)
- Overhydration
- Perinatally acquired viral infection (especially CMV)

Bronchopleural Fistula

= BRONCHOPULMONARY FISTULA
= communication between the bronchial system/lung parenchyma + pleural space

Cause:

Trauma
- Complication of resectional surgery (pneumonectomy, lobectomy, bullectomy)
- Blunt/penetrating trauma
- Barotrauma
Lung necrosis
- Putrid lung abscess
- Necrotizing pneumonia: Klebsiella, H. influenzae, Staphylococcus, Streptococcus; tuberculosis; fungus; Pneumocystis
- Infarction
Airway disease
- Bronchiectasis (very rare)
- Emphysema complicated by pneumonia/pneumothorax
Malignancy: lung carcinoma with postobstructive pneumonia/tumor necrosis following therapy
- large/persistent air leak
- acute/chronic empyema

HRCT:

direct visualization of bronchopleural fistula (in 50%)
peripheral air + fluid collection (indirect sign)

Dx:	(1) Introduction of methylene blue into pleural space, in 65% dye appears in sputum	(2) Sinography	(3) Bronchography
Rx:	tube thoracostomy, open drainage, decortication, thoracoplasty, muscle-pedicle closure, transbronchial occlusions

Bronchopulmonary Sequestration

= congenital malformation consisting of
- nonfunctioning lung segment
- no communication with tracheobronchial tree
- systemic arterial supply

Incidence:

0.15 6.4% of all congenital pulmonary malformations; 1.1 1.8% of all pulmonary resections

usually >6 cm in size
round/oval, smooth, well-defined solid homogeneous mass near diaphragm with mass effect
occasionally fingerlike appendage posteriorly + medially (anomalous vessel)
contrast enhancement of sequestration at the same time as thoracic aorta on rapid sequential CT scans
multiple/single air-fluid levels if infected
surrounded by recurrent pulmonary consolidation in a lower lobe that never clears completely
may communicate with esophagus/stomach
Pulmonary sequestration with communication to GI tract is termed bronchopulmonary foregut malformation!

DDx:

bronchiectasis, lung abscess, empyema, bronchial atresia, congenital lobar emphysema, cystic adenomatoid malformation, intrapulmonary bronchogenic cyst, Swyer-James syndrome, pneumonia, arteriovenous fistula, primary/metastatic neoplasm, hernia of Bochdalek

Intralobar Sequestration (75 86%)

= enclosed by visceral pleura of affected pulmonary lobe but separated from bronchial tree

Etiology:	controversial (1) probably acquired in majority of patients (2) early appearance of congenital accessory tracheobronchial bud leads to incorporation within one pleural investment
Path:	chronic inflammation fibrosis: multiple irregular cordlike adhesions to mediastinum, diaphragm, parietal pleura; multiple cysts filled with fluid/thick gelatinous/purulent material; vascular sclerosis
Age at presentation:	adulthood (50% >20 years); M:F = 1:1

Associated with congenital anomalies in 6 12%:

skeletal deformities (4%): scoliosis, rib + vertebral anomalies; esophagobronchial diverticula (4%); diaphragmatic hernia (3%); cardiac (including tetralogy of Fallot); renal: failure of ascent + rotation; cerebral anomalies; congenital pulmonary venolobar syndrome

about 50% have symptoms by age 20; asymptomatic in 15%
pain, repeated infection in same location (eg, recurrent acute lower lobe pneumonias)
high-output congestive heart failure (in neonatal period) from L-to-L shunt
cough + sputum production, hemoptysis

Location:

posterobasal segments, rarely upper lung/within fissure; L:R = 3:2

CXR:

recurrent/persistent pneumonia localized to lower lobe
cavitation and cysts fluid levels
- Aeration of sequestered lung via Kohn pores/communication with tracheobronchial tree!

Bronchogram:

NO communication of rudimentary bronchial system of sequestration with tracheobronchial tree (rare exceptions)

Angio:

usually single large artery (mean diameter of 6 mm) coursing through inferior pulmonary ligament from
- distal thoracic aorta (73%)
- proximal abdominal aorta (22%)
- celiac/splenic artery
- intercostal artery (4%)
- anomalous branch of coronary artery
multiple aa. in 16% (with vessel diameter of <3 mm)
combined systemic + pulmonary arterial supply
venous drainage via
- normal pulmonary veins to L atrium (in 95%)
- azygos/hemiazygos vv./intercostal vv./SVC into R atrium (in 5%)

CT:

single/multiple thin-walled cysts containing fluid/mucus/pus/air-fluid level/air alone
mucus-impacted ectatic bronchi (= fat density) in sequestered lung
emphysema bordering normal lung (37%)
= postobstructive hyperinflation of sequestered lung
homogeneous/inhomogeneous soft-tissue mass with irregular borders
irregular enhancement (rare)
one/two anomalous systemic arteries arising from aorta (DDx: AVM, interrupted pulmonary artery, isolated anomaly, chronic infection/inflammation of lung or pleura, surgically created shunt)
premature atherosclerosis of anomalous arteries
Mucoid impaction of bronchus surrounded by hyperinflated lung is CHARACTERISTIC!

OB-US:

spherical homogeneous highly echogenic mass

P.480

anomalous systemic artery seen by color Doppler

Cx:	massive spontaneous nontraumatic pleural hemorrhage, chronic inflammation, fibrosis
DDx of mass:	neurogenic tumor, lateral thoracic meningocele, extramedullary hematopoiesis, pleural tumor
DDx of cavity:	lung abscess, necrotizing pneumonia, fungal/mycobacterial pneumonia, cavitating neoplasm, empyema
DDx of cysts:	pulmonary abscess, empyema, bronchiectasis, emphysema, bronchogenic foregut cyst, pericardial cyst, eventration of diaphragm, congenital cystic malformation

Extralobar Sequestration (14 25%)

= accessory lobe with its own pleural sheath (= rokitansky lobe ), which prevents collateral air drift resulting in an airless round mass

Etiology:	development of an anomalous accessory/supernumerary tracheobronchial foregut bud
Path:	single ovoid/rounded/pyramidal airless lesion between 0.5 and 15 cm (generally 3 to 6 cm) in size
Histo:	resembles normal lung with diffuse dilatation of bronchioles + alveolar ducts + alveoli; dilatation of subpleural + peribronchiolar lymph vessels; covered by mesothelial layer overlying fibrous connective tissue; congenital cystic adenomatoid malformation type ii is present in 15 25%
Incidence:	0.5 6% of all congenital lung lesions
Age:	neonatal presentation; 61% within first 6 months of life; occasionally in utero; m:f = 4:1

Associated with congenital anomalies in 15 65%:

@ Lung: congenital diaphragmatic hernia (20 30%), eventration/diaphragmatic paralysis (up to 60%), cystic adenomatoid malformation (15 25%), lobar emphysema, bronchogenic cyst, pectus excavatum, congenital pulmonary venolobar syndrome may coexist/form part of spectrum with CAM
@ Heart: anomalous pulmonary venous return, cardiac/pericardial anomalies (8%)
@ Gi tract: epiphrenic diverticula (2%), Te fistula (1.5%), duplication of Gi tract, ectopic pancreas
@ others: renal anomaly, vertebral anomaly

respiratory distress + cyanosis + CHF in newborn (due to shunting of blood)
feeding difficulties
asymptomatic (rarely becomes infected) in 10%

Bronchopulmonary Sequestrations
	Intralobar	Extralobar
Prevalence	75%	25%
Venous drainage	pulmonary veins	systemic veins
symptomatic	adulthood	first 6 months
Etiology	acquired	developmental
congen. anomalies	15%	50%

Location:

L:r = 4:1; typically within pleural space in posterior costodiaphragmatic sulcus between diaphragm + lower lobe (63 77%); mediastinum; within pericardium; within/below diaphragm (5 15%)

airless (no communication with bronchial tree); in presence of air connection with Gi tract is inferred
may contain cystic areas
mediastinal shift (if large)
Angio (diagnostic):
- arterial supply from
  - aorta as single/several small branches (80%)
  - splenic, gastric, subclavian, intercostal branches(15%)
  - pulmonary artery (5%)
- venous drainage via
  - systemic veins (80%) to r heart (IvC, azygos, hemiazygos, SvC, portal vein)
  - pulmonary vein (25%)
CXR:
- single well-defined homogeneous triangular mass (most commonly located adjacent to posterior medial hemidiaphragm)
- no air bronchograms
- small bump on hemidiaphragm/inferior paravertebral region
- opaque hemithorax ipsilateral pleural effusion (if sequestration large)
- air-fluid level
CT:
- homogeneous well-circumscribed soft-tissue density mass (no bronchial communication)
NUC (radionuclide angiography):
- lack of perfusion during pulmonary phase followed by rapid perfusion in systemic phase
DDx: intrathoracic kidney, scimitar syndrome (with systemic supply to affected lung), hepatic herniation through diaphragm
OB-US:
- The vast majority in fetuses are extralobar!
- conical/triangular homogeneous highly echogenic mass (many interfaces from multiple microscopically dilated structures)
- color duplex may demonstrate vascular supply
- polyhydramnios (? esophageal compression, excessive fluid secretion by sequestration)
- fetal hydrops (? venous compression):
  - edema, ascites
  - hydrothorax (obstructed lymphatics + veins in torsed sequestration)

DDx for chest lesion:

congenital cystic adenomatoid malformation, neuroblastoma, teratoma, diaphragmatic hernia

DDx for infradiaphragmatic lesion:

neuroblastoma, teratoma, adrenal hemorrhage, mesoblastic nephroma, foregut duplication

Cx:	infection (in cases of communication with bronchus/GI tract)
Rx:	resection (delineation of vascular supply helpful)
Prognosis:	favorable (worse if pulmonary hypoplasia present); decreases in size/disappears in up to 65% before birth

P.481

Esophageal/Gastric Lung

= rare variant of pulmonary sequestration

Age:

infancy (as it is symptomatic)

cough related to feeding
recurrent pulmonary infections
communication of bronchial tree of sequestered lung with esophagus/stomach

Candidiasis

Organism:	ubiquitous human saprophyte (Candida albicans most commonly) characterized by blastospheres (yeasts) admixed with hyphae/pseudohyphae (conventional stains)
At risk:	patient with lymphoreticular malignancy

Entry:

aspiration
hematogenous dissemination from GI tract/infected central venous catheter

prolonged fever despite broad-spectrum antibacterial coverage
cough, hemoptysis

patchy airspace consolidation in lower lobe distribution
interstitial pattern
diffuse micro-/macronodular disease
pleural effusion (25%)

Cardiopulmonary Schistosomiasis

= form of parasitic embolism

Organism:	Schistosoma mansoni (endemic in Middle East, Africa, Atlantic coast of South America, Caribbean; S. japonicum and S. haematobium (less commonly)
At risk:	>5 years of continuous ova secretion
Prerequisite:	portal hypertension with periportal hepatic fibrosis
Cycle:	eggs travel as emboli via portosystemic collateral pathways to lodge in pulmonary muscular arteries and arterioles (50 150 m in diameter)
Pathogenesis:	trapped eggs are antigenic and incite an obliterative endarteritis (due to delayed host hypersensitivity)
Path:	intra- and perivascular granulomas, intimal hyperplasia, medial hypertrophy, concentric collagen deposition and fibrosis of vessel walls; localized alveolitis with eosinophilic infiltration; pulmonary infarction
Age:	25 35 (range of 1 93) years

gradually worsening hepatosplenomegaly
dyspnea, cough, chest pain
severe hypoxemia, cyanosis, digital clubbing

CXR:

cardiomegaly
central pulmonary arterial enlargement
tiny scattered lung nodules occasionally

HRCT:

nodules, interstitial thickening
patchy ground-glass attenuation
dilatation of right atrium + right ventricle + central pulmonary arteries

Cx:	cor pulmonale (2 33%)
Rx:	praziquantel, oxamniquine

Castleman Disease

= ANGIOFOLLICULAR LYMPH NODE HYPERPLASIA = BENIGN GIANT LYMPH NODE HYPERPLASIA = ANGIOMATOUS LYMPHOID HAMARTOMA = LYMPHOID HAMARTOMA
= diverse group of rare lymphoproliferative disorders of differing histopathologic properties + biologic behavior

Histo:

hyaline-vascular Castleman disease (76 91%) lymph node hyperplasia, hyalinization with involuted germinal centers penetrated by capillaries, prominent capillary proliferation with endothelial hyperplasia in interfollicular areas
plasma cell Castleman disease (4 9 24%)

Localized/Unicentric Angiofollicular Lymph Node Hyperplasia

Cause:	chronic viral antigenic stimulation with reactive lymphoid hyperplasia/developmental growth disturbance of lymphoid tissue
Age:	all age groups (peak in 4th decade); M:F = 1:4
Histo:	mostly hyaline-vascular cell type
Location:	middle mediastinum + hila, cervical lymph nodes, mesenteric + retroperitoneal lymph nodes

Morphologic types:

solitary well-circumscribed mass without associated adenopathy (50%)
dominant mass displacing/surrounding/invading contiguous structures + lymphadenopathy (40%)
multiple enlarged lymph nodes confined to one mediastinal compartment (10%)

asymptomatic in 58 97%
cough, dyspnea, hemoptysis
lassitude, weight loss, fever
growth retardation
elevated sedimentation rate
IgG, IgM, IgA hypergammaglobulinemia (50%)
refractory microcytic anemia

Size:

up to 16 cm in diameter

CT:

sharply marginated smooth/lobulated mass of muscle density
spotty coarse central calcifications (5 10%)
enhancing rim (vascular capsule)
intense enhancement almost equal to aorta (in hyalin-vascular type)
slight enhancement (in plasma cell type)
pleural effusion (uncommon)

MR:

heterogeneous mass hyperintense compared with muscle on T1WI
markedly hyperintense on T2WI
flow voids of feeding vessels surrounding mass

Angio:

hypervascular mass with intense homogeneous blush (hyalin-vascular type)

P.482

enlarged feeding vessels arising from bronchial/internal mammary/intercostal arteries
some hypervascularity (plasma cell type)

DDx:	indistinguishable from lymphoma
Prognosis:	treatment ~100% curative
Rx:
Rx:	(1) Complete surgical resection	(2) Radiation + steroid therapy

Disseminated/Generalized/Multicentric Angiofollicular Lymph Node Hyperplasia

= potentially malignant lymphoproliferative disorder

Cause:	disordered immunoregulation with polyclonal plasma cells from viral infection with uncontrolled B-cell proliferation + interleukin-6 dysregulation
Mean age:	40 60 years; M:F = 2:1
Histo:	mostly plasma cell type (66%) with infiltration of nodes by sheets of mature plasma cells

Associated with:

hyperplasia without neuropathy
- fatigue, anorexia, skin lesions, CNS disorders
hyperplasia with POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal proteinemia, skin changes) syndrome
- skin lesions: hypertrichosis, hirsutism, sclerodermatous thickening, hyperpigmentation, hemangiomas
- distal symmetric sensorimotor neuropathy (50%)
- papilledema, pseudotumor cerebri (66%)
- monoclonal IgG (75%)
osteosclerotic myeloma, Kaposi sarcoma, AIDS

1 6 cm large homogeneous lymph nodes in multiple mediastinal compartments
variable mild contrast enhancement
peripheral multicentric adenopathy
hepatosplenomegaly
salivary gland enlargement
ascites
lymphocytic interstitial pneumonitis (LIP):
- ill-defined centrilobular nodules
- ground-glass attenuation
- air-space consolidation
- cysts (due to partial airway obstruction by peribronchial + peribronchiolar LIP)
- thickening of bronchovascular bundles

Rx:	surgical resection, irradiation, systemic chemotherapy + corticosteroids
Prognosis:	mean survival of 24 33 months

Chemical pneumonitis

= inhalation of noxious chemical substances
- organic: organophosphates, paraquat, polyvinyl chloride, polymer fumes, smoke
- nonorganic: ammonia, hydrogen sulfide, nitrogen oxide, sulfur dioxide
- metal: cadmium, mercury, nickel, vanadium

Carbamates

= agricultural insecticides functioning as cholinesterase inhibitor (similar to organophosphates) but with poor penetration into CNS
pulmonary edema with respiratory failure

Paraquat

= agricultural herbicide

Exposure:	often intentional ingestion
Pathophysiology:	rapid accumulation in lungs with production of superoxide radicals damaging pulmonary cells

CXR (wide radiographic variation):

no abnormality
increased interstitial/granular opacities
pulmonary edema
pneumomediastinum

HRCT:

bilateral diffuse areas of ground-glass attenuation evolving into consolidation with bronchiectasis, irregular lines, traction bronchiectasis of interstitial fibrosis

Hydrogen Sulfide

= irritant + chemical asphyxiant gas

Industries:	coal mines, tanneries, petroleum manufacturing plants, geothermal power plants, aircraft factories, sewer works, rubber works
Effect:	toxic for respiratory (large quantities cause inhibition of medullary respiratory center) + neurologic systems

smell of rotten eggs
knockdown = brief loss of consciousness due to bronchial hyperresponsiveness
determination of urine thiosulfate levels (to monitor occupational exposure)

pulmonary edema

Ammonia

= highly soluble corrosive gas acts as a mucosal irritant

Industries:

production of explosives, petroleum, agricultural fertilizer, plastics

pulmonary edema

Prognosis:

complete recovery; bronchiectasis + bronchiolitis obliterans may develop

Hydrocarbon

Exposure:	ingestion/aspiration (eg, accidental poisoning in children; fire-eating performers)
Path:	(a) acute phase: intraalveolar, intrabronchial, peribronchial, interstitial accumulation of inflammatory cells + edema (b) chronic phase (1 2 weeks after initial onset): proliferative bronchiolitis, parenchymal fibrosis, pneumatocele formation

uni-/bilateral consolidation, well-defined nodules
pneumatoceles (from coalescing areas of bronchiolar necrosis/partial obstruction of bronchial lumen)

Mercury

Exposure:	inhalation of mercury vapor
Industries:	electrolysis, manufacture of thermometers, cleaning of boilers, smelting silver from dental amalgam containing mercury
Pathophysiology:	acute chemical bronchiolitis + pneumonitis followed by diffuse alveolar damage with hyaline membrane formation

P.483

pulmonary function impairment

perivascular haziness + fine reticular opacities
pulmonary interstitial fibrosis

Prognosis:

acute inhalation poisoning usually fatal

Chronic Eosinophilic Pneumonia

= numerous eosinophils, macrophages, histiocytes, lymphocytes, PMNs within lung interstitium + alveolar sacs

Etiology:	unknown
Age:	middle-age; M < F

common history of atopia (may occur during therapeutic desensitization procedure)
adult onset asthma (wheezing)
high fever, malaise, dyspnea (DDx to L ffler syndrome)
peripheral blood eosinophilia (with rare exceptions)

homogeneous alveolar lung infiltrates with distribution at lung periphery = photographic negative of pulmonary edema (best seen on CT)
frequently bilateral nonsegmental
unchanged for many days/weeks (DDx to L ffler syndrome)
fast regression of infiltrates under steroids

Rx:

dramatic response to steroid therapy (within 3 10 days)

Chronic Mediastinitis

Etiology:

Granulomatous infection: histoplasmosis (most frequent), tuberculosis, actinomycosis, Nocardia
Mediastinal granuloma
Fibrosing mediastinitis
Radiation therapy

Mediastinal Granuloma

= relatively benign massive coalescent adenitis with caseating/noncaseating lesions

Cause:	primary lymph node infection (commonly tuberculosis/histoplasmosis)
Histo:	thin fibrous capsule surrounding granulomatous lesion

lymphadenopathy

DDx:

fibrosing mediastinitis (infiltrative, rare)

Fibrosing Mediastinitis

= SCLEROSING MEDIASTINITIS = MEDIASTINAL COLLAGENOSIS = MEDIASTINAL FIBROSIS
= uncommon benign disorder characterized by progressive proliferation of dense fibrous tissue within mediastinum

Cause:	abnormal host immune response to Histoplasma capsulatum antigen (organisms recovered in 50%); autoimmune disease, methysergide-induced
May be associated with:	retroperitoneal fibrosis, orbital pseudotumor, sclerosing thyroiditis, riedel struma
Path:	ill-defined soft-tissue mass with minimal/no apparent granulomatous foci
Histo:	abundant paucicellular fibrous tissue infiltrating + obliterating adipose tissue
Age:	2nd 5th decade of life; m = f

symptoms of central airway obstruction:
- cough (41%), dyspnea (32%)
symptoms of pulmonary venous occlusion:
- pseudo-mitral stenosis syndrome = progressive exertional dyspnea, hemoptysis (31%)
- cor pulmonale (secondary to pulmonary arterial hypertension caused by compression of pulmonary arteries/veins)
dysphagia (2%)
superior vena cava syndrome (6 39%)
low left atrial pressure + widely differential elevation of pulmonary capillary wedge pressures

Location:	middle mediastinum (subcarinal + paratracheal regions) and hila
Site:	right > left side of mediastinum

CXR:

nonspecific widening of mediastinum:
- distortion of normally recognizable interfaces
- lobulated (in 86% calcified) paratracheal/hilar mass
typically unilateral pulmonary arterial obstruction:
- enlargement of main pulmonary artery + right heart
- diminution in size + quantity of vessels
- localized regional oligemia
pulmonary venous obstruction:
- peribronchial cuffing, septal thickening
- ipsilateral Kerley B lines
- pulmonary infarct
central airway narrowing:
- segmental/lobar atelectasis
- recurrent pneumonia

UGI:

circumferential narrowing/long-segment stricture of esophagus at junction of upper + middle thirds
downhill esophageal varices

CT:

focal mass (82%):
- calcified in 63%; in right paratracheal/subcarinal /hilar location
diffusely infiltrative process (18%):
- soft-tissue attenuation, no calcification
- obliteration of normal mediastinal fat planes
- encasement/invasion of adjacent structures
wedge-shaped peripheral consolidation of venous/arterial infarction

MR:

heterogeneous infiltrative mass of intermediate signal intensity on T1Wi
mixture of regions of increased + markedly decreased signal intensity on T2Wi

NUC:

unilateral decreased/absent perfusion with normal ventilation (in focal hilar fibrosis)
large segmental/smaller subsegmental unmatched perfusion defects
ventilation defects in lobar/segmental occlusion

Angio (with therapeutic intent):

unilateral/asymmetric narrowing of central pulmonary arteries/distal arterial cutoffs
funnel-like pulmonary vein stenosis/obstruction/focal dilatation near left atrium

Cx:	(1) Compression of SVC (64%) + pulmonary veins (4%) (2) Chronic obstructive pneumonia (narrowing of trachea/central bronchi) in 5% (3) Esophageal stenosis (3%) (4) Pulmonary infarcts + fibrosis (narrowing of pulmonary artery) (5) Prominent intercostal arteries (narrowing of pulmonary artery)
Rx:	resection, ketoconazole, steroid therapy (limited success)
DDx:	(1) Bronchogenic carcinoma (2) Lymphoma (3) Metastatic carcinoma (4) Mediastinal sarcoma

P.484

Churg-Strauss Syndrome

= ALLERGIC ANGITIS AND GRANULOMATOSIS

= variant of polyarteritis nodosa in asthmatic patients

Etiology:	? hypersensitivity response to an inhaled agent
Age:	20 40 (mean 28) years; M:F = 1:1

CLASSIC TRIAD:

Allergic rhinitis or asthma (phase 1)
Peripheral blood + tissue eosinophilia with L ffler syndrome (phase 2)
Systemic small-vessel granulomatous vasculitis (phase 3), usually develops within 3 years of onset of asthma

Path:

necrotizing vasculitis
eosinophilic tissue infiltration
- eosinophilic pneumonia
- eosinophilic gastroenteritis
extravascular allergic granulomas/eosinophilic abscesses

allergic rhinitis, sinus pain, headaches, asthma
fever, malaise, gastrointestinal symptoms, arthralgias
eosinophilia (almost 100%): peripheral eosinophilia in >30%
p-ANCA (perinuclear antineutrophil cytoplasmic autoantibodies) in 70%
elevated rheumatoid factor in 52%

vascular aneurysms + thrombosis
@ Lung: intraalveolar hemorrhage
- normal CXR (25%)
- often transient peripheral widespread nonsegmental air-space opacities without zonal predominance
- diffuse miliary nodules:
  - nodules may coalesce up to 2 cm (rare)
  - cavitation is atypical (and suggests infection)
- eosinophilic pleural effusions (29%)
  
  HRCT:
  - consolidation/ground-glass attenuation (59%)
  - pulmonary nodules
  - interlobar septal thickening
  - bronchial wall thickening
@ GI tract (20%): ulceration, hemorrhage, perforation
- diarrhea, bleeding, obstruction
- mesenteric vasculitis
- bowel wall infiltration by eosinophils
@ Heart (up to 47%): coronary vasculitis, myocarditis, pericardial tamponade (accounting for 50% of deaths)
- Higher frequency of cardiac involvement than Wegener granulomatosis
@ CNS: diffuse neuritis, mononeuritis multiplex, cerebral hemorrhage
@ Skin: palpable purpura
@ Kidney:
- renal artery-induced hypertension, hematuria
- glomerulonephritis
- Less frequent + less severe renal disease compared with Wegener granulomatosis + microscopic polyangitis

Prognosis:	85% 5-year survival; death from cardiac/intraabdominal complications, cerebral hemorrhage, renal failure, status asthmaticus
Rx:	corticosteroids, cyclophosphamide

Chylothorax

leakage of chyle (= lymph containing chylomicrons = suspended fat) from thoracic duct or its branches into pleural space secondary to obstruction/disruption of thoracic duct (in 2%)

Route of thoracic duct:

Origin:	arises from cisterna chyli anterior to L1 2 (10 15 mm in diameter and 5 7 cm long)
Course:	enters thorax through aortic hiatus; ascends in right prevertebral location (between azygos vein + descending aorta); swings to left at T4 6 posterior to esophagus; ascends for a short distance along right of aorta; crosses behind aortic arch; runs ventrally at T3 between left common carotid artery + left subclavian artery
Termination:	3 5 cm above clavicle at venous angle (= junction of left subclavian + internal jugular veins)
Variation:	two (33%) or more (in up to 50%) main ducts each consisting of up to 8 separate channels

Etiology:

Developmental defects
- Thoracic duct atresia
- Lymphangiectasia
- Lymphangioma
- Lymphangiomatosis (rare): mediastinal/thoracic cystic hygroma of neck growing into mediastinum
- Lymphangioleiomyomatosis tuberous sclerosis
Trauma
- Closed/penetrating chest trauma/birth trauma (25%): latent period of 10 days
- Surgery (2nd most common cause):
  
  esophagectomy/cardiovascular surgery, esp. coarctation repair (0.5%), retroperitoneal surgery, neck surgery
- Subclavian venous catheter
Neoplasm (54%)
- Lymphoma (most common cause)
- Metastatic cancer
Fibrosing conditions
- Mediastinitis
- Tuberculosis
- Filariasis (rare)
Obstruction of central venous system/thoracic duct

P.485

Idiopathic/cryptogenic (15%): most common cause in neonatal period
Transdiaphragmatic passage of chylous ascites

Age:	in full-term infants; may be present in utero; M:F = 2:1
Incidence:	1:10,000 deliveries

May be associated with:

Trisomy 21, TE-fistula, extralobar lung sequestration, congenital pulmonary lymphangiectasia
high in neutral fat + fatty acid (low in cholesterol):
- triglyceride level >110 mg/dL
milky viscoid fluid (chylomicrons) after ingestion of milk/formula and clear during fasting
usually unilateral loculated pleural effusion
- right chylothorax due to duct disruption inferior to T5 6 (more common)
- left-sided chylothorax if duct disrupted above T5 6
low attenuation (fat)/high attenuation (protein content)
leakage of lymphangiographic contrast
polyhydramnios (? result of esophageal compression)

Cx:	(1) Pulmonary hypoplasia (2) Hydrops (congestive heart failure secondary to impaired venous return)
Rx:	(1) Thoracentesis (leading to loss of calories, lymphocytopenia, hypogammaglobulinemia) (2) Total parenteral nutrition (3) Thoracic duct ligation (if drainage exceeds 1,500 mL/day for adults or 100 mL/yr-age/day for children >5 years of age; drainage >14 days) (4) Pleuroperitoneal shunt; tetracycline pleurodesis; mediastinal radiation; intrapleural fibrin glue; pleurectomy

Coal Worker's Pneumoconiosis

CWP = anthracosis = ANTHRACOSILICOSIS
coal dust inhalation taken up by alveolar macrophages, in part cleared by mucociliary action (particle size >5 m), in part deposited around bronchioles + alveoli, coal dust in itself is inert, but admixed silica is fibrogenic

Simple CWP

= aggregates of coal dust = coal macules (usually <3 mm)
NO progression in absence of further exposure

Histo:

development of reticulin fibers associated with bronchiolar dilatation (focal emphysema) + bronchiolar artery stenosis (decreased capillary perfusion)

poor correlation between symptoms, physiologic findings + roentgenogram
small round 1 5-mm opacities, frequently in upper lobes (radiographically only seen through superposition after an exposure of >10 years)
nodularity correlates with amount of collagen (NOT amount of coal dust)

Cx:

(1) Chronic obstructive bronchitis
(2) Focal emphysema
(3) Cor pulmonale

Coccidioidomycosis

Organism:

dimorphic soil fungus Coccidioides immitis; arthrospores in desert soil spread by wind aerosolized in dry dust; highly infectious

Geographic distribution:

endemic in southwest desert of USA (San Joaquin Valley, central southern Arizona, western Texas, southern New Mexico) + northern Mexico + in parts of Central + South America; similar to histoplasmosis

Mode of infection:	deposited in alveoli after inhalation + maturation into large thick-walled spherules with release of hundreds of endospores
Dx:	(1) Culture of organism (2) Spherules in pathologic material (demonstrated with Gomori-methenamine silver stain) (3) Positive skin test (4) Complement fixation titer

Primary Coccidioidomycosis

= ACUTE RESPIRATORY COCCIDIOIDOMYCOSIS
60 80% asymptomatic
valley fever = influenza-like symptoms
desert rheumatism (33%) most commonly in ankle
rash, erythema nodosum/multiforme (5 20%)
segmental/lobar consolidation
patchy infiltrates mainly in lower lobes (46 80%) frequently subpleural + abutting fissures
peribronchial thickening
hilar adenopathy (20%)
pleural effusion (10%)

Chronic Respiratory Coccidioidomycosis

Prevalence:

5% of infected patients

symptoms of postprimary tuberculosis
hemoptysis in 50%
one/several well-defined nodules (= coccidioidomycoma) of 5 30 mm in size (in 5%)
persistent/progressive consolidation
grape skin thin-walled cavities (in 10 15%), in 90% solitary, 70% in anterior segment of upper lobes (DDx: TB), 3% rupture into pleural space due to subpleural location (pneumothorax/empyema/persistent bronchopleural fistula)
bronchiectasis
mediastinal adenopathy (10 20%)

Disseminated Coccidioidomycosis (in 1%)

= secondary phase of hematogenous spread to meninges, bones, skin, lymph nodes, subcutaneous tissue, joints (except GI tract)
skin granulomas/abscesses
micronodular miliary lung pattern
pericardial effusion

Congenital Lobar Emphysema

= progressive overdistension of one/multiple lobes
M:F = 3:1

Etiology:

deficiency/dysplasia/immaturity of bronchial cartilage

P.486

endobronchial obstruction (mucosal fold/web, prolonged endotracheal intubation, inflammatory exudate, inspissated mucus)
bronchial compression (PDA, aberrant left pulmonary artery, pulmonary artery dilatation)
polyalveolar/macroalveolar hyperplasia

Associated with:

CHD in 15% (PDA, VSD)

respiratory distress (90%) + progressive cyanosis within first 6 months of life

Location:

LUL (42 43%), RML (32 35%), RUL (20%), two lobes (5%)

hazy masslike opacity immediately following birth (delayed clearance of lung fluid in emphysematous lobe over 1 14 days)
air trapping
hyperlucent expanded lobe (after clearing of fluid)
compression collapse of adjacent lobes
contralateral mediastinal shift
widely separated vascular markings

Mortality:	10%
Rx:	surgical resection

Congenital Lymphangiectasia

Primary Pulmonary Lymphangiectasia (2/3)

= abnormal development of lungs between 14 20th week of GA characterized by anomalous dilatation of pulmonary lymph vessels

Path:	subpleural cysts, ectatic tortuous lymph channels in pleura, interlobular septa + along bronchoarterial bundles; NO obstruction
Age:	usually manifest at birth; 50% stillborn; M = F
May be associated with:	total anomalous pulmonary venous return, hypoplastic left heart, Noonan syndrome

respiratory distress within few hours of birth

Site:

diffuse involvement of both lungs, occasionally only in one/two lobes (with good prognosis)

marked prominence of coarse interstitial markings (simulating interstitial edema)
hyperinflation
scattered radiolucent areas (dilated airways)
patchy areas of pneumonia + atelectasis
pneumothorax

Prognosis:

in diffuse form invariably fatal at <2 months of age

Generalized Lymphangiectasia

= DIFFUSE LYMPHANGIOMA
= proliferation of mainly lymphatic vascular spaces with relentless systemic progression

Age:	children, young adults
Location:	widespread visceral + skeletal involvement

diffuse pulmonary interstitial disease
chylous effusions in pleural + pericardial spaces
lytic bone lesions
lymphangiographic pooling of contrast material in dilated lymphatic channels/lymph nodes

Localized Lymphangioma

= rare benign usually cystic lesion

Histo:	collection of dilated + proliferated lymph vessels (? hamartoma/benign neoplasm/focal sequestration of ectatic lymph tissue)
Age:	first 3 years of life; m = f

asymptomatic (33%)
dyspnea (from tracheal compression)

Location:

neck (80%), mediastinum, axilla, extremity

discrete featureless mass
may have chylous/pleural effusion
may have lytic lesion in contiguous skeleton

Prognosis:	propensity for local recurrence
DDx:	hemangioma

Secondary Lymphangiectasia

secondary to elevated pulmonary venous pressure in ChD (TAPVR)

Congenital Pulmonary Venolobar Syndrome

= unique form of lung hypoplasia/aplasia affecting one/more lobes in a constellation of distinctly different congenital anomalies of the thorax that often occur together; m:f = 1:1.4

MAJOR COMPONENTS
- Hypogenetic lung (69%): lobar agenesis/aplasia/hypoplasia
- Partial anomalous pulmonary venous return (31%) = scimitar syndrome
- Absence of pulmonary artery (14%)
- Pulmonary sequestration (24%)
- systemic arterialization of lung without sequestration (10%)
- Absence/interruption of inferior vena cava (7%)
- duplication of diaphragm = accessory diaphragm (7%)
  - = thin membrane in right hemithorax fused anteriorly with the diaphragm coursing posterosuperiorly to join with the posterior chest wall + trapping all/part of RML/RLL
  - accessory fissurelike oblique line above right posterior costophrenic sinus (if trapped lung is aerated)
  - solid mass along posterior right hemidiaphragm (if trapped lung is unaerated)
  - CT:
    - ovoid area of increased density in posterior right hemithorax (= dome of accessory diaphragm)
MINOR COMPONENTS
- Tracheal trifurcation (extremely rare): 2 mainstem bronchi supply the right lung
- eventration of diaphragm
- Partial absence of diaphragm
- Phrenic cyst
- Horseshoe lung
- esophageal/gastric lung
- Anomalous superior vena cava
- Absence of left pericardium

? The most constant components of the syndrome are hypogenetic lung + PAPVR!

P.487

Associated with:

Vascular anomalies: hypoplastic artery, anomalous venous return, systemic arterial supply
Anomalies of hemidiaphragm on affected side:
- retrosternal band on lateral CXR due to mediastinal rotation
- phrenic cyst
- diaphragmatic hernia
- accessory hemidiaphragm
Hemivertebrae + scoliosis
CHD (25 50%): sinus venosus ASD, VSD, tetralogy of Fallot, PDA, coarctation of aorta, hypoplastic left heart, double-outlet right ventricle, double-chambered right atrium, endocardial cushion defect, persistent left SVC, pulmonary stenosis

asymptomatic (40%)
may have dyspnea/recurrent infections

Location:

right-sided predominance; M:F = 1.0:1.4

hypoplasia/aplasia of one/more lobes of the lung with errors of lobation (bilateral left bronchial branching pattern/horseshoe lung)
scimitar vein (90%) = partial anomalous pulmonary venous return (commonly infradiaphragmatic into IVC/portal vein/hepatic vein/R atrium), on CXR seen only in 1/3
systemic arterial supply to abnormal segment may be present from thoracic aorta (bronchial, intercostal, transpleural) or abdominal aorta (celiac artery, transdiaphragmatic)
reticular densities (enlarged bronchial/transpleural arterial collaterals)
small hilus (absent/small pulmonary artery)
small right hemithorax + mediastinal shift
haziness of right heart border
cardiac dextroposition (in right lung hypoplasia)
anomalies of bony thorax/thoracic soft tissues
absent inferior vena cava
rib hypoplasia/malsegmentation
rib notching
CT:
- small hemithorax + mediastinal shift
- abnormalities of bronchial branching
- anomalously located pulmonary fissure
- discontinuity of hemidiaphragm
- pulmonary arterial hypoplasia
- hyparterial right bronchus (instead of eparterial)
- one/more vessels increasing in diameter toward diaphragm
- rind of subpleural fatty tissue in affected hemithorax
- lack of normal venous confluence of right lung

DDx:

meandering pulmonary vein, dextrocardia, hypoplastic lung, Swyer-James syndrome

Costochondritis

musculoskeletal infection

Incidence:	increased with IV drug abuse
Agents:	Staphylococcus epidermidis, Streptococcus pneumoniae, Candida albicans, Aspergillus

CT:

soft-tissue swelling
cartilage fragmentation, bone destruction
low-attenuation cartilage
focal peripheral cartilaginous calcification

Rx:

surgical excision

Cryptococcosis

TORULOSIS = EUROPEAN BLASTOMYCOSIS

Organism:	encapsulated unimorphic yeastlike fungus Cryptococcus neoformans; spherical single-budding yeast cell with thick capsule, stains with India ink; often in soil contaminated with pigeon excreta
Histo:	granulomatous lesion with caseous necrotic center
Predisposed:	opportunistic invader in diabetics + immunocompromised patients

low-grade meningitis (affinity to CNS); M:F = 4:1
@ Lung
- well-circumscribed mass (40%) of 2 10 cm in diameter, usually peripheral location
- lobar/segmental consolidation (35%)
- cavitation (15%)
- hilar/mediastinal adenopathy (12%)
- calcifications (extremely rare)
- interstitial pneumonia (rare, in AIDS patients)
@ Musculoskeletal
- osteomyelitis (5 10%)
- arthritis (rare, usually from extension of osteomyelitis)

Cystic Adenomatoid Malformation

= CAM = congenital cystic abnormality of the lung characterized by an intralobar mass of disorganized pulmonary tissue communicating with bronchial tree + having normal vascular supply + drainage but delayed clearance of fetal lung fluid

Incidence:	25% of congenital lung disorders; 95% of congenital cystic lung lesions
Cause:	arrest of normal bronchoalveolar differentiation between 5th 7th week of gestation with overgrowth of terminal bronchioles
Path:	proliferation of bronchial structures at the expense of alveolar saccular development, modified by intercommunicating cysts of various size (adenomatoid overgrowth of terminal bronchioles, proliferation of smooth muscle in cyst wall, absence of cartilage)
TYPE I	(50%):
Histo:	single/multiple large cyst(s) >20 mm lined by ciliated pseudostratified columnar epithelium, mucus-producing cells in 1/3
Prognosis:	excellent following resection
TYPE II	(40%):
Histo:	multiple cysts 5 12 mm lined by ciliated cuboidal/columnar epithelium
Prognosis:	poor secondary to associated abnormalities
TYPE III	(10%):
Histo:	solitary large bulky firm mass of bronchuslike structures lined by ciliated cuboidal epithelium with 3 5-mm small microcysts
Prognosis:	poor secondary to pulmonary hypoplasia/hydrops

In 25% associated with:

cardiac malformation, pectus excavatum, renal agenesis, prune-belly syndrome, jejunal atresia, chromosomal anomaly, bronchopulmonary sequestration

P.488

Age of detection:

children, neonates, fetus; M:F = 1:1

respiratory distress + severe cyanosis in first week of life (66%)/within first year of life (90%) due to compression of normal lung + airways
superimposed chronic recurrent infection (10%) after first year of life

Location:

equal frequency in all lobes (middle lobe rarely affected); more than one lobe involved in 20%; mostly unilateral without side preference

CXR:

almost always unilateral expansile mass with well-defined margins (80%) (due to retained fetal lung fluid/type III lesion)
multiple air-/occasionally fluid-filled cysts
compression of adjacent lung
contralateral shift of mediastinum (87%)
hypoplastic ipsilateral lung
proper position of abdominal viscera
spontaneous pneumothorax (late sign)

CT:

Postnatally becoming obstructed and filled with air
solitary/multiple fluid or air-fluid filled cysts with thin walls
surrounding focal emphysematous changes

OB-US:

single large cyst/multiple large cysts of 2 10 cm in diameter (Type I)
multiple small cysts of 5 12 mm in diameter (type II)
large homogeneously hyperechoic mass compared with liver (type III)
contralateral mediastinal shift (89%)
polyhydramnios (25 75%,? from compression of esophagus or increased fluid production by abnormal lung)/normal fluid (28%)/oligohydramnios (6%)
fetal ascites (62 71%)
fetal hydrops in 33 81% (decreased venous return from compression of heart/vena cava)

Risk of recurrence:	none
Cx:	ipsi-/bilateral pulmonary hypoplasia
Prognosis:	50% premature, 25% stillborn

Polyhydramnios, ascites, hydrops indicate a poor outcome!
CAM becomes smaller in fetuses in many cases and occasionally almost disappears by birth!

DDx:

(1) Congenital lobar emphysema
(2) Diaphragmatic hernia
(3) Bronchogenic cyst (small solitary cyst near midline)
(4) Neurenteric cyst
(5) Bronchial atresia
(6) Bronchopulmonary sequestration (less frequently associated with polyhydramnios/hydrops)
(7) Mediastinal/pericardial teratoma

Cystic Fibrosis

= MUCOVISCIDOSIS = fibrocystic DISEASE
= autosomal recessive multisystem disease characterized by mucous plugging of exocrine glands secondary to
- dysfunction of exocrine glands forming a thick tenacious material obstructing conducting system
- reduced mucociliary clearance

Incidence:	1:2,000 1:2,500 livebirths; almost exclusively in Caucasians (5% carry a CF mutant gene allele); unusual in Blacks (1:17,000), Orientals, Polynesians The most common inherited disease among Caucasian Americans!
Cause:	cystic fibrosis transmembrane regulator gene (CFTR) on long arm of chromosome 7 builds a defective ion transport protein for an epithelial chloride channel; abnormal transmembrane conductance for Cl decreases osmotic forces and thus luminal water; >230 different gene mutations (in 70% F₅₀₈)

Screening (for 6 most common mutations of CF gene):

carrier detection rate of 85% of Northern Europeans, 90% of Ashkenazi Jews, 50% of American Blacks

Age at diagnosis:

1st year of life (70%), by age 4 years (80%), by age 12 years (90%); mean age of 2.9 years; M:F = 1:1

elevated concentrations of sodium + chloride (>40 mmol/L for infants) in sweat
decreased urinary PABA excretion
infertility in males
increased susceptibility to infection by Staphylococcus aureus + Pseudomonas aeruginosa

@ Lung
- chronic cough
- recurrent pulmonary infections (reduced mucociliary clearance encourages Pseudomonas colonization)
- progressive respiratory insufficiency due to obstructive lung disease

Location:

predilection for apical + posterior segments of upper lobes

gloved finger sign = mucous plugging (mucoid impaction in dilated bronchi) within 1st month of life
subsegmental/segmental/lobar atelectasis with right upper lobe predominance (10%)
progressive cylindrical/cystic bronchiectasis (in 100% at >6 months of age) air-fluid levels due to prolonged mucous plugging preponderant in upper lobes
parahilar linear densities + peribronchial cuffing
focal peripheral/generalized hyperinflation secondary to collateral air drift into blocked airways) with air trapping
hilar adenopathy
large pulmonary arteries (pulmonary arterial hypertension)
recurrent local pneumonitis (initiated by Staphylococcus aureus/Haemophilus influenzae, succeeded by Pseudomonas aeruginosa)
allergic bronchopulmonary aspergillosis (with bronchial dilatation + mucoid impaction)

CT:

cylindrical (varicose/cystic) bronchiectasis
peribronchial thickening
bronchiectatic cyst (= bronchus directly leading into sacculation) in 56%
interstitial cysts in 32%
emphysematous bulla (= peripheral air space with long pleural attachment + without communication to bronchus) in 12%
periseptal emphysema
mucus plugs = tubular structures branching pattern

P.489

subsegmental/segmental collapse/consolidations

NUC:

matched patchy areas of decreased ventilation + perfusion

Cx:	(1) Pneumothorax (rupture of bulla/bleb), common + recurrent (2) Hemoptysis (parasitized bronchial arteries connect to pulmonary arteries + veins resulting in AV fistulae) (3) Cor pulmonale (4) Hypertrophic pulmonary osteoarthropathy (rare)
Cause of death:	massive mucous plugging (95%)
Rx:	intratracheal instillation of aerosolized adenoviral + liposomal vector-CFTR gene preparations

@ GI tract (85 90%)
- chronic obstipation
- failure to thrive
- gastroesophageal reflux (21 27%) due to transient inappropriate lower esophageal sphincter relaxation
- meconium plug syndrome (25%, most common cause of colonic obstruction in the infant)
- distal intestinal obstruction syndrome (10 15 47%) = meconium ileus equivalent syndrome (in older child/young adult)
- meconium ileus (10 16% at birth)
  - Earliest clinical manifestation of cystic fibrosis!
- fibrosing colonopathy = stricture of right colon with longitudinal shortening secondary to high-dose lipase supplementation
- thickened nodular duodenal mucosal folds (due to unbuffered gastric acid, production of abnormal mucus, Brunner gland hypertrophy)
- mild generalized small bowel dilatation with diffuse distortion + thickening of mucosal folds (at times involving colon + rectum)
- large distended colon with mottled appearance (retained bulky dry stool)
- pneumatosis intestinalis of colon (5%) from air block phenomena of obstructive pulmonary disease
- microcolon = colon of normal length but diminished caliber
- jejunization of colon = coarse redundant + hyperplastic colonic mucosa (distended crypt goblet cells)
- Crohn disease
- appendicitis
- rectal prolapse between 6 months and 3 years in untreated patients (18 23%)
Cx: gastrointestinal perforation with meconium peritonitis (50%), volvulus of dilated segments, bowel atresia, intussusception at an average age of 10 years (1%)
@ Liver
- steatosis (30%) due to untreated malabsorption, dietary deficiencies, hepatic dysfunction, medications (= initial manifestation in infants)
- focal (40%)/multilobular (5 12%) biliary cirrhosis from inspissated bile:
  - signs of portal hypertension in multilobular form (clinically in 4 6%, autoptic in up to 50%)
- portal hypertension (in 1% of biliary cirrhosis) + hepatosplenomegaly
@ Biliary tree

Histo: mucus-containing cysts in gallbladder wall
- cholestasis (secondary to CBD obstruction)
- symptoms of gallbladder disease (3.6%)
- sludge (33%)
- cholelithiasis (12 24%): mostly cholesterol stones due to (1) interrupted enterohepatic circulation after ileal resection/(2) ileal dysfunction in distal intestinal obstruction syndrome
- gallbladder atony
- microgallbladder (25% at autopsy)
- thickened trabeculated gallbladder wall
- subepithelial cysts of gallbladder wall
- atresia/stenosis of cystic duct

@ Pancreas

Pathophysiology:	duct obstruction from inspissated secretions (= protein plugs) as a result of precipitation of relatively insoluble proteins
Path:	progressive ductectasia, pancreatic atrophy, increased pancreatic lobulation, fibrosis due to recurrent acute pancreatitis, replacement by fat
Histo:	dilatation of acini and ducts + cyst formation

steatorrhea + malabsorption + fat intolerance due to exocrine pancreatic insufficiency in 80 90% without affecting endocrine function (only after 98% of pancreas is damaged)
- Cystic fibrosis is the most common cause of exocrine pancreatic insufficiency in patients <30 years of age!
abdominal pain, bloating, flatulence, failure to thrive
abdominal pain, bloating, flatulence, failure to thrive
diabetes mellitus (secondary to pancreatic fibrosis) increasing with age (in 1% of children + 13% of adults):
- glucose intolerance in 30 50%
- 1 2% require insulin therapy
acute pancreatitis (clinically rare)
diffuse pancreatic atrophy without fatty replacement
lipomatous pseudohypertrophy of pancreas
generalized increased echogenicity (70 100%)
complete/partial fatty replacement (-90 to -120 Hu)
calcific chronic pancreatitis
pancreatic cystosis = microscopic/1 3-mm small cysts replacing pancreas (common), occasionally macroscopic cysts up to 12 cm

@ skull
- sinusitis with opacification of well-developed maxillary, ethmoid, sphenoid sinuses
- hypoplastic frontal sinuses
OB-US:
- hyperechogenic bowel (in up to 60 70% of fetuses affected with cystic fibrosis)
Prognosis: median survival of 28 years; pulmonary cx are the most predominant cause of morbidity and death (90%); 2.3 deaths/100 patients from cardiorespiratory causes (78%), hepatic disease (4%)

Diaphragmatic Hernia

Congenital diaphragmatic Hernia

= absence of closure of the pleuroperitoneal fold by 9th week of gestational age

P.490

Embryology:	ventral component of diaphragm formed by septum transversum during 3rd 5th week GA; gradually extends posteriorly to envelop esophagus + great vessels; fuses with foregut mesentery to form the posteromedial portions of the diaphragm by 8th week GA; lateral margins of diaphragm develop from muscles of the thoracic wall; the posterolaterally located pleuroperitoneal foramina (Bochdalek) close last
Incidence:	1: 2,200 3,000 livebirths (0.04%); M:F = 2:1; most common intrathoracic fetal anomaly Delayed onset following group B streptococcal infection!

Etiology:

delayed fusion of diaphragm (spontaneous self-correction may occur)/premature return of bowel from its herniated position within the umbilical coelom
insult that inhibits/delays normal migration of the gut + closure of the diaphragm between 8th and 12th week of embryogenesis

Classification (Wiseman):

I.	herniation early during bronchial branching leading to severe bilateral pulmonary hypoplasia; uniformly fatal
II.	herniation during distal bronchial branching leading to unilateral pulmonary hypoplasia; survival possible
III.	herniation late in pregnancy with compression of otherwise normal lung; excellent prognosis
IV.	postnatal herniation with compression of otherwise normal lung; excellent prognosis

Associated anomalies in 20% of liveborn and in 90% of stillborn fetuses:

CNS (28%): neural tube defects
Cardiovascular (9 23%)
Gastrointestinal (20%): particularly malrotation, oral cleft, omphalocele
Genitourinary (15%)
Chromosomal abnormalities (4%): trisomy 18 + 21
Spinal defects
IUGR (with concurrent major abnormality in 90%)

Location:

L:R = 5 9:1
Right-sided hernias are frequently fatal!

respiratory distress in neonatal period (life-threatening deficiency of small airways + alveoli)
scaphoid abdomen

Herniated organs:

small bowel (90%), stomach (60%), large bowel (56%), spleen (54%), pancreas (24%), kidney (12%), adrenal gland, liver, gallbladder

bowel loops in chest
contralateral shift of mediastinum + heart
complete (1 2%)/partial absence of diaphragm
absence of stomach, small bowel in abdomen
passage of nasogastric tube under fluoroscopic control entering intrathoracic stomach
incomplete rotation + anomalous mesenteric attachment of bowel

OB-US (diagnosis possible by 18 weeks GA):

solid/multicystic/complex chest mass
mediastinal shift
nonvisualization of fetal stomach below diaphragm
fetal stomach at level of fetal heart
peristalsis of bowel within fetal chest (inconsistent)
paradoxical motion of diaphragm with fetal breathing (defect in diaphragm sonographically not visible)
scaphoid fetal abdomen with reduced abdominal circumference
herniated liver frequently surrounded by ascites
polyhydramnios (common, due to partial esophageal obstruction or heart failure)/normal fluid volume/oligohydramnios
swallowed fetal intestinal contrast appears in chest (CT amniography confirms diagnosis)

Cx:	(1) Bilateral pulmonary hypoplasia (2) Persistent fetal circulation (postsurgical pulmonary hypertension)
Prognosis:	(1) Stillbirth (35 50%) (2) Neonatal death (35%)

Survival is determined by size of defect + time of entry + associated anomalies (34% survival rate if isolated, 7% with associated anomalies)

Indicators of poor prognosis:

large intrathoracic mass with marked mediastinal shift, IUGR, polyhydramnios, hydrops fetalis, detection <25 weeks MA, intrathoracic liver, dilated intrathoracic stomach, other malformations

Mortality:	in 10% death before surgery; 40 50% operative mortality; (a) stomach intrathoracic vs. intraabdominal = 60% vs. 6% (b) polyhydramnios vs. normal amniotic fluid = 89% vs. 45%
DDx:	congenital adenomatoid malformation, mediastinal cyst (bronchogenic, neurenteric, thymic)

Bochdalek hernia (85 90%)

= posterolateral defect caused by maldevelopment/defective fusion of the cephalic fold of the pleuroperitoneal membranes

Incidence:	1:2,200 12,500 livebirths
Location:	left (80%), right (15%), bilateral (5%)

Herniated organs:

on left: omental fat (6%), bowel, spleen, left lobe of liver, stomach (rare), kidney, pancreas
on right: part of liver, gallbladder, small bowel, kidney

mnemonic:

4 B's

Bochdalek
Back (posterior location)
Babies (age at presentation)
Big (usually large)

Morgagni Hernia (1 3 5%)

= anteromedial parasternal defect (space of Larrey = foramen of Morgagni located between ribs + sternum) caused by maldevelopment of septum transversum between 3rd and 7th week of GA

Incidence:

1:4,800 live births; M > F

Herniated organs:

abdominal viscera: omentum, liver, transverse colon

P.491

heart may herniate into upper abdomen
fat may herniate into pericardial sac

Often associated with:

congenital heart disease, bowel malrotation, chromosomal abnormality (Down syndrome, Turner syndrome), mental retardation, pericardial deficiency

Age:	children, adults
mnemonic:	4 M's

Morgagni
Middle (anterior + central location)
Mature (tend to present in older children)
Minuscule (usually small)

asymptomatic (majority), epigastric discomfort
chronic cough, choking, shortness of breath
respiratory distress, cyanosis (in neonates)
abdominal pain, nausea, vomiting
cardiophrenic angle mass; R:L = 9:1
gas-filled loops of bowel

DDx on CXR:

thymoma, teratoma, germ cell tumor, lymphoma, thyroid lesion, pericardial cyst, lymphangioma

Septum Transversum Defect

= defect in central tendon

Hiatal Hernia

= congenitally large esophageal orifice

Eventration (5%)

= upward displacement of abdominal contents secondary to a congenitally thin hypoplastic diaphragm

Unilateral eventration may be associated with:

Beckwith-Wiedemann syndrome, trisomy 13, trisomy 15, trisomy 18

Bilateral eventration may be associated with:

toxoplasmosis, CMV, arthrogryposis

Location:

anteromedial on right, total involvement on left side; R:L = 5:1

small diaphragmatic excursions
often lobulated diaphragmatic contour

Traumatic Diaphragmatic Hernia

= DIAPHRAGMATIC RUPTURE

Prevalence:

0.8 1.6% of all blunt trauma; 5% of all diaphragmatic hernias, but 90% of all strangulated diaphragmatic hernias

Etiology of traumatic rupture of diaphragm:

blunt trauma (5 50%) due to marked increase in intraabdominal pressure: motor vehicle accident (>90%), fall from height, bout of hyperemesis; L:R = 3:1, bilateral rupture in <3.6%
penetrating trauma (50%): knife, bullet, repair of hiatus hernia
- Usually <1 cm in diameter; detected at surgery

may be asymptomatic for months/years following trauma, onset of symptoms may be so long delayed that traumatic event is forgotten
virtually all become ultimately symptomatic, most in <3 years
Bergqvist triad:
- rib fractures
- fracture of spine/pelvis
- traumatic rupture of diaphragm

Location:	77 90 98% on left side; posterolateral portion of diaphragm medial to spleen in a radial orientation; medial central tendon with intrapericardial hernia (3.4%)
Size:	most tears are >10 cm in length

Herniation of organs (32 58%) in order of frequency:

stomach, colon, small bowel, omentum, spleen, kidney, pancreas

CXR:

The first posttraumatic CXR is abnormal in 46 77% but nonspecific!
Positive intrathoracic pressure from ventilation may delay herniation!
Serial CXRs may show progressive changes!
nonvisualization of diaphragmatic contour
elevated asymmetric/irregular contour of hemidiaphragm

Cave:

cephalad margin of bowel may simulate an elevated diaphragm (look for haustra)

herniation of air-filled viscus: stomach, colon
shift of mediastinum + lung to opposite side
lower lobe mass/consolidation (herniated solid organ/omentum/airless bowel loop)
inhomogeneous mass with air-fluid level in left hemithorax
mushroomlike mass of herniated liver in right hemithorax
hydrothorax/hemothorax indicates strangulation
collar sign = hourglass constriction of afferent + efferent bowel loops at orifice
fractures of lower left ribs
abnormal U-shaped course of nasogastric tube above suspected level of hemidiaphragm

N.B.:

tube first dips below diaphragm (rent spares esophageal hiatus with gastroesophageal junction remaining in its normal position)

location of diaphragm may be documented by
- gas-filled bowel constricted at site of diaphragmatic laceration
- barium study

CT (61% sensitive, 87% specific):

Best detected on reformatted SAG + COR images!

Associated with:

abdominal + pelvic injury in 90 94%

abrupt discontinuity of hemidiaphragm (73 82%)
herniation of omentum/bowel/abdominal organs into thorax (55%)
visualization of peritoneal fat/abdominal viscera lateral to lung or diaphragm/posterior to crus of hemidiaphragm
collar sign = waistlike constriction of viscera at level of diaphragm (27%)
absent diaphragm sign = failure to see diaphragm
concurrent pneumothorax, pneumoperitoneum, hemothorax, hemoperitoneum

MR:

interruption of hypointense band of diaphragmatic muscle outlined by hyperintense abdominal + mediastinal fat

P.492

Associated injuries:

fractures of lower ribs/pelvis (42%)
intraabdominal injuries (72%):
- perforation of hollow viscus
- rupture of spleen

Reasons for diagnostic misses:

left-sided defect covered by omentum
right-sided defect sealed by liver
positive pressure ventilation
associated injuries mask tear: atelectasis, pleural effusion, lung contusion, phrenic nerve paralysis

Cx:	life-threatening strangulation of bowel/stomach occurs in majority 90% of strangulated hernias are traumatic!
Prognosis:	30% mortality in unrecognized cases
DDx:	eventration; diaphragmatic paralysis; normal variant of acquired diaphragmatic discontinuity posteriorly related to congenital Bochdalek hernia (6 11%)

Emphysema

= group of pulmonary diseases characterized by permanently enlarged air spaces distal to terminal bronchioles accompanied by destruction of alveolar walls + local elastic fiber network
The clinical term chronic obstructive pulmonary disease (COPD) should not be used in image interpretation! It encompasses: asthma, chronic bronchitis, emphysema!

Prevalence:	1.65 million people in USA
Cause:	imbalance in elastase-antielastase system (due to increase in elastase activity in smokers/ ₁-antiprotease deficiency) causing proteolytic destruction of elastin resulting in alveolar wall destruction

dyspnea on exertion
irreversible expiratory airflow obstruction (due to decreased elastic recoil from parenchymal destruction)
decreased carbon monoxide diffusing capacity

CXR (moderately sensitive, highly specific):

hyperinflated lung (most reliable sign):
- low hemidiaphragm (= at/below 7th anterior rib)
- flat hemidiaphragm (= <1.5 cm distance between line connecting the costo- and cardiophrenic angles + top of midhemidiaphragm)
- retrosternal air space >2.5 cm
- barrel chest = enlarged anteroposterior chest diameter
saber-sheath trachea
pulmonary vascular pruning + distortion ( pulmonary arterial hypertension)
right-heart enlargement
bullae

HRCT:

well-defined areas of abnormally decreased attenuation without definable wall (< 910 HU)

Rx:

lung volume reduction surgery

Centrilobular Emphysema

= CENTRIACINAR EMPHYSEMA = PROXIMAL ACINAR EMPHYSEMA
= emphysematous change selectively affecting the acinus at the level of 1st + 2nd generations of respiratory bronchioles (most common form)

Path:	normal + emphysematous alveolar spaces adjacent to each other
Histo:	enlargement of respiratory bronchioles + destruction of centrilobular alveolar septa in the center of the secondary pulmonary lobule; CHARACTERISTICALLY surrounded by normal lung; distal alveoli spared; severity of destruction varies from lobule to lobule
Predisposed:	smokers (in up to 50%), coal workers
Cause:	excess protease with smoking (elastase is contained in neutrophils + macrophages found in abundance in lung of smokers)

blue bloater

Site:

apical and posterior segments of upper lobe + superior segment of lower lobe (relatively greater ventilationperfusion ratio in upper lobes favors deposition of particulate matter and release of elastase in upper lungs)

CXR (80% sensitivity for moderate/severe stages):

irregular scattered area of radiolucency (best appreciated if lung opacified by edema/pneumonia/hemorrhage) = area of bullae, arterial depletion + increased markings
hyperinflated lung

HRCT:

emphysematous spaces (= focal round area of air attenuation) >1 cm in diameter with central dot/line = centrilobular location (representing the centrilobular artery of secondary pulmonary lobule) without definable wall and surrounded by normal lung
pulmonary vascular distortion + pruning with lack of juxtaposition of normal lung (advanced stage)

Panacinar Emphysema

= PANLOBULAR EMPHYSEMA = DIFFUSE EMPHYSEMA = GENERALIZED EMPHYSEMA
= emphysematous change involving the entire acinus
= uniform nonselective destruction of all air spaces throughout both lungs (rare)

Path:	uniform enlargement of acini from respiratory bronchioles to terminal alveoli (from center to periphery of secondary pulmonary lobule) secondary to destruction of lung distal to terminal bronchiole
Cause:	autosomal recessive alpha-1 antitrypsin deficiency in 10 15% (proteolytic enzymes carried by leukocytes in blood gradually destroy lung unless inactivated by alpha-1 protease inhibitor)
Age:	6th-7th decade (3rd-4th decade in smokers)

pink puffer

Site:

affects whole lung, but more severe at lung bases (due to greater blood flow)

CXR:

hyperinflated lung
decreased pulmonary vascular markings
lung destruction extremely uniform

HRCT:

diffuse simplification of lung architecture with pulmonary septal and vascular distortion + pruning (difficult to detect early, ie, prior to considerable lung destruction for lack of adjacent normal lung)
paucity of vessels
bullae

P.493

Paracicatricial Emphysema

= PERIFOCAL/IRREGULAR EMPHYSEMA
= airspace enlargement + lung destruction developing adjacent to areas of pulmonary scarring

Usual cause:	granulomatous inflammation, organized pneumonia, pulmonary infarction
Path:	no consistent relationship to any portion of secondary lobule/acinus; frequently associated with bronchiolectasis producing honeycomb lung

little functional significance

CXR (rarely detectable):

fine curvilinear reticular opacities + interposed radiolucent areas

HRCT:

low-attenuation areas adjacent to areas of fibrosis (diagnosable only in the absence of other forms of emphysema)

Paraseptal Emphysema

= DISTAL ACINAR/LOCALIZED/LINEAR EMPHYSEMA
= focal subpleural enlargement + destruction of air spaces in one site in otherwise normal lung

Path:	predominant involvement of alveolar ducts + sacs
Site:	characteristically within subpleural lung and adjacent to interlobular septa + vessels

CXR:

area of lucency, frequently sharply demarcated from normal lung
bands of radiopacity (residual vessels/interstitium) may be present

HRCT:

peripheral low-attenuation area with remainder of lung normal

Cx:

spontaneous pneumothorax; bullae formation

Empyema

parapneumonic effusion characterized by presence of pus positive culture

Organism:

S. aureus, gram-negative + anaerobic bacteria

positive Gram stain
positive culture (anaerobic bacteria most frequent)

Stage:

exudative phase = inflammation of visceral pleura results in increased capillary permeability with weeping of proteinaceous fluid into pleural space = sterile exudate
- pH >7.20
- glucose >40 mg/dL (2.2 mmol/L)
- LDH <1,000 IU/L
fibrinopurulent phase = accumulation of inflammatory cells and neutrophils within pleural space + fibrin deposition on pleural surfaces
- early stage II empyema
  - WBCs >5x10⁹/mm³, but no gross pus
  - pH between 7.0 and 7.2
  - glucose level >40 mg/dL
  - LDH <1,000 IU/L
- late stage II empyema
  - gross pus (WBC >15,000/cm³) = frank pus
  - pH <7.0
  - glucose level <40 mg/dL
  - LDH >1,000 IU/L
Cx: multiloculation

Rx: chest tube drainage
organizing phase = recruitment of fibroblasts + capillaries results in deposition of collagen + granulation tissue on pleural surfaces = pleural fibrosis = pleural peel/pleural rind

Cx: limited expansion of lung

Rx: decortication (with persistent sepsis despite appropriate antibiotic Rx + drainage/persistent thick pleural rind trapping underlying lung)

CT:

thickening of parietal pleura in 60% on NECT, in 86% on CECT
increased thickness + density of paraspinal subcostal tissue (inflammation of extrapleural fat)
curvilinear enhancement of chest wall boundary in 96% (inflammatory hyperemia of pleura)
split pleura sign = pleural fluid between enhancing thickened parietal + visceral pleura
gas bubbles in pleural space (gas-forming organism/bronchopleural fistula)

DDx:

simple/complicated parapneumonic effusion (negative Gram + culture stain), malignant effusion after sclerotherapy, malignant invasion of chest wall, mesothelioma, pleural tuberculosis, reactive mesothelial hyperplasia, pleural effusion of rheumatoid disease

Eosinophilic pneumonia

Classification:

Idiopathic (primary) eosinophilic pneumonia
- Simple pulmonary esosinophilia (L ffler syndrome)
- Acute eosinophilic pneumonia
- Chronic eosinophilic pneumonia
- hypereosinophilic syndrome
Secondary eosinophilic pneumonia (due to specific cause)
- drug-induced: nitrofurantoin, penicillin, sulfonamides, ASA, tricyclic antidepressants, hydrochlorothiazide, cromolyn sodium, mephenesin
- parasite-induced: ascariasis, schistosomiasis, strongyloidasis, etc.
- fungus-induced: allergic bronchopulmonary aspergillosis, bronchocentric granulomatosis
- pulmonary eosinophilia with asthma
Eosinophilic lung disease associated with angitis and granulomatosis: Wegener granulomatosis, Churg-Strauss syndrome, rheumatoid disease, scleroderma, Sj gren syndrome

P.494

Maybe associated with:

rheumatoid arthritis

M:F = 1:2

pulmonary opacities
pulmonary eosinophilia (regardless of eosinophilia in peripheral blood/in alveolar lavage)

Acute Eosinophilic Pneumonia

Etiology:	idiopathic (no evidence of infection/exposure to potential antigens) with abrupt increase in lung cytokines
Age:	32 17 years; M > F
Histo:	eosinophilic infiltrates + pulmonary edema (from release of eosinophilic granules altering vascular permeability)

acute febrile illness of 1 5 day's duration, myalgia
chest pain
acute respiratory failure in previously healthy individuals
markedly elevated levels of eosinophils in bronchoalveolar lavage fluid
no peripheral eosinophilia
bilateral interstitial infiltrates
peripheral air space opacities (rare)
small pleural effusion
HRCT:
- ground-glass opacities
- interlobular septal thickening

Rx:	IV corticosteroids
Dx:	bronchoscopy with bronchopulmonary lavage
DDx:	chronic eosinophilic pneumonia (infiltrates with peripheral predominance)

Chronic Eosinophilic Pneumonia

fever, cough, chest pain
occasionally history of allergic rhinitis/asthma
(CLASSIC) peripheral opacities persist for days to weeks

Hypereosinophilic Syndrome

= overproduction of eosinophils that eventually leads to organ injury
congestive heart failure
occasionally peripheral pulmonary opacities

Cx:

mitral + tricuspid insufficiency

Extrinsic Allergic Alveolitis

HYPERSENSITIVITY PNEUMONITIS
characterized by an inappropriate host response to inhaled organic allergens that are often related to patient's occupation

Cause:	inhalation of organic dust (= particulate organism/protein complex) typically of 1 2 m (always <5 m) particle size deposited in distal airspaces of lung acting as antigen for a type III + type IV immune reaction
Histo:	diffuse predominantly mononuclear cell inflammation of bronchioles (bronchiolitis) + pulmonary parenchyma (alveolitis); ill-defined granulomas of <1 mm in diameter

asymptomatic (10 40%)
recurrent episodes of fever, chills, dry cough, dyspnea following exposure after 6-hour interval
resolution of episodic symptoms after cessation of exposure, abate spontaneously over 1 2 days
insidious onset of gradually progressive dyspnea
reduction in vital capacity, diffusing capacity, arterial pO₂
intracutaneous injection of antigen results in delayed hypersensitivity reaction
presence of serum precipitins against antigen
positive aerosol provocation inhalation test
markedly increased cell count with often >50% T-lymphocytes on bronchoalveolar lavage

Location:

predominantly midlung zones, occasionally lower lung zones, rarely upper lung zones

Specific antigens for immune complex disease (type III = Arthus reaction):

Farmer's lung from moldy hay (Thermoactinomyces vulgaris or Micropolyspora faeni)
Hypersensitivity pneumonitis from forced-air equipment = Pandora's pneumonitis with heating/humidifying/air conditioning systems (thermophilic actinomycetes)
Bird-fancier's lung, pigeon breeder's lung from protein in bird serum/excrements/feathers
Mushroom worker's lung from mushroom compost (Thermoactinomyces vulgaris or Micropolyspora faeni)
Bagassosis from moldy sugar cane in sugar mill (contamination with Thermoactinomyces sacchari /vulgaris and Micropolyspora faeni)
Malt worker's lung from malt dust (Aspergillus clavatus)
Maple bark disease from moldy maple bark in saw mill (Cryptostroma corticale)
Suberosis from moldy cork dust (Penicillium frequentans)
Sequoiosis from redwood dust (Graphium species)

Thermophilic actinomycetes:

= bacteria <1 m in diameter with morphologic characteristics of fungi; found in soil, grains, compost, fresh water, forced-air heating, cooling system, humidifier, air-conditioning system

Isocyanates:

used for large-scale production of polyurethane polymers in the manufacture of flexible/rigid foams, elastomers, adhesives, surface coating
Principal cause of occupational asthma!

Rx:

mask, filter, industrial hygiene, alterations in forced-air ventilatory system, change in patient's habits/occupation/environment

Acute Extrinsic Allergic Alveolitis

= heavy exposure to inciting antigen in domestic, occupational, atmospheric environment

Histo:	filling of air spaces by polymorph neutrophils + lymphocytes
Onset of symptoms:	4 8 hours after exposure

fever, chills, malaise, chest tightness, cough, dyspnea
scanty mucoid expectoration
frontal headache, arthralgia (common)
No CXR abnormalities in 30 95%
diffuse acinar consolidative pattern (edema + exudate filling alveoli) resolving within a few days
lymph node enlargement (unusual, more common with recurrence)
HRCT:
- small + medium rounded opacities (large active granulomas)
- diffuse dense airspace consolidation (confluent collections of intraalveolar histiocytes, interstitial + intraalveolar edema)

Dx:

classical presentation of a known exposure history + typical symptoms + detection of serum precipitins to suspected antigen

Subacute Extrinsic Allergic Alveolitis

= less intense but continuous exposure to inhaled antigens, usually in domestic environment

Histo:	predominantly interstitial lymphocytic infiltrate, poorly defined granulomas, cellular bronchiolitis
Onset of symptoms after exposure:	weeks months

recurrent respiratory/systemic symptoms:
- breathlessness upon exertion, fever + cough
- weight loss, muscle + joint pain
changes may be completely reversible if present less than 1 year
interstitial nodular/reticulonodular pattern
HRCT:
- widespread patchy/diffuse ground-glass attenuation in 52% (obstructive pneumonitis, filling of alveoli by large mononuclear cell infiltrates)
- poorly defined centrilobular micronodules <5 mm (cellular bronchiolitis + small granulomas)
- areas of decreased attenuation + mosaic perfusion (86%)
- irregular reticular changes, septal lines, parenchymal bands

Chronic Extrinsic Allergic Alveolitis

= prolonged insidious dust exposure

Onset of symptoms after exposure:

months years

insidious progressive exertional dyspnea indistinguishable from idiopathic pulmonary fibrosis

Histo:	proliferation of epithelial cells + predominantly peribronchiolar interstitial fibrosis
Location:	usually in mid zones, relative sparing of lung apices + costophrenic sulci

irregular linear opacities (fibrosis)
loss of lung volume (cicatrization atelectasis)
pleural effusion (rare)
lymph node enlargement may occur

CT:

fibrosis of middle + lower lung zones with relative sparing of lung bases:
- intralobular interstitial thickening
- irregular interlobular septal thickening
- honeycombing
- traction bronchiectasis
focal air trapping/diffuse emphysema
coexistent subacute changes (due to continuing exposure)

Fat Embolism

obstruction of pulmonary vessels by fat globules followed by chemical pneumonitis from unsaturated plasma fatty acids producing hemorrhage/edema

Incidence:	in necropsy series in 67 97% of patients with major skeletal trauma; however, symptomatic fat embolism syndrome in <10% (M > F)
Onset:	24 72 hours after trauma

dyspnea (progressive pulmonary insufficiency)
fever
systemic hypoxemia
mentation changes: headaches, confusion
petechiae (50%) from coagulopathy (release of tissue thromboplastin)
initial chest film usually negative (normal up to 72 hours)
platelike atelectasis
bilateral diffuse alveolar infiltrates
consolidation (may progress to ARDS)
NUC:
- mottled peripheral perfusion defects (1 4 days after injury), later enlarging secondary to pneumonic infiltrates

Focal Organizing Pneumonia

= unresolving pneumonia/pneumonia with incomplete resolution beyond 8 weeks

Prevalence:	5 10% of all pneumonias (87% of pneumonias resolve within 4 weeks, 12% within 4 8 weeks)
Predisposing factors:	? age, diabetes mellitus, chronic bronchitis, overuse of antibiotics
Histo:	organization of intraalveolar exudate + thickening of alveolar septa/chronic inflammatory change of bronchial mucosa + obstructive lesion in bronchioles with organization

cough, sputum, fever, hemoptysis (in 1/4)
ill-defined localized parenchymal abnormality with irregular margin
decrease in size of mass within 3 4 weeks
HRCT:
- flat/ovoid lesion with irregular margin in subpleural location/along bronchovascular bundle
- satellite lesions (44%) + air bronchogram (22%)

Fracture of Trachea/Bronchus

= TRACHEOBRONCHIAL TEAR

Cause:

blunt chest trauma (in 1.5%)

delayed diagnosis is common

Location:

(a) mainstem bronchus within 2.5 cm of carina (80%); r > L
(b) just above carina (20%)

Associated injuries:
- fracture of first 3 ribs (53 91%), rare in children
- fracture of clavicle, sternum, scapula (40%)
pneumothorax (70%)
increasing mediastinal subcutaneous emphysema
absence of pleural effusion
fallen lung sign = collapsed lung droops to dependent position peripherally (loss of anchoring support in bronchial transection)
inadequate reexpansion of lung despite adequate placement of one/more chest tubes (due to large size of air leak)
elevation of hyoid bone above level of c3 vertebral body/elevation of greater cornu to <2 cm from angle of mandible (on LAT radiograph of spine) due to infrahyoid muscle rupture + unopposed action of suprahyoid mm.
atelectasis (may be late development)
CT:
- focal peribronchial collections of air

P.496

discontinuity/irregularity of bronchial wall
abnormal position of endotracheal tube:
- overdistension of tube cuff
- protrusion of tube wall beyond expected margins of trachea
- extraluminal position of tip of tube

Prognosis:	30% mortality (in 15% within 1 hour)
Long-term Cx:	airway stenosis/bronchomalacia; recurrent atelectasis/pneumonia

Giant Cell Interstitial Pneumonia

Almost pathognomonic for hard metal pneumoconiosis
diffuse micronodular pattern
reticular pattern; in advanced disease coarse and accompanied by small cystic spaces
lymph node enlargement
HRCT:
- bilateral areas of ground-glass attenuation
- areas of consolidation
- extensive reticulations
- traction bronchiectasis

Goodpasture Syndrome

ANTI-GLOMERULAR BASEMENT MEMBRANE ANTIBODY DISEASE
autoimmune disease characterized by
- glomerulonephritis
- circulating antibodies against glomerular + alveolar basement membrane
- pulmonary hemorrhage

Pathogenesis:

cytotoxic antibody-mediated disease = type II hypersensitivity; alveolar basement membrane becomes antigenic (perhaps viral etiology); IgG/IgM antibody with complement activation causes cell destruction + pulmonary hemorrhage, leads to hemosiderin deposition and pulmonary fibrosis

Age peak:

26 years (range 17 78 years); M:F = 7:1

iron-deficiency anemia
hepatosplenomegaly
systemic hypertension
@ Lung
- preceding upper respiratory infection (in 2/3) + renal disease
- mild hemoptysis (72%) with hemosiderin-laden macrophages in sputum, commonly precedes the clinical manifestations of renal disease by several months
- cough, mild dyspnea, basilar rales
- extensive bilateral air-space consolidation:
  - symmetric consolidation of perihilar area + lung bases with sparing of lung apices
  - air bronchogram
  - consolidation replaced by interstitial pattern within 2 3 days (due to organization of hemorrhage resulting in interlobular septal thickening)
- hilar lymph nodes may be enlarged during acute episodes
@ Kidney
- glomerulonephritis with IgG deposits in characteristic linear pattern in glomeruli
- hematuria

Prognosis:	death within 3 years (average 6 months) because of renal failure
Rx:	cytotoxic chemotherapy, plasmapheresis, bilateral nephrectomy
DDx:	idiopathic pulmonary hemosiderosis

Granuloma of Lung

Cause:

Sarcoidosis
Non-sarcoid granulomatous disease
- infectious
  - bacterial: TB, gumma
  - opportunistic: cryptococcosis
  - parasitic: Dirofilaria immitis (dog heartworm)
  - fungal: histoplasmosis, coccidioidomycosis, nocardiosis
- noninfectious
  - foreign body: talc, beryllium, algae, pollen, cellulose, lipids, abuse of nasally inhaled drugs, aspiration of medication
  - angiocentric lymphoproliferative disease
  - vasculitides
  - extrinsic allergic alveolitis
  - Langerhans cell histiocytosis
  - pulmonary hyalinizing granuloma
  - peribronchial granuloma
  - chronic granulomatous disease of childhood

Histo:	epithelial cells, lymphocytes, macrophages, giant cells of Langhans type
Frequency:	constitutes the majority of solitary pulmonary nodules

nonproductive cough
shortness of breath
spontaneous pneumothorax
CXR:
- CXR detection requires multiple granulomas/clusters of granulomas (individual granuloma too small)!
- central nidus of calcification in a laminated/diffuse pattern
- absence of growth for at least 2 years
CT (most effective in nodules 3 cm of diameter with smooth discrete margins):
- 50 60% of pulmonary nodules demonstrate unsuspected calcification by CT

DDx:

carcinoma (in 10% eccentric calcification in preexisting scar/nearby granuloma/true intrinsic stippled calcification in larger lesion)

Hamartoma of Chest Wall

MESENCHYMOMA (incorrect as it implies neoplasm)
focal overgrowth of normal skeletal elements with a benign self-limited course; extremely rare

Age:

1st year of life

moderate/large extrapleural well-circumscribed mass affecting one/more ribs
ribs near center of mass partially/completely destroyed
ribs at periphery deformed/eroded
significant amount of calcification/ossification (DDx: aneurysmal bone cyst)
mass compresses underlying lung

Rx:

resection curative

P.497

Hamartoma of Lung

most common benign tumor of the lung

Incidence:

0.25% in population (autopsy); 6 8% of all solitary pulmonary neoplasms; 77% of all benign lung tumors

Etiology:

Congenital malformation of a displaced bronchial anlage
Hyperplasia of normal structures
Cartilaginous neoplasm
Response to inflammation

Path:	solitary mass composed of tissues normally found in this location in abnormal quantity, mixture, and arrangement
Histo:	columnar, cuboidal, ciliated epithelium, fat (in 50%), bone, cartilage (predominates), muscle, vessels, fibrous tissue, calcifications, plasma cells originating in fibrous connective tissue beneath mucous membrane of bronchial wall
Age peak:	5th + 6th decade; M:F = 2:1 3:1

May be associated with:

Carney triad (pulmonary chondromatous lesion, gastric leiomyosarcoma, functioning extraadrenal paraganglioma); pulmonary hamartoma syndrome

mostly asymptomatic
hemoptysis (rare)
cough, vague chest pain, fever (with postobstructive pneumonitis)

Location:

2/3 peripheral; endobronchial in 3 10 20%; multiplicity (rare)

round smooth lobulated mass <4 cm (averages 2.5 cm)
calcification in 15 20% (almost pathognomonic if of chondroid popcorn type)
fat density in 50% (DIAGNOSTIC)
cavitation (extremely rare)
growth patterns: slow/rapid/stable with later growth
usually diameter increase by 1.5 mm/year doubling in size every 14 years
HRCT:
- fat density detectable in 34% ( 80 to 120 HU)
- calcium + fat detectable in 19%

Transthoracic needle biopsy:	85% diagnostic accuracy
DDx:	lipoid pneumonia (ill-defined mass/lung infiltrate); granulomatous disease, carcinoid tumor; metastatic mucinous adenocarcinoma, amyloidoma

Hereditary Hemorrhagic Telangiectasia

= RENDU-OSLER-WEBER SYNDROME
= group of autosomal dominant inherited disorders that result in a variety of systemic fibrovascular dysplasias affecting mucous membranes, skin, lung, brain, GI tract:
- telangiectasias
- arteriovenous malformations (AV hemangiomas)
- aneurysms

Etiology:

gene that encodes transforming growth factor binding protein

Path:

direct connections between arteries + veins with absence of capillaries (telangiectases are small AVMs)
(a) small telangiectasis = focal dilatation of postcapillary venules with prominent stress fibers in pericytes along luminal borders
(b) fully developed telangiectasis = markedly dilated + convoluted venules with excessive layers of smooth muscle without elastic fibers directly connecting to dilated arterioles

frequent bleeding into mucous membranes, skin, lungs, genitourinary system, gastrointestinal system (due to vascular weakness)
@ Nose (telangiectasis of nasal mucosa)
- recurrent epistaxis (32 85%): more severe over time in 66%; begins by age 10, present by age 21 in most cases; up to 45 episodes per month
@ Skin
- telangiectases = small red vascular blemishes
  
  Age: present in most cases by age 40; increase in number + size with age
  
  Location: lips, tongue, palate, fingers, face, conjunctiva, trunk, arms, nail beds
@ Lung (5 15%)
- 5 15% of patients with hereditary hemorrhagic telangiectasia have pulmonary AVMs
- Up to 60% of patients with pulmonary AVMs have hereditary hemorrhagic telangiectasia
- see PULMONARY ARTERIAL MALFORMATION
@ CNS (cerebral or spinal AVMs)
- subarachnoid hemorrhage
- seizure; paraparesis (less common)
- headache
@ GI tract (stomach, duodenum, small bowel, colon) occasionally associated with AVMs/angiodysplasia
- recurrent GI bleeding (in 5th 6th decade)
@ Liver (8 31%)
- hepatomegaly
- presence of multiple AVMs (between hepatic artery branches + branches of hepatic/portal veins:
  - simultaneous enhancement of hepatic arteries + veins
  - multiple transient peripheral wedge-shaped areas of hepatic enhancement on hepatic arterial phase
- widened tortuous hepatic arteries
- dilatation of hepatic veins
- diffuse mottled capillary blush on angio

Cx:	atypical cirrhosis, portal hypertension, variceal GI hemorrhage, ascites, encephalopathy
Cx:	(1) congestive heart failure (due to AV shunting) (2) cerebral abscess (from paradoxical emboli)

Histoplasmosis

Prevalence:	nearly 100% in endemic area; up to 30% in Central + South America, Puerto Rico, West Africa, Southeast Asia; annually 500,000 infected in USA; up to 30% of US population has a positive skin reaction
Organism:	Histoplasma capsulatum = dimorphic fungus; worldwide most often in temperate climates; widespread in soil enriched by bird droppings of central North America (endemic in Ohio, Mississippi, St. Lawrence River valley; exists as a spore in soil + transforms into yeast form at normal body temperatures
Vector:	fowl + other birds (passes through feces without infection due to high body temperature); bats
Infection:	inhalation of wind-borne spores (microconidia of 2 6 m, macroconidia of 6 14 m), which germinate within alveoli releasing yeast forms, which are phagocytized but not killed by macrophages; invasion of pulmonary lymphatics with spread to hilar + mediastinal lymph nodes; hematogenous dissemination of parasitized macrophages throughout reticuloendothelial system (spleen!)
Path:	spores incite formation of epithelioid granulomas, necrosis, calcification
Dx:	(1) Culture (sputum, lung tissue, urine, bone marrow, lymph node) (2) Identification of yeast forms stained with PAS/Gomori methenamine silver (3) Complement fixation test (absolute titer of 1:64 or 4-fold rise in convalescent titer suggest active/recent infection) (4) Serum immunodiffusion: agar gel diffusion test (H precipitin band)
Rx:	ketoconazole

P.498

Pulmonary Histoplasmosis

ACUTE HISTOPLASMOSIS
- mostly asymptomatic and self-limiting illness (in 99.5%)
- fever, cough, malaise simulating viral upper respiratory infection 3 weeks after massive inoculum/in debilitated patients (infants, elderly)
- positive skin test for histoplasmosis; hypersensitivity develops in 1 2 weeks
- generalized lymphadenopathy
- bilateral nonsegmental bronchopneumonic pattern with tendency to clear in one area + appear in another
- multiple nodules changing into hundreds of punctate calcifications (usually >4 mm) after 9 24 months
- target lesion = central calcification is PATHOGNOMONIC
- hilar/mediastinal lymph node enlargement (DDx: acute viral/bacterial pneumonia)
- popcorn calcification of mediastinal lymph nodes >10 mm (80% probability of being caused by histoplasma)
- >5 splenic calcifications (40%)
- CT:
  - paratracheal/subcarinal mass with regions of low attenuation (necrosis) + enhancing septa
CHRONIC HISTOPLASMOSIS (0.03%)

Predisposed: individuals with chronic obstructive pulmonary disease + cigarette smoking

Age: middle-aged white men

Pathophysiology: hyperimmune reaction
- cough, low-grade fever, night sweats simulating postprimary tuberculosis
- segmental wedge-shaped peripheral consolidation of moth-eaten appearance from scattered foci of emphysematous lung
- fibrosis in apical posterior segments of upper lobes (indistinguishable from postprimary TB) adjacent to emphysematous blebs

DISSEMINATED HISTOPLASMOSIS

Predisposed:	impaired T-cell immunity; AIDS; immunosuppression after organ transplant
Prevalence:	1:50,000 exposed individuals
Pathophysiology:	progression of exogenous infection/reactivation of latent focus

acute rapidly fatal infection:
fever, weight loss, anorexia, malaise
cough (<50%)
abdominal pain, nausea, vomiting, diarrhea
chronic intermittent illness:
low-grade fever, weight loss, fatigue
adrenal insufficiency
normal CXR (>50%)
miliary <3 mm nodules
linear irregular reticulonodular opacities
segmental/lobar/diffuse airspace opacities
hilar + mediastinal adenopathy (uncommon in immunocompromised patients)
hepatosplenomegaly

Cx:

arthritis (most often knee), tenosynovitis, osteomyelitis

DELAYED MANIFESTATIONS
- Organism recovered in only 50%!
- histoplasmoma (= continued growth of primary focus at 0.5 2.8 mm/year) adjacent to pleura + typically with laminated calcific rings ( lung stone )
  
  in 20% associated with: mediastinal granulomas
- broncholithiasis = erosion of peribronchial calcified lymph node into bronchus:
  - hemoptysis, fever, chills, productive cough
  - change in position of stone on serial radiographs
- mediastinal granuloma (more common)
  - = direct infection of mediastinal lymph nodes
    
    Histo: involved nodes with varying degrees of central caseation calcification
  - usually asymptomatic
    
    Location: subcarinal/right paratracheal/hilar lymph nodes
  - widened mediastinum (enlarged nodes + veins)
  - lobulated mass of low-density lymph nodes 3 10 cm in thickness surrounded by a 2 5-mm thick fibrous capsule crisscrossed by irregularly shaped enhancing septa (CHARACTERISTIC)
  - displacement of SvC/esophagus
- fibrosing mediastinitis (less common)

Hodgkin Disease

= disease of T cells

Incidence:	0.75% of all cancers diagnosed each year; 40% of all lymphomas
Age:	bimodal peaks at age 25 30 years and 75 80 years
Histo:	Reed-Sternberg cell = binucleate cell with prominent centrally located nucleolus

Lymphocyte predominance (5%)
- = abundance of normal-appearing lymphocytes + relative paucity of abnormal cells
- often diagnosed in younger people <35 years
- systemic symptoms are uncommon
- frequently in early stage + localized disease
Prognosis: most favorable natural history

P.499

nodular sclerosis (78%)
- = lymph nodes traversed by broad bands of birefringent collagen separating nodules, which consist of normal lymphocytes, eosinophils, plasma cells, and histiocytes
- 1/3 with systemic symptoms
- typically localized anterior mediastinal involvement
Prognosis: good
Mixed cellularity (17%)
- = diffuse effacement of lymph nodes with lymphocytes, eosinophils, plasma cells + relative abundance of atypical mononuclear and reed-sternberg cells; more commonly advanced stage at presentation and older age
- more commonly abdominal than mediastinal
Prognosis: less favorable
Lymphocyte depletion (1%)
- = paucity of normal-appearing lymphocytes + abundance of abnormal mononuclear and reed-sternberg cells; least common subtype with worst prognosis
  
  Age: older patients
- systemic symptoms
- disseminated advanced stage
Prognosis: rapidly fatal

Ann Arbor Staging Classification:

Stage I	= limited to one/two contiguous anatomic regions on same side of diaphragm
Stage II	= >2 anatomic regions/two noncontiguous regions on same side of diaphragm
Stage III	= on both sides of diaphragm, not extending beyond lymph nodes, spleen (Stage III_S), Waldeyer's ring
III_E	= with extralymphatic organ/site
Stage IV	= organ involvement (bone marrow, bone, lung, pleura, liver, kidney, GI tract, skin) lymph node involvement
E	= extralymphatic site
S	= splenic involvement
Substage A	= absence of systemic symptoms
Substage B	= fever, night sweats, pruritus, 10% weight loss in past 6 months

painless lymphadenopathy
alcohol-induced pain
unexplained fevers, night sweats, weight loss
generalized pruritus
@ CHEST

At presentation: 67% with intrathoracic disease
- Sites of lymphoid aggregates:
  - Lymph nodes in mediastinum
  - Lymph nodes at bifurcation of 1st + 2nd order bronchi
  - Encapsulated lymphoid collections on thoracic surface deep to parietal pleura
  - Unencapsulated nodules at points of divisions of more distally situated bronchi, bronchioles, and pulmonary vessels
  - Unencapsulated lymphoid aggregates within peribronchial connective tissue
  - Small accumulations of lymphocytes in interlobular septa + lymphatic channels

INTRAPULMONARY MANIFESTATIONS

Frequency: 6 11%; in 4.3% bilateral (more frequent in recurrent disease)
- Most commonly in nodular sclerosing type
- Subsequent to hilar adenopathy in ipsilateral lung
- Bronchovascular form (most common type of involvement)
  - coarse reticulonodular pattern contiguous with mediastinum = direct extension from mediastinal nodes along lymphatics
  - nodular parenchymal lesions
  - miliary nodules
  - endobronchial involvement
  - lobar atelectasis secondary to endobronchial obstruction (rare)
  - cavitation secondary to necrosis (rare)
- Subpleural form
  - circumscribed subpleural masses
  - pleural effusion (20 50%) from lymphatic obstruction
- Massive pneumonic form (68%)
  - diffuse nonsegmental infiltrate (pneumonic type)
  - massive lobar infiltrates (30%)
  - homogeneous confluent infiltrates with shaggy borders
  - air bronchogram
- Nodular form
  - multiple nodules <1 cm in diameter (DDx: metastatic disease)
- DDx in treated patients:
  - relapse, infection, radiation pneumonitis, drug-induced lung disease
EXTRAPULMONARY MANIFESTATIONS
- Mediastinal + hilar lymphadenopathy
  
  Most common manifestation, present in 90 99%, in thorax commonly multiple lymph node groups involved
  
  Location:
  - anterior mediastinal + retrosternal nodes commonly involved (DDx: sarcoidosis); confined to anterior mediastinum in 40%; 20% with mediastinal nodes have hilar lymphadenopathy also; hilar lymph nodes involved bilaterally in 50%
  Spread from anterior mediastinum to:
  - other mediastinal locations, pleura, pericardium, chest wall
  - Involvement of multiple lymph node groups in 95%!
  - CXR: on initial film adenopathy identified in 50%
  - necrotic lymph nodes (commonly nodular sclerosing type)
  - lymph nodes may calcify following radiation/chemotherapy
- Pleural effusion (13%)
  - Not of prognostic significance
  Prognosis: usually resolves following treatment
- Pleural masses + plaques
  - sternal erosion
  - invasion of anterior chest wall
P.500

Cx:
- Superimposed infection
  - consolidation with bulging borders: necrotizing bacterial pneumonia
  - multiple nodular foci: aspergillosis + nocardiosis
  - bilateral diffuse consolidation: Pneumocystis carinii
  - rapidly developing cavitation within consolidation: anaerobes/fungus
  Dx: by culture, sputum cytology, lung biopsy
- Drug toxicity

Extranodal Hodgkin Disease (15 30%)

@ BONE (5 20%)
During course of disease 5 32% will develop bone marrow involvement

At presentation: 1 4%; indicative of widespread aggressive disease with poor prognosis

Location: dorsolumbar spine > pelvis > ribs > femora > sternum
solitary (33%)/polyostotic (66%) lesions:
- usually wide ill-defined lesion edge/sclerotic margin
- lamellated/ sunburst periosteal reaction
- predominantly osteolytic with blurred borders; rarely sclerotic/mixed lytic-sclerotic
fractures occur rarely at presentation
vertebral osteolysis with collapse/patchy sclerosis/ ivory vertebra /mixed lytic + blastic lesion
gouge defect of anterior vertebral body margin (due to erosion by lymph nodes)
osteolysis of sternum (due to its proximity to thoracic lymph ducts)
@ HEAD & NECK (<1%)
- nasopharyngeal biopsy positive in 20%
- thyroid mass as secondary involvement (2%)
@ CNS (uncommon)

Frequency: secondary hematogenous involvement in 0.2 0.5%

Location: supratentorial cerebral cortex + meninges in inferior aspect of brain (most frequent)
- leptomeningeal + choroid plexus masses
- white matter mass, typically periventricular/basal ganglionic/cerebellar
- paraneoplastic cerebellar atrophy
- epidural mass with spinal cord compression (in 3 7.6%) from extension of paraspinal nodes through intervertebral neural foramen:
- concomitant vertebral bone involvement (32 42%)
@ THYMUS (30 56%)
- Considered a lymph node in staging
- remains enlarged after treatment in 33% (due to recurrent disease/rebound hyperplasia/persistence of thymic cysts)
@ CHEST WALL (6.4%)
- infiltration of parasternal soft tissues by direct extension from internal mammary nodes
- mass beneath/between pectoralis muscles (rare)
@ HEART (7.5% at autopsy)
- pericardial effusion (with large mediastinal mass)
- invasion of pericardium + SVC
- pericardial nodular mass
@ LIVER (6 20%)
- Primary involvement very rare
  
  Associated with: splenic disease (almost invariable)
- discrete nodules (10%) = miliary lesions of <10 mm
- diffuse disease (87%) = patchy irregular infiltrates in portal areas
@ SPLEEN
- Considered a nodal organ
  
  Frequency: 30 40% at staging laparotomy
- diffuse involvement (not detectable by imaging) splenomegaly
- hypoechoic hypoattenuating nodules with reduced contrast enhancement
- MR:
  - hypo-/isointense nodules on T1WI + hyperintense on T2WI
  - reduced enhancement compared with normal spleen
DDx: reactive splenomegaly (in 30%)
@ PANCREAS (extremely rare)
- Secondary to contiguous lymph node disease
@ GI TRACT (10 15%)
@ Esophagus (extremely rare):
- esophageal nodules/irregular narrowing
@ Stomach (9% of all intestinal lymphomas):
- narrow rigid obstructive lesion (DDx: scirrhous ca.)
- wall thickening + smoothly lobulated outer border
@ Small intestine:
- spruelike symptoms, steatorrhea
- abundance of desmoplastic reaction (DDx from NHL)
- infiltrating (60%); polypoid (26%); ulcerated (14%)
Prognosis: poorer 5-year survival rate than with other forms of the disease
@ GU TRACT (extremely rare)
- perirenal/renal masses (due to invasion from surrounding nodes)

CX:

increased risk for other malignancies from aggressive therapy (acute leukemia, NHL, radiation-induced sarcoma)

Hydatid Disease

= LUNG ECHINOCOCCOSIS
Most common site of secondary involvement in children + 2nd most frequent site in adults

Source:	hematogenous spread from liver lesion
Frequency:	15 25% of hydatid disease

asymptomatic
eosinophilia (<25%)
sudden cough attacks, hemoptysis, chest pain, fever
expectoration of cyst fluid/membranes/scolices
positive Casoni skin test in 60%
hypersensitivity reaction (if cyst rupture occurs)

Location:

lower lobes in 60%; bilateral in 20%

solitary (70 75%)/multiple (25 30%) sharply circumscribed spherical/ovoid masses
size of 1 20 cm in diameter (16 20 weeks doubling time)
cyst communication with bronchial tree:
- meniscus sign , double arch sign, moon sign, crescent sign (5%) = thin radiolucent crescent in uppermost part of cyst (due to rupture of pericyst with air dissecting between pericyst + laminated membrane)
- air-fluid level = rupture of all cyst walls with air entering the endocyst
- Cumbo sign = air-fluid level inside endocyst + air between pericyst and endocyst with an onion peel appearance
- serpent sign = collapsed membranes inside cyst outlined by air (after expectoration of cyst contents)
- water lily sign, sign of the Camalotte = completely collapsed crumpled cyst membrane floating on the cyst fluid
- mass within cavity = crumpled membranes fall to most dependent portion of cavity after complete expectoration of cyst fluid
- hydropneumothorax
calcification of cyst wall (0.7%)
rib + vertebral erosion (rare)
mediastinal cyst: posterior (65%), anterior (26%), middle (9%) mediastinum

CX:

bacterial infection (after cyst rupture)

Hypogenetic Lung Syndrome

= collective name for congenital underdevelopment of one/more lobes of a lung separated into 3 forms:
- Pulmonary agenesis
  - = complete absence of a lobe + its bronchus
  - CT:
    - missing bronchus + lobe(s)
- Pulmonary aplasia
  - = rudimentary bronchus ending in blind pouch + absence of parenchyma + vessels
    
    Incidence: 1:10,000; R:L = 1:1
  - CT:
    - absence of ipsilateral pulmonary artery
    - bronchus terminates in dilated blind pouch
    - absence of ipsilateral pulmonary tissue
- Pulmonary hypoplasia (38%)
  - = completely formed but congenitally small bronchus with rudimentary parenchyma + small vessels
  - Developmental causes:
    - resulting in intrauterine compression of chest
    - Idiopathic (rare)
    - Extrathoracic compression (= Potter syndrome)
      - Oligohydramnios (renal agenesis, bilateral cystic renal disease, obstructive uropathy, premature rupture of membranes)
      - Fetal ascites
    - Thoracic cage compression
      - Thoracic bone dysplasia (Jeune, thanatophoric dystrophy, Ellis-van Creveld, severe achondroplasia)
      - Muscular disease
    - Intrathoracic compression
      - Diaphragmatic defect
      - Excess pleural fluid
      - Large intrathoracic cyst/tumor
    - CT:
      - small bronchus + lobe
      - arterial supply from thoracic/abdominal aorta secondary to absent/hypoplastic pulmonary a.
      - venous drainage into IVC, hepatic vein, portal vein, right atrium, coronary sinus

Hypogenetic lung is the most constant component of congenital pulmonary venolobar syndrome

May be associated with:

congenital tracheal stenosis, bronchogenic cyst, accessory diaphragm, diaphragmatic hernia, bronchitis, bronchiectasis

Location:

R:L = 3:1; RML (65%) > RUL (40%) > RLL (20%) > LUL (20%) > LLL (15%); multiple lobes (45%)

usually asymptomatic (in isolated hypogenetic lung)
exertional dyspnea
small ipsilateral hemithorax + elevated hemidiaphragm
diminished pulmonary vascularity on involved side
small hilum on involved side (absent/small pulmonary artery)
mediastinum + heart shifted toward involved side
indistinct cardiomediastinal border on involved side
diminished radiolucency on involved side
large ipsilateral apical cap + blunted costophrenic angle
broad retrosternal band of opacity (LAT view)

Horseshoe Lung

= uncommon variant of hypogenetic lung syndrome in which RLL crosses midline between esophagus and heart + fuses with opposite LLL

oblique fissure in left lower hemithorax (if both lungs separated by pleural layers)
pulmonary vessels + bronchi crossing midline

Idiopathic Interstitial Pneumonia

Acute interstitial Pneumonia

= AIP = [ACCELERATED INTERSTITIAL PNEUMONIA]
- = DIFFUSE ALVEOLAR DAMAGE = IDIOPATHIC ARDS
- = ACUTE DIFFUSE INTERSTITIAL FIBROSIS = HAMMANRICH SYNDROME
= rapidly progressive fulminant disease of unknown etiology that usually occurs in previously healthy subjects + produces diffuse alveolar damage

Path:

temporally homogeneous organizing diffuse alveolar damage; little mature collagen deposition/architectural distortion/honeycombing (as opposed to UIP)

P.502

Histo:

acute exudative phase: thickening of alveolar wall due to alveolar/interstitial edema + inflammatory cells; extensive alveolar damage with hyaline membrane formation (most prominent in 1st week after lung injury)
marked interstitial fibroblast proliferation with stabilizing nonprogressive scarring

Mean age:

50 years; M = F

prodromal viral upper respiratory infection: cough, fever
rapidly increasing dyspnea + acute respiratory failure
requires ventilation within days to 1 4 weeks
decreased diffusing capacity for carbon monoxide

Location:	mainly lower lung zones
Site:	predominantly central/subpleural (in 22%)

CXR:
- progressive extensive bilateral hetero-/homogeneous airspace opacification: symmetric, bilateral, basilar
CT:
- diffuse extensive bilateral airspace consolidation (in 67%) with basal predominance (similar to Ards)
- patchy (67%)/diffuse (38%) bilateral ground-glass opacities
- anteroposterior lung attenuation gradient
- marked architectural distortion + honeycomb lung if fibrosis progressive

Dx:	negative bacterial/viral/fungal cultures; no inhalational exposure to noxious agents; no pulmonary drug toxicity
Prognosis:	death within 1 6 months (60 90%); recovery in 12%

Subacute Interstitial Pneumonia

BOOP see BRONCHIOLITIS OBLITERANS

Nonspecific Interstitial Pneumonia with Fibrosis

= NONCLASSIFIABLE INTERSTITIAL PNEUMONIA
= interstitial pneumonia that cannot be classified as UIP/DIP/acute interstitial pneumonia/BOOP

Histo: temporal uniformity of

cellular interstitial infiltrate with little/no fibrosis (48%)
inflammation + fibrosis (38%)
dense fibrosis dominant (14%); occasionally intraalveolar accumulation of macrophages + focal areas of bronchiolitis obliterans organizing pneumonia

Cause:	collagen vascular disease (16%), inhalational exposure to noxious agents (17%), recent surgery/severe pneumonia/Ards (8%)
Mean age:	46 years; M < F

dyspnea + dry cough (1-week to 5-year history)
low-grade fever, malaise
decreased diffusing capacity for carbon monoxide

Location:

no zonal predominance

normal CXR in 14%
bibasilar irregular linear opacities + diffuse heterogeneous airspace consolidation
normal/slightly decreased lung volume

HRCT:

bilateral areas of scattered ground-glass opacities (100%) without zonal preference
bibasilar airspace consolidation (71%)
irregular linear/reticular opacities (29%)
traction bronchiectasis/bronchiolectasis in areas of consolidation (71%)
mediastinal lymphadenopathy (29%)
NO honeycombing

Prognosis:	11% overall mortality
Rx:	corticosteroids (clinical + functional + radiographic improvement in 50 86%)
DDx:	usual interstitial pneumonia (irregular reticular pattern + honeycombing involving subpleural + lower lung zones

Respiratory Bronchiolitis-Interstitial Lung Disease

= interstitial pneumonia of smokers in which respiratory bronchiolitis is associated with limited peribronchiolar interstitial inflammation;? early manifestation of DIP

Mean age:	36 years; M = F
Cause:	heavy cigarette smoking
Histo:	accumulation of brown-pigmented macrophages in respiratory bronchioles + surrounding air spaces

mild dyspnea + cough
pulmonary function test: mixed restrictive + obstructive
normal CXR (21%)
diffuse bibasilar small linear + nodular opacities (71%)
bibasilar atelectasis (12%)
bronchial wall thickening

CT:

scattered ground-glass opacities (66%)
centrilobular micronodules
centrilobular emphysema

Prognosis:

excellent (after cessation of smoking/corticoid therapy) without progression to end-stage lung fibrosis

Chronic Interstitial Pneumonia

= ORGANIZING INTERSTITIAL PNEUMONIA = CHRONIC DIFFUSE SCLEROSING ALVEOLITIS

Usual Interstitial Pneumonia

= UIP = IDIOPATHIC PULMONARY FIBROSIS (IPF)
- = MURAL TYPE OF FIBROSING ALVEOLITIS
- = CRYPTOGENIC FIBROSING ALVEOLITIS
= commonest (90%) form of idiopathic interstitial pneumonia (may represent late stage of DIP)

Etiology:	50% idiopathic; 25% familial; drug exposure (bleomycin, cyclophosphamide (Cytoxan ), busulfan, nitrofurantoin); 20 30% associated with collagen vascular disease/immunologic disorder (mostly rheumatoid arthritis)
Pathophysiology:	repetitive episodes of lung injury to the alveolar wall causing alveoli to flood with proteinaceous fluid + cellular debris; incomplete lysis of intraalveolar fibrin; type II pneumocytes regenerate over the intraalveolar collagen incorporating the fibrous tissue into alveolar septa (= injury-inflammation-fibrosis sequence)
Mean age:	64 years; M>F
Path:	simultaneous presence of inflammatory cell infiltration + fibrotic alveolar walls + honeycombing + areas of normal lung tissue (= temporal variegation)
Histo:	proteinaceous exudate in interstitium + hyaline membrane formation in alveoli; necrosis of alveolar lining cells followed by cellular infiltration of mono- and lymphocytes + regeneration of alveolar lining; intraalveolar histiocytes; proliferation of fibroblasts + deposition of collagen fibers + smooth muscle proliferation; progressive disorganization of pulmonary architecture

P.503

progressive dyspnea, dry cough, fatigue (over 1 3 years)
Velcro rales = crepitations
clubbing of fingers (83%)
lymphocytosis on bronchoalveolar lavage (marker of alveolitis)
pulmonary function tests: restrictive defects + decreased diffusing capacity for carbon monoxide
occasionally ground-glass pattern in early stage of alveolitis (alveolar wall injury, interstitial edema, proteinaceous exudate, hyaline membranes, infiltrate of monocytes + lymphocytes) in 15 62%
bilateral diffuse linear/small irregular reticulations (100%); basilar (85%) + peripheral (59%)
reticulonodular pattern = superimposition of linear opacities
heart border shaggy
honeycombing = numerous cystic spaces (up to 74%)
elevated diaphragm = progressive loss of lung volume (45 75%)
1.5 3-mm diffusely distributed nodules (15 29%)
pleural effusion (4 6%), pleural thickening (6%)
pneumothorax in 7% (in late stages)
normal CXR (2 8%)

HRCT (88% sensitive):

Location:	lung bases (68 80%)
Site:	predominantly subpleural regions (79%)

patchy distribution with areas of normal parenchyma, active alveolitis, early + late fibrosis present at the same time (HALLMARK)
irregular linear intralobular opacities (82%) with architectural distortion of secondary pulmonary lobule
interlobular septal thickening (10%)
subpleural areas of honeycombing with cystic spaces outlined by thick fibrous walls (up to 96%)
subpleural lines (= fibrosis/functional atelectasis)
small peripheral convoluted cysts (= traction bronchiectasis) in 50%
ground-glass opacities (= diffuse inflammatory mononuclear cell infiltrates of active disease + fibroblast proliferation) in 65 76%

Cx:	bronchogenic carcinoma (more frequent occurrence)
Rx:	response to steroids in only 10 15%
Prognosis:	average survival of 3 6 years; 45% 5-year mortality rate (overall 87%); no recovery

Desquamative Interstitial Pneumonia

= DIP = DESQUAMATIVE TYPE OF FIBROSING ALVEOLITIS = ALVEOLAR MACROPHAGE PNEUMONIA
= second commonest (although rare) form of interstitial pneumonia with more benign course than UIP, may be self-limited disease or lead to UIP

Mean age:	42 years (approximately 8 years younger than in UIP); M > F
Path:	focal filling of alveolar spaces with foamy histiocytes + relative preservation of lung architecture + mild fibrosis (temporally uniform)
Histo:	alveoli lined by large cuboidal cells + filled with heavy accumulation of mononuclear cells (macrophages, NOT desquamated alveolar cells); relative preservation of alveolar anatomy; histologic uniformity from field to field
Predisposed:	smokers (history in up to 90%)

asymptomatic
weight loss
dyspnea + nonproductive cough (for 6 12 months)
clubbing of fingers
mild pulmonary function abnormalities
normal chest x-ray (3 22%)
ground-glass alveolar pattern sparing costophrenic angles (25 33%), diffuse ground-glass opacities (15%)
linear irregular opacities (60%), bilateral + basilar (46 73%)
lung nodules (15%)
honeycombing (13%)
preserved lung volume

HRCT:

Location:	mainly middle + lower lung zones (73%); bilateral + symmetric (86%)
Site:	predominantly subpleural distribution (59%)

patchy ground-glass attenuation
irregular linear opacities (= fibrosis) + architectural distortion (50%)
honeycombing + traction bronchiectasis (32%)
fibrosis of lower lung zones in late stage

Prognosis:

better response to corticosteroid Rx than UIP (in 60 80%); median survival of 12 years; 5% 5-year mortality rate (overall 16 27%);70% 10 year survival

Idiopathic Pulmonary Fibrosis

clinical syndrome

Age:

50 70 years; M > F

dry cough, exertional dyspnea
Velcro-type inspiratory crackles
digital clubbing (25 50%)
restrictive pulmonary function tests
decreased total lung capacity + functional residual capacity + residual volume
reduced diffusing capacity for carbon monoxide

CXR:

decreased lung volume, progressive over time
bibasilar subpleural reticulations
honeycombing (30%)
bibasilar ground-glass appearance (uncommon)
small nodules (<10 15%)

HRCT:

patchy bibasilar subpleural reticular (= irregular linear) opacities (= intralobular, interstitial thickening)

P.504

traction bronchiectasis
honeycombing (90%)
ground-glass opacities (occasionally)
discrete nodules (occasionally)
mild mediastinal lymph node enlargement (common)

Rx:	corticosteroids, immunosuppressive/cytotoxic agents (<10% respond); lung transplantation
Prognosis:	30 50% 5-year survival

Idiopathic Pulmonary Hemosiderosis

IPH = probable autoimmune process with clinical + radiologic remissions + exacerbations characterized by eosinophilia + mastocytosis, immunoallergic reaction, pulmonary hemorrhage, iron deficiency anemia

Age:

Chronic form: most commonly <10 years of age
Acute form (rare): in adults; M:F = 2:1

iron deficiency anemia
clubbing of fingers
hepatosplenomegaly (25%)
bilirubinemia
recurrent episodes of severe hemoptysis
bilateral patchy alveolar-filling pattern (= blood in alveoli); initially for 2 3 days with return to normal in 10 12 days unless episode repeated
reticular pattern (= deposition of hemosiderin in interstitial space) later
moderate fibrosis after repeated episodes
hilar lymph nodes may be enlarged during acute episodes

Prognosis:

death within 2 20 years (average survival 3 years)

DDx:SECONDARY PULMONARY HEMOSIDEROSIS

caused by mitral valve disease
septal lines (NOT in idiopathic form)
lung ossifications (NOT in idiopathic form)

Inflammatory Myoblastic Pseudotumor

= PLASMA CELL GRANULOMA = INFLAMMATORY PSEUDOTUMOR = (FIBROUS) HISTIOCYTOMA = XANTHOMA

= XANTHOFIBROMA = XANTHOGRANULOMA
= SCLEROSING HEMANGIOMA

Prevalence:	<1% of all tumors of lung + airways
Histo:	composed of variable portions of plasma cells, lymphocytes, fibroblasts, blood vessels; foamy histiocytes + multinucleated giant cells + spindle cells (70% of tumor) grouped in CHARACTERISTIC pinwheel/whorled pattern
Age:	young patient

asymptomatic
airway obstruction (symptoms often attributed to asthma/pneumonia)

Location:

lung > bronchus/trachea > pleura

smoothly marginated mass in trachea

Rx:

surgical excision

Kartagener Syndrome

= IMMOTILE/DYSMOTILE CILIA SYNDROME

Incidence:	1:40,00; high familial incidence
Etiology:	abnormal mucociliary function secondary to generalized deficiency of dynein arms of cilia affecting respiratory epithelium, auditory epithelium, sperm

Triad:

Situs inversus (in 50%)
- 50% of patients with immotile cilia syndrome have situs inversus!
- Kartagener syndrome is present in 20% of patients with situs inversus!
Nasal polyposis with chronic sinusitis
Bronchiectasis

deafness
infertility (abnormal sperm tails)

Associated anomalies:

transposition of great vessels, tri-/bilocular heart, pyloric stenosis, postcricoid web, epispadia

Klebsiella Pneumonia

Most common cause of gram-negative pneumonias; community acquired

Incidence:	responsible for 5% of adult pneumonias
Organism:	Friedl nder bacillus = encapsulated, nonmotile, gram-negative rod
Predisposed:	elderly, debilitated, alcoholic, chronic lung disease, malignancy

bacteremia in 25%
propensity for posterior portion of upper lobe/superior portion of lower lobe
dense lobar consolidation
bulging of fissure (large amounts of inflammatory exudate) CHARACTERISTIC but unusual
empyema (one of the most common causes)
patchy bronchopneumonia may be present
uni-/multilocular cavities (50%) appearing within 4 days
pulmonary gangrene = infarcted tissue (rare)

Cx:	meningitis, pericarditis
Prognosis:	mortality rate 25 50%
DDx:	Acute pneumococcal pneumonia (bulging of fissures, abscess + cavity formation, pleural effusion/empyema frequent)

Pulmonary Langerhans cell histiocytosis

PLCH = LANGERHANS CELL GRANULOMATOSIS
rare pulmonary disorder that typically affects the young adult and is associated with cigarette smoking

Age:

most frequently in 3rd 4th decade (range 3 months to 69 years); m:f = 4:1; caucasians > Blacks

Pathogenesis:
- heavy cigarette smoking in young men with accumulation + activation of Langerhans cells (90% smokers) as a result of excess neuroendocrine cell hyperplasia + secretion of bombazine-like peptides
Path:
- multifocal granulomatous infiltration centered on walls of bronchioles (= bronchiolitis) often extending into surrounding alveolar interstitium with subsequent bronchiolar destruction leading to thick-walled cysts presumably caused by checkvalve bronchial obstruction + pneumothorax (no necrosis); in end-stage disease foci of LCG are replaced by fibroblasts forming ChARACTERISTIC stellate starfish scars with central remnants of persisting inflammatory cells
Histo:
- granuloma containing Langerhans cells, foamy histiocytes, lymphocytes, plasma cells, eosinophils

P.505

Langerhans cell:
- dendritic antigen-presenting cell found in basal layer of skin + in liver (Kupffer cell), lymph nodes, spleen, bone marrow, lung
- contains unique mostly rod-shaped cytoplasmatic inclusion bodies known as Birbeck granules (identifiable only with electron microscopy)

CXR abnormalities more severe than clinical symptoms + pulmonary function tests!
asymptomatic (up to 25%)
nonproductive cough (75%)
combination of obstructive + restrictive pulmonary function: presenting with pneumothorax in 15%
dyspnea (40%)
fatigue, weight loss, fever (15 30%)
chest pain (25%) from pneumothorax/eosinophilic granuloma in rib
diabetes insipidus (10 25%)
lymphocytosis with predominance of T-suppressor cells on bronchoalveolar lavage (DDx: excess of T-helper cells in sarcoidosis)

Location:

usually bilaterally symmetric, upper + mid lung predominance, sparing of bases + costophrenic angles

Evolutionary sequence on radiography:

nodule - cavitated nodule - thick-walled cyst - thin-walled cyst (secondary to progressive enlargement + air trapping of original cavitary nodule)
nodules 1 10 mm (granuloma stage):
- ill-defined/stellate with irregular borders
- cavitation of large nodules (rare)
diffuse fine reticular/reticulonodular pattern (cellular infiltrate)
honeycomb lung = multiple 1 5-cm cysts + subpleural blebs (fibrotic stage)
increased lung volumes in 1/3 (most other fibrotic lung diseases have decreased lung volumes!)
pleural effusion (8%), hilar adenopathy (unusual)
thymic enlargement
HRCT (combination virtually diagnostic obviating need for further testing/lung biopsy):
- centrilobular peribronchiolar nodules
- complex/branching thin-walled (<1 mm) cysts: individual cyst <5 mm in size
  - confluent contiguous cysts 2 3 cm in size
  - equally distributed in central + peripheral zones
  - As cysts become more numerous in later stages nodules occur less frequently!
- intervening lung appears normal

DDx for nodules:

sarcoidosis, hypersensitivity pneumonitis, berylliosis, TB, atypical TB, metastases, silicosis, coal worker's pneumoconiosis

DDx for cysts:

emphysema, bronchiectasis, idiopathic pulmonary fibrosis, lymphangiomyomatosis

DDx:

sarcoidosis (equal sex distribution, always multisystem disease, not related to smoking, erythema nodosum, bilateral hilar lymphadenopathy, lung cavitation + pneumothorax rare, epithelioid cells)

Cx:

Recurrent pneumothorax in 25% (from rupture of subpleural cysts) CHARACTERISTIC
Pulmonary hypertension
Superimposed Aspergillus fumigatus infection

Prognosis: poor with multisystem disease + organ dysfunction (especially with skin lesions);

complete/partial regression (13 55%)
stable (33%)
rapid progression (7 21%) to air-flow obstruction + impaired diffusing capacity + respiratory failure
- May recur in transplanted lung if smoking is continued or resumed!

Mortality:	2 25%
Rx:	cessation of smoking, chemotherapy (vincristine sulfate, prednisone, methotrexate,6-mercaptopurine)

Legionella Pneumonia

= LEGIONNAIRES' DISEASE

Organism:	Legionella pneumophila, 1 2 m, aerobic, gram-negative bacillus, weakly acid-fast, silver-impregnation stain
Predisposed:	middle-aged/elderly, immunosuppressed, alcoholism, chronic obstructive lung disease, diabetes, cancer, cardiovascular disease, chronic renal failure, transplant recipients
Transmission:	direct inhalation (air conditioning systems)
Prevalence:	6% of community-acquired pneumonias
Histo:	leukocytoclastic fibrinopurulent pneumonia with histiocytes in intraalveolar exudate

fever
absence of sputum/lack of purulence (22 75%)

Clue: involvement of other organs with

diarrhea (0 25%), myalgia, toxic encephalopathy
liver + renal disease
hyponatremia (20%)
elevated serum transaminase/transpeptidase levels
lack of quick response to penicillin/cephalosporin/aminoglycoside

Concomitant infection (in 5 10%):

Streptococcus pneumoniae, Chlamydia pneumoniae, Mycobacterium tuberculosis, Pneumocystis carinii

Location:

unilateral/bilateral (less frequent); lobar/segmental

patchy bronchopneumonia (= multifocal consolidation)
moderate volume of pleural effusion (6 30 63%)
cavitation (rare)

Cx:	progressive respiratory failure (most common cause of death; 6% mortality in healthy patients)
Rx:	erythromycin

Lipoid Pneumonia

Acute Exogenous Lipoid Pneumonia

= FIRE-EATER PNEUMONIA

Material:	liquid paraffin, petroleum (hydrocarbons)
Cause:	accidental poisoning in children, fire-eaters

ill-defined nodular areas of increased radiopacity
pneumatoceles/thin-walled collections of air

P.506

Chronic Exogenous Lipoid Pneumonia

Etiology:

aspiration/inhalation of fatlike material

Types of oils:

vegetable oil: sesame oil used in medical suspensions for the treatment of constipation
animal oil: cod liver oil (commonly given to children); squalene = derivative of shark liver oil (folk remedy in some Asian countries); milk
mineral oil (most common): as liquid paraffin in nose drops (taken at bedtime)/oral laxatives = inert pure hydrocarbon that does not initiate cough reflex

Predisposed:	elderly, debilitated, neuromuscular disease, swallowing abnormalities (eg, scleroderma)
Path:	pool of oil emulsified by lung lipase + surrounded by giant cell foreign body reaction (mineral oil aspiration)/necrotizing hemorrhagic bronchopneumonia (higher content of free fatty acid in animal fat aspiration)

The degree + type of tissue reaction depend on the frequency of aspiration + chemical character of the oil

Histo:

numerous lipid-laden macrophages distending alveolar walls + interstitium, accumulation of lipid material, inflammatory cellular infiltration, variable amount of fibrosis

mostly asymptomatic
fever, constitutional symptoms
lipid-laden macrophages in sputum/lavage fluid
oil droplets in bronchial washing/needle aspirate

Location:

predilection for RML + lower lobes

homogeneous segmental airspace consolidation (most common)
interstitial reticulonodular pattern (rare)
paraffinoma = circumscribed peripheral mass (granulomatous reaction + fibrosis often causing stellate appearance)
slow progression/no change

CT:

diffuse ground-glass opacity of centri-/panlobular distribution (= acinar pattern) + thickening of interlobular septa as earliest finding
airspace consolidation (filling of alveoli with exudate + inflammatory cells) at 1 week
return to ground-glass opacity (due to expectoration + lymphatic drainage of lipid droplets and inflammatory cells) at 2 4 weeks
volume loss + fibrosis of interlobular septa and pleura at 14 16 weeks
mass of low-attenuation approaching that of subcutaneous fat ( 150 to 50 HU)

Dx:

bronchoalveolar lavage, transbronchial biopsy

L ffler Syndrome

= Simple pulmonary eosinophilia
= disorder of unknown etiology characterized by local areas of transient parenchymal consolidation associated with blood eosinophilia

Path:

interstitial + alveolar edema containing a large number of lymphocytes

no/mild symptoms
high WBC + peripheral eosinophilia
history of asthma + atopy (common)
single/multiple areas of homogeneous ill-defined consolidation
uni- or bilateral, nonsegmental distribution, predominantly in lung periphery
fleeting infiltrates = transient + shifting in nature (changes within one to several days)

Prognosis:

may undergo spontaneous remission

Lung Transplant

Indications for transplantation:

emphysema/COPD (39%), idiopathic pulmonary fibrosis (17%), cystic fibrosis (16%), alpha-1 antitrypsin deficiency (9%), CHD, primary pulmonary hypertension, sarcoidosis, pneumoconiosis, malignancy (lung cancer contraindicated)

Unilateral lung transplants:

in selected cases of emphysema, pulmonary fibrosis

Contraindicated in: c	ystic fibrosis, bronchiectasis (due to cross-contamination)
Operative mortality:	up to 8%

Recurrence of primary disease:

sarcoidosis (in 35%); others (in 1%): lymphangioleiomyo matosis, Langerhans cell histiocytosis, talc granulomatosis, diffuse panbronchiolitis, alveolar cell proteinosis

Survival rate:

90% for 1 month, 84% for 3 month, 74% for 1 year, 58% for 3 years, 47% for 5 years, 24% for 10 years

Acute Rejection of Lung Transplant

Incidence:

60 80% with 2 3 significant episodes in first 3 months

Does not develop until 7 to 10 days after surgery!
Most patients will have at least 1 episode in the year following transplantation!

Histo:	mononuclear cell infiltrate around arteries, veins, bronchioles, alveolar septa with alveolar edema (initially) + fibrinous exudate (later)
Time of onset:	first episode 5 10 days after transplantation; occasionally by 48 hours

drop in arterial oxygen pressure WITHOUT infection /airway obstruction/fluid overload
pyrexia, fatigue, decreased exercise tolerance
heterogeneous opacities in perihilar areas
ground-glass attenuation on HRCT
new increasing pleural effusion + septal thickening (most common, 90% specific, 68% sensitive) WITHOUT concomitant signs of LV dysfunction (increase in cardiac size/vascular pedicle width/vascular redistribution)
subpleural edema, peribronchial cuffing, airspace disease

Dx:

Transbronchial biopsy
Rapid improvement of radiologic abnormalities after treatment with IV bolus of corticosteroids for 3 days

Rx:

methylprednisolone, polyclonal T-cell antibody (antithymocyte globulin), monoclonal antibodies (CD3, OKT3), lymphoid irradiation

Anastomotic Complications of Lung Transplant

1. Airway dehiscence (2 8%)
- presence of extraluminal air collections at anastomotic site (80%)
P.507

DDx: telescoped anastomosis
2. Airway stricture/stenosis

DDx: telescoped anastomosis

Rx: laser resection, balloon bronchoplasty
3. Vascular stenosis
4. Diaphragmatic hernia from omentopexy

Procedure: omental pedicle is harvested at time of transplantation through a small diaphragmatic incision + wrapped around anastomosis to prevent dehiscence

Chronic Rejection of Lung Transplant

= BRONCHIOLITIS OBLITERANS SYNDROME (BOS)

Prevalence: 24%

Probably develops in all transplant patients given sufficient time!

Risk factor:	frequent/severe bouts of acute rejection, gastroesophageal reflux
Path:	obliterative bronchiolitis (36%), interstitial pneumonitis, rejection-mediated vasculopathy
Time of onset:	3 75 months after transplantation

persistent coughing and wheezing
slowly worsening exertional dyspnea

HRCT:

air trapping on expiratory HRCT
mosaic perfusion
central + peripheral cylindrical bronchiectasis
bronchial wall thickening

CXR:

increased/diminished lung volumes
localized airspace disease
diminished peripheral lung markings
partial lobar atelectasis
thin irregular areas of increased opacity
pleural thickening
nodular/reticular opacities associated with peribronchial thickening

Hyperacute Rejection of Lung Transplant

= rejection in cases of an immunoglobulin G donor-specific HLA antibody positive crossmatch

Path:

acute diffuse alveolar damage

Posttransplantation Infection

Cause:

immunosuppression, reduced mucociliary clearance, interruption of lymphatic drainage, direct contact of transplant with environment via airways

May occur at any time during postoperative period!

Incidence:

35 86% of transplant recipients

INFECTION OF LUNG TRANSPLANT

Prevalence: 35 50%; major cause of morbidity + mortality in early postoperative period

Cause: ? absent cough reflex, impaired mucociliary transport in denervated lung

Organism: bacteria (23%): Staphylococcus, Pseudomonas > CMV > Aspergillus (6%) > Pneumocystis
- within 1st month: gram-negative bacteria, fungi (candidiasis, aspergillosis)
- after 1st month: CMV, Pneumocystis carinii, bacteria, fungi
- fever, leukocytosis
- lobar/multilobar consolidation (due to bacterial > fungal pathogens)
- diffuse heterogeneous air-space/ground-glass opacities (due to viral/disseminated fungal pathogens)
- nodules (due to fungal/unusual bacterial pathogens/CMV/septic emboli)
- septal lines
- pleural effusion
Cx: may progress rapidly to respiratory failure + death

Dx: transbronchial/open biopsy (80% accurate)
EXTRAPULMONARY INFECTION
- thoracotomy wound infection, bacteremia, sepsis, empyema, central venous line infection
Prognosis: primary cause of of postoperative mortality in up to 50%; 2 12% mortality for CMV; 50% mortality for Aspergillus

Posttransplantation Lymphoproliferative Disease

Incidence:	4 6%
Histo:	spectrum from benign polyclonal B-cell proliferation of lymphoid tissue to aggressive monoclonal non-Hodgkin lymphoma
Associated with:	Epstein-Barr virus
Time of onset:	1 month to several years; related to immunosuppressive regimen
Location:	intrathoracic (most common in 1st year), extrathoracic (late development) in GI tract, skin, oropharynx, solid organs

solitary/multiple discrete nodules ground-glass halo
mediastinal/hilar lymphadenopathy
parenchymal consolidation
pleural masses

Reperfusion Edema

= REIMPLANTATION RESPONSE
= infiltrate appearing within 48 hours after transplantation unrelated to fluid overload, LV failure, infection, atelectasis, or rejection; diagnosed by exclusion
most frequent immediate postoperative complication!

Risk factors:	poor organ preservation, prolonged ischemic time, unsuspected donor pathology (contusion, aspiration), interrupted lymphatic supply, cytokine-mediated injury
Pathogenesis:	permeability edema due to lymphatic disruption, pulmonary denervation, organ ischemia, trauma
Histo:	fluid accumulation in interstitium consistent with noncardiogenic pulmonary edema
Time course:	manifests within 24 hours, peaks at 2nd-4th postoperative day, resolves at variable rate ranging from days to 1 2 weeks to months

increasing hypoxia before extubation; poor correlation between radiographic severity + physiologic parameters

Location:

perihilar areas + basal regions in transplanted lung

perihilar haze/rapid uni- or bilateral heterogeneously dense interstitial and/or airspace disease
small pleural effusions

P.508

Dx:	per exclusion (radiographic changes not due to LV failure, hyperacute rejection, fluid overload, infection, atelectasis)
Prognosis:	usually resolves over 7 to 10 days
Rx:	diuresis, mechanical support

Lymphangiomyomatosis

= LAM = LYMPHANGIOLEIOMYOMATOSIS
= rare disorder characterized by
- gradually progressive diffuse interstitial lung disease
- recurrent chylous pleural effusions
- recurrent pneumothoraces

Prevalence:	1:1,000,000
Etiology:	unknown; hamartomatous proliferation of a particular form of HMB-45 positive smooth muscle (? forme fruste of tuberous sclerosis)
Age:	17 62 (mean, 34) years, exclusively in women of childbearing age
Path:	hyperaerated lungs with extensive diffuse 5 20 mm cysts affecting both lungs + distorting pleural surfaces
Histo:	abnormal proliferation of atypical smooth muscle cells (LAm cells) in pulmonary lymphatic vessels, blood vessels, and airways

Pathogenesis:

proliferation of immature smooth muscle cells in a haphazard fashion causes obstruction of
- bronchioles (trapping of air, overinflation, formation of cysts, pneumothorax),
- venules (pulmonary edema, hemorrhage, hemosiderosis)
- lymphatics (thickening of lymphatics, chylothorax)

Hormonal influence:

menstruation, pregnancy, exogenous estrogen treatment may result in exacerbation of symptoms

Cause of thin-walled lung cysts:

air trapping distal to small airways narrowed by smooth muscle proliferation
destruction of collagen + elastin in the interstitium from metalloproteinases elaborated by LAM cells

May be associated with: Tuberous sclerosis (lung involvement in 1%)

progressive exertional dyspnea (59%) + cough (39%)
hemoptysis (30 40%), chyloptysis (rare)
combination of restrictive + obstructive ventilatory defects:
radiologic-physiologic discrepancy = severe airflow obstruction in 100% (reduced FEV₁, reduced ratio of FEV₁/FVC) despite relatively normal findings on CXR
decreased D_LCO = diffusing capacity for lung carbon monoxide (54%)
hypoxemia without hypercapnia on arterial blood gas
positive immunohistochemical staining of LAM cells with HMB-45 (monoclonal antibody for melanocytic lesion)

CXR:

classic signs:
- coarse reticular/reticulonodular interstitial pattern diffusely + equal in all lung zones caused by summation of multiple cyst walls (80 90%)
- recurrent pneumothorax (39 53% at presentation; in up to 81% during course of disease)
- recurrent large chylothorax (14% at presentation; in up to 39% during course of disease)
- normal (55 78%)/increased (22 45%) lung volume
- The only interstitial lung disease to develop increase in lung volume!
- Kerley B lines = interlobular septal thickening (due to dilatation of lymphatics)
- pulmonary cysts (visible if >1 cm) + honeycombing
- pericardial effusion/chylous pericardial effusion (rare)
- mediastinal + retroperitoneal adenopathy (from smooth muscle proliferation)

CT:

numerous randomly scattered thin-walled (<2 mm) cysts of various sizes (typically 2 5 mm, up to 30 mm) surrounded by normal lung parenchyma

Parenchymal involvement related to cyst size:

<25% of parenchyma with cyst sizes <5 mm

25 80% of parenchyma with cyst sizes 5 10 mm

>80% of parenchyma with cyst sizes >10 mm
consolidations (due to hemorrhage following destruction of pulmonary microvasculature)
dilated thoracic duct
chylous effusion (-17 HU)
precarinal + retrocrural lymph nodes

NUC (V/Q scan):

speckling = well-defined hot spots on ventilation scan (presumably due to accumulation of coalescing droplets of DTPA aerosol trapped in peripheral cysts) in 66%

@ Abdomen (in 76% positive findings)
- bloating, increased abdominal girth, abdominal pain
- flank/pelvic pain
- perineal swelling, chylous vaginal discharge
- lymphadenopathy of up to 4 cm (33%):
  
  Histo: replacement of lymph node with smooth muscle
  
  Location: retroperitoneum (77%) > pelvis (11%) > mesentery > posterior mediastinum > axilla > neck
  - central hypoattenuating areas of 72 to +50 HU (due to chylous lymph collections/fat)
- lymphangioleiomyoma (5 21%) = well-defined lobulated complex lymphatic mass:
  - volumes of 10 1,500 mL
  - hypoattenuating center of 3 25 HU
  - anechoic irregularly shaped thin-walled cysts with intraluminal septa (= ectatic lymphatic vessels)
    
    Path: smooth muscle proliferation in walls of lymphatics resulting in lymphatic dilatation + mural thickening
- chylous ascites (10 33%): low-density ascites of 10 to +21 HU due to rupture of overdistended lymph cysts
- dilatation of thoracic duct (10%)
- fatty liver masses (5%): AML/lipoma
- uterine leiomyomas

@ Kidneys

flank pain, hematuria, severe hypotension, chyluria
angiomyolipoma (in 20 54%):
- occasionally lacking fat
- multiplicity in <20%
simple cysts (occasionally large enough to lead to renal insufficiency)

Dx:	open/transbronchial lung biopsy; image-guided biopsy of an extrapulmonary mass
Rx:	hormone therapy, oophorectomy, lung transplantation
Prognosis:	8.5-year survival rate of 38 78%; invariably death within 10 years from progressive respiratory failure + cor pulmonale

P.509

DDx:

Tuberous sclerosis (cortical tubers, subependymal nodules, retinal hamartomas, facial angiofibromas, periungual fibromas, mental retardation, epilepsy, multiple renal AML in 40 80%)
Histiocytosis (cysts in upper 2/3 of lung with sparing of costophrenic angles, cyst walls more variable in thickness, pulmonary nodules + cavitation, septal thickening)
Emphysema (imperceptible cyst walls, cysts may be segmentally distributed, lobular architecture preserved with bronchovascular bundle in central position, areas of lung destruction without arcuate contour)
Idiopathic pulmonary fibrosis = fibrosing alveolitis (small irregular thick-walled cysts + predominantly peripheral interstitial thickening)
Bronchiectasis (bronchial wall thickening)
Neurofibromatosis (cystic air spaces predominantly in apical location)

Lymphangitic Carcinomatosis

= INTERSTITIAL CARCINOMA = LYMPHANGITIS CARCINOMATOSA
= tumor cell accumulation within connective tissue (bronchovascular bundles, interlobular septa, subpleural space, pulmonary lymphatics) from tumor embolization of blood vessels followed by lymphatic obstruction, interstitial edema, and collagen deposition (fibrosis from desmoplastic reaction when tumor cells extend into adjacent pulmonary parenchyma)

Incidence:	7% of all pulmonary metastases
Tumor origin:	bronchogenic carcinoma, carcinoma of breast (56%), stomach (46%), thyroid, pancreas, larynx, cervix
mnemonic:	Certain Cancers Spread By Plugging The Lymphatics

Cervix
Colon
Stomach
Breast
Pancreas
Thyroid
Larynx

Path:

interstitial edema
interstitial fibrotic changes
lymphatic dilatation
tumor cells within connective tissue planes

dyspnea (often preceding radiographic abnormalities)
rarely dry cough + hemoptysis

Location:

bilateral; unilateral if secondary to lung primary

CXR (accuracy 23%):

normal chest radiograph
reticular/reticulonodular opacities
coarsened bronchovascular markings
Kerley A + B lines
small lung volume
hilar (20 50%)/mediastinal lymphadenopathy
pleural effusion

HRCT:

normal lung architecture without distortion
focal/diffuse, uni-/bilateral distribution
well-defined smoothly thickened polygonal reticular network of 10 25 mm in diameter (= thickened interlobular septa)
irregular/nodular = beaded thickening of interlobular septa
central dot within secondary pulmonary lobule = thickened centrilobular bronchovascular bundle
smooth/nodular thickening of fissures
subpleural thickening
pleural effusion (30 50%)
hilar/mediastinal lymphadenopathy (30 50%)

Prognosis:

death within 1 year

DDx:

Fibrosing alveolitis (peripheral predominance)
Extrinsic allergic alveolitis (no polygonal structures, pleural changes rare)
Sarcoidosis (nodules of irregular outline more frequent in upper lobes, polygonal structures uncommon)
pulmonary edema (smooth septal thickening)

Lymphoid Interstitial Pneumonia

= LYMPHOCYTIC INTERSTITIAL PNEUMONITIS = LIP
= benign lymphoproliferative disorder characterized by diffuse interstitial lymphocytic infiltration (probably immunologic disorder) with highly variable course

Histo:	extensive infiltration of bronchovascular bundles, interlobular septa, and pleura by polyclonal mature small lymphocytes + plasma cells; many cases reclassified as lymphoma
Associated with:	Sj gren syndrome, autoimmune thyroid disease, AIDS, Castleman disease, systemic lupus erythematosus, myasthenia gravis, pernicious anemia, chronic active hepatitis

Indicative of AIDS when present in child under 13 years of age!
dyspnea + cough
cyanosis + clubbing (50%)
enlargement of salivary glands (20%)
NO lymphocytosis or history of atopia
monoclonal gammopathy (usually IgM)

Distribution: bilateral, involving all lung zones
fine reticular changes in both lungs
reticulonodular pattern
resembling airspace disease (in severe form)

CT:

ill-defined centrilobular nodules (100%)
ground-glass attenuation (100%)
thickening of bronchovascular bundles + interlobular septa (in majority)
subpleural small nodules (in majority)
airspace consolidation
cysts (due to partial airway obstruction by peribronchial + peribronchiolar LIP) in 68%
mediastinal lymph node enlargement (50%)

Prognosis:

recovery/slowly improving/stable disease
progressive disease (in 33%)

P.510

Rx:	responsive to steroids
DDx:	Hypersensitivity pneumonitis (ground-glass attenuation, small centrilobular nodules, NOT cystic airspaces/thickening of interlobular septa or bronchovascular bundles)

Localized form = PSEUDOLYMPHOMA

Lymphoma

Non-Hodgkin Lymphoma (NHL)
7th leading cause of death from cancer in United States

Pathogenesis:	? viral cause
Incidence:	3% of all newly diagnosed cancers; 3rd most common cancer in childhood (behind leukemia + CNS neoplasms); 4 times more common than Hodgkin disease
Predisposed:	(40 100 times greater risk) congenital immunodeficiency syndromes, organ transplant patients undergoing immunosuppression, patients with HIV infection, collagen vascular diseases
Age:	all ages; median age of 55 years; M:F = 1.4:1

chest/shoulder pain, dyspnea, dysphagia
CHF, hypotension, SVC syndrome

Modified Rappaport Classification:

= categorization according to histologic distribution of lymphomatous cells

Nodular form = organized in clusters
- Poorly differentiated lymphocytic (PDL)
- Mixed lymphocytic/histiocytic (mixed cell)
- Large cell (histiocytic)
Diffuse form = distortion of tissue architecture
- Well-differentiated lymphocytic (WDL)
- Intermediate-differentiated lymphocytic (IDL)
- Poorly differentiated lymphocytic (PDL)
- Mixed lymphocytic/histiocytic large cell (histiocytic) (DLCL); undifferentiated Burkitt lymphoma; undifferentiated non-Burkitt lymphoma (pleiomorphic); lymphoblastic (LBL); unclassified

Luke and Collins Classification:

= categorization by morphologic characteristics of cell + cell of origin (T cell, B cell, non-B, non-T cell)

Working Formulation Classification (Kiel/Lennert):

= categorization by grade

Low grade
- Small lymphocytic (3.6%)median age 61 years, 59% 5-year survival
- Follicular, small cleaved cell (22.5%) median age 54 years, 70% 5-year survival
- Follicular, mixed (7.7%)median age 56 years, 50% 5-year survival
Intermediate grade
- Follicular, large cell (3.8%) median age 55 years, 45% 5-year survival
- Diffuse, small cleaved cell (6.9%) median age 58 years, 33% 5-year survival
- Diffuse, mixed (6.7%) median age 58 years, 38% 5-year survival
- Diffuse, large cell (19.7%) median age 57 years, 35% 5-year survival
High grade
- Large cell, immunoblastic (7.9%)median age 51 years, 32% 5-year survival
- Lymphoblastic (4.2%)median age 17 years, 26% 5-year survival
- Small noncleaved cell (5%M)median age 30 years, 23% 5-year survival
Miscellaneous (12%)
- composite, mycosis fungoides, histiocytic, extramedullary plasmacytoma
Staging: same Ann Arbor system as for Hodgkin disease

Extranodal Involvement of NHL

@ GI tract:
- stomach (3%), small bowel (5%), large bowel (2%), pancreas (0.7%), peritoneal nodules + ascites (1.4%)
@ Chest (40 50%):
- lung (6%), pleural fluid (3.3%), pericardial fluid (0.7%), heart (0.2%)
- hilar + mediastinal adenopathy (DDx: sarcoidosis; anterior nodes favor lymphoma)
  - Nodes frequently not involved!
- isolated lymph nodes may enhance (ddx: castleman disease)
- lung nodules + air bronchograms
- pleural effusion
Prognosis: unfavorable
@ GU tract (10%):
- kidneys (6%), testes (1.2%), ovaries (1.8%), uterus (1.2%)
@ Bone (3.8%)
@ CNS (2.4%)
@ Breast (1.2%)
@ Skin (6.4%)
@ Head and neck (1.7%)
@ Liver (14%)
@ Spleen (41%)

Differences Between NHL and hodgkin Disease
Organ Involvement	NHL	HD
Thoracic involvement	45%	85%
Mediastinal nodes	posterior	anterior
Lung involvement	4%	12%
Lymphadenopathy
Periaortic adenopathy	49%	25%
Mesenteric adenopathy	51%	4%
Liver involvement	14%	8%
Hepatomegaly	57%	<30%
Splenic involvement	41%	37%

Nodal involvement of NHL

@ Paraaortic lymph nodes (49%)
@ mesenteric lymph nodes (51%):
- predominantly in middle mediastinum, cardiophrenic angle
  - single lymph node involvement is often the only manifestation of intrathoracic disease!

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@ splenic hilar lymph nodes (53%)
- Lymphography 89% sensitive + 86% specific

Differences Between NHL and hodgkin Disease
Organ Involvement	NHL	HD
Thoracic involvement	45%	85%
Mediastinal nodes	posterior	anterior
Lung involvement	4%	12%
Lymphadenopathy
Periaortic adenopathy	49%	25%
Mesenteric adenopathy	51%	4%
Liver involvement	14%	8%
Hepatomegaly	57%	<30%
Splenic involvement	41%	37%

Comparison of Histologic Classifications of Non-Hodgkin Lymphoma
International Working Formulation	Rappaport Classification
Low grade
A. small lymphocytic	Well-differentiated lymphocytic
B. follicular, predominantly small cleaved cell	Nodular, poorly differentiated lymphocytic
C. follicular, mixed small and large cell	Nodular, mixed
Intermediate grade
D. Follicular, predominantly large cell	Nodular, histiocytic
E. Diffuse, small cleaved cell	Diffuse, poorly differentiated lymphocytic
F. Diffuse, mixed small and large cell	Diffuse, mixed
G. Diffuse, large cell, cleaved or noncleaved
High grade
H. Diffuse large cell, immunoblastic
I. Small, noncleaved cell
J. Lymphoblastic	Undifferentiated

Differences Between Nhl And Hodgkin Disease

HD:	contiguous spread requires scanning of abnormal area only
NHL:	noncontiguous spread requires scanning of chest, abdomen, pelvis

@ Thoracic lymphadenopathy

anterior mediastinal, pretracheal, hilar, subcarinal, axillary, periesophageal, paracardiac, superior diaphragmatic internal mammary lymph nodes
- anterior mediastinum: nodular sclerosing type of Hd (75%); m < f
- posterior mediastinum: NHL
@ spleen

HD: most common site of abdominal involvement

NHL: 3rd most common site of abdominal involvement; may be initial manifestation in large cell nHL
- staging laparotomy necessary as 2/3 of tumor nodules <1 cm in size
@ Gastrointestinal involvement
- in 10% of patients with abdominal lymphoma (uncommon in Hd, common in histiocytic nHL); nHL accounts for 80% of all gastric lymphomas
@ renal involvement
- late manifestation, most commonly in nHL
@ Adrenal involvement
- more common in N HL
@ extranodal involvement
- more frequent with histologically diffuse forms of NHL

Differences between Adult and Childhood NHL
Characteristics	Adult NHL	Childhood NHL
Primary site	nodal	extranodal
Histology	50% follicular, 50% diffuse	diffuse
Grade	low, intermediate, high	high
Histologic subtype	many	three
Sex predilection	none	70% male

Non-Hodgkin Lymphoma in Childhood

Incidence:	3rd most common childhood malignancy (after leukemia + cns tumors); 7% of all malignancies in children <15 years of age
Origin:	B or T cell (in 90%) located outside marrow; (rarely) non-B and non-T cells located within bone marrow
Age:	median age of 10 years; <15 years of age (most common); unusual <5 years of age; m > f

chest pain, back pain, cough, dyspnea
fever, anorexia, weight loss
peripheral blood + bone marrow involvement (particularly in lymphoblastic nHL): with lymphoblastic bone marrow involvement of <25%
patient is classified as having lymphoma

Staging (St. Jude):

I	single extranodal tumor/single anatomic area
II	single extranodal tumor + regional nodes 2 nodal areas on same side of diaphragm 2 single extranodal tumors nodes on same side of diaphragm primary gastrointestinal tract tumor nodes
III	2 single extranodal tumors on opposite sides of diaphragm 2 nodal areas on both sides of the diaphragm primary intrathoracic tumors (mediastinum, pleura, thymus) extensive primary intraabdominal disease paraspinal/epidural tumor
IV	any of the above + initial CNS/bone marrow involvement

Prognosis:	80% cure rate with multiple-agent chemotherapy
DDx:	Acute lymphocytic leukemia (>25% lymphoblasts within bone marrow) Hodgkin disease (contiguous spread, nodes are site of origin)

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Undifferentiated/Small Noncleaved NHL (39%)

Path:

non-Burkitt lymphoma; Burkitt lymphoma

abdominal mass ascites
pain similar to appendicitis/intussusception

Primary site:	abdomen (distal ileum, cecum, appendix); ovaries
Common site:	mesenteric, inguinal, iliac nodes; CNS; bone marrow; kidney
Rare site:	orbit, supradiaphragmatic paraspinal region, mediastinum, paranasal sinuses, bone, testes, pulmonary parenchyma
Cx:	leukemic transformation (= extensive bone marrow involvement)

Lymphoblastic (T-cell) NHL (28%)

Primary site:	mediastinum (66%)
Common site:	neck, thymus, liver, spleen, CNS, bone marrow, gonads
Rare site:	subdiaphragmatic (ileum, cecum, kidney, mesentery, retroperitoneum), orbit, paranasal sinus, thyroid, parotid

respiratory distress, dysphagia
SVC syndrome, pericardial tamponade

Large Cell (histiocytic) NHL (26%)

Origin:	B cell, T cells (small percentage)
Location:	nodal + extranodal
Primary site:	variable (Waldeyer ring, Peyer patches)
Common site:	peripheral lymph nodes, lung, bone, brain, skin
Rare site:	hard palate, esophagus, trachea

Lymphomatoid Granulomatosis

= angiocentric + angiodestructive lymphoproliferative + granulomatous disease

Age:	7 85 (mean of 48) years; M:F = 2:1
Path:	multiple sharply marginated masses adjacent to a bronchus causing obstructive pneumonitis
Histo:	angiocentric infiltrate of atypical lymphoid cells (of B-cell lineage containing Epstein-Barr virus) with vascular invasion + destruction; necrotic lung parenchyma in higher grade lesions; giant cells absent (DDx to Wegener granulomatosis)

malaise, weight loss (35%)
no specific serum markers
Less commonly found in lymph nodes, bone marrow, spleen
Involvement of upper respiratory tract + sinuses is very unusual
@ Lung (100%)
- fever (60%), cough (56%), dyspnea (29%)
- normal CXR
- diffuse reticulonodular opacities (= granulomas)
- large masslike opacities (= granulomas + pulmonary infarcts)
- multiple bilateral nodules in middle + lower lobes (80%)
- unilateral involvement (21%)
- small pleural effusions (40%)
- hilar lymphadenopathy (25%)
CT:
- peripheral subpleural 0.6 8 cm large nodules/masses
- central cavitation (30%)
- reticular/nodular airspace opacities (10 43%)
@ Skin (39 53%)
- nodules, ulcers, maculopapular rash (20 39%)
@ CNS (37 53%)
- neurologic complaints (21%)
@ Kidneys (32 40%)

Cx:	lymphoma (12 47%)
Mortality:	in 53 90% from sepsis, respiratory failure, pulmonary embolism, massive hemoptysis, CNS lesions

Lymphoproliferative Disease After Transplantation

abnormal proliferation of lymphoid cells in immunocompromised organ transplant recipients in a spectrum ranging from mild lymphoid hyperplasia to malignant lymphoma

Incidence:

2% of all allograft recipients:
bone marrow transplantation 0.6%
renal graft transplantation 1 5%
cardiac transplantation 1.8 20%
liver transplantation 2%
lung transplantation 6.2 9.4%

Pathophysiology of B-cell (in 86%) origin:

Infection of B lymphocytes with EBV (Epstein-Barr virus) causes increased proliferation of B cells (= polyclonal B-cell expansion)
Loss of protective immune control by T cells allows for uncontrolled proliferation of EBV-infected B lymphocytes (= oligoclonal B-cell expansion)
Genetic mutation transforms some B cells into malignant cells

14% of posttransplantation LPD is of T-cell origin

Time of onset:

2 5 months (mean) after bone marrow, lung, heart-lung transplantation; 23 32 months (mean) after kidney, heart, liver transplantation
Under cyclosporine/OKT3 within 1 month

Unique features:

predilection for extranodal sites
varied morphologic appearance
strong/probably causal association with EBV infection
frequent absence of immunophenotypic/genotypic evidence of monoclonality
poor response to cytolytic chemotherapy/irradiation

illness resembling infectious mononucleosis = pharyngitis, fever, lymphadenopathy, hepatosplenomegaly
@ any site, including CNS, lymph nodes, thorax, GI tract, or allograft
@ Chest
- well-circumscribed nodules low-attenuation center
- patchy air space consolidation
- mediastinal/hilar lymphadenopathy
@ Liver
- focal hepatic mass in orthotopic liver transplant
- periportal adenopathy

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Meconium Aspiration Syndrome

most common cause of neonatal respiratory distress in full term/postmature infants (hyaline membrane disease most common cause in premature infants)

Etiology:	fetal circulatory accidents/placental insufficiency/postmaturity result in perinatal hypoxia + fetal distress with meconium defecated in utero
Pathogenesis:	severe hypoxemia induces gasping reflex with inhalation of tenacious meconium that produces medium and small airway obstruction + chemical pneumonitis
Incidence:	10% of all deliveries have meconium-stained amniotic fluid, 1% of all deliveries have respiratory distress

cyanosis (rare)
persistent fetal circulation syndrome = neonatal pulmonary hypertension (secondary to thick-walled pulmonary arterioles) + R-to-L shunt through PDA and foramen ovale + severe cyanosis

Rx:

extracorporeal membrane oxygenation (major indication besides diaphragmatic hernia + neonatal pneumonia)

large infant
bilateral diffuse grossly patchy opacities (atelectasis + consolidation)
hyperinflation with areas of emphysema (air trapping)
spontaneous pneumothorax + pneumomediastinum (25 40%) requiring no therapy
small pleural effusions (10 20%)
NO air bronchograms
rapid clearing usually within 48 hours

Cx:

morbidity from anoxic brain damage is high

Mediastinal Lipomatosis

excess unencapsulated fat deposition

Etiology:

exogenous steroids (average daily dose of >30 mg prednisone):
- Chronic renal disease, renal transplant (5%)
- Collagen vascular disease, vasculitis
- Hemolytic anemia
- Asthma
- Dermatitis
- Crohn disease
- Myasthenia gravis
endogenous steroid elevation:
- Adrenal tumor
- Pituitary tumor/hyperplasia = Cushing disease
- Ectopic ACTH-production (carcinoma of the lung)
obesity

moon facies
buffalo hump
supraclavicular + episternal fat

Location:

upper mediastinum (common), cardiophrenic angles + paraspinal areas (less common)

upper mediastinal widening
paraspinal widening
increase in epicardial fat-pads
symmetric slightly lobulated extrapleural deposits extending from apex to 9th rib laterally

OTHER FEATURES:

osteoporosis
fractures
aseptic necrosis
increased rectosacral distance

Mesothelioma

Benign Mesothelioma

= LOCALIZED FIBROUS MESOTHELIOMA = LOCALIZED FIBROUS TUMOR OF THE PLEURA = SOLITARY FIBROUS TUMOR OF PLEURA = BENIGN LOCALIZED MESOTHELIOMA = BENIGN PLEURAL FIBROMA = FIBROSING MESOTHELIOMA = PLEURAL FIBROMYXOMA

Incidence:

<5% of all pleural tumors

No recognized association with asbestos exposure!

Age:	3rd 8th decade; mean age of 50 60 years; M:F = 1:1
Path:	usually solitary mass arising from visceral pleura in 80% + parietal pleura in 20%
Histo:	tumor originates from submesothelial fibroblasts, lined by layer of mesothelial cells relatively acellular fibrous tissue rounded spindle-shaped densely packed cells resembling hemangiopericytoma of lung

asymptomatic in 50%
cough, fever, dyspnea, chest pain (larger mass)
digital clubbing (rare) + hypertrophic pulmonary osteoarthropathy in 20 35%
episodic hypoglycemia (4%)
sharply circumscribed spherical/ovoid lobular mass of 2 30 cm in diameter located near lung periphery/adjacent to pleural surface/within fissure
sessile with smooth tapered margin (common)/pedunculated with obtuse angle toward chest wall (rare, benign feature)
tumor may change in shape + location upon alteration of patient's position (if pedunculated)
areas of hemorrhage/necrosis may be present (favors malignancy)
ipsilateral pleural effusion (rare) containing hyaluronic acid
CT:
- substantial contrast enhancement
- heterogeneous enhancement due to myxoid degeneration + hemorrhage
MR:
- hypointense on T1WI + hyperintense on T2WI

Cx:	malignant degeneration in 37%
DDx:	metastatic deposit
Rx:	excision is curative (recurrence rate lower for pedunculated versus nodular tumor)

Malignant Mesothelioma

= DIFFUSE MALIGNANT MESOTHELIOMA
= uncommon fatal neoplasm of serosal lining of pleural cavity, peritoneum, or both
Most common primary neoplasm of pleura!

Prevalence:	7 13:1,000,000 persons/year; 2,000 3,000 cases/year in USA
Etiology:	asbestos exposure (13 100%); zeolite (nonasbestos mineral fiber); chronic inflammation (TB, empyema); irradiation

P.514

Carcinogenic potential:
- proportional to aspect ratio (= length-to-diameter) of fiber and durability in human tissue:
  - crocidolite > amosite > chrysotile > actinolite, anthophyllite, tremolite
Occupational exposure of asbestos found in only 40 80% of all cases!
5 10% of asbestos workers will develop mesothelioma in their lifetime (risk factor of 30 compared with general population)
No relation to duration/degree of exposure or smoking Hx!

Latency period:	20 35 45 years (earlier than asbestosis; later than asbestos-related lung cancer)
Peak age:	50 70 years (66%); M:F = 2 4 6:1
Path:	multiple tumor masses involving predominantly the parietal pleura + to a lesser degree the visceral pleura; progression to thick sheetlike/confluent masses resulting in lung encasement
Histo:	(a) epithelioid (60%), (b) sarcomatoid (15%), (c) biphasic (25%); intracellular asbestos fibers in 25%
Associated with:	peritoneal mesothelioma; hypertrophic osteoarthropathy (10%)

Staging (Boutin modification of Butchart staging):

IA	confined to ipsilateral parietal/diaphragmatic pleura
IB	+ visceral pleura, lung, pericardium
II	invasion of chest wall/mediastinum (esophagus, heart, contralateral pleura) or metastases to thoracic lymph nodes
III	penetration of diaphragm with peritoneal involvement or metastases to extrathoracic lymph nodes
IV	distant hematogenous metastases
Stage at presentation:	II in 50%, III in 28%, IV in 4%

nonpleuritic (56%)/pleuritic chest pain (6%)
dyspnea (53%)
fever + chills + sweats (30%)
weakness, fatigue, malaise (30%)
cough (24%), weight loss (22%), anorexia (10%)
expectoration of asbestos bodies (= fusiform segmented rodlike structures = iron-protein deposition on asbestos fibers [a subset of ferruginous bodies])

Spread:

contiguous: chest wall, mediastinum, contralateral chest, pericardium, diaphragm, peritoneal cavity; lymphatics, blood, lung
lymphatic: hilar + mediastinal (40%), celiac (8%), axillary + supraclavicular (1%), cervical nodes
hematogenous: lung, liver, kidney, adrenal gland

extensive irregular lobulated bulky pleural-based masses typically >5 cm/pleural thickening (60%)
exudative/hemorrhagic unilateral pleural effusion (30 60 80%) without mediastinal shift ( frozen hemithorax
- = fixation by pleural rind of neoplastic tissue); effusion contains hyaluronic acid in 80 100%; bilateral effusions (in 10%)
distinct pleural mass without effusion (<25%)
associated pleural plaques in 50% = HALLMARK of asbestos exposure
pleural calcifications (20%)
circumferential encasement = involvement of all pleural surfaces (mediastinum, pericardium, fissures) as late manifestation
extension into interlobar fissures (40 86%)
superficial invasion of underlying lung (primarily as extension into interlobular septa)
rib destruction in 20% (in advanced disease)
ascites (peritoneum involved in 35%)
CT:
- pleural thickening (92%)
- thickening of interlobar fissure (86%)
- pleural effusion (74%)
- contraction of affected hemithorax (42%):
  - ipsilateral mediastinal shift
  - narrowed intercostal spaces
  - elevation of ipsilateral hemidiaphragm
- calcified pleural plaques (20%)
MR (best modality to determine resectability):
- minimally hyperintense relative to muscle on T1Wi
- moderately hyperintense relative to muscle on T2Wi
Metastases to:
- ipsilateral lung (60%), hilar + mediastinal nodes, contralateral lung + pleura (rare), extension through chest wall + diaphragm

Prognosis:	10% of occupationally exposed individuals die of mesothelioma (in 50% pleural + in 50% peritoneal mesothelioma); mean survival time of 5 11 months
DDx:	pleural fibrosis from infection (TB, fungal, actinomycosis), fibrothorax, empyema, metastatic adenocarcinoma (differentiation impossible)
Dx:	video-assisted thoracoscopic surgery (postprocedural radiation therapy of all entry ports for tumor seeding of needle track [21%])

Metastasis to Lung

Pulmonary metastases occur in 30% of all malignancies; mostly hematogenous

Age:

>50 years (in 87%)

Incidence of pulmonary metastases:

mnemonic:

CHEST

Choriocarcinoma 60%
Hypernephroma/Wilms tumor 30/20%
Ewing sarcoma 18%
Sarcoma (rhabdomyo-/osteosarcoma) 21/15%
Testicular tumor 12%

Common primaries of intravascular metastases:
- breast, stomach, liver, kidney, lung, prostate, choriocarcinoma
- right atrial myxoma + RCC tend to embolize to large central + segmental pulmonary arteries
progressive dyspnea
subacute pulmonary hypertension
symptoms of acute pulmonary thromboembolism
multiple nodules (in 75%), 82% subpleural:
- often smooth + well-defined
- varying sizes (most typical)
- usually in random distribution
fine micronodular pattern: highly vascular tumor (renal cell, breast, thyroid, prostate carcinoma, bone sarcoma, choriocarcinoma)

P.515

pneumothorax (2%): especially in children with sarcoma + frequently with osteosarcoma (due to bronchopleural fistula caused by subpleural metastasis)
CT:
- noncalcified multiple (>10) round lesions >2.5 cm likely to be metastatic
- lesions connected to pulmonary arterial branches (75%):
  - filling defects in large pulmonary arteries (tumor thromboemboli)
  - multifocal dilatation/beading of subsegmental arteries
  - tree-in-bud appearance of arterioles in secondary pulmonary lobules

Frequency of Pulmonary Metastases
Origin of pulmonary mets		Probability of pulmonary mets
Breast	22%	for Kidney cancer	75%
Kidney	11%	for osteosarcoma	75%
Head and neck	10%	for choriocarcinoma	75%
Colorectal	9%	for Thyroid cancer	65%
Uterus	6%	for melanoma	60%
Pancreas	5%	for Breast cancer	55%
Ovary	5%	for Prostate cancer	40%
Prostate	4%	for Head and neck cA	30%
Stomach	4%	for esophagus cA	20%

Solitary Metastatic Lung Nodule

A solitary lung nodule represents a primary lung tumor in 62% in patients with known Hx of neoplasm
0.4 5 9% of all solitary nodules are metastatic; most likely origin: colon carcinoma (30 40%), melanoma, osteosarcoma, renal cell carcinoma, bladder cancer, testicular tumor, breast carcinoma

Calcifying Lung Metastases (<1%)

mnemonic:

BOTTOM

Breast
Osteo-/chondrosarcoma
Thyroid (papillary)
Testicular
Ovarian
Mucinous adenocarcinoma (colon)

+ others:

synovial sarcoma, giant cell tumor of bone, lung metastases following radiation/chemotherapy

Cavitating Lung Metastases

Frequency:	4% (compared with 9% in primary bronchogenic carcinoma)
Histo:	squamous cell carcinoma (10%), adenocarcinoma (9.5%)
mnemonic:	Squamous Cell Metastases Tend to Cavitate

Squamous cell carcinoma, Sarcoma
Colon
Melanoma
Transitional cell carcinoma
Cervix, during Chemotherapy

Hemorrhagic Lung Metastases

CT:

ill-defined nodules with fuzzy margin + halo sign (= surrounding ground-glass opacity)
- Angiocarcinoma
- Choriocarcinoma
- Renal cell carcinoma
- Melanoma
- Thyroid carcinoma

Endobronchial Metastasis

Frequency:

subsegmental/segmental atelectasis or atelectasis of entire unilateral lung
round endobronchial lesion on CT

Bronchogenic carcinoma
Lymphoma
Renal cell carcinoma
Breast cancer
Colorectal carcinoma

Lung Metastases in Childhood

mnemonic:

ROWE

Rhabdomyosarcoma
Osteosarcoma
Wilms tumor
Ewing sarcoma

Metastases with Airspace Pattern

= lepedic growth along intact alveolar walls similar to bronchioloalveolar carcinoma mimicking pneumonia
airspace nodules
consolidation with air bronchogram
focal /extensive ground-glass opacities

Adenocarcinoma of GI tract (10%)
Adenocarcinoma of breast/ovary

Sterilized Metastasis

= persistence of metastatic nodule without significant change in size after adequate chemotherapy

Histo:

necrotic nodule fibrosis without viable tumor cells

Choriocarcinoma
Testicular cancer
- growing teratoma syndrome = conversion to a benign mature teratoma
- pulmonary lacunae (= transformation into thin-walled cavity) may persist for years

Metastasis of Benign Tumor to Lung

Leiomyoma of uterus
Hydatidiform mole of uterus
Giant cell tumor of bone
Chondroblastoma
Pleomorphic adenoma of salivary gland
Meningioma

Metastasis to Pleura

Lung (36%)
Breast (25%)
Lymphoma (10%)
Ovary (5%)
Stomach (2%)

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Mycoplasma Pneumonia

= PRIMARY ATYPICAL PNEUMONIA (PAP)
Varied radiographic + clinical picture!
Commonest cause of community-acquired nonbacterial pneumonia with a mild course (only 2% require hospitalization), usually lasts 2 3 weeks; only 10% of infected subjects develop pneumonia

Incidence:	10 33% of all pneumonias; autumn peak
Organism:	Eaton agent = pleuropneumonia-like organism (PPLO) = 350 m long pleomorphic Mycoplasma pneumoniae with lack of cell wall
Spread:	direct contact/aerosol
Age:	most common between 5 20 years (esp. in closed populations
Histo:	peribronchial mononuclear cell infiltrates (similar to viral lower respiratory infection)

incubation period: 1 2 weeks
gradual onset beginning with pharyngitis, headache, myalgia (rhinorrhea + nasal congestion uncommon)
mild symptoms of dry cough + low fever, malaise, otitis
sputum with PMNs but few bacteria
mild leukocytosis (20%)
most common respiratory cause of cold agglutinin production (60%)
Severity of radiologic findings discrepant to mild clinical condition!
Pulmonary infiltrates show a significant lag time
focal reticular interstitial infiltrate:
- unilobar from hilum into lower lobe as earliest change (52%), bilobar (10%)
- parahilar peribronchial opacification (12%)
- atelectasis (29%)
alveolar infiltrates:
patchy inhomogeneous unilateral (L > R) airspace consolidation in segmental lower lobe in 50%, bilateral in 10 40%
small pleural effusions in 20%
hilar adenopathy (7 22%)

Rx:	erythromycin, azithromycin, tetracycline
Cx:	? as an autoimmune response Acute disseminated encephalomyelitis Cerebral arteriovenous occlusion Erythema nodosum, erythema multiforme, Stevens-Johnson syndrome pulmonary: Swyer-James syndrome, pulmonary fibrosis, bronchiolitis obliterans, ARDS
Prognosis:	20% with recurrent symptoms of pharyngitis + bronchitis infiltrations
DDx:	viral infection of lower respiratory tract, pertussis, chlamydia (indistinguishable)

Near Drowning

asphyxiation due to water inhalation followed by survival for a minimum of 24 hours

Stage 1:

acute laryngospasm after inhalation of a small amount of water
- no roentgenographic abnormality
prolonged laryngospasm = dry drowning due to negative pressure edema arising from a prolonged episode of the M ller maneuver as in postobstructive pulmonary edema
- Kerley lines, peribronchial cuffing
- patchy perihilar alveolar airspace consolidation

Prognosis:

resolution within 24 48 hours (under therapy)

Stage 2:

= laryngospasm + swallowing of water into the stomach

Stage 3:

persistent laryngospasm with dry drowning (10 15%)
- pressure edema
aspiration of water after hypoxia-induced relaxation of laryngospasm (85 90%)
- permeability edema (due to hypoxia + diffuse alveolar damage)

Cx:

ARDS, aspiration of gastric fluid, infection by fresh-water saprophytic bacteria

Sea-water drowning
- hemoconcentration, hypovolemia
Fresh-water drowning
- hemodilution, hypervolemia
- hemolysis
Secondary drowning
- pneumonia due to toxic debris
- progressive pulmonary edema
Dry drowning (20 40%)
- = laryngeal spasm prevents water from entering
- no roentgenographic abnormality

Similarities of all 4 types:

hypoxemia
metabolic acidosis
central extensive fluffy areas of increased opacity (alveolar edema indistinguishable from other types):
- tendency for opacities to coalesce
hyaline membrane formation = considerable loss of protein from blood

Cx:

pneumonia (due to aspirated bacteria/fungi /mycobacteria)

Necrotizing Sarcoid Granulomatosis

Etiology:	? variant of sarcoidosis
Age:	3rd 7th decade (mean age, 49 years); M:F = 1:2.2
Path:	pleural + subpleural + peribronchovascular scattered nodules/conglomerate masses central cavitation
Histo:	confluent noncaseating granulomas, extensive necrosis, vasculitis of muscular pulmonary arteries + veins with frequently total vascular occlusion, bronchiolar obstruction, bronchiolitis obliterans, obstructive pneumonitis

asymptomatic (15 40%)
cough, chest pain, dyspnea, fever, weight loss, fatigue
uveitis, hypothalamic insufficiency (13%)
Almost exclusively affects lungs
multiple bilateral subpleural + peribronchovascular pulmonary nodules
numerous ill-defined parenchymal opacities
cavitation
hilar lymphadenopathy (8 79%)

P.517

pleural thickening
No upper airway disease/glomerulonephritis/systemic vasculitis

Rx:	corticosteroid therapy alone
DDx:	sarcoidosis (high prevalence of mediastinal + hilar lymphadenopathy, little propensity for cavitation)

Neonatal Pneumonia

Pathogenesis:

in utero infection (ascending from premature rupture of membranes or prolonged labor/transplacental route) = major risk factor
aspiration of infected vaginal secretions during delivery
infection after birth

Organism:

Group B streptococcus (GBS) = most common cause: in low birth-weight premature infants; 50% mortality
- pulmonary opacities (87%):
  - appearance identical to RDS (in 52%)
  - appearance suggesting retained lung fluid/focal infiltrates (35%)
- normal CXR (13%)
- cardiomegaly (common)
- pleural effusions (in 2/3, but RARE in RDS)
Associated with: delayed onset of diaphragmatic hernia (evidenced by clinical deterioration)

Prognosis: often lethal
Pneumococci: RDS-like
Listeria: RDS-like
Candida: progressive consolidation + cavitation
Chlamydia trachomatis: bronchopneumonic pattern

others:

H. influenzae, Staphylococcus aureus, E. coli, CMV, pneumocystis

afebrile
lower ventilatory pressure requirements
bilateral focal/diffuse areas of opacities (may initially appear similar to fetal aspiration syndrome)
hyperaeration
may cause lobar atelectasis
may cause pneumothorax/pneumomediastinum
pleural effusion (exceedingly rare)

Nocardiosis

Organism:	gram-positive acid-fast bacterium resembling fungus
Predisposed:	immunocompromised

multiple poorly/well-defined nodules cavitation
lobar consolidation
empyema without sinus tracts
SVC obstruction (rare)

Nontuberculous Mycobacterial Infection Of Lung

Atypical Tuberculosis

Organism:

M. kansasii:	lung infection in subjects with good immune status
M. marinum:	swimming pool granuloma
M. ulcerans:	Buruli ulcer in tropical areas
M. scrofulaceum:	cervical lymphadenitis in infants
m. avium intracellulare:	esp. in Aids

Organism causing pulmonary disease (Runyon classification): ubiquitous organisms as part of normal environmental flora

Photochromogens
- kansasii, M. simiae, M. asiaticum
- colonies turn yellow with exposure to light
- 70 80% of individuals from rural areas test positive on PPd-B (= antigen from M. kansasii)!
Scotochromogens
- scrofulaceum, M. xenopi, M. szulgai, M. gordonae
- yellow colonies turn orange with exposure to light
Nonchromogens
- avium-intracellulare, M. malmoense, M. terrae
- white/beige colonies without color change
Rapid growers
- fortuitum-chelonei
- appear in culture in 3 5 days (all other groups appear in culture in 2 4 weeks)

Histo:	lesions indistinguishable from m. tuberculosis
Source:	soil, water, dairy products, bird droppings
Infection:	inhalation of aerosolized water droplets (M.avium-intracellulare complex), food aspiration in patients with achalasia (M. fortuitum-chelonei), GI tract (in AIDS)

cough (60 100%), hemoptysis (15 20%)
asthma, dyspnea
fever distinctly uncommon (10 13%)
weakness + weight loss (up to 50%)
weekly positive tuberculin skin test

cLAssic form

Age: 6th-7th decade, in Whites (80 90%), m > f

Predisposing factors:
- COPD (25 72%), previous TB (20 24%), interstitial lung disease (6%), smoking >30 pack-years (46%), alcohol abuse (40%), cardiovascular disease (36%), chronic liver disease (32%), previous gastrectomy (18%)
Location: apical + anterior segments of upper lobes
- chronic fibronodular/fibroproductive apical opacities (indistinguishable from reactivation TB)
- cavitation in 80 95%
- apical pleural thickening in 37 56%
- additional patchy nodular alveolar opacities (due to bronchogenic spread) in ipsi-/contralateral lung in 40 70%
- adenopathy (0 4%)
- pleural effusion (5 20%)
- typically no hilar elevation
Nonclassic Form (20 30%)

Age: 7th-8th decade, 86% in Whites; m:f = 1:4

Predisposing factors: none

Location: predominantly in middle lobe + lingula
- multiple bilateral nodular opacities throughout both lungs in random distribution
- irregular curvilinear interstitial opacities (resembling bronchiectasis)
Asymptomatic Granulomas
- cluster of similar-sized nodules
Achalasia-Related Infection
- with M. fortuitum-chelonei

P.518

DISSEMINATED DISEASE
- in immunocompromised patients: AIDS, transplant patients, lymphoproliferative disorders (esp. hairy cell leukemia), steroid + immunosuppressive therapy

CT:
- multifocal bronchiectasis (79 94%), esp. middle lobe + lingula
- centrilobular nodules of varying sizes, usually <1 cm (= micronodules) in 76 97%
- bronchial wall thickening (97%)
- airspace disease (76%)
- cavitation (21%), esp. in upper lobes
- interlobular septal thickening (12%)
Unfavorable response to antituberculous therapy is suspicious for atypical TB!

DDx:

M. tuberculosis (bronchiectasis less common + less extensive), bronchiolitis obliterans, sarcoidosis, fungal disease

Panbronchiolitis

inflammatory lung disease, prevalent in Orientals but rare in Europeans + North Americans

Pathogenesis:

unknown

HRCT:

centrilobular branching structures (segments of bronchiolectasis filled with secretions) + nodules surrounding respiratory bronchioles
mosaic perfusion
air trapping
bronchial dilatation

DDx:

bronchiolitis obliterans

Paragonimiasis Of Lung

= parasitic disease caused by trematode Paragonimus (usually P. westermani = lung fluke) endemic to certain areas of East + Southeast Asia (China, Korea, Japan, Thailand, Laos, Philippines, India)

Infection:	ingestion of raw/incompletely cooked freshwater crab/crayfish infected with metacercaria; larva exists in small intestine + penetrates the intestinal wall + enters peritoneal cavity; larva penetrates diaphragm + pleura to enter the lung
Cycle:	from the final host (tiger, cat, dog, fox, weasel, opossum, human) eggs of worm pass to the outside with blood-streaked sputum; in fresh water ciliated embryos (miracidia) develop; they become tailed larvae (cercariae) after invading a fresh-water snail; when the infected snail is eaten by a crustacean, their tails detach and they become 300 m encysted larvae (metacercariae)

@ CNS
- meningoencephalitis (in 25%)
- shell-like/soap bubble-like calcifications of varying size (~50%)
@ Chest

Location: pulmonary lesions in 83%, pulmonary + pleural lesions in 44%, pleural lesions in 17%):

early findings (lesions occur 3 8 weeks after ingestion):
- uni-/bilateral pneumo-/hydropneumothorax (17%)
- uni-/bilateral pleural effusion (3 54%)
- focal patchy migrating airspace consolidation (= worm migration causing focal hemorrhagic pneumonia) (45%)
- lobar/segmental collapse (airway obstruction from egg granuloma/intrusion of worm)
- 2 4-mm thick and 2 7-cm long linear opacities abutting the pleura (41%) due to worm migration track
late findings:
- lung cyst (cyst formation from infarction after arteriolar/venous obstruction by worm or egg; expansion of small airway by intraluminal parasite):
  - thick-walled cyst (due to fibrosis)
  - eclipse effect = eccentric thickening of cyst wall (due to intracystic one/two worms)
  - thin-walled cyst (when cyst connected to airway)
- 10 15-mm nodules + masslike consolidation (24%) (due to cyst initially masked by pericystic airspace consolidation cyst filled with chocolate-colored necrotic fluid)
- bronchiectasis (35%)

DDx:

tuberculosis (nodular slowly changing lesion, residual fibrosis after treatment, no subpleural linear opacities)

Pericardial Cyst

Etiology:

defect in embryogenesis of coelomic cavities
sequelae of pericarditis

Histo:	lined by single layer of mesothelial cells
Age:	30 40 years; M:F = 3:2

asymptomatic (50%)

Location:

(a) cardiophrenic angle (75%), R:L = 3:1/3:2, 25% higher; may extend into major fissure
(b) mediastinum (rare)

sharply marginated round/ovoid/triangular mass usually 3 8 cm (range 1 28 cm) in diameter
change in size + shape with respiration/body position
attenuation values of 20 40 HU, occasionally higher

Pneumatocele

= cystic air collection within lung parenchyma due to obstructive overinflation
= regional obstructive emphysema
Does not indicate destruction of lung parenchyma
Occurs during healing phase
Appears to enlarge while patient improves
Frequently multiple

Developmental theories:

small bronchioles undergo severe distension secondary to check-valve endobronchial/peribronchial obstruction
focus of necrotic lung evacuates through a bronchus narrowed by edema/inflammation; airspace subsequently enlarges due to check-valve mechanism from enlarging pneumatocele/inflammatory exudate
air from ruptured alveoli/bronchioles dissects along interstitial interlobular tissue and accumulates between visceral pleura and lung parenchyma = subpleural emphysematous bulla = subpleural air cyst

P.519

Pneumatocele Associated with Infection

Organism:

pneumococci, E. coli, Klebsiella, Staphylococcus (in childhood)

appears within 1st week, disappears within 6 weeks
thin-walled + completely air-filled cavity
air-fluid level + wall thickening (during infection)
pneumothorax
spontaneous resolution (in most)

Traumatic Pneumatocele = Pneumatocyst

Cause:

air trapped within area of pulmonary laceration is initially obscured by surrounding contusion (hematoma); pneumatocyst appears within hours after blunt chest trauma
intensive inflammatory response from hydrocarbon (furniture polish, kerosene) inhalation/ingestion

single/multiple pneumatoceles
spontaneous resolution over several weeks to months

Pulverized Lung

Cause:severe chest trauma

multiple 5 10-mm air cysts in an area of airspace opacification

Pneumococcal Pneumonia

Most common gram-positive pneumonia

90% community-acquired, 10% nosocomial

Incidence:	15% of all adulthood pneumonias, uncommon in child; peaks in winter + early spring; increased during influenza epidemics
Organism:	Streptococcus pneumoniae (formerly Diplococcus pneumoniae), gram-positive, in pairs/chains, encapsulated, capsular polysaccharide responsible for virulence + serotyping
Susceptible:	elderly, debilitated, alcoholics, CHF, COPD, multiple myeloma, hypogammaglobulinemia, functional/surgical asplenia

rusty blood-streaked sputum
left-shift leukocytosis
impaired pulmonary function

Location:

usually involves one lobe only; bias for lower lobes + posterior segments of upper lobes (bacteria flow under gravitational influence to most dependent portions as in aspiration)

extensive airspace consolidation abutting against visceral pleura (lobar/beyond confines of one lobe through pores of Kohn) CHARACTERISTIC
slight expansion of involved lobes
prominent air bronchograms (20%)
patchy bronchopneumonic pattern (in some)
pleural effusion (parapneumonic transudate) uncommon with antibiotic therapy
cavitation (rare, with type III)

Variations (modified by bronchopulmonary disease, eg, chronic bronchitis, emphysema):

bronchopneumonia-like pattern
effusion may be only presentation (esp. in COPD)
empyema (with persistent fever)
in children:
- round pneumonia = sharply defined round lesion

Prognosis:	prompt response to antibiotics (if without complications); 5% mortality rate
Dx:	blood culture (positive in 30%)
Cx:	meningitis, endocarditis, septic arthritis, empyema (now rarely seen)

Pneumocystosis

PNEUMOCYSTIS CARINII PNEUMONIA
Most common cause of interstitial pneumonia in immuno-compromised patients, which quickly leads to airspace disease
Organism:
- ubiquitous obligate extracellular protozoan/fungus Pneumocystis carinii
  - trophozoite develops into a cyst
  - cyst produces up to eight daughter sporozoites, which are released at maturity + develop into trophozoites
Pathomechanism:
- trophozoite attaches to cell membrane of type I alveolar pneumocytes with subsequent cell death + leakage of proteinaceous fluid into alveolar space
Predisposed:
- debilitated premature infants, children with hypogammaglobulinemia (12%)
- AIDS (60 80%)
- other immunocompromised patients: congenital immunodeficiency syndrome, lymphoproliferative disorders, organ transplant recipients (renal transplant patients in 10%), patients on long-term corticosteroid therapy (nephrotic syndrome, collagen vascular disease), patients on cytotoxic drugs [under therapy for leukemia (40%), lymphoma (16%)]
- Often associated with simultaneous infection by CMV, Mycobacterium avium-intracellulare, herpes simplex
severe dyspnea + cyanosis over 3 5 days
subacute insidious onset of malaise + minimal cough (frequent in AIDS patients)
respiratory failure (5 30%)
WBC slightly elevated (PMNs)
lymphopenia (50%) heralds poor prognosis
normal CXR in 10 39%
bilateral diffuse symmetric finely granular/reticular interstitial/airspace infiltrates (in 80%) with perihilar + basilar distribution (CHARACTERISTIC central location)
response to therapy within 5 7 days
rapid progression to diffuse alveolar homogeneous consolidation (DDx: pulmonary edema)
air bronchogram
fine/coarse linear/reticular pattern = thickened coarse interstitial lung markings (in healing phase)
pleural effusion + hilar lymphadenopathy (uncommon)
atypical pattern (in 5%):
- isolated lobar disease/focal parenchymal opacities
- lung nodules cavitation
- hilar/mediastinal lymphadenopathy
- thin-/thick-walled regular/irregular cysts/cavities with predilection for upper lobes + subpleural regions
effect of prophylactic use of aerosolized pentamidine:
- redistribution of infection to upper lobes
- cystic lung disease
- spontaneous pneumothorax, frequently bilateral (6 7%)
- disseminated extrapulmonary disease (1%)
- punctate/rimlike calcifications in enlarged lymph nodes + abdominal viscera
CT:
- patchwork pattern (56%)
  - = bilateral asymmetric patchy mosaic appearance with sparing of segments/subsegments of pulmonary lobe
- ground-glass pattern (26%)
  - = bilateral diffuse/perihilar airspace disease (fluid + inflammatory cells in alveolar space) in symmetric distribution
- interstitial pattern (18%)
  - = bilateral symmetric/asymmetric, linear/reticular markings (thickening of interlobular septa)
- air-filled spaces (38%):
  - pneumatoceles = thin-walled spaces without lobar predilection resolving within 6 months
  - subpleural bullae (due to premature emphysema)
  - thin-walled cysts (? check-valve obstruction of small airways from aerosolized pentamidine)
  - necrosis of PCP granuloma
- pneumothorax (13%)
- lymphadenopathy (18%)
- pleural effusion (18%)
- pulmonary nodules usually due to malignancy (leukemia, lymphoma, Kaposi sarcoma, metastasis)/septic emboli
- pulmonary cavities/cyst formation (chronic) usually due to superimposed fungal/mycobacterial infection

NUC:

bilateral and diffuse Ga-67 uptake without mediastinal involvement prior to roentgenographic changes

DDx:	TB/MAI infection (with mediastinal involvement)
Dx:	sputum collection bronchoscopy with lavage transbronchial/transthoracic/open lung Bx
Prognosis:	rapid fulminant disease; death within 2 weeks
Rx:	co-trimoxazole IV, nebulized pentamidine

Pneumonectomy Chest

Early signs (within 24 hours):

partial filling of thorax
ipsilateral mediastinal shift + diaphragmatic elevation

Late signs (after 2 months):

complete obliteration of space

N.B.:

Depression of diaphragm/shift of mediastinum to contralateral side indicates a bronchopleural fistula/empyema/hemorrhage!

Postobstructive Pneumonia

chronic inflammatory disease distal to bronchial obstruction

Cause:

Bronchogenic carcinoma (most commonly)
Bronchial adenoma
Granular cell myoblastoma (almost always tracheal lesion)
Bronchostenosis

Histo:

golden pneumonia = cholesterol pneumonia endogenous lipid pneumonia = mixture of edema, atelectasis, round cell infiltration, bronchiectasis, liberation of lipid material from alveolar pneumocytes secondary to inflammatory reaction
frequently associated with some degree of atelectasis
persists unchanged for weeks
recurrent pneumonia in same region after antibiotic rx

Progressive Massive Fibrosis

= (PMF) = COMPLICATED PNEUMOCONIOSIS
= CONGLOMERATE ANTHRACOSILICOSIS
may develop/progress after cessation of dust exposure

Path:	avascular amorphous central mass of insoluble proteins stabilized by cross-links + ill-defined bundles of coarse hyalinized collagen at periphery
Location:	almost exclusively restricted to posterior segment of upper lobe/superior segment of lower lobe

large >1 cm opacities initially in middle + upper lung zones at periphery of lung
discoid contour (44%) = mass flat from front to back (thin opacity on lateral view, large opacity on PA view), medial border often ill-defined, lateral borders sharp + parallel to rib cage
migration toward hila starting at lung periphery; bilateral symmetry
apparent decrease in nodularity (incorporation of nodules from surroundings)
cavitation (occasionally) due to ischemic necrosis/superimposed TB infection
bullous scar emphysema
pulmonary hypertension

Pseudolymphoma

= reactive benign lesion = localized form of lymphocytic interstitial pneumonitis (LIP); no progression to lymphoma

Histo:	aggregates of plasma cells, reticulin cells, large + small lymphocytes with preserved lymphoid architecture resembling lymphoma histologically without lymph node involvement
Associated with:	sj gren syndrome

mostly asymptomatic
well-demarcated dense infiltrate
infiltrate typically in central location extending to visceral pleura
prominent air bronchogram
no lymphadenopathy

Prognosis:	occasionally progression to non-Hodgkin lymphoma
Rx:	most patients respond well to steroids initially

Pseudomonas Pneumonia

= most dreaded nosocomial infection because of resistance to antibiotics in patients with debilitating diseases on multiple antibiotics + corticosteroids; rare in community

Organism: Pseudomonas aeruginosa, gram-negative

bradycardia
temperature with morning peaks
widespread patchy bronchopneumonia (secondary to bacteremia; unlike other gram-negative pneumonias)

P.521

predilection for lower lobes
extensive bilateral consolidation
spongelike pattern with multiple nodules >2 cm (= extensive necrosis with formation of multiple abscesses)
small pleural effusions

Pulmonary Arterial Malformation

= PAVM = PULMONARY ARTERIOVENOUS ANEURYSM
- = PULMONARY ARTERIOVENOUS FISTULA = PULMONARY ANGIOMA = PULMONARY TELANGIECTASIA
= abnormal vascular communication between pulmonary artery and vein (95%) or systemic artery and pulmonary vein (5%)

Etiology:

congenital defect of capillary structure (common)
acquired in cirrhosis (hepatogenic pulmonary angiodysplasia), cancer, trauma, surgery, actinomycosis, schistosomiasis, TB (Rasmussen aneurysm)

Path:

hemangioma of cavernous type

Pathophysiology:

low-resistance extracardiac R-to-L shunt (which may result in paradoxical embolism); quantification with Tc-99m labeled albumin microspheres by measuring fraction of dose reaching kidneys

Age:

3rd 4th decade; manifest in adult life, 10% in childhood

Occurrence:

isolated abnormality (40%)
multiple (in 1/3)

associated with Rendu-Osler-Weber syndrome (in 30 60 88%) = hereditary hemorrhagic telangiectasia
- 15 50% of patients with Rendu-Osler-Weber disease have pulmonary AVMs!

Types:

Simple type (79%)
- = single feeding artery empties into a bulbous nonseptated aneurysmal segment with a single draining vein
Complex type (21%)
- = more than one feeding artery empties into septated aneurysmal segment with more than one draining vein

asymptomatic in 56% (until 3rd 4th decade) if AVM single and <2 cm
orthodeoxia (= increased hypoxemia with PaO₂ <85 mm Hg in erect position due to gravitational shift of pulmonary blood flow to base of lung)
cyanosis with normal-sized heart (R-to-L shunt) in 25 50%, clubbing
bruit over lesion (increased during inspiration)
dyspnea on exertion (60 71%), palpitation, chest pain
hemoptysis (10 15%)
No CHF

Location:

lower lobes (65 70%) > middle lobe > upper lobes; bilateral (8 20%); medial third of lung

sharply defined, lobulated oval/round mass (90%) of 1 to several cm in size ( coin lesion )
cordlike bands from mass to hilum (feeding artery + draining veins)
in 2/3 single lesion, in 1/3 multiple lesions
enlargement with advancing age
change in size with Valsalva/Mueller maneuver/erect vs. recumbent position (decrease with Valsalva maneuver)
phleboliths (occasionally)
increased pulsations of hilar vessels

CT (98% detection rate):

homogeneous circumscribed noncalcified nodule/serpiginous mass up to several cm in diameter
vascular connection of mass with enlarged feeding artery + draining vein
sequential enhancement of feeding artery + aneurysmal part + efferent vein on dynamic CT

MR (if contraindication to contrast material/if flow slow due to partial thrombosis/for follow-up):

signal void on standard spin echo/high signal intensity on GRASS images

Angio (mostly obviated by MR/CT unless surgery or embolization contemplated):

100% sensitive for detection of vessels >2 mm

Cx: CNS symptoms are commonly the initial manifestation

Cerebrovascular accident: stroke (18%), transient ischemic attack (37%) secondary to paradoxical bland emboli
Brain abscess (5 9%) secondary to loss of pulmonary filter function for septic emboli
Hemoptysis (13%) secondary to rupture of PAVM into bronchus, most common presenting symptom
Hemothorax (9%) secondary to rupture of subpleural PAVM
Polycythemia

Prognosis:	26% morbidity, 11% mortality
Recommendation:	screening of first-degree relatives
DDx:	solitary/multiple pulmonary nodules
Rx:	embolization with coils/detachable balloons

Pulmonary capillary hemangiomatosis

bilateral pulmonary disease behaving like a low-grade nonmetastatic vascular neoplasm with slowly progressive pulmonary hypertension

Histo:

sheets of thin-walled capillary blood vessels infiltrating pulmonary interstitium + invading pulmonary vessels, bronchioles, and pleura

Pathomechanism of pulmonary hypertension:

venoocclusive phenomenon secondary to invasion of small pulmonary veins
progressive vascular obliteration secondary to in situ thrombosis + infarction
pulmonary scar formation secondary to recurrent pulmonary hemorrhage

Age:

20 40 years

dyspnea on exertion
cor pulmonale: jugular venous distension, pedal edema, ECG signs of RV failure (DDx: pulmonary venoocclusive disease)
elevated PA pressures + normal pulmonary wedge pressure
hemoptysis + pleuritic chest pain in 1/3 (DDx: pulmonary thromboembolic disease)

CXR:

diffuse reticulonodular pattern
focal areas of interstitial fibrosis (recurrent episodes of pulmonary hemorrhage + thrombotic infarction)

P.522

CT:

thickening + nodularity of inter- and intralobular septa + walls of pulmonary veins
areas of ground-glass attenuation (= increased perfusion to extensive proliferating hemangiomatous tissue)

Angio:

combination of increased flow (to hemangiomatous areas) + decreased flow (to regions of thrombosis, infarction, and scarring)

Prognosis:	death after 2 12-year interval from onset of symptoms
Rx:	bilateral lung transplantation

DDx:

Pulmonary venoocclusive disease
Idiopathic interstitial fibrosis
Primary pulmonary hypertension (no increase in lung markings)
Pulmonary hemangiomatosis (only in children, cavernous hemangiomas involving several organs)

Pulmonary contusion

most common manifestation of blunt chest trauma, esp. deceleration trauma

Path:	exudation of edema + blood into airspace + interstitium
Time of onset:	apparent within 6 hours after trauma

clinically inapparent
hemoptysis (50%)

Location:	posterior (in 60%)
Site:	directly deep to site of impact/contrecoup

irregular patchy/diffuse homogeneous extensive consolidation (CT is more sensitive)
opacity may enlarge for 48 72 hours
rapid resolution beginning 24 48 hours, complete within 2 10 days
overlying rib fractures (frequent)

CT:

nonsegmental coarse ill-defined crescentic (50%)/amorphous (45%) opacification of lung parenchyma without cavitation
subpleural sparing = 1 2-mm rim of uniformly nonopacified subpleural portion of lung

Cx:	pneumothorax
DDx:	fat embolism (1 2 days after injury)

Pulmonary Infarction

ischemic coagulative necrosis of lung parenchyma

Frequency:	rare (due to protective effect of collateral blood flow from bronchial circulation)
Path:	dark necrotic material (with faint ghostlike structures of lung tissue remaining evident on histology) sur-rounded by a narrow rim of hyperemia + inflammation
Cause:	pulmonary artery occlusion (medium- to small-sized vessel)

Pathogenesis:

increased vascular permeability (ischemic capillary endothelial injury) + reperfusion via bronchial circulation causes intraalveolar extravasation of blood cells in a confined area with possible progression to infarction

Co-condition to progress to infarction:

CHF, high embolic burden, underlying malignancy, diminished bronchial flow (due to shock, hypotension, chronically impaired circulation), vasodilator use, elevated pulmonary venous pressure, interstitial edema

Prognosis:

replacement by vascular fibrous tissue folding into a collagenous platelike mass producing pleural retraction

Pulmonary Interstitial Emphysema

PIE = complication of respirator therapy with PEEP

Pathogenesis:

gas escapes from overdistended alveolus, dissects into perivascular sheath surrounding arteries, veins, and lymphatics, tracks into mediastinum forming clusters of blebs
sudden deterioration in patient's condition during respiratory Rx
meandering tubular + cystic lucencies following distribution of bronchovascular tree
bilateral, symmetrical distribution
pseudocysts (localized form of PIE) = multiple circular well-defined air collections with uniformly thin walls

Location: right parahilar region
lobar overdistension (occasionally)

Cx:

pneumothorax (77%) from rupture of cyst
pneumomediastinum (37%)
subcutaneous emphysema, pneumopericardium, intracardiac air, pneumoperitoneum, pneumatosis intestinalis
air-block phenomenon = buildup of pressure in mediastinum/pericardial tamponade impeding blood flow in low-pressure pulmonary veins causing diminished blood return to heart (obstruction esp. during expiration); particularly common in neonatal period
- microcardia

Rx:
DDx:	high-frequency jet/oscillatory ventilation placing affected side of infant down for 24 48 hours selective bronchial intubation

Pulmonary Lymphangiomatosis

increased number of communicating lymphatic channels
smooth thickening of bronchovascular bundles + interlobular septa
CT:
- diffuse increased attenuation of mediastinal fat
- mild perihilar infiltration
- pleural effusion
- pleural thickening

Pulmonary Mainline Granulomatosis

PULMONARY TALCOSIS
pulmonary microembolism in drug addicts due to chronic IV injection of suspensions prepared from crushed tablet compounds (talc is a common insoluble additive)

Drugs:	amphetamines, methylphenidate hydrochloride ( West coast ), tripelen amine ( blue velvet ), methadone hydrochloride, dilaudid, meperidine, pentazocine, propylhexedrine, hydromorphone hydrochloride
Pathogenesis:	talc (= magnesium silicate) particles incite a pronounced granulomatous foreign-body reaction + subsequent fibrosis in perivascular distribution
Path:	multiple scattered whitish nodules of 0.3 3 mm converging into gritty fibrotic masses in central + upper lungs measuring several cm
Histo:	widespread granulomas packed with doubly refractile talc particles expanding the walls of muscular pulmonary arteries and arterioles + perivascular connective tissue + alveolar septa

P.523

talc retinopathy (80%) = small glistening crystals
angiothrombotic pulmonary hypertension + cor pulmonale

Early changes:

widespread micronodularity of pinpoint size (1 2 3 mm) with perihilar/basilar predominance
well-defined nodules predominantly in middle zones

Late changes:

loss of lung volume of upper lobes + hilar elevation + hyperlucency at lung bases
indistinctly marginated coalescent opacities similar to progressive massive fibrosis (DDx: in silicosis slightly further away from pulmonary hila + distinct margin)

Cx:

mycotic pulmonary artery aneurysm; right-sided endocarditis with septic emboli; chronic respiratory failure; emphysema; systemic talc breakthrough to liver + spleen + kidneys + retina

DDx of late changes:

Progressive massive fibrosis of silicosis/coal worker's pneumoconiosis
Chronic sarcoidosis

Dx:

lung biopsy

Clinical Classification of Pulmonary Thromboembolic disease according to Severity
Signs & Symptoms	Class 1	Class 2	Class 3	Class 4
occlusion of pulmonary arteries	<20%	20 30%%	30 50%	>50%
symptoms	asymptomatic	anxiety, hyperventilation	dyspnea, collapse	shock, dyspnea
Arterial Po₂	normal	<80 torr	<65 torr	<50 torr
Arterial Pco₂	normal	<35 torr	<30 torr	<30 torr
central venous pessure	normal	normal	elevated	elevated
mean PA pressure	normal			>20 mm Hg
systolic blood pressure	normal			<100 mm Hg

Pulmonary Thromboembolic Disease

= PULMONARY EMBOLISM (PE)

Incidence:	600,000 Americans/year (0.23%) with missed/delayed diagnosis in 400,000, causing death in 100,000; diagnosed in 1% of all hospitalized patients; in 12 64% at autopsy; in 9 56% of patients with deep venous thrombosis
Age:	60% >60 years of age
Cause:	deep vein thrombosis (DVT) of extremities/pelvis (>90%), right atrial neoplasia/thrombus, thrombogenic intravenous catheters, endocarditis of tricuspid/pulmonic valves
Time of onset:	PE usually occurs within first 5 7 days of thrombus formation

Predisposing factors:

primary thrombophlebitis (39%), immobilization (32%), recent surgery (31%), venous insufficiency (25%), recent fracture (15%), myocardial infarction (12%), malignancy (8%), CHF (5%), no predisposition (6%)

Pathophysiology:

A clot from the deep veins of the leg breaks off + fragments in right side of heart + showers lung with emboli varying in size

On average >6 8 vessels are embolized!
Clinical presentation is protean + nonspecific!
False-positive clinical diagnosis in 62%
Classic triad (<33%):
- hemoptysis (25 34%)
- pleural friction rub
- thrombophlebitis

symptoms (nonfatal Pe versus fatal Pe):
- pleuritic chest pain (88% vs. 10%)
- acute dyspnea (84% vs. 59%)
- apprehension (59% vs. 17%)
- cough (53% vs. 3%)
- hemoptysis (30% vs. 3%)
- sweats (27% vs. 9%)
- syncope (13% vs. 27%)
signs (nonfatal Pe versus fatal Pe):
- respiratory rate >16 (92% vs. 66%)
- rales due to loss of surfactant (58% vs. 42%)
- tachycardia >100 bpm (44% vs. 54%)
- temperature >37.8 c (43% vs. 30%)
- diaphoresis (36% vs. 10%)
- heart gallop (34% vs. 10%)
- phlebitis (32% vs. 7%)
- heart murmur (23%)
- cyanosis (19% vs. 12%)
ECG changes (83%), mostly nonspecific: P-pulmonale, right-axis deviation, right bundle branch block, classic s1q3T3 pattern
elevated levels of fibrinopeptide-A (FPA) = small peptide split off of fibrinogen during fibrin generation
positive D-dimer assay (generated during clot lysis)

Location of PE:	bilateral emboli (in 45%), R lung only (36%), L lung only (18%); multiple emboli [3 6 on average] in 65%
Distribution:	RUL (16%), RML (9%), RLL (25%), LUL (14%), LLL (26%)
Site:	central = segmental/larger (in 58%); peripheral = subsegmental/smaller (in 42%); in subsegmental branches exclusively (in 30%)

emboli are occlusive in 40%!
RESOLUTION OF PE
(through fibrinolysis + fragmentation):
- in 8% by 24 hours, in 56% by 14 days, in 68% by 6 weeks, in 77% by 7 months; complete in 65%, incomplete in 39% by 11 months, partial in 23%, no resolution in 12%

P.524

resolution less favorable with increasing age + cardiac disease
resolution improved with urokinase > heparin within first week (after 1 year 80% for both)

Embolism Without Infarction (90%)

Histo: hemorrhage + edema
EMBOLISM WITH INFARCTION (10 60%)
- = any opacity developing as a result of thromboembolic disease; more likely to develop in presence of cardiopulmonary disease with obstruction of pulmonary venous outflow (diagnosed in retrospect)
- Histo:
  - incomplete infarction = reversible transient hemorrhagic congestion/edema usually resolving over several days to weeks
  - complete infarction = hemorrhagic infarction with necrosis of lung parenchyma remaining permanently

Acute Pulmonary Thromboembolism

Hypertension disappears as emboli lyse
Mortality:
- 3:1,000 surgical procedures; 200,000 deaths in 1975; 7 10% of all autopsies (death within first hour of Pe in most patients); 26 30% if untreated; 3 10% if treated; fatal if >60% of pulmonary bed obstructed; healthy patients may survive obstruction of 50 60% of vascular bed
- sudden onset of chest pain
- sudden onset of chest pain
- acute dyspnea
- hemoptysis occasionally
- enzyme-limked immunosorbent D-dimer assay test (detects one of the products of fibrin breakdown) > 500 g/L

CXR (33% sensitive, 59% specific):

Abnormal nonspecific CXR in 84%; a normal CXR has a negative predictive value of only 74%!
general findings (patients with PE vs. no PE):
- atelectasis/infiltrate (68% vs. 48%)
- pleural effusion (48% vs. 31%)
- pleural opacity (35% vs. 21%)
- elevated diaphragm (24% vs. 19%)
- decreased vascularity (21% vs. 12%)
- prominent pulmonary artery (17% vs. 28%)
- cardiomegaly (12% vs. 11%)
- pulmonary edema (4% vs. 13%)
local findings:
- Westermark sign = area of oligemia (due to vasoconstriction distal to embolus) in 2 7%
- Fleischner sign = local widening of artery by impaction of embolus (due to distension by clot/pulmonary hypertension developing secondary to peripheral embolization)
- knuckle sign = abrupt tapering of an occluded vessel distally
- Fleischner lines = long-line shadows (fibrotic scar) from invagination of pleura at the base of the collapse resulting in pseudofissure
- Hampton hump = segmentally distributed pleura-based shallow wedge-shaped consolidation with base against pleural surface + convex medial border:
  - NO air-bronchogram (hemorrhage into alveoli)
  - cavitation
  - melting sign = within few days to weeks regression from periphery toward center
  - subsequent nodular/linear scar
- thoracentesis: bloody (65%), predominantly PMNs (61%), exudate (65%)

NECT (purpose):

depiction of acute changes of PE:
- atelectasis/linear bands (100%)
- pleural effusion (87%)
- consolidation (57%)
- ground-glass opacification (57%)
- Hampton's hump (50%)
- intraluminal area of high attenuation (hyperdense artery)
- dilated central/segmental pulmonary artery
depiction of chronic changes of PE (see below)
chest findings leading to alternative diagnosis
localization of volume-of-interest for CECT

CECT angio (method of choice):

N.B.:

In the adult a CT (2.2 6.0 mSv) has a 1.6 4.3 times higher radiation dose than a V/Q scan (1.4 mSv)!

Helical CT equal to angio in detection of emboli within proximal arteries of 5th/6th generation
Subsegmental intraluminal filling defects (in 2 30%) usually not detectable!
Detection poor in middle lobe + lingular branches (in 18%)!

N.B.:

evaluate the vessel adjacent to a bronchus

complete filling defect of low attenuation occupying entire arterial section enlargement of artery
railway track sign = partial filling defect = embolus floating freely within lumen surrounded by areas of intravascular contrast enhancement
peripheral mural filling defect forming acute angles with arterial wall
RV dysfunction (ratio RV:LV = >1:1)

Pseudo-filling defects:

Breathing artifact in tachypneic patient
Too short/long scanning delay
Unilateral increase in vascular resistance
R-to-L shunt

Technical failure rate: 3 4% due to severe dyspnea

CT of lung parenchyma:
- peripheral wedge-shaped area of infarct/hemorrhage in arteries of <3 mm in diameter
- linear parenchymal band

NUC (V/Q scan = guide for angiographic evaluation) interpreted in reference to Biello or PIOPED criteria:

N.B.:

In the fetus a V/Q scan (640 800 mSv) has a 5 267 times higher radiation dose than CT scan (3 131 mSv)!

low-/intermediate-probability scans in 50 70%:
- results in recommending additional studies; although only 12 14% will undergo angiography
- 25 30% disagreement between expert readers in interpreting intermediate- and low-probability V/Q scans
high-probability scan: in 12% normal angiogram

N.B.:

V/Q abnormalities vary over time due to autoregulation (hypoxic vasoconstriction, hypercapneic bronchoconstriction) and resolution

P.525

Angio (>95% sensitive + specific):

Indication:

Indeterminate NUC scan (angio within 24 hours)
Mismatch between interpretation + clinical findings
Significant risk for anticoagulation + high probability for PE
Prior to intervention: pulmonary embolectomy, caval ligation, caval filter placement
Patients too ill to undergo V/Q scan

Technique: AP & ipsilateral posterior oblique projection

intraluminal defect (94%)
abrupt termination of pulmonary arterial branch
pruning + attenuation of branches
wedge-shaped parenchymal hypovascularity
absence of draining vein in affected segment
tortuous arterial collaterals

Risks in pulmonary angiography:

left bundle branch block: requires temporary pacing wire prior to right heart catheterization
marginal cardiac function: therapy must be available to treat frank pulmonary edema
Right ventricular end diastolic pressure >20 mm Hg: selective catheterization with occlusion balloon

Cx of pulmonary angiography (1 2%):

arrhythmia, endocardial injury, cardiac perforation, cardiac arrest, contrast reaction

Mortality rate of pulmonary angiography:

0.2 0.5%

False-negative rate:

1 4 9% due to difficulty in visualizing subsegmental emboli (with only 30% interobserver agreement about presence of subsegmental emboli)

Rx:

Heparin IV: 10,000 15,000 units as initial dose; 8,000 10,000 units/hour during diagnostic evaluation; continued for 10 14 days
Streptokinase: better results with massive PE
Urokinase: slightly better than streptokinase
Coumadin: maintained for at least 3 months (15% complication rate)

Chronic Pulmonary Thromboembolism

= CHRONIC THROMBOEMBOLIC DISEASE

Frequency:	1 5% of patients with acute pulmonary thromboembolism, especially in patients with large emboli/recurrent episodes
At risk:	underlying malignancy, cardiovascular disease, pulmonary disease; M < F
Path:	fibrous webs and bands (= organized thromboemboli), often with overlying recent thrombosis; embolic material is incorporated into vessel wall + covered over by a thin layer of endothelial cells

Pathogenesis:

patent pulmonary arteries develop medial hypertrophy + intimal thickening + atherosclerotic plaques in response to pressure elevation; bronchial arteries may dilate + form extensive collateral pathways to minimize areas of lung infarction
may be clinically silent/asymptomatic for years ( honeymoon period )
history of previous embolic episodes
recurrent acute/gradual progressive exertional dyspnea (DDx: interstitial lung disease)
chronic nonproductive cough, atypical chest pain
tachycardia, syncope
elevated pulmonary arterial pressure (36 78 mm Hg), normal pulmonary capillary wedge pressure
high right atrial pressures, reduced cardiac output
lupus anticoagulant (11 24%)

CXR:

prominence of right side of heart
asymmetric enlargement of central pulmonary arteries
oligemic vascularity in patchy distribution
triangular/rounded opacity + adjacent pleural thickening (from pulmonary infarction)
patchy bilateral perihilar alveolar opacities of reperfusion edema after thrombendarterectomy

CT (77% sensitive):

cardiac changes:
- hypertrophy of RA + RV
- cardiomegaly
  - transverse diameter of RA >35 mm
  - transverse diameter of RV >45 mm
- vascular abnormalities:
pulmonary hypertension:
- main pulmonary artery diameter >28.6 mm
- right + left pulmonary arteries >18 mm in diameter measured in their intrapericardial portion 1 cm beyond origin
peripheral flattened filling defect of organized thrombus forming obtuse angles with arterial wall
complete filling defect at level of stenosed pulmonary artery (retracted thrombus):
- occlusion of main pulmonary artery (3%)
- abrupt narrowing/cutoff of distal lobar/segmental branches
- decrease in caliber of small branches + narrowing of peripheral pulmonary vessels
clot may become calcified
evidence of recanalization:
- contrast material flowing through arteries with thickened walls
- arterial stenosis/flap/web
collateral systemic supply of occluded pulmonary arterial bed:
- bronchial artery dilatation + tortuosity (77%) within mediastinum
parenchymal abnormalities:
- wedge-shaped pleura-based parenchymal bands with tip pointing to hila, often multiple, esp. involving lower lung (70%) = infarcted tissue replaced by scar
- mosaic perfusion on HRCT:
  - scattered geometric areas of low attenuation in 55% (due to oligemia) associated with vessels of small cross-sectional diameter
  - regional sharply demarcated areas of high attenuation (perfused lung on background of oligemic/nonperfused lung)
  - [DDx: primary pulmonary hypertension (more diffuse pattern of mosaic perfusion)]
  - cylindric bronchial dilatation of segmental/subsegmental bronchi (64%) adjacent to stenotic/obstructed pulmonary arterial segment

MR (lowest sensitivity):

discrete fixed areas of low-to-medium signal intensity on T1WI

Disadvantage:

slow flow in central vessels may obscure embolic fixed signal

NUC:

V/Q scan characteristically of high probability

Angio (highest specificity):

webs, bands
stenotic/absent arterial segments
pouchlike filling defects
abrupt cutoffs often confined to 1/2 lung segments
unilateral occlusion/hypoperfusion
selective bronchial arteriography shows dilated bronchial artery collaterals (up to 30% of systemic blood flow) filling pulmonary arteries downstream from sites of occlusion
markedly elevated pulmonary artery pressure

Prognosis:	30% 5-year survival with a mean PA pressure of 30 mm Hg
RX:	thrombendarterectomy (7 40% operative mortality); supplemental warfarin anticoagulation therapy vasodilators

Tumor Embolism

Diagnosis frequently missed until postmortem exam!

Frequency:	2 26% of patients with known malignancy
Primary:	gastric carcinoma (most common), breast, prostate, lung, hepatocellular, ovarian, osteosarcoma, lymphoma, choriocarcinoma Right atrial myxoma + RCC tend to embolize to large central + segmental pulmonary arteries!
Pathogenesis:	tumor cells form emboli in vena cava subsequently occlude small muscular pulmonary arteries + arterioles
Histo:	intravascular malignant cells, acute and organizing platelet-fibrin thrombi, small artery intimal fibrosis, adjacent intralymphatic tumor

progressive dyspnea, cough, pleuritic chest pain
hemoptysis, syncope
hypoxemia <50 mm Hg

CXR:

enlarged central pulmonary arteries
cardiomegaly
ill-defined nodular/confluent peripheral parenchymal opacities (with multiple pulmonary infarcts)

CT:

subpleural linear + wedge-shaped opacities (at sites of pulmonary infarctions)
companion manifestations: lymphadenopathy, pulmonary venous hypertension, lymphangitic carcinomatosis

CECT:

filling defects in main pulmonary artery branches
multifocal beading + dilatation of subsegmental pulmonary arteries

NUC:

multiple small subsegmental unmatched perfusion defects on V/Q scan

Angio:

delayed arterial phase
filling defects/occlusions of subsegmental arterial branches
arterial wall irregularities
peripheral pruning of smaller arteries

Cx:

subacute cor pulmonale (heralds death within 4 12 weeks)

Mercury Embolism

Cause:	accidental/suicidal IV injection
Pathomechanism:	intravascular mercury becomes encased in thrombus or migrates into pulmonary interstitium/alveolar spaces resulting in significant granulomatous response

high-density fine-caliber branching structures in symmetric distribution
mercury collection within apex of right ventricle

Pulmonary Venous Varix

= abnormal tortuosity + dilatation of pulmonary vein just before entrance into left atrium

Etiology:

congenital/associated with pulmonary venous hypertension

usually asymptomatic; may cause hemoptysis

Location:

medial third of either lung below hila close to left atrium

well-defined lobulated round/oval mass
change in size during Valsalva/mueller maneuver
opacification at same time as LA (on CECT)

Risk:	death upon rupture during worsening heart failure source of cerebral emboli
DDx:	pulmonary arteriovenous fistula

Radiation Pneumonitis

= damage to lungs after radiation therapy depends on:
- irradiated lung volume (most important):
  - asymptomatic in <25% of lung volume
- radiation dose (almost always exceeds critical value for tumoricidal doses):
  - pneumonitis unusual if <20 Gy given in 2 3 weeks
  - pneumonitis common if >60 Gy given in 5 6 weeks
  - significantly increased risk for pneumonitis if daily dose fraction > 2.67 Gy
- fractionation of dose
- concurrent/later chemotherapy
Pathologic phases:
- exudative phase = edema fluid + hyaline membranes
- organizing/proliferative phase
- fibrotic phase = interstitial fibrosis

Time of onset:	usually 4 6 months after treatment
Location:	confined to radiation portals

Acute Radiation Pneumonitis

Onset: within 4 8 (1 12) weeks after radiation Rx

Path: depletion of surfactant (1 week to 1 month later), plasma exudation, desquamation of alveolar + bronchial cells

P.527
- asymptomatic (majority)
- nonproductive cough, shortness of breath, weakness, fever (insidious onset)
- acute respiratory failure (rare)
- changes usually within portal entry field
- patchy/confluent consolidation, may persist up to 1 month (exudative reaction)
- atelectasis + air bronchogram
- spontaneous pneumothorax (rare)
- CT:
  - homogeneous slight hazy increase in attenuation obscuring vessel outlines (2 4 months after rx)
  - coalescing patchy consolidations (1 12 months after therapy) not conforming to shape of portals
  - nonuniform discrete consolidation (most common; 3 months to 10 years after therapy) forming sharp edge, which conforms to treatment portals
Prognosis: recovery/progression to death/fibrosis

Rx: steroids
Chronic Radiation Damage

Onset: 9 12 (6 24) months after radiation therapy; stabilized by 1 2 years after therapy

Histo: permanent damage of endothelial + type i alveolar cells
- May be associated with:
  - thymic cyst
  - calcified lymph nodes (in Hodgkin disease)
  - pericarditis + effusion (within 3 years)
- severe loss of volume
- dense fibrous strands from hilum to periphery
- thickening of pleura
- pericardial effusion
- CT:
  - solid consolidation with parenchymal distortion (due to radiation fibrosis + atelectasis)
  - traction bronchiectasis
  - mediastinal shift
  - pleural thickening

Respiratory Distress Syndrome Of Newborn

RDS = Surfactant deficiency disorder = Hyaline membrane disease
acute pulmonary disorder characterized by generalized atelectasis, intrapulmonary shunting, ventilation-perfusion abnormalities, reduced lung compliance

Frequency:	6:1,000 neonates (in 2002); M:F = 1.8:1
Cause:	relative lack of mature type II pneumocytes causes deficiency of endogenous surfactant (production usually begins at 18 20 weeks of gestational age) which leads to increased alveolar surface tension + decreased alveolar distensibility causing acinar atelectasis (persistent collapse of alveoli) + dilatation of terminal airways
Histo:	uniformly collapsed alveoli + variable distension of alveolar ducts + terminal bronchioles; lined by fibrin ( hyaline membranes ) 2 to protein seepage from damaged hypoxic capillaries
Predisposed:	perinatal asphyxia, maternal/fetal hemorrhage, term infants of diabetic mothers, multiple gestations, premature infants (<1,000 g in 66%; 1,000 g in 50%; 1,500 g in 16%; 2,000 g in 5%; 2,500 g in 1%)
Onset:	<2 5 hours after birth, increasing in severity from 24 to 48 hours, gradual improvement after 48 72 hours

nonspecific tachypnea, nasal flaring
expiratory grunting (expiratory breathing against a partially closed glottis to augment alveolar distension)
circumoral cyanosis (carbon dioxide retention)
substernal + intercostal retraction of chest wall
decreased lung expansion (counteracted by respirator therapy)
symmetric generalized consolidation of variable severity:
- complete white out of lung
- diffuse reticulogranular texture (coincides with onset of clinical signs, maximum severity at 12 24 hours of life) = summation of collapsed alveoli, transudation of fluid into interstitium, air distension of terminal bronchioles + alveolar ducts
- evolving hazy opacities to clearing over several days
effacement of normal pulmonary vessels
prominent air bronchograms (distension of compliant airways)

Prognosis:	spontaneous clearing within 7 10 days (mild course in untreated survivors); death in 18%
Rx:	Antenatal maternal corticosteroid therapy Surfactant replacement therapy (liquid bolus of exogenous surfactant delivered into tracheobronchial tree Nasal continuous positive airway pressure (CPAP) High-frequency oscillatory ventilation (HFOV) Extracorporeal membrane oxygenation (ECMO)
DDx:	Diffuse pneumonia accompanying sepsis Retained fetal lung fluid (first few hours) Pulmonary hemorrhage Pulmonary venous congestion (eg, TAPVR, pulmonary vein atresia, hypoplastic left heart) Premature with accelerated lung maturity (PALM baby)

Causes of Asymmetric Clearing after Surfactant

maldistribution of surfactant into right mainstem bronchus
insufficient surfactant requiring additional application
regional differences in aeration before surfactant treatment

DDx: neonatal pneumonia, meconium aspiration, unilateral tension pneumothorax, hemorrhagic pulmonary edema

Acute & Subacute Complications of RDS

Persistent patency of ductus arteriosus (PDA) oxygen stimulus is missing to close duct; gradual decrease in pulmonary resistance (by end of 1st week) leads to significant L-to-R shunt
Barotrauma with air-block phenomena
Hemorrhage
- Pulmonary hemorrhage
- Cerebral hemorrhage
Focal atelectasis (usually from mucus plug)
Persisting fetal circulation
Myocardial ischemia
Diffuse opacity
- Worsening RDS (first 1 2 days only)
- Congestive heart failure (PDA, fluid overload)
- Pulmonary hemorrhage
- Superimposed pneumonitis
- Massive aspiration
- Stage II bronchopulmonary dysplasia
- Weaning effect from removal of endotracheal tube/diminished ventilator pressure
- Extracorporeal membrane oxygenation
Disseminated intravascular coagulopathy
Necrotizing enterocolitis
Acute renal failure
Metabolic disturbance (eg, hyperbilirubinemia, hypocalcemia)

Chronic Complications of RDS

Bronchopulmonary dysplasia (10 20%)
Subglottic stenosis (intubation)
Localized interstitial emphysema
Hyperinflation
Retrolental fibroplasia
Malnutrition, rickets
Lobar emphysema
Delayed onset of diaphragmatic hernia
Recurrent inspiratory tract infections

Complication of Continuous Positive Pressure Ventilation (CPAP)

Cause:

airway overdistension (volutrauma) rather than high airway pressure (barotrauma)

Path:

rupture of alveoli along margins of interlobular septa + vascular structures (= parenchymal pseudocyst)
air dissecting along interlobular septa + perivascular spaces = pulmonary interstitial emphysema (PIE)
- pseudoclearing of RDS
interstitial air migrating centripetally into pleural space
- (= pneumothorax)/into mediastinum
- (= pneumomediastinum)/into pericardial cavity
- (= pneumopericardium)
interstitial air rupturing into peritoneal space
- (= pneumoperitoneum)/retroperitoneal space
- (=pneumoretroperitoneum)
air dissecting into skin (= subcutaneous emphysema)
air rupturing into vessel (= gas embolism)

streaky/mottled lucencies radiating from hila without branching/tapering often outlining bronchovascular bundles (DDx: air bronchogram)
large subpleural cysts without definable wall usually at diaphragmatic + mediastinal surface compressing adjacent lung
pneumothorax (in up to 25%)

Rx:

mechanical ventilatory assistance with positive end-expiratory pressure (to increase oxygen diffusion)

Retained Fetal Lung Fluid

= NEONATAL WET LUNG DISEASE = TRANSIENT RESPIRATORY DISTRESS OF THE NEWBORN = TRANSIENT TACHYPNEA OF THE NEWBORN

Incidence:	6%; most common cause of respiratory distress in newborn
Cause:	cesarean section, precipitous delivery, breech delivery, prematurity, maternal diabetes

Pathophysiology:

delayed resorption of fetal lung fluid (normal clearance occurs through capillaries (40%), lymphatics (30%), thoracic compression during vaginal delivery (30%); stiff lungs cause labored ventilation until fluid is cleared

Onset:

within 6 hours of life; peaks at 1st day of life

increasing respiratory rates during first 2 6 hours of life
intercostal + sternal retraction
normal blood gases during hyperoxygenation
linear opacities + perivascular haze + thickened fissures + interlobular septal thickening (interstitial edema):
- symmetric perihilar radiating congestion
mild hyperaeration
mild cardiomegaly
small amount of pleural fluid

Prognosis:

resolving within 1 2 4 days (retrospective Dx)

DDx:

Normal (during first several hours of life)
Diffuse pneumonitis/sepsis
Mild meconium aspiration syndrome
Alveolar phase of RDS
Drowned newborn syndrome = clear amniotic fluid aspiration
Pulmonary venous congestion (eg, left heart failure, overhydration, placental transfusion)
Pulmonary hemorrhage
Hyperviscosity syndrome = thick blood
Immature lung syndrome = premature with accelerated lung maturity (PALM baby)

Rheumatoid Lung

= autoimmune disease of unknown pathogenesis

Prevalence:

2 54% of patients with rheumatoid arthritis; M:F = 5:1 (although incidence of rheumatoid arthritis: M < F)

rheumatoid arthritis

Stage 1:	multifocal ill-defined alveolar infiltrates
Stage 2:	fine interstitial reticulations (histio- and lymphocytes)
Stage 3:	honeycombing

PLEURAL DISEASE (most frequent thoracic manifestation)
- Hx of pleurisy (21%)
Associated with: pericarditis, subcutaneous nodules
- pleural effusion (3%) with little change over months:
  - unilateral (92%), may be loculated
  - most often without other pulmonary changes
- M:F = 9:1
- Usually late in the disease, but may antedate rheumatoid arthritis
- exudate (with protein content >4 g/dL)
- low in sugar content (<30 mg/dL) without rise during glucose infusion (75%)
- low WBC high in lymphocytes
- positive for rheumatoid factor, LDH, RA cells
- pleural thickening, usually bilateral
DIFFUSE INTERSTITIAL FIBROSIS (30%)

Prevalence: 2 9% of patients with rheumatoid arthritis
- restrictive ventilatory defect
Location: lower lobe predominance

Histo: deposition of IgM in alveolar septa (DDx to IPF)

P.529
- punctate/nodular densities (mononuclear cell infiltrates in early stage)
- reticulonodular densities
- medium to coarse reticulations (mature fibrous tissue in later stage):
  - irregular interlobular septal thickening on HRCT, predominantly in periphery of lower lung zones
- honeycomb lung (uncommon in late stage) with progressive volume loss
NECROBIOTIC NODULES (rare)
- = well-circumscribed nodular mass in lung, pleura, pericardium identical to subcutaneous nodules associated with advanced rheumatoid arthritis
Path: central zone of eosinophilic fibrinoid necrosis surrounded by palisading fibroblasts; nodule often centered on necrotic inflamed blood vessel (? vasculitis as initial lesion)
- subcutaneous nodules (same histology)
Associated with: interstitial lung disease
- well-circumscribed usually multiple nodules of 3 70 mm in size
- commonly located in lung periphery
- cavitation with thick symmetric walls + smooth inner lining (in 50%)
- NO calcification

CAPLAN SYNDROME

= RHEUMATOID PNEUMOCONIOSIS
= pneumoconiosis + rheumatoid arthritis in coal workers with rheumatoid disease;
= hypersensitivity reaction to irritating dust particles in lungs of rheumatoid patients

Incidence:	2 6% of all men affected by pneumoconioses (exclusively in Wales)
Path:	disintegrating macrophages deposit a pigmented ring of dust surrounding the central necrotic core + zone of fibroblasts palisading the zone of necrosis

NOT necessarily evidence of long-standing pneumoconiosis
concomitant with joint manifestation (most frequent)/may precede arthritis by several years
concomitant with systemic rheumatoid nodules
rapidly developing well-defined nodules of 5 50 mm in size with a tendency to appear in crops predominantly in upper lobes + in periphery of lung
nodules may remain unchanged/increase in number/calcify/result in thick-walled cavities
background of pneumoconiosis
pleural effusion (may occur)

BRONCHIAL ABNORMALITIES (30%)
- bronchiectasis
- bronchiolitis obliterans (may be transient + regardless of penicillamine/gold therapy):
  - mosaic pattern (= areas of decreased attenuation + vascularity) on end-inspiratory HRCT
  - air trapping on end-expiratory HRCT
- bronchiolitis obliterans organizing pneumonia (BOOP):
  - bilateral air-space consolidation in peripheral/peribronchial distribution
- follicular bronchiolitis (in 66%):
  - small centrilobular nodules with patchy areas of ground-glass attenuation
PULMONARY ARTERITIS
- = fibroelastoid intimal proliferation of pulmonary arteries
- pulmonary arterial hypertension + cor pulmonale
CARDIAC ENLARGEMENT
- (pericarditis + carditis/congestive heart failure)
BONE ABNORMALITIES ON CXR
- erosive arthritis of acromioclavicular joint, sternoclavicular joint, shoulder joint:
  - resorption of distal end of clavicles
- ankylosis of vertebral facet joints
- vertebral body collapse due to steroid use

Round Pneumonia

= NUMMULAR PNEUMONIA
= fairly spherical pneumonia caused by pyogenic organisms

Organism:	Haemophilus influenzae, Streptococcus, Pneumococcus
Age:	children >> adults

cough, chest pain, fever

Location:

always posterior, usually in lower lobes

spherical infiltrate with slightly fluffy borders + air bronchogram
triangular infiltrate abutting a pleural surface (usually seen on lateral view)
rapid change in size and shape

Sarcoidosis

= BOECK SARCOID [sarkos, Greek = flesh; sarcoid = sarcoma-like; caesar Boeck describes skin lesions in 1899]
= immunologically mediated multisystem granulomatous disease of unknown etiology with variable presentation, progression, and prognosis

Prevalence:	10 40:100,000 in USA
Age peak:	20 40 years; m:f = 1:3 (more common in women + people of West African descent); American Blacks:American Whites = 10:1 (rare in African/south American Blacks); more common in blood group A

Epidemiology:
- found with varying frequency in every country in the world; higher prevalence in temperate climates compared to tropical regions (< 10/100,000)
Immunology:
- unknown antigen activates alveolar macrophages, which release
  - interleukin-1 (T-cell activator)
  - fibronectin (fibroblast chemotactic factor)
  - alveolar macrophage-derived growth factor (stimulates fibrosis)
and activates T-lymphocytes, which release
- interleukin-2 (stimulates growth of T-helper/cytolytic cells)
- immune interferon (polyclonal B-cell activator)
- monocyte chemotactic factor (attracts circulating monocytes and stimulates granuloma formation)

Histo:	alveolitis (earliest changes); noncaseating epithelioid granulomas [composed of lymphocytes, peripheral fibroblasts, multinucleated giant cells] with occasional minimal central necrosis
Location:	along course of lymphatic vessels: subpleural, septal, perivascular, peribronchial
DDx:	indistinguishable from granulomas of berylliosis, treated TB, leprosy, fungal disease, hypersensitivity pneumonitis, crohn disease, primary biliary cirrhosis

P.530

angiotensin-converting enzyme (Ace) elevated in 70% [Ace is a product of macrophages and an indicator for the granuloma burden of the body]

DDx: tuberculosis, leprosy, histoplasmosis, berylliosis, cirrhosis, hyperthyroidism, diabetes
hypercalcemia + hypercalciuria in 2 15% [result of hydroxylation of 1,25-dihydroxy vitamin d in macrophages leading to increased intestinal resorption of calcium]
Kveim-Siltzbach test (positive in 70%) = intracutaneous injection of 0.1 0.2 mL of a previously validated saline suspension of human sarcoid spleen/lymph nodes, rarely used
functional pulmonary impairment (even with no radiographic abnormality):
- reduced VC + FRC + TLC [from generalized reduction in lung volume]
- low lung compliance [f rom diffuse interstitial disease]
- obstructive airway disease [from endobronchial lesions, peribronchial fibrosis]
no identification of infectious/inflammatory agent

Dx:

based on a combination of clinical + radiological + histologic features after exclusion of other infectious/inflammatory entities

Clinical Forms:

ACUTE FORM = L fgren Syndrome (17%)
- fever + malaise + bilateral hilar adenopathy
- erythema nodosum
- arthralgia of large joints
- (occasionally) uveitis + parotitis
CHRONIC FORM
- asymptomatic (50%)
- fever, malaise, weight loss
- dry cough + shortness of breath (25%)
- hemoptysis in 4% (from endobronchial lesion/vascular erosion/cavitation)

Stage at presentation:

0	normal chest radiograph	5%
I	hilar + mediastinal lymphadenopathy only	50%
II	lymphadenopathy + parenchymal disease	30%
III	diffuse parenchymal disease only	15%
IV	pulmonary fibrosis	20%

Prognosis:

80%	spontaneous remission of stage 1 + 2 disease
75%	complete resolution of hilar adenopathy
33%	complete resolution of parenchymal disease
30%	improve significantly
20%	irreversible pulmonary fibrosis (may persist unchanged for >15 years)
5%	mortality (cor pulmonale/CNS/lung fibrosis/liver cirrhosis)
25%	relapse (in 50% detected by CXR)

Abdominal Sarcoidosis

strikingly elevated ACE levels in 91%
@ Liver (pathologic involvement in 24 59%):
- homogeneous hepatomegaly (18 29%)
- 2 5-mm nodular lesions in liver and spleen in 5 15% (= coalescent granulomata) occurring within 5 years of diagnosis
- abdominal adenopathy (mean size of 2.6 cm)
MR:
- heterogeneous/nodular hepatic texture and periportal high signal intensity on T2WI
@ Spleen (pathologic involvement in 24 59%)
- splenomegaly (20 33%)
- scattered nodular lesions (18%)
@ Lymphadenopathy (10 31%)
- frequently associated with thoracic adenopathy
- mean lymph node size of 2.6 cm
@ Pancreas
- mass + pain mimicking pancreatic carcinoma

Bone Sarcoidosis (6 15 20%)

densely sclerotic lesions in spine, pelvis, ribs
lesions of distal + middle phalanges of hand + foot:
- pain and swelling
- lytic lesion with lacelike trabecular pattern
- sharply marginated cystlike area of rarefaction

Gastrointestinal Sarcoidosis

Location:

anywhere from esophagus to rectum

@ Stomach (most common, 60 cases)
- polypoid/nodular mass
- ulcer (simulating peptic ulcer disease)
- diffuse fold thickening
- circumferential narrowing + loss of antral compliance (resembling scirrhous carcinoma)
@ Colon (2nd most common)
- plaque-like lesions/ulcers
- fold thickening, focal nodularity
- annular segmental narrowing with obstruction
@ Esophagus
- plaquelike lesions, narrowing, aperistalsis
@ Small bowel
- circumferential thickening of terminal ileum (rare)

Genitourinary Sarcoidosis (0.2 5%)

@ Kidney
- renal calculi
@ Scrotum (0.5%)
- hypoechoic lesions in epididymis + testis

Skin Sarcoidosis (10 30%)

erythema nodosum = multiple bilateral tender erythematous nodules mostly on anterior aspect of lower extremities:
- often associated with fever + arthralgia
- hilar lymph node enlargement
lupus pernio = indurated bluish purple elevations mainly on nose + digits
skin plaques/scars

P.531

Thoracic Sarcoidosis (90%)

Extrathoracic manifestations without intrathoracic involvement occur in <10%!
mild symptoms in spite of extensive radiographic changes (DIAGNOSTICALLY SIGNIFICANT)
adenopathy alone (43%)
adenopathy + parenchymal disease (41%)
parenchymal disease alone (16%)

Associated with:

tuberculosis in up to 13%

intrathoracic lymphadenopathy (>85%):

Location:
- 1 2-3 sign = Garland triad = symmetric bilateral hilar nodes + right paratracheal and aortopulmonary window nodes (75 95%)
- isolated unilateral hilar enlargement (1 8%)
- mediastinal nodes are regularly enlarged on CT
Prognosis: adenopathy commonly decreases as parenchymal disease gets worse; subsequent parenchymal disease in 32%; adenopathy does not develop subsequent to parenchymal disease

eggshell calcification of lymph nodes (in 3% after 5 years, in 20% after 10 years)
parenchymal disease (60%); without adenopathy in 16 20%:
Parenchymal granulomas are invariably present on open lung biopsy!

Site:

predominantly mid-zone + upper lung involvement

reticulonodular pattern (46%)
acinar pattern (20%) = ill-defined 6 7-mm nodules/coalescent opacities
alveolar/acinar sarcoidosis (2 10%) = multiple nodules >10 50 mm (= coalescence of numerous interstitial granulomas):
- indistinct margins
- air bronchogram
- cavitation of occasional nodule
progressive fibrosis with upper lobe retraction + bullae (20%)
irreversible fibrotic changes of end-stage lung disease (11 20%)

airway disease:
- tracheal stenosis
- bronchial stenosis (extrinsic compression by large lymph nodes/endobronchial granulomas)
- bronchiectasis (scarring/fibrosis)

HRCT:

irregular bronchovascular + interlobular septal + pleural thickening
architectural distortion frequent
perilymphatic nodules (= small nodules along broncho-arterial bundles and veins, in subpleural + interlobular septal lymphatics representing epithelioid cell granulomas)
traction bronchiectasis (TYPICAL)
ground-glass opacity (in alveolitis)
bullae in honeycombing
irregular/nodular bronchial wall thickening
air trapping

Atypical manifestations (25%):

pleural effusion (2%) = exudate with predominance of lymphocytes, effusion clears in 2 3 months
focal pleural thickening
solitary/multiple pulmonary nodules:
- cavitation of nodules (0.6%)
isolated hilar/mediastinal nodal enlargement
bronchostenosis (2%) with lobar/segmental atelectasis
pulmonary arterial hypertension (periarterial granulomatosis without extensive pulmonary fibrosis)

Cx:

pneumothorax secondary to chronic lung fibrosis (rare)
cardiomegaly from cor pulmonale (rare)
aspergilloma formation in apical bulla (in >50% of stage IV disease)

Diagnostic criteria:

compatible clinical + radiologic picture
noncaseous epithelioid granulomas on bronchial/transbronchial biopsy (diagnostic results in 60 95% and 80 95% respectively)
negative results of special stains/cultures for other entities

Assessment of activity:

ACE titer (= angiotensin I converting enzyme)
Bronchoalveolar lavage: 20 50% lymphocytes with number of T-suppressor lymphocytes 4 20 times above normal
Gallium scan
- uptake in lymph nodes + lung parenchyma + salivary glands (correlates with alveolitis + disease activity); monitor of therapeutic response (indicator of macrophage activity)

Sarcoidosis of Other Organs

@ Peripheral lymph node enlargement (30%)
@ Muscle (25%): myopathy
@ Myocardium (6 25%)
- ventricular arrhythmia, heart block, cardiomyopathy, congestive failure, angina, ventricular aneurysm
@ Eyes (5 25%)
- uveitis, photophobia, blurred vision, glaucoma (rare)
@ CNS (9%)
- hypothalamus, basal granulomatous meningitis, facial nerve palsy
@ Salivary gland (4%)
- bilateral parotid enlargement

Septic Pulmonary Emboli

= lodgment of an infected thrombus in a pulmonary artery

Organism:	S. aureus, Streptococcus
Predisposed:	IV drug abusers, alcoholism, immunodeficiency, CHD, dermal infection (cellulitis, carbuncles)

Source:

infected venous catheter/pacemaker wires, arteriovenous shunts for hemodialysis, drug abuse producing septic thrombophlebitis (eg, heroin addicts), pelvic thrombophlebitis, peritonsillar abscess, osteomyelitis
tricuspid valve endocarditis (most common cause in IV drug abusers)

Age:

<40 years

sepsis, cough, dyspnea, chest pain
shaking chills, high fever, severe sinus tachycardia

Location:

predilection for lung bases

P.532

multiple nondescript pulmonary infiltrates (initially)
migratory infiltrates (old ones heal, new ones appear)
cavitation (frequent), usually thin-walled
pleural effusion (rare)
CT (more sensitive than CXR):
- multiple peripheral parenchymal nodules cavitation/air bronchogram (83%)
- wedge-shaped subpleural lesion with apex of lesion directed toward pulmonary hilum (50%)
- feeding vessel sign = pulmonary artery leading to nodule (67%)
- cavitation (50%), esp. in staphylococcal emboli
- air bronchogram within pulmonary nodule (28%)

Cx:

empyema (39%)

Siderosis

= inert iron oxide/metallic iron deposits

Path:

iron phagocytized by macrophages in alveoli/respiratory bronchioles, elimination from lung by lymphatic circulation

Occupational exposure:

electric arc welding, oxyacetylene torch workers (iron oxide in fumes), mining + processing of iron ores, cutting/burning of iron + steel, foundry workers, grinders, fettlers, silver polishers (jewelry industry)
diffuse fine reticulonodular opacities (may disappear after exposure discontinued)
small round opacities (indistinguishable from silica/coal)
NO secondary fibrosis + NO hilar adenopathy (unless mixed dust inhalation as in siderosilicosis/silicosiderosis = mixed-dust pneumoconiosis)
HRCT:
- widespread poorly defined centrilobular micronodules
- branching linear structures
- extensive ground-glass attenuation without zonal predominance

DDx:

silicosis (nodular opacities more dense + profuse)

Silicosis

= inhalation of silicon dioxide; most prevalent silicosis of progressive nature after termination of exposure; similar to CWP (because of silica component in CWP)

Substance:

crystalline silica (quartz); one of the most widespread elements on earth

Occupational exposure:

tunneling, mining, quarrying, stone cutting, polishing, glass manufacturing, foundry work, sandblasting, pottery, brick lining, boiler scaling, vitreous enameling, ceramic industry

Dust deposition:

dependent on

airflow: deposition of 1 5- m particles predominantly around respiratory bronchioles in a centrilobular location within secondary pulmonary lobule
lymphatic clearance: related to pulmonary arterial pressure (gravity-related vertical gradient) + blood flow (higher blood flow through LUL) + passive milking of lymphatics by respiratory motion (lateral > anterior > posterior chest wall)

Path:	small particles engulfed by macrophages; liberation of silica results in cell death; 2 3-mm nodules with layers of laminated connective tissue around smaller vessels
Cx:	predisposes to tuberculosis
DDx:	coal worker pneumoconiosis (identical radiographs)

Acute Silicosis

= SILICOPROTEINOSIS
= heavy exposure to respirable free silica in enclosed space with minimal/no protection of airways

Histo:	proliferation of type II pneumatocytes + profuse surfactant production
Exposure time:	as short as 6 8 months
Associated with:	increased risk to develop autoimmune disease
Distribution:	lung periphery; predominantly lower lung zones; bilateral

diffuse airspace/ground-glass disease
air bronchograms
HRCT:
- patchy ground-glass opacities
- fine intralobular reticulations (= crazy paving )

Cx:	infection with TB + atypical mycobacteria
Prognosis:	often rapidly progressive with death from respiratory failure
DDx:	alveolar proteinosis

Chronic Simple Silicosis

At least 10 20 years of dust exposure before appearance of roentgenographic abnormality

Location:

upper + posterior lung zones

small 2 5 (range, 1 10)-mm rounded opacities
may calcify centrally in 5 10% (rather typical for silicosis)
hilar + mediastinal lymphadenopathy, may calcify in 5% ( eggshell pattern )
reticulonodular pattern
HRCT:
- nodules of 3 10 mm in size
- thickened intra- and interlobular lines
- subpleural curvilinear lines (peribronchiolar fibrosis)
- ground-glass pattern = mild thickening of alveolar wall+ interlobular septa (fibrosis/edema)
- parenchymal fibrous bands
- multiple subpleural nodules
- pseudoplaques = aggregate of subpleural nodules
- traction bronchiectasis
- honeycombing

Complicated Silicosis

= PROGRESSIVE MASSIVE FIBROSIS
= appearance of large opacities >1 cm in diameter

Location:	midzone/periphery of upper lung migrating toward hila
Distribution:	often bilateral symmetric + nonsegmental

conglomerate sausage-shaped masses with ill-defined margins (in advanced stages)
compensatory emphysema in unaffected portion between mass + pleura
slow change over years
may calcify + cavitate (ischemic necrosis)

Silicotuberculosis

Doubtful synergistic relationship between silicosis + tuberculosis

P.533

little change over years with intermittently positive sputa

Caplan Syndrome

more common in coal worker's pneumoconiosis

Staphylococcal Pneumonia

most common cause of bronchopneumonia!
- common nosocomial infection (patients on antibiotic drugs most susceptible)
- accounts for 5% of community-acquired pneumonias (esp. in infants + elderly)
secondary invader to influenza (commonest cause of death during influenza epidemics)

Organism:

staphylococcus aureus = gram-positive, appears in clusters, coagulase-producing

rapid spread through lungs
empyema (esp. in children)
pneumothorax, pyopneumothorax
abscess formation
bronchopleural fistula

in CHILDREN:
- rapidly developing lobar/multilobar consolidation
- pleural effusion (90%)
- pneumatocele (40 60%)
in ADULTS:
- patchy often confluent bronchopneumonia of segmental distribution, bilateral in >60%
- segmental collapse (air bronchograms absent)
- late development of thick-walled lung abscess (25 75%)
- pleural effusion/empyema (50%) (ddx from other pneumonias)
Cx: meningitis, metastatic abscess to brain/kidneys, acute endocarditis

Streptococcal Pneumonia

Incidence:	1 5% of bacterial pneumonias (rarely seen); most common in winter months
Organism:	Group A -hemolytic streptococcus = Streptococcus pyogenes, gram-positive cocci appearing in chains
Predisposed:	newborns, following infection with measles
Associated with:	delayed onset of diaphragmatic hernia (in newborns)

rarely follows tonsillitis + pharyngitis

patchy bronchopneumonia
lower lobe predominance (similar to staphylococcus)
empyema

Cx:

(1) Residual pleural thickening (15%)
(2) Bronchiectasis
(3) Lung abscess
(4) Glomerulonephritis

Swyer-James Syndrome

= MACLEOD SYNDROME = UNILATERAL LOBAR EMPHYSEMA = IDIOPATHIC UNILATERAL HYPERLUCENT LUNG
= chronic complication of bronchiolitis

Etiology:	acute viral bronchiolitis in infancy/early childhood (adenovirus, RSV) preventing normal development of lung
Path:	variant of postinfectious constrictive bronchiolitis with acute obliterative bronchiolitis, bronchiectasis, distal airspace destruction (developing in 7 30 months)

asymptomatic
cough, dyspnea on exertion, hemoptysis
history of recurrent lower respiratory tract infections during childhood

Location:

one/both lungs (usually entire lung, occasionally lobar/subsegmental)

hyperlucency of one lung
diminished number + size of pulmonary vessels:
small ipsilateral hilum (diminuted hilar vessels + attenuated arteries)
small hemithorax with decreased/normal volume (collateral air drift)
air trapping during expiration

DDx:

no air trapping with proximal interruption of pulmonary artery (no hilum), hypogenetic lung syndrome, pulmonary embolus

mild cylindrical bronchiectasis with paucity of bronchial subdivisions (cutoff at 4th 5th generation = pruned tree bronchogram)
HRCT (most useful modality):
- bilateral areas of decreased attenuation:
  - areas of normal lung attenuation within hypoattenuating lung
  - air trapping within hypoattenuating lung
  - bronchiectasis
- diminished size of pulmonary vessels in hyperlucent areas
Angio:
- pruned tree appearance
NUC (V/Q scan):
- matched defects of perfusion + ventilation (with delayed washout) in hyperlucent regions
Bronchography:
- dilated bronchi with sharply terminating segments

DDx:

pulmonary artery atresia (uncommon in adults), localized bullous emphysema (deviation of vessels), bronchial obstruction

Systemic Lupus Erythematosus

= SLE = most prevalent of the potentially grave connective tissue diseases characterized by involvement of vascular system, skin, serous + synovial membranes

Prevalence:	1:2,000; Blacks:Caucasians = 3:1; increased risk in relatives
Cause:	local deposition of antigen-antibody complexes/antibodies inducing necrotizing vasculitis (type III immune complex phenomenon) of the small blood vessels
Age:	16 41 years; M:F = 1:10 (women of childbearing age)

Diagnostic criteria:
- malar rash
- discoid rash
- photosensitivity
- oral ulcers
- arthritis
- serositis
- antinuclear antibodies
- renal disease
- neurologic disease
- hematologic disease
- immunologic disorder

fatigue, malaise, anorexia, fever, weight loss
clinically heterogeneous due to different types of serum antibodies
antinuclear DNA antibodies (87%)
hypergammaglobulinemia (77%)
LE cells (= antigen-antibody complexes engulfed by PMNs) in 78%
chronic false-positive Wassermann test for syphilis (24%)
Sj gren syndrome (frequent)
anemia (78%)
leukopenia (66%)
thrombocytopenia (19%)

Prognosis:

60 90% 10-year survival; death from renal failure/sepsis/CNS involvement/myocardial infarction

Drug-induced Lupus Erythematosus (DIL)

temporary phenomenon

Agents:

procainamide, hydralazine, isoniazid, phenytoin account for 90%

pulmonary + pleural disease more common than in SLE

Gastrointestinal SLE (in up to 50%)

buccal erosions/ulcerations
GI tract bleeding

mesenteric ischemia: colitis, pseudoobstruction, ileus, thumbprinting, luminal narrowing
motility disorder of lower esophagus (similar to scleroderma)
esophagitis ulcers
gastritis
nodularity of folds
pneumatosis intestinalis, perforation
painful ascites
hepatomegaly, hepatitis, cirrhosis
splenomegaly

Renal SLE

Prevalence:	kidneys involved in 100% with renal disease developing in 30 50%
Histo:	focal membranoproliferative glomerulonephritis

renal failure (fibrinoid thickening of basement membrane)

aneurysms in interlobular + arcuate arteries (similar to but less frequent than polyarteritis nodosa)
normal/decreased renal size
hydronephrosis (due to detrusor muscle spasm with vesicoureteral reflux/fibrosis of ureterovesical junction)

US:

kidney enlarged (early)/diminutive (late stage)
increased parenchymal echogenicity

CT:

multiple linear hypoattenuating bands (due to vasculitis)

Cx:	(1) Nephrotic syndrome (common) (2) Renal vein thrombosis (in 33%)
Prognosis:	end-stage renal disease is common cause of death

Skin SLE (81%)

butterfly rash (= facial erythema), discoid lupus erythematosus, alopecia, photosensitivity
Raynaud phenomenon (15%)

Thoracic SLE (30 70%)

Affects respiratory system more commonly than any other connective tissue disease

dyspnea, pleuritic chest pain (35%)
respiratory dysfunction (>50%): single-breath diffusing capacity for carbon monoxide most sensitive indicator

Pulmonary disease

Cause: chronic antibody damage to alveolar-capillary membrane
- parenchymal opacification:
- pneumonia (most common) due to bacteria/opportunistic organism
- lung hemorrhage
- pulmonary edema
- lupus pneumonitis (acute form) = poorly defined patchy areas of increased density peripherally at lung bases (alveolar pattern) secondary to infection/uremia in 10%
- cavitating nodules (vasculitis)
- pulmonary fibrosis (30%):
- interstitial reticulations in lung periphery of lower lung fields (chronic form) in 3%
- fleeting platelike atelectasis in both bases (? infarction due to vasculitis)
- progressive loss of lung volume:
- elevated sluggish diaphragms (due to diaphragmatic dysfunction)
- hilar + mediastinal lymphadenopathy (extremely rare)
Pleural disease (50%)
- recurrent uni-/bilateral pleural effusions (70%) from pleuritis
- pleural thickening
Cardiovascular disease
- pericardial effusion (from pericarditis)
- cardiomegaly (primary lupus cardiomyopathy)

@ Joints
- arthralgia (95%)
- nonerosive arthritis of hands (characteristic) without deformity
- tumoral calcinosis

Talcosis

= prolonged inhalation of magnesium silicate dust containing amphibole fibers (tremolite and anthophyllite) and silica
talcosis resembles:

Asbestosis (indistinguishable)
- massive and bizarre pleural plaques
- may encase lung with calcification
Silicosis
- small rounded + large opacities
- fibrogenic process (NO regression after removal of patient from exposure)

Teratoid Tumor Of Mediastinum

= MEDIASTINAL GERM CELL TUMOR [= TERATOMA]
The anterior mediastinum is the most common extragonadal site of primary germ cell tumors (1 3% of all germ cell tumors)!

P.535

Pathogenesis:

misplaced multipotential primitive germ cells during migration from yolk endoderm to gonad

Incidence:

adults: 15% of anterior mediastinal tumors
children: 24% of anterior mediastinal tumors

16 28% of all mediastinal cysts!
Occurs in same frequency as the usually larger thymoma!
1/3 of primary neoplasms in this area are in children

Classes:	(1) Mature teratoma (solid) (2) Cystic teratoma (dermoid cyst) (3) Immature teratoma (4) Malignant teratoma (teratocarcinoma) (5) Mixed teratoma
Location:	mediastinum is 3rd most common site for teratoid lesions (after gonadal + sacrococcygeal location); 5% of all teratomas occur in mediastinum, mostly anterosuperiorly (in only 1% posteriorly)

often inseparable from thymus gland

Cx:

Hemorrhage
Pneumothorax (from bronchial obstruction with air trapping + alveolar rupture)
Respiratory distress (rapid increase in size from fluid production) with compression of trachea/SVC (SVC syndrome)
Fistula formation to aorta, SVC, esophagus
Rupture into bronchus (expectoration of oily substance/trichoptysis in 5 14%, lipoid pneumonia)
Rupture into pericardium (pericardial effusion), pleural cavity (pleural effusion)

DDx:

thymoma

Benign Teratoid Tumor (75 86%)

= MATURE TERATOMA
Most common histologic type

Epidermoid (52%) = ectodermal derivatives
Dermoid (27%) = ecto- + mesodermal derivatives
Teratoma (21%) = ecto- + meso- + endodermal derivatives

Path:

spherical lobulated well-encapsulated tumor; typically multi-/unilocular cystic cavities with clear/yellow/brown liquid

Histo:

ectoderm: skin, sebaceous material, hair, cysts lined by squamous epithelium
mesoderm: bone, cartilage, muscle
endoderm: GI + respiratory tissue, mucus glands

Tumor capsule commonly has remnants of thymic tissue!
Cyst formation is typical (usually lined by mucus-secreting tall epithelial cells)!

Age:

young adults/children; M = F

asymptomatic (in up to 53%)
cough, dyspnea, chest pain, pulmonary infection, respiratory distress (due to compression by large tumor)

Location:

anterior superior mediastinum near thymus/within thymic parenchyma
posterior mediastinum (rare = 3 8%)

rounded mass bulging into right/left hemithorax sharply demarcated against adjacent lung
variations in density (may all be present):
fat-fluid level (rare but SPECIFIC)
water density
homogeneous soft-tissue density (indistinguishable from lymphoma/thymoma)
curvilinear peripheral/central calcification (20 43%, 4 more common in benign lesions) in tumor wall/substance, ossification in mature bone
visualization of tooth (PATHOGNOMONIC)
often inseparable from thymic gland
enhancement of rim/tissue septa

Prognosis:	approx. 100% 5-year survival rate
Rx:	complete surgical excision

Malignant Teratoid Tumor (14 20%)

Histo:

similar to mature teratoma but with primitive/immature tissue elements; commonly neural tissue arranged in rosettes/primitive tubules

Teratocarcinoma/malignant teratoma = identical to teratoma with components of seminoma, endodermal sinus tumor, embryonal carcinoma, choriocarcinoma, sarcoma, carcinoma

Seminoma = germinoma = dysgerminoma

2nd most common mediastinal germ cell tumor!
Most common primary malignant germ cell tumor of mediastinum!

Incidence:	2 6% of all mediastinal tumors; 5 13% of all malignant mediastinal tumors
Age:	3rd 4th decade; M > F; white
Histo:	uniform polyhedral/round cells arranged in sheets or forming small lobules separated by fibrous septa; varying amounts of mature lymphocytes
Path:	large unencapsulated well-circumscribed mass

asymptomatic (20 30%)
chest pain/pressure, shortness of breath, weight loss, hoarseness, dysphagia, fever
SVC obstruction (10%)
elevated serum levels of hCG (7 18%)
elevated serum levels of LdH (80%) correlate with tumor burden + rate of tumor growth

Metastases:

to regional lymph nodes, lung, bone, liver

large bulky well-marginated lobulated mass
usually no calcification
homogeneous soft-tissue density with slight enhancement

Prognosis:	75 100% 5-year survival rate; death from distant metastases
Rx:	surgery + radiation therapy (very radiosensitive) cisplatin

Nonseminomatous malignant germ cell tumor

embryonic tissue
- embryonal carcinoma
extraembryonic tissue
- yolk sac = endodermal sinus tumor
- choriocarcinoma (least frequent)
combination = mixed germ cell tumor

Path:	large unencapsulated heterogeneous soft-tissue mass with tendency for invasion of adjacent structures
Age:	during 2nd 4th decade m:f = 9:1; in children m = f
Associated with:	Klinefelter syndrome (in 20%), hematologic malignancy

P.536

chest pain, dyspnea, cough, weight loss, fever, sVc syndrome (90 100%)
elevated serum level of -fetoprotein (80%) with endodermal sinus tumor/embryonal carcinoma
elevated serum level of LDH (60%)
elevated serum level of HCG (30%) [ddx: lung cancer; hepatocellular carcinoma; adenocarcinoma of pancreas, colon, stomach]

Metastases to:

lung, liver

large tumor of heterogeneous texture with central hemorrhage/necrosis
well circumscribed/with irregular margins
enhancement of tumor periphery
lobulation suggests malignancy
invasion of mediastinal structures (sVc obstruction is ominous)
pleural/pericardial effusion (from local invasion)
Absence of primary testicular tumor/retroperitoneal mass proves primary!

Rx:	cisplatin-based chemotherapy + tumor resection
Prognosis:	50% long-term survivors

Thoracic Paraganglioma

= CHEMODECTOMA
= rare neural tumor arising from paraganglionic tissue

Age:	3rd 5th decade; m:f = 1:1
Path:	extremely vascular well-marginated/irregular mass that may adhere to/envelop/invade adjacent mediastinal structures (bronchus, spinal canal)
Histo:	anastomosing cords of granule-storing chief cells arranged in a trabecular pattern; identical appearance for benign and malignant tumors

May be associated with:

syn-/metachronous adrenal/extrathoracic paragangliomas; multiple endocrine neoplasia type 2; bronchial carcinoid tumor
asymptomatic
dyspnea, cough, chest pain, hemoptysis, neurologic deficits, SVC syndrome (if tumor large)
signs of excessive catecholamine production: hypertension, headache, tachycardia, palpitations, tremor

Location:

base of heart + great vessels (adjacent to pericardium/heart, within interatrial septum/left atrial wall); paravertebral sulci

CT:

sharply marginated 5 7-cm middle/posterior mediastinal mass
hypodense areas due to extensive cystic degeneration/hemorrhage
exuberant enhancement

MR:

heterogeneous intermediate signal intensity with areas of signal void from flowing blood on T1WI
high signal intensity on T2WI

NUC (I-123/I-131 metaiodobenzylguanidine):

useful for localization as relatively specific

Angio (may precipitate cardiovascular crisis):

marked hypervascularity, multiple feeding vessels
homogeneous capillary blush

Rx:

surgical excision with preoperative administration of - or -blockers (hypertensive crisis, tachycardia, dysrhythmia during manipulation)

Thymic Cyst

Pathogenesis:

Congenital cyst (persistent tubular remnants of 3rd pharyngeal pouch = thymopharyngeal duct, develops during 5th 8th week of gestation)
Acquired reactive multilocular cysts = progressive cystic degeneration of thymic (Hassall) corpuscles + thymic epithelial reticulum induced by an inflammatory process: eg, HIV
Neoplastic cyst (cystic teratoma, cystic degeneration within a thymoma), S/P radiation therapy for Hodgkin disease

No association with myasthenia gravis/neoplasia!

Incidence:	very uncommon lesion; 1 2% of mediastinal masses
Age:	2/3 in 1st decade; 1/3 in 2nd + 3rd decades; M>F
Path:	unilocular thin-walled cyst with thymic tissue
Histo:	squamous/cuboidal/respiratory epithelium in cyst wall; lobulated lymphoid tissue in cyst wall containing Hassall corpuscles; cholesterol crystals; small foci of thyroid/parathyroid tissue

commonly asymptomatic slowly enlarging painless mass
hoarseness, dysphagia, stridor, respiratory distress in newborns
sudden symptomatic enlargement with Valsalva maneuver/hemorrhage/recent viral infection

Location:

adjacent to carotid sheath from angle of mandible to thoracic inlet (along path of thymopharyngeal duct) parallel to sternocleidomastoid muscle; L > R
anterior mediastinum

unilocular cyst with thin walls containing clear fluid/multilocular cyst with thick walls containing turbid fluid or gelatinous material
direct extension/fibrous cord along migratory tract of thymic tissue into mediastinum in 50%: through thyrohyoid membrane into pyriform sinus
may show partial wall calcification (rare)
low-density fluid (0 10 HU), may be higher depending on cyst contents

US:

typically anechoic

DDx:

branchial cleft cysts (no thymic tissue), benign thymoma, teratoma, dermoid cyst, Hodgkin disease, non-Hodgkin lymphoma, pleural fibroma

Thymic Hyperplasia

Most common anterior mediastinal mass in pediatric age group through puberty

Age:

particularly in young individual

Histo:

true thymic hyperplasia = enlargement of a normally organized thymus rebound hyperplasia

P.537

lymphoid hyperplasia = increase in number of active lymphoid germinal centers myasthenia gravis, SLE, rheumatoid arthritis, scleroderma, vasculitis, thyrotoxicosis, Graves disease

Etiology:

Hyperthyroidism (most common), Graves disease, treatment of primary hypothyroidism, idiopathic thyromegaly
Rebound hyperplasia in children recovering from severe illness (eg, thermal burns), after treatment for Cushing disorder, after chemotherapy/irradiation
- thymus may regrow more than 50% (transient overgrowth, reducible with steroids)
Myasthenia gravis (65%)
Acromegaly
Addison disease

diffuse symmetric enlargement
normal thymus visible in 50% of neonates 0 2 years of age
notch sign = indentation at junction of thymus + heart
sail sign = triangular density extending from superior mediastinum
wave sign = rippled border due to indentation by ribs
shape changes with respiration + position

DDx:

thymic neoplasm (focal mass)

Thymolipoma

Incidence:	2 9% of thymic tumors
Age:	3 60 years (mean age of 22 years); M:F = 1:1
Path:	lobulated pliable encapsulated tumor capable of growing to large size (in 68% >500 g, in 20% >2,000 g, the largest >16 kg)
Histo:	benign adult adipose tissue interspersed with areas of normal/hyperplastic/atrophic thymus tissue (thymic tissue <33% of tumor mass)

usually asymptomatic
chest pain, dyspnea, cough (in 50%)
fatty mass with fibrous septa
large lesions slump inferiorly from anterior mediastinum toward diaphragm
may drape around heart enlarging cardiac silhouette on frontal view
apparent elevation of diaphragm on lateral view
NO compression/invasion of adjacent structures

DDx:

mediastinal lipoma (most common of intrathoracic fatty tumors), liposarcoma

WHo Classification for Thymic Epithelial Tumors
Tumor Type	Description
A	medullary
AB	mixed
B1	lymphocyte rich, predominantly cortical
B2	cortical
B3	epithelial = well-differentiated thymic carcinoma
C	thymic carcinoma

Thymoma

= Thymic epithelial tumors
Most common primary neoplasm of anterior superior mediastinum

Age:	majority >40 years; 70% occur in 5th 6th decade; less frequent in young adults, rare in children; M:F = 1:1
Associated with:	parathymic syndromes (40%) such as

Myasthenia gravis:
- = autoimmune disorder characterized by antibodies against nicotinic acetylcholine receptors of the postjunctional muscle membrane:
- progressive weakness, fatigue
- tigability of skeletal muscles innervated by cranial nerves, eg, ptosis, diplopia, dysphagia, dysarthria, drooling, difficulty with chewing
- elevated serum level of anti-acetylcholine receptor antibodies
- 7 30 54% of patients with thymoma have myasthenia gravis; removal of thymic tumor often results in symptomatic improvement; myasthenia gravis may develop after surgical thymoma excision
- 10 15 25% of patients with myasthenia gravis have a thymoma (in 65% due to thymic hyperplasia)
Rx: edrophonium chloride
Pure red cell aplasia = aregenerative anemia
- = almost total absence of marrow erythroblasts + blood reticulocytes resulting in severe normochromic normocytic anemia
- 50% of patients with red cell aplasia have thymoma
- 5% of patients with thymoma develop red cell aplasia
Acquired hypogammaglobulinemia
- 10% of patients with hypogammaglobulinemia have thymoma
- 6% of patients with thymoma have hypogammaglobulinemia
Paraneoplastic syndromes occur with thymic carcinoid (10%): eg, Cushing syndrome (ACTH production)
SLE, rheumatoid arthritis
Nonthymic cancers

Path:

round/ovoid slow-growing primary epithelial neoplasm with smooth/lobulated surface divided into lobules by fibrous septa; areas of hemorrhage + necrosis may form cysts

encapsulated = thick fibrous capsule calcifications
locally invasive = microscopic foci outside capsule
metastasizing = benign cytologic appearance with pleural + pulmonary parenchymal seeding
thymic carcinoma

Histo:

biphasic thymoma (most common)
- = epithelial + lymphoid elements in equal amounts
predominantly lymphocytic thymoma
- = >2/3 of cells are lymphocytic
predominantly epithelial thymoma
- = >2/3 of cells are epithelial

Prognosis unrelated to cell type!

asymptomatic (50% discovered incidentally)
signs of mediastinal compression (25 30%): cough, dyspnea, chest pain, respiratory infection, hoarseness (recurrent laryngeal n.), dysphagia

P.538

signs of tumor invasion (rare): SVC syndrome

Location:	any anterior mediastinal location between thoracic inlet and cardiophrenic angle; rare in neck, other mediastinal compartments, lung parenchyma, or tracheobronchial tree
Size:	1 10 cm (up to 34 cm)

Noninvasive [Benign] Thymoma

Age peak:

5th 6th decade, almost all are >25 years of age

oval/round sharply demarcated asymmetric homogeneous mass of soft-tissue density (equal to muscle), usually on one side of the midline
abnormally wide mediastinum
displacement of heart + great vessels posteriorly

CT:

homogeneous soft-tissue mass with smooth/lobulated border partially/completely outlined by fat
homogeneous enhancement
areas of decreased attenuation (fibrosis, cysts, hemorrhage, necrosis)
amorphous, flocculent central/curvilinear peripheral calcification (5 25%)

MRI:

isointense to skeletal muscle on T1WI
increased heterogeneous signal intensity (approaching that of fat) on T2WI
fluid characteristics of cysts with high water content

Invasive [Malignant] Thymoma

= Thymic carcinoma
Malignancy defined according to extent of invasion into adjacent mediastinal fat + fascia!

Frequency:

in 30 35% of thymomas

Stages:

Stage I:	intact capsule
Stage II:	pericapsular growth into mediastinal fat
Stage III:	invasion of surrounding organs such as lung, pericardium, SVC, aorta
Stage IVa:	dissemination within thoracic cavity (metastases to pleura + lung in 6%)
Stage IVb:	distant metastases (liver, bone, lymph nodes, kidneys, brain)

lobulated/irregular contour
heterogeneous attenuation
mediastinal fat invasion
spread by contiguity along pleural reflections, extension along aorta reaching posterior mediastinum/crus of diaphragm/retroperitoneum (transdiaphragmatic tumor extension)
unilateral diffuse nodular pleural thickening/pleural masses encasing lung circumferentially
vascular encroachment
pleural effusion UNCOMMON

DDx:	malignant mesothelioma, lymphoma, thymic carcinoma/malignant germ cell tumor (older male, no diffuse pleural seeding), peripheral lung carcinoma (no dominant mediastinal mass), metastatic disease (not unilateral)
Rx:	radical excision adjuvant radiation therapy
Prognosis:	5-year survival of 93% for stage I, 86% for stage II, 70% for stage III, 50% for stage IV; 2 12% rate of recurrence for resected encapsulated thymomas

Torsion of Lung

= rare complication of severe chest trauma

Incidence:	rare (<30 cases)
Age:	almost invariably in children
Cause:	compression of lower thorax, tear on inferior pulmonary ligament, completeness of fissures
Mechanism:	compression of lower thorax with lung twisted through 180 ; usually in presence of a large amount of pleural air/fluid
Associated with:	surgery (lobectomy), trauma, diaphragmatic hernia, pneumonia, pneumothorax, bronchus-obstructing tumor
Histo:	hemorrhagic infarction + excessive air trapping

collapsed/consolidated lobe in unusual position + configuration:
- hilar displacement of atelectatic-appearing lobe in an inappropriate direction
- change in position of opacified lobe on sequential radiographs
alteration in normal course of pulmonary vasculature:
- main lower lobe artery sweeping upward toward apex
rapid opacification of an ipsilateral lobe from edema + hemorrhage into airspaces secondary to infarction (DDx: pleural effusion)
bronchial cutoff/distortion
lobar air trapping
lower lung vessels diminutive

Tracheobronchomegaly

= MOUNIER-KUHN SYNDROME
= primary atrophy/dysplasia of supporting structures of trachea + major bronchi with abrupt transition to normal bronchi at 4th 5th division

Incidence:	0.5 1.5%
Age:	discovered in 3rd 5th decade

cough with copious sputum
shortness of breath on exertion
long history of recurrent pneumonias

May be associated with:

Ehlers-Danlos syndrome

marked dilatation of trachea (>29 mm), right (>20 mm) + left (>15 mm) mainstem bronchi
sacculated outline/diverticulosis of trachea on lateral CXR (= protrusion of mucous membrane between rings of trachea)
may have emphysema, bullae in perihilar region

Tracheobronchopathia Osteochondroplastica

= rare benign disease characterized by multiple submucosal cartilaginous/osseous nodules projecting into tracheobronchial lumen

Cause:

unknown; may be due to chronic inflammation, degenerative process, irritation by oxygen/chemical, metabolic disturbance, amyloidosis, tuberculosis, syphilis, heredity (high prevalence in finland)

P.539

Pathogenetic theories:

ecchondrosis/exostosis of cartilage rings
cartilaginous/osseous metaplasia of internal elastic fibrous membrane of trachea

Path:	foci of submucosal hyaline cartilage with areas of lamellar bone
Histo:	adipose tissue + calcified areas with foci of bone marrow; thinned normal overlying mucosa with inflammation + hemorrhage
Average age:	50 years (11 78 years); m:f = 3:1

usually asymptomatic (incidentally diagnosed)
dyspnea, productive cough, hoarseness, hemoptysis, fever, recurrent pneumonia

Location:

distal 2/3 of trachea, larynx, lobar/segmental bronchi, entire length of trachea; spares posterior membrane of trachea

CXR:

scalloped/linear opacities surrounding + narrowing the trachea (best on lateral view)

CT:

deformed thickened narrowed tracheal wall
irregularly spaced 1 3-mm calcific submucosal nodules of trachea + bronchi (similar to plaques)

Dx:	bronchoscopy
DDx:	relapsing polychondritis, tracheobronchial amyloidosis (does not spare posterior membranous wall of trachea),

sarcoidosis, papillomatosis, tracheobronchomalacia

Traumatic Lung Cyst

Age:

children + young adults are particularly prone

thin-walled air-filled cavity (50%) air-fluid level preceded by homogeneous well-circumscribed mass (hematoma)
oval/spherical lesion of 2 14 cm in diameter
single/multiple lesions; uni- or multilocular
usually subpleural under point of maximal injury
persistent up to 4 months + progressive decrease in size(apparent within 6 weeks)

Tuberculosis

Prevalence:	10 million people worldwide, active TB develops in 5 10% of those exposed
Organism:	mycobacterium = acid-fast aerobic rods staining red with carbol-fuchsin; m. tuberculosis (95%), atypical types increasing: m. avium-intracellulare, m. kansasii, m. fortuitum
Susceptible:	infants, pubertal adolescents, elderly, alcoholics, Blacks, diabetics, silicosis, measles, Aids (30 40% infected with HIV), sarcoidosis (in up to 13%)
At risk:	immunocompromised, minorities, poor, alcoholics, immigrants from 3rd world countries, prisoners, the aged, nursing home residents, homeless

Pathologic phases:

exudative reaction (initial reaction, present for 1 month)
caseous necrosis (after 2 10 weeks with onset of hypersensitivity)
hyalinization = invasion of fibroblasts (granuloma formation in 1 3 weeks)
calcification/ossification
chronic destructive form in 10% (>1 year of age, adolescents, young adults)

Spread:

regional lymph nodes, hematogenous dissemination, pleura, pericardium, upper lumbar vertebrae

Positive PPD tuberculin test: 3 weeks after infection
Negative PPD test:
- Overwhelming tuberculous infection (miliary TB)
- Sarcoidosis
- Corticosteroid therapy
- Pregnancy
- Infection with atypical Mycobacterium

Former Rx:	plombage with insertion of plastic packs, Lucite balls, polythene spheres; oleothorax = injection of oil/paraffin
Mortality:	1:100,000

Tuberculoma

= manifestation of primary/postprimary TB
round/oval smooth sharply defined mass
0.5 4 cm in diameter remaining stable for a long time
lobulated mass (25%)
satellite lesions (80%)
may calcify

Cavitary Tuberculosis

= hallmark of reactivation tuberculosis
= semisolid caseous material is expelled into bronchial tree after lysis
moderately thick-walled cavity with smooth inner surface

Cx:

Dissemination to other bronchial segments
- multiple small acinar shadows remote from massive consolidation
Colonization with Aspergillus
- aspergilloma
Rasmussen aneurysm = aneurysm of terminal branches of pulmonary artery within wall of TB cavity secondary to inflammatory necrosis of the vessel wall (4% at autopsies of cavitary TB):
- hemoptysis (source is usually a bronchial artery)
- central cavity near hilum:
- enlargement of intracavitary solid protrusion
- replacement of cavity by a nodule
- rapidly growing mass
- opacification of pseudoaneurysm on CT/angio

Endobronchial (Acinar) Tuberculosis

Most common complication of tuberculous cavitation with active organisms spreading via airways following caseous necrosis of bronchial wall

Path:

ulceration of bronchial mucosa followed by fibrosis leads to
(a) bronchial stenosis (lobar consolidation)
(b) bronchiectasis
(c) acinar nodules reflecting airway spread

HRCT:

clustered centrilobular nodules
tree-in-bud appearance = small poorly defined centrilobular nodules + branching centrilobular areas of increased opacity (= severe bronchiolar impaction with clubbing of distal bronchioles) occurring at multiple contiguous branching sites
masslike areas of consolidation

P.540

cavitation in larger nodules/masses
bronchiectasis

Primary Pulmonary Tuberculosis

Mode of infection:	inhalation of infected airborne droplets
Age:	most common form in infants + childhood; increasingly encountered in adults (23 34% of all adult cases)

asymptomatic (91%)
symptomatic (5 10%)

one/more areas of homogeneous dense well-defined airspace consolidation of 1 7 cm in diameter in 25 50 78% (requires several weeks for complete clearing with antituberculous therapy):
absent response to antibiotic Rx for pneumonia

Location:

middle lobe, lower lobes, anterior segment of upper lobes

fine discrete nodular areas of increased opacity

DDx:

varicella pneumonia, histoplasmosis, metastases, sarcoidosis, pneumoconiosis, hemosiderosis

in children: massive hilar (60%)/paratracheal (40%)/subcarinal lymphadenopathy, in 80% on right side;
in adults: mediastinal lymphadenopathy in 5 35 48%

DDx of Lnn:

metastases, histoplasmosis

atelectasis (8 18%), esp. in right lung (anterior segment of upper lobe/medial segment of middle lobe) secondary to
- endobronchial tuberculosis
- bronchial/tracheal compression by enlarged lymph nodes (68%)
pleural effusion (10% in childhood, 23 38% in adulthood) most commonly 3 7 months after initial exposure (from subpleural foci rupturing into pleural space)
pneumonic reaction (mid or lower lung zones) with segmental/lobar consolidation
calcified lung lesion (17%)/parenchymal scar <5 mm = Ghon lesion
calcified lymph node (36%) in hilus/mediastinum
Ranke complex = Ghon lesion + calcified lymph node (22%)
Simon focus = healed site of primary infection in lung apex

CT:

tuberculous adenopathy may demonstrate necrotic center with low attenuation after enhancement

Outcome of primary infection:

Immunity prevents multiplication of organism (containment of initial infection by delayed hypersensitivity response + granuloma formation in 1 3 weeks)
Progressive primary TB (inadequate immune mechanism with local progression) in 10%, most common in older children/teenagers
Miliary tuberculosis (uncontrolled massive hematogenous dissemination overwhelming host defense system)
Postprimary TB = reactivation TB (reactivation of dormant organisms after asymptomatic years)

Prognosis:	3.6% mortality rate
Cx:	(1) Bronchopleural fistula + empyema (2) Fibrosing mediastinitis

Postprimary Pulmonary Tuberculosis

= REACTIVATION TB = recrudescent TB
= infection under the influence of acquired hypersensitivity and immunity secondary to longevity of bacillus + impairment of cellular immunity

Incidence:	1% per year in persons with normal immunity, up to 10% in persons with deficient T-cell immunity
Age:	predominantly in adolescence + adulthood

Etiology:

reactivation of focus acquired in childhood (90%)
continuation of initial infection = progressive primary tuberculosis (rare)
initial infection in individual vaccinated with BCG

Path:	foci of caseous necrosis with surrounding edema, hemorrhage, mononuclear cell infiltration; formation of tubercles = accumulation of epithelioid cells + Langhans giant cells; bronchial perforation leads to intrabronchial dissemination (19 21%)
Site:	85% in apical + posterior segments of upper lobe, 10% in superior segment of lower lobe, 5% in mixed locations (anterior + contiguous segments of upper lobe); R > L (DDx: histoplasmosis tends to affect anterior segment)

Local Exudative Tuberculosis

patchy/confluent ill-defined areas of acinar consolidation (87 91%), commonly involving two/more segments (earliest finding)
thin-walled cavitation with smooth inner surface (present in more advanced disease):
- cavity under tension (air influx + obstructed efflux)
- air-fluid level is strong evidence for superimposed bacterial/fungal infection
- air-crescent sign = mobile intracavitary mycetoma
accentuated drainage markings toward ipsilateral hilum
acinar nodular pattern (20%) due to bronchogenic spread
pleural effusion (18%)

CT:

micronodules in centrilobular location (62%) = solid caseation material in/surrounding the terminal/respiratory bronchioles
interlobular septal thickening (34 54%) = increase in lymphatic flow as inflammatory response/impaired lymphatic drainage due to hilar lymphadenopathy

Local Fibroproductive Tuberculosis

@ Parenchymal disease:
- sharply circumscribed irregular + angular masslike fibrotic lesion (in up to 7%)
- thick-walled irregular cavitation (HALLMARK) secondary to expulsion of caseous necrosis into airways, esp. in apical/posterior segments of upper lobes (rare in children, in up to 45 51% in adults), often multiple (high likelihood of activity)
- reticular pulmonary scars
- cicatrization atelectasis = volume loss in affected lobe
@ Airway involvement:
- bronchial stenosis::
  - persistent segmental/lobar collapse
  - lobar hyperinflation
  - obstructive pneumonia
  - mucoid impaction
- traction bronchiectasis in apical/posterior segments of upper lobes
@ Pleural extension:
- apical cap = pleural rind = thickening of layer of extra-pleural fat (3 25 mm) + pleural thickening (1 3 mm)
- pleural thickening
- air-fluid level in pleural space = bronchopleural fistula
- rim-enhancing/calcified soft-tissue mass of chest wall with destruction of bone/costal cartilage
- fistulization to skin
@ Lymphadenopathy:
- tuberculous lymphadenitis = enlarged nodes with central areas of low attenuation
- calcified hilar/mediastinal nodes:
  - broncholithiasis = erosion into adjacent airway

Miliary Pulmonary Tuberculosis

= massive hematogenous dissemination of organisms any time after primary infection

Cause:

severe immunodepression during postprimary state of infection
impaired defenses during primary infection
- = PROGRESSIVE PRIMARY TB

Incidence:

2 3.5% of TB infections

chronic focus often not identifiable
radiographically recognizable after 6 weeks post hematogenous dissemination
generalized granulomatous interstitial small foci of pinpoint to 2 3 mm size
rapid complete clearing with appropriate therapy
HRCT (earlier detection than CXR):
- diffusely scattered discrete 1 2-mm nodules in random distribution

Cx:

dissemination via bloodstream affecting lymph nodes, liver, spleen, skeleton, kidneys, adrenals, prostate, seminal vesicles, epididymis, fallopian tubes, endometrium, meninges

Unilateral Pulmonary Agenesis

= one-sided lack of primitive mesenchyme
Associated with:
- anomalies in 60% (higher if right lung involved): PDA, anomalies of great vessels, tetralogy of Fallot (left-sided pulmonary agenesis), bronchogenic cyst, congenital diaphragmatic hernia, bone anomalies
may be asymptomatic
respiratory infections
complete opacity of hemithorax
ipsilateral absence of pulmonary artery + vein
absent ipsilateral mainstem bronchus
symmetrical chest cage with approximation of ribs
overdistension of contralateral lung
ipsilateral shift of mediastinum + diaphragm

Varicella-Zoster Pneumonia

Incidence:	14% overall; 50% in hospitalized adults
Age:	>19 years (90%); 3rd 5th decade (75%); contrasts with low incidence of varicella in this age group

vesicular rash
patchy diffuse airspace consolidation
tendency for coalescence near hila + lung bases
widespread nodules (30%) representing scarring
tiny 2 3-mm calcifications widespread throughout both lungs (2%)

Cx:	unilateral diaphragmatic paralysis
Prognosis:	11% mortality rate

Wegener Granulomatosis

= probable autoimmune disease characterized by systemic necrotizing granulomatous destructive angitis

Path:	peribronchial necrotizing granulomas + vasculitis not intimately related to arteries
Mean age of onset:	40 years (range of all ages);M:F = 2:1

CLASSIC TRIAD:

respiratory tract granulomatous inflammation
systemic small-vessel vasculitis
necrotizing glomerulonephritis

The most common presenting symptoms are those of upper respiratory tract involvement (in up to 67%):
- rhinitis, sinusitis, otitis media

@ Pulmonary disease (94%)

stridor (from tracheal inflammation + sclerosis)
intractable cough, occasionally with hemoptysis
fever, chest pain, dyspnea

Path:

vasculitis of medium-sized and small pulmonary arteries + veins + capillaries, geographic necrosis, granulomatous inflammation

bilateral interstitial reticulonodular opacities, most prominent at lung bases (earliest stage)
widely distributed irregular masses/nodules of varying sizes (5 mm to 10 cm), especially in lower lung fields (69%) usually sparing apices:
- usually multiple masses, solitary in up to 25%
- cavitation of nodules with thick wall + irregular shaggy inner lining (25 50%)
bilateral multifocal patchy air-space opacities (in up to 50%):
- acute airspace pneumonia
- intraalveolar pulmonary hemorrhage
smooth/nodular thickening of subglottic/tracheal/bronchial wall producing stenosis with oligemia + emphysema + lobar/segmental atelectasis (60%)
pleural effusion (usually exudative) in 10 25 50%
focal pleural thickening
hilar/mediastinal lymphadenopathy (very unusual)
interstitial pulmonary edema cardiomegaly (from renal/cardiac involvement)
CT:
- nodules in peribronchovascular distribution:
  - central cavitation in nodules >2 cm in diameter
  - feeding vessels entering nodules (= angiocentric distribution)
- pleural-based wedge-shaped lesions (= infarcts)
- CT halo sign (= rim of ground-glass attenuation surrounding a pulmonary lesion) due to angiocentric parenchymal microinfarction (nonspecific)
- focal/elongated segments of tracheobronchial stenosis intra- and extraluminal soft-tissue masses/thickening
Cx: (1) dangerous airway stenosis (15% of adults, 50% of children)
(2) massive life-threatening pulmonary hemorrhage
(3) spontaneous pneumothorax (rare)
@ renal disease (85%)
- focal glomerulonephritis in 20% at presentation, as disease progresses in 83%
Histo: focal necrosis, crescent formation, paucity/ absence of immunoglobulin deposits
@ Paranasal sinuses (91%)

Location: maxillary antra most frequently
- sinus pain, purulent sinus drainage, rhinorrhea
- thickening of mucous membranes of paranasal sinuses
@ nasopharynx (64%)
- epistaxis from nasal mucosal ulceration
- necrosis of nasal septum
- saddle nose deformity
- progressive destruction of nasal cartilage + bone (ddx: relapsing polychondritis)
- granulomatous masses filling nasal cavities
@ other organ involvement:
- Joints (67%): migratory polyarthropathy
- ear (61%): otitis media
- eye (58%): ocular inflammation, proptosis
- skin + muscle (45%): inflammatory nodular skin lesions, cutaneous purpura
- Heart + pericardium (12 28%): coronary vasculitis, pancarditis, valvular lesions
  
  Cx: acute pericarditis, dilated congestive cardiomyopathy, acute valvular insufficiency with pulmonary edema, cardiac arrest due to ventricular arrhythmia, myocardial infarction
- cns (22%): central/peripheral neuritis
- splenic disease
- Gi tract (10%):
  - abdominal pain, diarrhea, blood loss
  - ischemia, inflammation, ulceration, perforation

Cx:	1) Hypertension (2) uremia (3) facial nerve paralysis
Dx:	(1) c-ANCA (cytoplasmic pattern of antineutrophil cytoplasmic autoantibodies): 96% sensitive for generalized disease, 99% specific (2) Lung/renal biopsy
Prognosis:	death within 2 years from renal (83%)/respiratory failure; 90 95% mean 5-year survival under rx
Rx:	corticosteroids, cytotoxic drugs (cyclophosphamide), renal transplantation; 93% remission with therapy
DDx:	churg-strauss (asthma, 47% cardiac involvement, less severe renal + sinus disease, p-ANCA)

Limited Wegener Granulomatosis

= Wegener granulomatosis largely confined to lung
WITHOUT renal/upper airway involvement

Dx:	c-ANCA (96% sensitive, 99% specific) M < F
Prognosis:	more favorable than classical Wegener's

Midline Granuloma

= mutilating granulomatous + neoplastic lesions limited to nose + paranasal sinuses with very poor prognosis; considered a variant of Wegener granulomatosis WITHOUT the typical granulomatous + cellular components

Williams-Campbell Syndrome

= congenital bronchial cartilage deficiency in the 4th 6th bronchial generation either diffuse or restricted to focal area
HRCT:
- cystic bronchiectasis distal to 3rd bronchial generation
- emphysematous lung distal to bronchiectasis
- inspiratory ballooning + expiratory collapse of dilated segments

Wilson-Mikity Syndrome

= PULMONARY dysmaturity
= similarity to bronchopulmonary dysplasia in normal preterm infants breathing room air; rarely encountered anymore due to mechanical assisted ventilation

Predisposed: premature infants <1,500 g who are initially well
gradual onset of respiratory distress between 10 and 14 days
hyperinflation
reticular pattern radiating from both hila
small bubbly lucencies throughout both lungs (identical to bronchopulmonary dysplasia)

Prognosis:	resolution over 12 months
DDx:	perinatally-acquired infection (especially CMV)

Zygomycosis

= PHYCOMYCOSIS
= group of severe opportunistic sinonasal + pulmonary disease caused by a variety of Phycomycetes (soil fungi)

Organism:	ubiquitous Mucor (most common), Rhizopus, Absidia with broad nonseptated hyphae of irregular branching pattern
At risk:	immunoincompetent host with 1. lymphoproliferative malignancies and leukemia 2. acidotic diabetes mellitus 3. immunosuppression through steroids, antibiotics immunosuppressive drugs (rare)
Entry:	inhalation/aspiration from sinonasal colonization
Path:	angioinvasive behavior similar to aspergillosis

RHINOCEREBRAL FORM
- = involvement of paranasal sinuses (frontal sinus usually spared) with extension into:
- orbit = orbital cellulitis
- base of skull = meningoencephalitis + cerebritis
PULMONARY FORM
- segmental homogeneous consolidation
- cavitary consolidation + air-crescent sign
- nodules (from arterial thrombi + infarction)
- rapidly progressive (often fatal) pneumonia

Dx:	culture of fungus from biopsy specimen/demonstration within pathologic material
DDx:	aspergillosis

Use:	CNS glioma, lymphoma, myeloma
Toxicity:	in 50% after doses >1500 mg/m²; sensitivity increased after radiation Rx

Use:	refractory ventricular tachyarrhythmia
Toxicity:	in 5 10%; risk increased with daily dose > 400 mg + in elderly
Prognosis:	good after discontinuation of drug

Use:	inflammatory arthritis
Toxicity:	in 1% within 2 6 months

Organism:	viruses, S. pneumoniae, Mycoplasma
Mortality:	10%

ground glass =	hazy area of increased attenuation not obscuring bronchovascular structures
consolidation =	marked increase in attenuation with obliteration of underlying anatomic features

pCa <0.05	observation
pCa >0.05 and <0.6	biopsy
pCa 0.60	immediate surgical resection

Cause:	rupture of subpleural blebs in apical region of lung
Age:	20 40 years; M:F = 8:1; esp. in patients with tall asthenic stature; mostly in smokers

Prognosis:	recurrence in 30% on same side, in 10% on contralateral side
Rx:	simple aspiration (in >50% success)/tube thoracostomy (in 90% effective)

Metastases to:	lung, occasionally lymph nodes
Prognosis:	infiltrative growth with high risk of local recurrence

Metastases to:	bone, CNS, liver, adrenal
DDx:	Ewing sarcoma, lymphoma, chest wall hamartoma in infancy

	UL + ML:	anterior + lateral + juxtamediastinal
	LL:	anterior + diaphragmatic regions

Location:	pulmonary involvement (8 15%), CNS, GI tract, liver, spleen, bone marrow
Site:	primarily extranodal

Prevalence:	3% (increases with increasing levels of asbestos exposure)
Latency period:	8 10 years after exposure

Overall incidence:	20%
Latency period:	>20 years to become visible; in 40% after 40 years
Histo:	calcification starts in parietal pleura; calcium deposits may form within center of plaques

Cx:	bronchiectasis (from long retention)
DDx:	impacted esophageal foreign body

Age:	middle age
Pathogenesis:	probably autoimmune phenomenon caused by viral respiratory infection and often provoked by infection, exercise, pharmaceuticals; no environmental antigen

Associated with:	severe bronchial infection
Path:	<5 subdivisions of bronchi

Cx:	limited expansion of lung
Rx:	decortication (with persistent sepsis despite appropriate antibiotic Rx + drainage/persistent thick pleural rind trapping underlying lung)

Age:	present in most cases by age 40; increase in number + size with age
Location:	lips, tongue, palate, fingers, face, conjunctiva, trunk, arms, nail beds

Predisposed:	individuals with chronic obstructive pulmonary disease + cigarette smoking
Age:	middle-aged white men
Pathophysiology:	hyperimmune reaction

At presentation:	1 4%; indicative of widespread aggressive disease with poor prognosis
Location:	dorsolumbar spine > pelvis > ribs > femora > sternum

Frequency:	secondary hematogenous involvement in 0.2 0.5%
Location:	supratentorial cerebral cortex + meninges in inferior aspect of brain (most frequent)

DDx:	telescoped anastomosis
Rx:	laser resection, balloon bronchoplasty

Prevalence:	35 50%; major cause of morbidity + mortality in early postoperative period
Cause:	? absent cough reflex, impaired mucociliary transport in denervated lung

Cx:	may progress rapidly to respiratory failure + death
Dx:	transbronchial/open biopsy (80% accurate)

<25% of parenchyma with cyst sizes	<5 mm
25 80% of parenchyma with cyst sizes	5 10 mm
>80% of parenchyma with cyst sizes	>10 mm

Histo:	replacement of lymph node with smooth muscle
Location:	retroperitoneum (77%) > pelvis (11%) > mesentery > posterior mediastinum > axilla > neck

HD:	most common site of abdominal involvement
NHL:	3rd most common site of abdominal involvement; may be initial manifestation in large cell nHL

Associated with:	delayed onset of diaphragmatic hernia (evidenced by clinical deterioration)
Prognosis:	often lethal

Age:	7th-8th decade, 86% in Whites; m:f = 1:4
Predisposing factors:	none
Location:	predominantly in middle lobe + lingula