6. Breast

Authors: Dahnert, Wolfgang

Title: Radiology Review Manual, 6th Edition

Copyright 2007 Lippincott Williams & Wilkins

> Table of Contents > Breast

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Breast

Differential Diagnosis of Breast Disorders

Variations in breast development

Unilateral Breast Development

may exist 2 years before other breast becomes palpable

Premature Thelarche

• = breast development <8 years of age

• Cause:

  • isolated idiopathic = mostly subtle overfunction of pituitary-ovarian axis

    • NO growth spurt/advanced bone age/menses

  • central precocious puberty

    • enlargement of uterus + ovaries

• uni-/bilateral normal breast tissue

Congenital Anomalies

• Polythelia

  • = more than normal number of nipples

• Polymastia

  • = more than normal number of breasts

• Amastia

  • = absence of mammary glands

Breast density

Asymmetric Breast Density

• Benign

  • Postsurgical scarring

  • Noniatrogenic trauma

  • Postinflammatory fibrosis

  • Radial scar

  • Ectopic/accessory breast tissue (in axillary tail/close to abdomen)

  • Asymmetric breast development/asymmetric involution

  • Simple cyst

  • Fibrocystic conditions: fibrosis/sclerosing adenosis

  • Hormonal therapy: replacement, contraceptives

• Malignant

  • Invasive ductal carcinoma: desmoplastic reaction

  • Invasive lobular carcinoma

  • Tubular carcinoma

  • Primary lymphoma of breast

• Imaging Problems

  • Superimposed normal fibroglandular tissue

  • Lesion obscured by overlapping dense parenchyma

  • Lesion outside field of view

Breast Imaging Reporting and Data System (BI-RADS ) Categories

• Additional image evaluation may be necessary: off-angle/spot compression mammographic views; ultrasound

• Unexplained abnormalities warrant biopsy

• Asymmetric Breast Tissue

  • = greater volume/density in one breast compared with corresponding area in contralateral breast

• Density in One Projection

  • = density seen on only one standard mammographic view

• Architectural Distortion

  • = focal area of distorted breast tissue (spiculations with common focal point/focal retraction/tethering) without definable central mass

• Focal Asymmetric Density

  • = focal asymmetric density seen on two mammographic views but not identified as a true mass

Diffuse Increase in Breast Density

• generalized increased density

• skin thickening

• reticular pattern in subcutis

• CANCER

  • Inflammatory breast cancer

  • Diffuse primary noninflammatory breast cancer

  • Diffuse metastatic breast cancer

  • Lymphoma/leukemia due to obstructive lymphedema of breast

• INFECTIOUS mastitis

  • usually in lactating breast

• RADIATION

  • diffuse exudative edema within weeks after beginning of radiation therapy

  • indurational fibrosis months after radiation therapy

• EDEMA

  • Lymphatic obstruction: extensive axillary/intrathoracic lymphadenopathy, mediastinal/anterior chest wall tumor, axillary surgery

  • Generalized body edema: congestive heart failure (breast edema may be unilateral if patient in lateral decubitus position), hypoalbuminemia (renal disease, liver cirrhosis), fluid overload

• HEMORRHAGE

  • Posttraumatic

  • Anticoagulation therapy

  • Bleeding diathesis

• ACCIDENTAL INFUSION OF FLUID

  • into subcutaneous tissue

Enhancing Lesions on Breast MRI

Unilateral Diffuse Enhancement on MRI

• Common

  • Parenchymal asymmetry

  • Fibrocystic changes

  • Adenosis

  • Unilateral implant

    P.544

    
    

    Rare

  • Normal: unfavorable cycle phase, HRT

  • Mastitis

  • Inflammatory breast cancer

  • Extensive carcinoma: diffuse lobular carcinoma, lymphangiosis, extensive DCIS

  • Prior ipsilateral radiotherapy within last few months

Round Homogeneously Enhancing Well-Demarcated Lesion on MRI

• Common

  • Fibroadenoma: endotumoral septa

  • Adenoma

  • Papilloma

  • Carcinoma

    Rare

  • Intramammary node:

    • lipomatous hilum

  • Fat necrosis:

    • macrocalcifications on mammogram

  • Granuloma

  • Carcinoma: esp. medullary form

  • Phylloides tumor

  • Metastasis

Ring-Enhancing Lesion on MRI

• Common

  • 1. Complicated cyst:

    • narrow hyperintense ring on T2

  • 2. Invasive carcinoma:

    • broad ring of vital tumor, hypointense/isointense on T2

    • shaggy rim

  • 3. Superimposition of blood vessels: tubular structures on MIP

• Rare

  • 4. Adenosis

  • 5. Abscess

  • 6. Lymphadenitis

Multiple Homogeneously Enhancing Lesions with Well-defined Borders on MRI

• Common

  • Fibrocystic changes

  • Fibroadenomas

  • Adenoma

  • Papilloma

    Rare

  • Multicentric carcinoma

  • Metastases

Dendritic Enhancement on Breast MRI

• Common

  • Adenosis

  • Fibrocystic change

  • DCIS

  • Motion artifacts on subtraction image

  • Superposition of intramammary veins

    Rare

  • Previous galactography: history

  • Chronic mastitis

Lesion-in-Lesion Morphology on MRI

• Giant juvenile fibroadenoma

• Phyllodes tumor

• Papilloma

• Papillary carcinoma

• Hemorrhage

Oval-shaped breast lesions

Mammographic Evaluation of Breast Masses

True mass or pseudomass?

• SIZE

  • well-defined nodules <1.0 cm are of low risk for cancer

  • most likely benign nodules approaching 1 cm should be considered for ultrasound/aspiration/biopsy

• SHAPE

  • increase in probability of malignancy: architectural distortion > irregular > lobulated > oval > round

• MARGIN/CONTOUR (most important factor)

  • well-circumscribed mass with sharp abrupt transition from surrounding tissue is almost always benign

  • halo sign of apparent lucency = optical illusion of Mach effect + true radiolucent halo is almost always (92%) benign but not pathognomonic for benignity

  • microlobulated margin worrisome for cancer

  • obscured margin may represent infiltrative cancer

  • irregular ill-defined margin has a high probability of malignancy

  • spiculated margin due to

    • fibrous projections extending from main cancer mass

    • previous surgery

    • sclerosing duct hyperplasia (radial scar)

• LOCATION

  • intramammary lymph node typically in upper outer quadrant (in 5% of all mammograms)

  • large hamartoma + abscess common in retro-/periareolar location

  • sebaceous cyst in subcutaneous tissue

• X-Ray Attenuation = Density

  • fat-containing lesions are never malignant

  • high-density mass suspicious for carcinoma (higher density than equal volume of fibroglandular tissue due to fibrosis)

• NUMBER

  • multiplicity of identical lesions decreases risk

• INTERVAL CHANGE

  • enlarging mass needs biopsy

• PATIENT RISK FACTORS

  • increasing age increases risk for malignancy

  • positive family history

  • history of previous abnormal breast biopsy

  • history of extramammary malignancy

Well-circumscribed Breast Mass

• Well-defined nonpalpable lesions have a 4% risk of malignancy!

  P.545

  
  

  • BENIGN

    • Cyst (45%)

    • Fibroadenoma

    • Sclerosing adenoma

    • Intraductal papilloma (intracystic/solid)

    • Galactocele

    • Sebaceous cyst

    • Pseudoangiomatous stromal hyperplasia

  • MALIGNANT

    • Medullary carcinoma

    • Mucinous carcinoma

    • Intracystic papillary carcinoma

    • Invasive ductal cancer not otherwise specified (rare)

    • Pathologic intramammary lymph node

    • Metastases to breast: melanoma, lymphoma/leukemia, lung cancer, hypernephroma

  Well-circumscribed De Novo Mass in Woman >40 Years of Age

  • Cyst

  • Papilloma

  • Carcinoma

  • Sarcoma (rare)

  • Fibroadenoma (exceedingly rare)

  • Metastasis (extremely rare)

Fat-containing Breast Lesion

Fat contained within a lesion proves benignity!

• Lipoma

• Galactocele

  • = fluid with high lipid content (last phase)

  • during/shortly after lactation

• Traumatic lipid cyst = fat necrosis = oil cyst

  • site of prior surgery/trauma

• Focal collection of normal breast fat

Mixed Fat- and Water-density Lesion

• Fibroadenolipoma/hamartoma

• Intramammary lymph node

• Galactocele

• Hamartoma = lipofibroadenoma = fibroadenolipoma

• Small superficial hematoma

Breast Lesion with Halo Sign

• HIGH-DENSITY LESION

  • =vessels + parenchymal elements not visible in superimposed lesion

  • Cyst

  • Sebaceous cyst

  • Wart

• LOW-DENSITY LESION

  • = vessels + parenchyma seen superimposed on lesion

  • Fibroadenoma

  • Galactocele

  • Cystosarcoma phylloides

Stellate/Spiculated Breast Lesion

• = mass/architectural distortion characterized by thin lines radiating from its margins

• The majority of invasive breast cancers are stellate (stellate:circular = 65:35)

• 93% of all stellate lesions are malignant (malignant:benign = 93:7)

• Risk of malignancy:

  • 75% for nonpalpable spiculated masses

  • 32% for nonpalpable irregular masses

• PSEUDOSTELLATE STRUCTURE

  • = Summation Shadow/Artifact

  • caused by fortuitous superimposition of normal fibrous + glandular structures; unveiled by rolled views, spot compression views microfocus magnification technique

• BLACK STAR

  • groups of fine straight/curvilinear fibrous strands bunched together like a broom

  • circular/oval lucencies within center

  • change in appearance from view to view

  • Radial scar = sclerosing duct hyperplasia (86%)

  • Sclerosing adenosis

  • Posttraumatic fat necrosis (11%)

• WHITE STAR

  • individual straight dense spicules

  • central solid tumor mass

  • little change in different views

  • malignant lesions

    • Invasive ductal carcinoma (65%) = scirrhous carcinoma

      • = desmoplastic reaction + secondary retraction of surrounding structures

      • clinical dimensions larger than mammographic size

      • distinct central tumor mass with irregular margins

      • length of spicules increases with tumor size

      • localized skin thickening/retraction when spiculae extend to skin

      • commonly associated with malignant-type calcifications

    • Invasive lobular carcinoma (21%)

      • palpable mass

      • lack of central tumor mass

    • Tubular carcinoma (9%)

    • Other (5%)

  • benign lesions

    • Postoperative scar

      • correlation with history + site of biopsy

      • scar diminishes in size + density over time

    • Postoperative hematoma

      • clinical information

      • short-term mammographic follow-up confirms complete resolution

    • Breast abscess

      • clinical information

      • high-density lesion with flamelike contour

    • Hyalinized fibroadenoma with fibrosis

      • changing pattern with different projections

      • may be accompanied by typical coarse calcifications of fibroadenomas

    • Granular cell myoblastoma

    • Fibromatosis

    • Extra-abdominal desmoid

P.546

mnemonic: Starfash

• Summation shadow

• Tumor (malignant)

• Abscess

• Radial scar

• Fibroadenoma (hyalinized),

• Fat necrosis

• Adenosis (sclerosing)

• Scar (postoperative)

• Hematoma (postoperative)

Tumor-mimicking lesions

• Phantom breast tumor = simulated mass

  • asymmetric density

    • scalloped concave breast contour

    • interspersed fatty elements

  • summation artifact = chance overlap of normal glandular breast structures

    • failure to visualize tumor on more than one view

• Silicone injections

• Skin lesions

  • Dermal nevus

    • sharp halo/fissured appearance

  • Skin calcifications

    • lucent center (clue)

    • superficial location (tangential views)

  • Sebaceous/epithelial inclusion cyst

  • Neurofibromatosis

  • Biopsy scar

• Lymphedema

• Lymph nodes

  Frequency:	5.4% for intramammary nodes
  Location:	axilla, subcutaneous tissue of axillary tail, lateral portion of pectoralis muscle, intramammary (typically in upper outer quadrant)

  • ovoid/bean-shaped mass(es) with fatty notch representing hilum

  • central zone of radiolucency (fatty replacement of center) surrounded by crescent rim of cortex

  • usually <1.5 cm (up to 4 cm) in size

  • well-circumscribed with slightly lobulated margin

  • US:

    • Vreniform hypoechoic rim with echogenic center

    • echogenic hilum for entry and exit of vessels

• Hemangioma

Malignant Sonographic Characteristics (according to data from A.T. Stavros)
US Characteristic	Sens.	Specif.	PPV	Rel. risk
Spiculation	36.0	99.4	91.8	5.5
Taller than wide	41.6	98.1	81.2	4.9
Angular margins	83.2	92.0	67.5	4.0
Acoustic shadowing	48.8	94.7	64.9	3.9
Branch pattern	29.6	96.6	64.0	3.8
Markedly hypoechoic	68.8	60.1	60.1	3.6
Calcifications	27.2	96.3	59.6	3.6
Duct extension	24.8	95.2	50.8	3.0
Microlobulation	75.2	83.8	48.2	2.9

Solid Breast lesion by Ultrasound

Malignant Sonographic Characteristics

• Approximately 5 malignant features are found per cancer. The combination of 5 findings increases the sensitivity to 98.4%!

• spiculation = alternating straight lines radiating perpendicularly from surface of nodule

  • hypoechoic relative to echogenic fibrous tissue

  • hyperechoic relative to surrounding fat

• taller-than-wide lesion = AP dimension greater than craniocaudal/transverse dimension

• angular margin = contour of junction between hypo- or isoechoic solid nodule and surrounding tissue at acute /obtuse/90 angles

• acoustic shadowing behind all/part of nodule

  • (= fibroelastic host response to scirrhous cancer)

• central part of solid lesion very hypoechoic with respect to fat

• punctate echogenic calcifications within hypoechoic mass (acoustic shadowing commonly not present)

• radial extension/branch pattern (= intraductal component of breast cancer)

• microlobulation = many small lobulations at surface of solid nodule

Benign Sonographic Characteristics

• absence of any malignant characteristics

  • A single malignant feature prohibits classification of a nodule as benign!

• marked hyperechogenic well-circumscribed nodule compared with fat = normal stromal fibrous tissue (may represent a palpable pseudomass/fibrous ridge)

• smooth well-circumscribed ellipsoid shape

• 2 3 smooth well-circumscribed gentle lobulations

• thin echogenic capsule

• kidney-shaped lesion = intramammary lymph node

• If specific benign features are not found the lesion is classified as indeterminate!

Benign Sonographic Characteristics (according to data from A.T. Stavros)
US Characteristic	Sens.	Specif.	NPV	Rel. risk
Hyperechoic	100.0	7.4	100.0	0.00
3 lobulations	99.2	19.4	99.2	0.05
Ellipsoid shape	97.6	51.2	99.1	0.05
Thin echogenic capsule	95.2	76.0	98.8	0.07

Breast calcifications

Indicative of focally active process; often requiring biopsy

• 75 80% of biopsied clusters of calcifications represent a benign process

• 10 30% of microcalcifications in asymptomatic patients are associated with cancers

Composition:

hydroxyapatite/tricalcium phosphate/calcium oxalate

Results of breast biopsies for microcalcification:

(without any other mammographic findings)

P.547

• benign lesions (80%)

  1. Mastopathy without proliferation	44%
  2. Mastopathy with proliferation	28%
  3. Fibroadenoma	4%
  4. Solitary papilloma	2%
  5. Miscellaneous	2%

• malignant lesions (20%)

  1. Lobular carcinoma in situ     in 8% no spatial relationship to LCIS	10%
  2. Infiltrating carcinoma	6%
  3. Ductal carcinoma in situ	4%

• A positive biopsy rate of >35% is desirable goal!

• Location

  • intramammary

    • Ductal microcalcifications

      • 0.1 0.3 mm in size, irregular, sometimes mixed linear + punctate

      Occurrence:

      secretory disease, epithelial hyperplasia, atypical ductal hyperplasia, intraductal carcinoma

    • Lobular microcalcifications

      • smooth round, similar in size + density

      Occurrence:	cystic hyperplasia, adenosis, sclerosing adenosis, atypical lobular hyperplasia, lobular carcinoma in situ, cancerization of lobules (= retrograde migration of ductal carcinoma to involve lobules), ductal carcinoma obstructing egress of lobular contents
      N.B.:	lobular and ductal microcalcifications occur frequently in fibrocystic disease + breast cancer!

  • extramammary: arterial wall, duct wall, fibroadenoma, oil cyst, skin, etc.

• Size

  • malignant calcifications usually <0.5 mm; rarely >1.0 mm

• Number

  • <4 5 calcifications per 1 cm² have a low probability for malignancy

• Morphology

  • benign

    • Smooth round calcifications: formed in dilated acini of lobules

    • Solid/lucent-centered spheres: usually due to fat necrosis

    • Crescent-shaped calcifications that are concave on horizontal beam lateral projection = sedimented milk of calcium at bottom of cyst

    • Lucent-centered calcifications: around accumulated debris within ducts/in skin

    • Solid rod-shaped calcifications/lucent-centered tubular calcifications: formed within/around normal/ectatic ducts

    • Eggshell calcifications in rim of breast cysts

    • Calcifications with parallel track appearance = vascular calcifications

  • malignant

    • = calcified cellular secretions/necrotic cancer cells within ducts

      • calcifications of

        • vermicular form

        • varying in size

        • linear/branching shape

• Distribution

  • Clustered heterogeneous calcifications: adenosis, peripheral duct papilloma, hyperplasia, cancer

  • Segmental calcifications within single duct network: suspect for multifocal cancer within lobe

  • Regional/diffusely scattered calcifications with random distribution throughout large volumes of breast: almost always benign

• Time course

  • malignant calcifications can remain stable for >5 years!

• Density

Malignant Calcifications

• Granular calcifications = resembling fine grains of salt

  • amorphous, dotlike/elongated, fragmented

  • grouped very closely together

  • irregular in form, size, and density

• Casting calcifications = fragmented cast of calcifications within ducts

  • variable in size + length

  • great variation in density within individual particles + among adjacent particles

  • jagged irregular contour

  • Y-shaped branching pattern

  • clustered (>5 per focus within an area of 1 cm²)

Benign Calcifications

• Lobular calcifications = arise within a spherical cavity of cystic hyperplasia, sclerosing adenosis, atypical lobular hyperplasia

  • sharply outlined, homogeneous, solid, spherical pearl-like

  • little variation in size

  • numerous + scattered

  • associated with considerable fibrosis

  • adenosis

    • diffuse calcifications involving both breasts symmetrically

  • periductal fibrosis

    • diffuse/grouped calcifications + irregular borders, simulating malignant process

• Sedimented milk of calcium

  Frequency: 4%

  • multiple, bilateral, scattered/occasionally clustered calcifications within microcysts

  • smudge-like particles at bottom of cyst on vertical beam

  • crescent-shaped on horizontal projection = teacup-like

• Plasma cell mastitis = periductal mastitis

  • sharply marginated calcifications of uniform density = intraductal form

  • sharply marginated hollow calcifications = periductal form

P.548




• Peripheral eggshell calcifications

  • with radiolucent lesion

    • liponecrosis micro-/macrocystica calcificans (= fatty acids precipitate as calcium soaps at capsular surface) as calcified fat necrosis/calcified hematoma

    • May mimic malignant calcifications!

  • with radiopaque lesion

    • degenerated fibroadenoma

    • macrocyst

    • high uniform density in periphery

    • usually subcutaneous

    • no associated fibrosis

• Papilloma

  • solitary raspberry configuration in size of duct

  • central/retroareolar

• Degenerated fibroadenoma

  • bizarre, coarse, sharply outlined, popcornlike very dense calcification within dense mass (= central myxoid degeneration)

  • eggshell type calcification (= subcapsular myxoid degeneration)

• Arterial calcifications

  • parallel lines of calcifications

• Dermal calcifications

  Site: sebaceous glands

  • hollow radiolucent center

  • polygonal shape

  • peripheral location (may project deep within breast even on 2 views at 90 angles)

  • linear orientation when caught in tangent

  • same size as skin pores

  Proof:

  superficial marking technique

• Metastatic calcifications

  Cause:

  2 hyperparathyroidism (in up to 68%)

Calcifications in Branching Tubular Opacity

• Ductal carcinoma in situ

• Atypical ductal hyperplasia

• Secretory disease

• Peripheral papillomatosis

• Vascular: calcified artery; Mondor disease (= thrombophlebitis of superficial vein)

• Fat necrosis

• S/P Galactography

Nipple & skin

Nipple Retraction

• Positional

• Relative to inflammation/edema of periareolar tissue

• Congenital

• Acquired (carcinoma, ductal ectasia)

Galactographic Filling Defect
Type of Tumor	Single	Multiple
Multiple papilloma	5.6%	14.0%
Cancer	0.05%	9.7%

Nipple Discharge

Prevalence:

7.4 % of breast surgeries

Classification:

• provoked

  • postovulatory state, duct ectasia, medication, stimulation by exercise, breast self-examination, sexual manipulation

• Spontaneous

  • physiologic: pregnancy, lactation, galactorrhea, duct ectasia

  • pathologic: benign/malignant neoplasm, galactorrhea due to hyperprolactinemia from a pituitary adenoma

• Unilateral

  • Unilateral spontaneous discharge is significant + requires investigation!

• Bilateral

  • Expressed bilateral multipore blood-negative discharge is physiologic and benign!

Type of discharge:

• Lactating breast: galactorrhea

• Nonlactating breast:

  • normal:

    • 1. milky

    • 2. multicolored sticky (blue, green, gray, brown, black)

  • abnormal:

    • 3. purulent: antibiotics, incision, drainage

  • surgically significant (in 14.3% cancerous)

    • 4. clear/watery: cancer in 33%

    • 5. bloody/sanguineous: cancer 28%,

    • 6. pink/serosanguineous: cancer in 13%

    • 7. yellow/serous: cancer in 6%

    • The most common cause of bloody and serosanguineous discharge is intraductal papilloma (in 40%)!

    • Exfoliative cytology not helpful (true positive in only 11%, false negative in 18%)

Site of origin:

• Lobules + terminal duct lobular unit:

  • Galactorrhea

  • Fibrocystic changes

• Larger lactiferous ducts (collecting duct, segmental duct, subsegmental duct)

  • Solitary papilloma

  • Papillary carcinoma

  • Duct ectasia

Galactography/Ductography

• = injection of 0.2 0.3 mL of water-soluble contrast material (Conray 60 , Isovue ) through straight blunt 27-gauge pediatric sialography cannula (0.4 0.6 mm outer diameter)/30-gauge cannula/Jabczenski cannula (tip bent 90 )

• Results of positive galactography:

  • papilloma (48%), benign conditions (42%), intraductal carcinoma (10%)

• Contraindications to ductography:

  • history of severe allergy to iodinated contrast material, inability of patient to cooperate (debilitating anxiety, mental disorder), history of prior nipple surgery

P.549




• DDx of intraductal defects:

  • gas bubble, clot, inspissated secretions, solitary intraductal papilloma, epithelial hyperplastic lesion, duct carcinoma

Secretory Disease

• Retained lactiferous secretions

  • result of incomplete/prolonged involution of lactiferous ducts

  • branching pattern of fat density in dense breast (high lipid content)

• Prolonged inspissation of secretion + intraductal debris

  • = MAMMARY DUCT ECTASIA

  • duct dilatation

  • calcifications with linear orientation toward subareolar area a few mm long: rod-shaped/sausage-shaped/spherical with hollow center

• Galactocele

• Plasma cell mastitis

Skin Thickening of Breast

Normal skin thickness:

0.8 3 mm; may exceed 3 mm in inframammary region

• Localized Skin Thickening

  • Trauma (prior biopsy)

  • Carcinoma

  • Abscess

  • Nonsuppurative mastitis

  • Dermatologic conditions

• GENERALIZED SKIN THICKENING

  • Skin is thickened initially and to the greatest extent in the lower dependent portion of breast!

  • overall increased density with coarse reticular pattern (= dilated lymph vessels + interstitial fluid triggering fibrosis)

  • Axillary lymphatic obstruction

    • Primary breast cancer

      • advanced breast cancer

      • invasive comedocarcinoma in large area

      • Primary breast cancer not necessarily seen due to small size/hidden location (axillary tail, behind nipple)!

    • Primary malignant lymphatic disease (eg, lymphoma)

  • Intradermal + intramammary obstruction of lymph channels

    • Lymphatic spread of breast cancer from contralateral side

    • Inflammatory breast carcinoma = diffusely invasive ductal carcinoma

  • Mediastinal lymphatic blockage

    • Sarcoidosis

    • Hodgkin disease

    • Advanced bronchial/esophageal carcinoma

    • Actinomycosis

  • Advanced gynecologic malignancies from thoracoepigastric collaterals

    • Ovarian cancer

    • Uterine cancer

  • Inflammation

    • Acute mastitis

    • Retromamillary abscess

    • Fat necrosis

    • Radiation therapy

    • Reduction mammoplasty

  • Right heart failure

    • may be unilateral (R > L)/migrating with change in patient position (to avoid decubitus ulcer)

  • Nephrotic syndrome, anasarca

    • Dialysis

    • Renal transplant

  • Subcutaneous extravasation of pleural fluid following thoracentesis

Lymphadenopathy

• nonpalpable

Radiographic features of normal lymph nodes:

• mass of low to moderate density

• sharply defined

• round to oval

• radiolucent fatty hilus (visible in 78%)

• <1 cm within breast tissue, <1.5 cm within axilla

Intramammary Lymphadenopathy

• = adenopathy >1 cm surrounded by breast tissue

N.B.:

nodes located high within axillary tail (= tail of Spence) are mammographically difficult to differentiate from inferior axillary lymph nodes

Axillary Lymphadenopathy

• = solid node >1.5 cm in size without fatty hilum

N.B.:

lymph nodes of up to 3 cm may be normal if largely replaced by fat

• MALIGNANT

  • Metastasis from breast cancer in 26%

    • Primary breast lesion may not be found in 33% of cases!

  • Metastases from non-breast primary (lung, melanoma, thyroid, GI tract, ovary)

  • Lymphoproliferative disease: lymphoma/chronic lymphocytic leukemia (17%)

    • Bilateral axillary lymphadenopathy is suggestive of lymphoproliferative disease!

• BENIGN

  • Nonspecific benign lymphadenopathy (29%)

  • Reactive nodal hyperplasia (breast infection/abscess/biopsy)

  • Collagen vascular disease: rheumatoid arthritis, systemic lupus erythematosus

  • Granulomatous disease: sarcoidosis

  • Psoriasis

  • HIV-related adenopathy

  • Silicone adenopathy

Radiographic features suspicious for malignancy:

• size increase of >100% over baseline

• size >3.3 cm

• change in shape

• spiculation of margins

• intranodal microcalcifications (without history of gold therapy)

P.550




• loss of radiolucent center/hilar notch

• increase in density

Mammography Report

based on BI-RADSR (Breast Imaging Reporting and Data System) published by the ACR (American College of Radiology)

Report Contents

• Indication for exam

• Comparison to previous studies

• Breast Composition

• Findings

• Overall Assessment

Bi-RADS Categories (American College of Radiology)
Mammography	Ultrasound	MRI
0 need additional imaging evaluation or prior mammogram for comparison: eg, spot compression, magnification, special views, ultrasound	Need additional imaging: eg, an MRI for (1) palpable confirmed mass (2) recurrence versus scar after lumpectomy	Need additional imaging evaluation: eg, (1) technically unsatisfactory scan (2) screening MRI without kinetic imaging (3) incomplete information
1 negative: symmetric breasts, no masses, architectural distortion, suspicious calcifications	Negative: no mass, architectural distortion, skin thickening, microcalcifications	Negative: symmetric breasts; no architectural distortion, abnormal enhancement, or mass
2 Benign findings: eg, involuting calcified fibroadenoma, multiple secretory calcifications, oil cyst, lipoma, galactocele, hamartoma, intramammary node, vascular calcifications, implants, architectural distortion related to prior surgery	Benign findings: eg, simple cyst, intramammary lymph node, breast implant, stable postsurgical changes, probable fibroadenoma	Benign findings: hyalinized nonenhancing fibroadenoma, cyst, scar, fat-containing lesion (oil cyst, lipoma, galactocele, mixed-density hamartoma), breast implant
3 probably benign (<2% risk of malignancy) initial short-interval follow-up suggested (in 6 months), not expected to change (over >2 years) after complete diagnostic work-up: eg, noncalcified circumscribed solid mass, focal asymmetry, cluster of round punctate calcifications	Probably benign short-interval followup suggested (<2% risk of malignancy): eg, classic findings of a fibroadenoma, nonpalpable complicated cyst, clustered microcysts	Probably benign short-interval follow-up suggested: a malignancy is highly unlikely
4 Suspicious abnormality biopsy should be considered: not classic appearance of malignancy	Suspicious abnormality biopsy should be considered: intermediate (3 94%) probability of malignancy: e.g., a solid mass without all criteria of a fibroadenoma	Suspicious abnormality biopsy should be considered: lesion morphology not characteristic of breast cancer but of concern
4a Low probability
4b Intermediate probability
4c Moderate probability
5 Highly suggestive of malignancy ( 95% probability of cancer) appropriate action should be taken: eg, lesion could be considered for one-stage surgical treatment, however, biopsy usually required	Highly suggestive of malignancy (>95% probability) appropriate action should be taken: image-guided core needle biopsy	Highly suggestive of malignancy appropriate action should be taken: almost certainly malignant
6 Known biopsy-proven malignancy eg, mammogram during neoadjuvant chemotherapy comparing it to pre-therapy mammogram	Known biopsy-proven malignancy eg, prior to chemotherapy, lumpectomy, mastectomy	Known biopsy-proven malignancy corresponding to the lesion imaged with MRI

P.551

Lexicon Descriptors for Reporting

• Mass

  size shape	round, oval, lobulated, irregular
  margins	circumscribed, lobulated, obscured, indistinct, spiculated
  density	relative to an equal volume of breast tissue: high, equal, low, fat
  location	based on face of clock; depth (anterior, middle, posterior); subareolar; central; axillary

• Calcifications

  benign	skin, vascular, coarse popcornlike, large rodlike (secretory), round, lucent center, eggshell/rim, milk of calcium, suture, dystrophic, punctate
  indeterminate	amorphous/indistinct
  probably malignant	pleomorphic/heterogeneous (granular), linear branching/casting
  number size distribution	grouped/clustered, linear, segmental, regional (within large volume of breast tissue), scattered/diffuse, multiple groups

• Associated Findings

  skin	thickening (diffuse, focal), retraction
  nipple	retraction, inverted
  trabeculae	thickening, architectural distortion
  axilla	adenopathy

P.552

Breast Anatomy and Mammographic Technique

Breast development

Embryology

Milk line develops from ectodermal elements + extends from axillary region to groin; lack of regression leads to development of accessory breast tissue/accessory nipples

Tanner Stages

Stage I (prepubertal)

• nipple elevates

• ill-defined hyperechoic retroareolar tissue

Stage II

Cause:

estrogen for ductal + progesterone for lobuloalveolar development

• palpable subareolar bud = thelarche begins with onset of puberty (mean age, 9.8 years)

• breast tissue + nipple arise as a single mound of tissue

• hyperechoic retroareolar nodule

• central star-shaped/linear hypoechoic area (simple branched ducts)

Stage III

• enlargement + elevation of single mound

• hyperechoic glandular tissue extending away from retroareolar area

• central spider-shaped hypoechoic area

Stage IV (areolar mounding)

• secondary mound develops (very transient) with nipple + areola projecting above the breast tissue

• hyperechoic periareolar fibroglandular tissue

• prominent central hypoechoic nodule

Stage V (mature breast)

• regression of areola forming a smooth contour with the rest of the breast tissue

• hyperechoic glandular tissue

• increased subcutaneous adipose tissue anteriorly

• NO hypoechoic central nodule

Terminal Ductal Lobular Unit

Breast Anatomy

Lobes

15 20 lobes disposed radially around nipple, each lobe has a main lactiferous duct of 2.0 4.5 mm converging at the nipple with an opening in the central portion of nipple

Main duct:	branches dichotomously eventually forming terminal ductal lobular units
Histo:	epithelial cells, myoepithelial cells surrounded by extralobular connective tissue with elastic fibers

Terminal Duct Lobular Unit (TDLU)

• Extralobular terminal duct

  Histo:

  lined by columnar cells + prominent coat of elastic fibers + outer layer of myoepithelium

• Lobule

  • intralobular terminal duct

    Histo:

    lined by 2 layers of cuboidal cells + outer layer of myoepithelium

  • ductules/acini

  • intralobular connective tissue

  Size:

  1 8 mm (most 1 2 mm) in diameter

• Change:

  • reproductive age: cyclic proliferation (up to time of ovulation) + cyclic involution (during menstruation)

  • post menopause: regression with fatty replacement

• Significance:

  • TDLU is site of fibroadenoma, epithelial cyst, apocrine metaplasia, adenosis (= proliferation of ductules + lobules), epitheliosis (= proliferation of mammary epithelial cells within preexisting ducts + lobules), ductal + lobular carcinoma in situ, infiltrating ductal + lobular carcinoma

Components of Normal Breast Parenchyma

• Nodular densities surrounded by fat

  • 1 2 mm = normal lobules

  • 3 9 mm = adenosis

• Linear densities

  • = ducts and their branches + surrounding elastic tissue

• Structureless ground-glass density

  • = stroma/fibrosis with concave contours

Parenchymal Breast Pattern (L szl Tab r)

• Pattern I

  • named QDY = quasi dysplasia (for Wolfe classification)

  • concave contour from Cooper's ligaments

  • evenly scattered 1 2 mm nodular densities (= normal terminal ductal lobular units)

  P.553

  
  

  • oval-shaped/circular lucent areas (= fatty replacement)

• Pattern II

  • similar to N1 (Wolfe)

  • total fatty replacement

  • NO nodular densities

• Pattern III

  • similar to P1 (Wolfe)

  • normal parenchyma occupying <25% of breast volume in retroareolar location

• Pattern IV = adenosis pattern

  • similar to P2 (Wolfe)

  Cause:	hypertrophy + hyperplasia of acini within lobules
  Histo:	small ovoid proliferating cells with rare mitoses

  • scattered 3 7 mm nodular densities (= enlarged terminal ductal lobular units) = adenosis

  • thick linear densities (= periductal elastic tissue proliferation with fibrosis) = fibroadenosis

  • no change with increasing age (genetically determined)

• Pattern V

  • similar to DY (Wolfe)

  • uniformly dense parenchyma with smooth contour (= extensive fibrosis)

Parenchymal Breast Patterns

Breast composition and parenchymal pattern
Composition (BI-RADS )	Descriptor	Pattern (Tab r)	Descriptor
1	Almost entirely fatty breast	II	Completely involuted breast
2	Scattered fibroglandular tissue that could obscure a lesion	I	Normal premenopausal parenchyma
		III	Involution with prominent retroareolar ducts
3	Heterogeneously dense tissue that may lower the sensitivity of mammography	IV	Adenosis pattern of dominant nodular and linear densities
4	Extremely dense breast tissue that lowers the sensitivity of mammography	V	Extensive structureless fibrosis

Enhancement of Normal Parenchyma on MRI

• Image 7 20 days after beginning of LMP

• Proper enhancement present if:

  • veins contrasted on MIP

  • both internal mammary arteries depicted

  • nipple enhances

• increased enhancement under HRT with estrogen/during lactation (with great interindividual variations):

  • linear patchy enhancement

  • bilateral symmetric patchy enhancement

  • confluent enhancement on late dynamic scan

  • Hormone effects reverse after 30 60 days

  • Breast involution after lactation takes 3 months

• decreased enhancement under antiestrogen treatment (eg, tamoxifen)

Lymphatic Drainage

• Axillary nodes (97%)

  • level I = lateral to lateral edge of pectoralis minor

  • level II = behind pectoralis minor

  • level III = medial to medial edge of pectoralis minor

• Internal mammary nodes (3%)

  • characteristic radiolucent center (fat)

P.554

• US:

  • hypoechoic periphery + hyperechoic center

• MR:

  • T1WI

    • not recognizable within parenchyma

    • recognizable in extraparenchymal location as oval well-circumscribed hypointense lesion with central hyperintense area

  • enhanced T1WI:

    • no/slight enhancement in bland nodes

    • strong enhancement + wash-out phenomenon simulating ring enhancement of malignancy in reactive inflammatory nodes

  • T2WI:

    • no characteristic finding

Descriptor of Signal Enhancement in Breast MRI
Enhancement	SI increase compared to precontrast
None	0%
Slight	<50%
Moderate	50 100%
Strong	>100%

Mammographic Film Reading Technique

• Compare with earlier films

• Scan forbidden areas

  • Milky Way = 2 3 cm wide area parallel to the edge of the pectoral muscle on MLO projection

  • No man's land = fatty replaced area between posterior border of parenchyma + chest wall on CC projection

  • Medial half of breast on CC view

• Look for increased retroareolar density

• Look for parenchymal contour retraction

• Look for architectural distortion

• Look for straight lines superimposed on normal scalloped contour

• Compare left with right side

• Don't stop looking after one lesion is found

Mammographic Technique

• BEAM QUALITY

  • Molybdenum target material with characteristic emission peaks of 17.9 + 19.5 keV (lower average energy than tungsten)

• FOCAL SPOT

  • 0.1 0.4 mm (0.1 mm for magnification views)

• TUBE OUTPUT

  • 80 100 mA

• EXPOSURE

  • without grid: 25 kV (optimum between contrast + penetration), exposure time of 1.0 seconds

  • with grid: 26 27 kV; exposure time of 2.3 seconds

  • microfocus magnification: 26 27 kV; 1.5 2.0 times magnification with 16 30 cm air gap

  • specimen radiography: 22 24 kV

• FILTER

  • beryllium window (absorbs less radiation than glass tube)

  • molybdenum filter (0.03 mm): allows more of lower energy radiation to reach breast

• REDUCTION OF SCATTER RADIATION

  • adequate compression (also improves contrast + decreases radiation dose)

  • beam collimation to <8 10 cm

  • air gap with microfocus magnification

    • (greater spatial resolution, 2 3-fold increase in radiation exposure)

  • Moving grid

    • grid if compressed breast >5 cm/very dense breast (facilitates perception, 2 3-fold increase in radiation exposure)

• SCREEN-FILM COMBINATION

  • Intensifying screen phosphor

    • single screen systems

  • Film-screen contact

  • Mammography film with minimal base fog, sufficient maximum density + contrast

• FILM PROCESSING

  • Processing time of 3 minutes (42 45 seconds in developing fluid) superior to 90-second processor for double-emulsion film (which creates underdevelopment + compensatory higher radiation exposure)

  • Developing temperature of 35 C (95 F)

  • Developing fluid replenishment rate:

    • 450 500 mL replenisher per square meter of film

• QUALITY CONTROL

  • Processor (daily)

    • with sensito-/densitometric measurements

    • (a) base fog <0.16 0.17

    • (b) maximum density >3.50

    • (c) contrast >1.9 2.0

  • X-ray unit (semiannually)

    • beam quality

    • phototimer

• Average glandular dose:

  • <0.6 MGY per breast for nonmagnification film-screen mammogram (ACR accreditation requirement)

  • Screen/film technique (molybdenum target; 0.03 mm molybdenum filter, 28 kVp):

    mean absorbed dose:

    0.05 rad for CC view
    0.06 rad for LAT view

• Effective dose equivalent H_E:

  • screen-film mammography 0.11 mSv

  • xeroradiographic mammography 0.78 mSv

  • chest 0.05 mSv

  • skull 0.15 mSv

  • abdomen 1.40 mSv

  • lumbar spine 2.20 mSv

• Advantages of magnification mammography:

  • Sharpness effect = increased resolution

  • Noise effect = noise reduced by a factor equal to the degree of magnification

  • Air-gap effect = increased contrast by reduction in scattered radiation

  • Visual effect = improved perception and analysis of small detail

P.555

Factors Affecting Mammographic Image Quality

Radiographic Sharpness

• = subjective impression of distinctness/perceptibility of structure boundary/edge

• Radiographic contrast

  • = magnitude of optical density difference between structure of interest + surroundings influenced by

    • subject contrast

      • = ratio of x-ray intensity transmitted through one part of the breast to that transmitted through a more absorbing adjacent part; affected by

      • absorption differences in the breast (thickness, density, atomic number)

      • radiation quality (target material, kilovoltage, filtration)

      • scattered radiation (beam limitation, grid, compression)

    • receptor contrast

      • = component of radiographic contrast that determines how the x-ray intensity pattern will be related to the optical density pattern in the mammogram

  • affected by

    • film type

    • processing (chemicals, temperature, time, agitation)

    • photographic density

    • fog (storage, safelight, light leaks)

• Radiographic blurring

  • lateral spreading of a structural boundary

    • (= distance over which the optical density between the structure and its surroundings changes)

  • motion

    • reduced by compression + short exposure time

  • geometric blurring

    • affected by

      • focal spot: size, shape, intensity distribution

      • focus-object distance (= cone length)

      • object-image distance

  • receptor blurring

    • = light diffusion (= spreading of the light emitted by the screen) affected by

      • phosphor thickness + particle size

      • light-absorbing dyes + pigments

      • screen-film contact

Radiographic Noise

• = unwanted fluctuation in optical density

• Radiographic mottle

  • = optical density variations consist of

  • receptor graininess

    • = optical density variation from random distribution of finite number of silver halide grains

  • quantum mottle (principal contributor to mottle)

    • = variation in optical density from random spatial distribution of x-ray quanta absorbed in image receptor

    • affected by

    • film speed + contrast

    • screen absorption + conversion efficiency

    • light diffusion

    • radiation quality

  • structure mottle

    • = optical density fluctuation from nonuniformity in the structure of the image receptor (eg, phosphor layer of intensifying screen)

• Artifacts

  • = unwanted optical density variations in the form of blemishes on the mammogram

  • (a) improper film handling (static, crimp marks, fingerprints, scratches)

  • (b) improper exposure (fog)

  • (c) improper processing (streaks, spots, scratches)

  • (d) dirt + stains

P.556

Breast Disorders

Breast Cancer

Incidence:	1.5 4.5 cases per 1,000 women per year
Origin:	terminal ductal lobular unit

Distribution of Breast Cancers in Screening Population (numbers are percentages)

Noninvasive Breast Cancer (15%)

• = malignant transformation of epithelial cells lining mammary ducts + lobules confined within boundaries of basement membrane

  Rx:

  few data are available to provide insight into proper treatment

Ductal carcinoma in situ (DCIS)

• = intraductal carcinoma

  • ( cancer waiting to become malignant )

  • 30% become invasive over 10 years

Incidence:	20 40% in screening population; 70% of noninvasive carcinomas
Age:	most >55 years (40 60 years)
Histo:	heterogeneous group of malignancies originating within extralobular terminal duct + without invasion of basement membrane; causes duct diameter increase from 90 to 360 m
Subgroups:	comedocarcinoma, non-comedocarcinomas (solid, micropapillary, cribriform)
Associated with:	ADH + invasive ductal carcinoma

• may persist for years without palpable abnormality (in screening population)

• palpable mass (10%)/Paget disease of nipple/nipple discharge (in symptomatic patients)

• 50% of DCIS are >5 cm in size

• Histologic size of DCIS is independent of histologic subgroup

• Almost all comedo type DCIS contain significant microcalcifications

• DCIS often involves the nipple + subareolar ducts

Spectrum of mammographic findings:

• calcifications only (72%)

• soft-tissue abnormality + calcification (12%)

• soft-tissue abnormality only (10%)

• invisible (6%)

MR (50 60% sensitive, 18 100% FN [!]):

• T1WI:

  • isointense to surrounding parenchyma

• enhanced T1WI:

  • branching/spiculated/round enhancing lesion with ill-defined margins (in 90%)

  • enhancement pattern typical of malignancy (in 30 50%)/nonspecific (in 40 55%)

  • no enhancement (in 5 10%)

  • no ring enhancement

• T2WI:

  • no specific findings

Prognosis:	98% survival after 13 years
Rx:	(1) Simple/modified mastectomy: cure rate of almost 100% (2) Local excision alone:       local recurrence in 4 years:        19% for poorly differentiated        10% for moderately differentiated        0% for well differentiated (3) Lumpectomy + radiotherapy:       2 17% rate of recurrence

Treatment problems:

• Occult invasion in 5 20% of patients

• Multifocality in 30%

  • (= >2 foci in same breast quadrant)

• Multicentricity

  • (= >1 focus in different breast quadrants with a minimum distance of 2 cm)

  • in 14% of lesions <25 mm,

  • in 100% of lesions >50 mm

• Axillary metastases in 1 2%

HIGH NUCLEAR GRADE DCIS ( COMEDO TYPE )

Prevalence:	60% of all DCIS
Precursor:	none; one stage development
Path:	comedo = pluglike appearance of necrotic material that can be expressed from the cut surface

• Characteristics:

  • nuclear grade: large/intermediate nuclei, numerous mitoses, aneuploidy

  • growth pattern: predominantly solid cell proliferation; atypically micropapillary/cribriform

  • necrosis: extensive (HALLMARK)

  • calcifications (90%): dystrophic/amorphous within necrosis in center of dilated ductal system outlining most of the lobe in classic solid growth pattern

• estrogen- + progesterone-receptor negative

• overexpression of c-erb B-2 oncogene product and P53 suppressor gene mutation

P.557




• often symptomatic lesion with nipple discharge

• ductal system enlarged to 300 350 m

• linear/branching pattern of calcifications scattered in a large part of lobe/whole lobe

• large solid high-density casting calcifications (fragmented, coalesced, irregular) in solid growth pattern

  • snake skin like / birch tree flowerlike dotted casting calcifications within necrosis of micropapillary/cribriform growth pattern

• palpable dominant mass without calcifications (very unusual)

• nipple discharge (rare)

Prognosis:

higher recurrence rate than noncomedo-group

LOW NUCLEAR GRADE DCIS ( NONCOMEDO TYPE )

Prevalence:

40% of all DCIS

• Precursor lesion:

  • atypical ductal hyperplasia (ADH) with slight/moderate/severe atypia

  • 52 56% of ADH at core biopsy are associated with malignancy at excision!

• Characteristics:

  • nuclear grade: monomorphic small round nuclei, few/no mitoses

  • growth pattern: predominantly micropapillary/cribriform; atypically solid cell proliferation (often coexist)

  • necrosis: not present in classic micropapillary/cribriform growth pattern

  • calcifications (50%): laminated/psammoma-like due to active secretion by malignant cells into duct lumen

• fine granular cotton ball calcifications in micropapillary/cribriform growth pattern

• coarse granular crushed stone / broken needle tip / arrowhead calcifications in less common solid growth pattern

  • Size of noncomedo DCIS often underestimated mammographically (? due to lower density of calcifications at periphery of lesion)!

• palpable dominant mass without calcifications (intracystic papillary carcinoma, multifocal papillary carcinoma in situ)

• nonpalpable asymmetric density with architectural distortion

• occasionally serous/bloody nipple discharge + ductal filling defects on galactography

Prognosis:	30% eventually develop into invasive cancer
Risk of recurrence:	2%
Dx:	surgical biopsy Core needle biopsy could result in diagnosis of only proliferative breast disease that is usually intermixed!

Lobular Carcinoma In Situ (LCIS)

• = arises in epithelium of blunt ducts of mammary lobules

• NOT a precancerous lesion BUT a marker for an increased risk of subsequent invasive cancer in either breast!

  • ( Risk factor waiting to become malignant )

Incidence:	0.8 3.6% in screening population; 3 6 % of all breast malignancies;25% of all noninvasive carcinomas; high incidence during reproductive age but decreasing with age
Age:	most 40 54 years (earlier than DCIS/invasive tumors)
Histo:	monomorphous small cell population filling + expanding ductules of the lobule Synchronous invasive cancer in 5%!

• not palpable

• mammographically occult

• may atypically present as a noncalcified mass (in 7%), calcifications + mass (in 10%), asymmetric opacity (2%)

• MR:

  • T1WI:

    • isointense to breast parenchyma

  • enhanced T1WI:

    • ill-defined enhancement with nonspecific intensity curves

• High frequency of multicentricity (50 70%) + bilaterality (30%)!

Dx:

incidental microscopic finding depending on accident of biopsy (performed for unrelated reasons + findings)

• Prognosis:

  • 20 30% develop invasive ductal > lobular carcinoma within 20 years after initial diagnosis

  • 1% per year lifetime risk for invasive malignancy

  • LCIS serves as a marker of increased risk for developing invasive carcinoma in either breast!

Rx:

recommendations range from observation (with follow-up examinations every 3 6 months + annual mammograms) to unilateral/bilateral simple mastectomy

Intracystic Papillary Carcinoma In Situ (0.5 2%)

• = rare variant of noncomedo DCIS

Age:	usually older postmenopausal woman; peak prevalence between 34 and 52 years
Histo:	papillary fronds within the wall of a cystically dilated duct

• well-circumscribed + freely movable

• aspiration yields straw-colored/dark red/brown fluid (due to ruptured capillaries in cyst wall/necrosis of tumor cells); reaccumulation of fluid within 3 4 weeks

• fluid cytology negative for cancer in 80%

• mean tumor size of 1.9 cm (range 0.4 7.5 cm) due to fast growth (from accumulation of fluid + proliferation of neoplastic cells)

• intracystic mass on pneumocystography

• solid intracystic mass on US

• round benign appearing mass with sharply circumscribed lobulated borders on mammography

Rx:	lumpectomy
Prognosis:	10-year survival of 100%; 10-year disease-free survival rate of 91%
DDx for mammogram:	mucinous/medullary ca., hematoma, metastasis

P.558

Invasive Breast Cancer (85%)

• MR:

  • peripheral/rim enhancement

Infiltrating/Invasive Ductal Carcinoma (65%) of no special type/otherwise not specified (NOS)

• Most frequently encountered breast malignancy

• 10% false-negative ratio

Age:

any (peak, 50 60 years)

Histo:

• grade I = well-differentiated

• grade II = moderately differentiated

• grade III = poorly differentiated

• Strong fibrotic component!

• palpable (70% are first palpated by the patient)

• larger by palpation than on mammogram

• often poorly movable + indolent

Location:

multifocal in 15%; bilateral in 5%

• spiculated mass (36%) is PRINCIPAL FINDING

• lobulated/round/oval

• increased central density

• malignant calcifications (45 60%)

• US:

  • ill-defined hypoechoic mass with hyperechoic margins

  • central/peripheral acoustic shadowing

• MR (88 98% sensitive):

  • T1WI:

    • isointense to parenchyma; hypointense to fat

  • enhanced T1WI:

    • round/ovoid/spiculated lesion with ill-defined margins

    • ring enhancement in up to 50% with centripetal progression

    • strong (in 60%)/moderate (in 35%)/mild (in 5%) contrast uptake

    • plateau (most frequent)/wash-out (often)/continuous increase (rare) on postinitial phase

    • dilated veins draining the tumor

  • T2WI:

    • iso- to hypointense to parenchyma

    • occasionally hyperintense edematous zone

  Infiltrating/Invasive Lobular Carcinoma (5 10%)

  • = neoplasm arising from terminal ductules of breast lobules

  • 2nd most common form of invasive breast cancer; 30 50% of patients will develop a second primary in same/opposite breast within 20 years

  • Most frequently missed breast cancer (difficult to detect mammographically + clinically) with 19 43% false-negative rate (occult in dense breast)

  Median age:	45 56 years; 2% of all ILC occur in women <35 years
  Path:	multicentricity (30%) + bilaterality (10%); tendency to grow around ducts, vessels, and lobules without destruction of anatomic structures ( Indian file /targetoid growth); desmoplastic stromal reaction
  Histo:	20% grade I, 64% grade II, 16% grade III
  Metastases:	GI tract, gynecologic organs, peritoneum, retroperitoneum, carcinomatous meningitis

  • palpable in 69%:

  • area of subtle skin thickening/induration

  • large hard mass/fine nodularity

  • architectural distortion (= retraction of normal glandular tissue with thickening + disturbance of fibrous septa) in 18 30% is MOST COMMON MAMMOGRAPHIC FINDING

    Histo:

    straight single file of uniform small cells with round oval nuclei ( Indian files ) growing around ducts resulting in subtle changes in architecture

  • irregular spiculated mass >1 cm (16 28%)

  • poorly defined mass spicules <1 cm (22%)

  • asymmetric opacity (= ill-defined area of increased opacity without central tumor nidus) in 8 19%

  • round/ovoid mass with regular borders (1%)

  • microcalcifications (0 24%)

  • retraction of skin (25%) + nipple (26%)

  • skin thickening

  • May be evident on ONLY one standard view CC > ML > MLO view)!

  • MR (83 100% sensitive):

    • T1WI:

      • isointense to parenchyma

    • enhanced T1WI:

      • moderate/strong initial enhancement

      • postinitial plateau (frequently)/wash-out (occasionally)/continuous increase (rare)

      • lack of mass effect + amorphous asymmetry

      • lack of mass effect + amorphous asymmetry

      • ring enhancement of nodular tumor form (in up to 50%)

    • T2WI:

      • iso- to hypointense to breast parenchyma

  Prognosis:	poor due to late diagnosis
  N.B.:	difficulties in early diagnosis result in disproportionate potential for malpractice suits!

  Tubular Carcinoma (6 8%)

  = well-differentiated form of ductal carcinoma

  • low grade: bilateral in 1:3

  • high grade: bilateral in 1:300

  Associated with:	lobular carcinoma in situ in 40%
  Mean age:	40 49 years

  • positive family history in 40%

  • nonpalpable

  • high-opacity nodule with spiculated margins

  • <17 mm in diameter; mean diameter of 8 mm

  • MR:

    • T1WI:

      • stellate hypointense lesion well seen in fat

    • enhanced T1WI:

      • stellate tumor with moderate/strong initial uptake

      • ring enhancement rare

      • postinitial plateau (frequent)/wash-out (rare) /continuous increase (very rare)

    • T2WI:

      • iso-/slightly hypointense to parenchyma

      • occasional peritumoral edematous zone

  DDx:

  radial scar

  Medullary Carcinoma (2%)

  • = SOLID CIRCUMSCRIBED CARCINOMA

  • Fastest growing breast cancer!

  • distinct/indistinct margins

  P.559

  
  

  • Often associated with BRCA gene!

  Path:	well-circumscribed mass with nodular architecture + lobulated contour; central necrosis is common in larger tumors; reminiscent of medullary cavity of bone
  Histo:	intense lymphoplasmocytic reaction (reflecting host resistance); propensity for syncytial growth; no glands
  Incidence:	11% of breast cancers in women <35 years of age; 40 50% of medullary cancers in women <50 years of age
  Mean age:	46 54 years

  • softer than average breast cancer

  Mean size:

  2 3 cm

  • well-defined round/oval noncalcified uniformly dense mass (hemorrhage) with lobulated margin

  • may have partial/complete halo sign

  • US:

    • hypoechoic mass with some degree of through transmission

    • distinct/indistinct margins

    • large central cystic component

  • MR:

    • irregular internal architecture (no septa!)

    • T1WI:

      • well-circumscribed hypointense lesion difficult to detect in parenchyma

    • enhanced T1WI:

      • moderately/strongly enhancing round/ovoid lesion with smooth edge

      • ring enhancement occasionally

      • postinitial plateau (frequent)/wash-out (occasionally)/continuous increase (rare)

    • T2WI:

      • iso- or mildly hypointense to parenchyma

  DDx:	myxoid fibroadenoma
  Prognosis:	92% 10-year survival rate

  Mucinous/Colloid Carcinoma (1.5 2%)

  • Path:

    • pure form: aggregates of tumor cells surrounded by abundant pools of extracellular mucin (gelatinous/colloid fluid)

    • mixed form: contains areas of infiltrating ductal carcinoma not surrounded by mucin

  Age:

  1% in women <35 years; 7% of carcinomas in women >75 years

  • slow growth rate of pure form

  • swish / crush sensation during palpation

  • 60% estrogen-receptor positive

  • well-circumscribed usually lobulated mass of round/ovoid shape

  • pleomorphic clustered/clumped amorphous/punctate calcifications (rare)

  • may enlarge fast (through mucin production)

  • solid mass on US

  • MR:

    • T1WI:

      • well-circumscribed round/ovoid hypointense lesion difficult to detect in parenchyma

    • enhanced T1WI:

      • very strong (usually)/moderate (occasionally)/slight (rare) initial uptake

      • rarely ring enhancement

      • postinitial plateau (frequent)/wash-out (occasionally)/continuous increase (very rare)

    • T2WI:

      • iso-/slightly hypointense to parenchyma

      • hyperintense center with thin rim

  Prognosis:

  favorable

  Papillary Carcinoma (1 2 4%)

  • = rare ductal carcinoma forming papillary structures

  N.B.:	Do not confuse with micropapillary/cribriform growth pattern of ductal carcinoma
  Histo:	multilayered papillary projections extending from vascularized stalks; no myoepithelial layer (as in benign lesions); neurosecretory granules + positive CEA-reactivity in 85% (absent in benign lesions)
  Types:	(a) multiple intraductal carcinomas with papillary configuration (b) Intracystic papillary carcinoma = in situ malignancy (c) invasive carcinoma with papillary growth pattern (microscopic frond formation)
  Age:	25 89 (mean 50 60) years; peak age of 40 75 years

  • palpable mass (67%)

  • nipple discharge (22 35%) often tinged with blood

  • rich in estrogen and progesterone receptors

  Location:

  single nodule in central portion of breast; multiple nodules extending from subareolar area to periphery of breast

  • multinodular pattern (55%) = lobulated mass/cluster of well-defined contiguous nodules

  • solitary well-circumscribed round/ovoid nodule with average diameter of 2 3 cm

  • usually confined to single quadrant

  • associated microcalcifications in 60%

  • multiple filling defects/disruption of an irregular duct segment/complete obstruction of duct system at galactography

  • US:

    • solid hypoechoic mass with lobulated smooth margins + acoustic enhancement

    • blood flow on color Doppler

  • MR:

    • T1WI:

      • well-circumscribed hypointense retroareolar lesion

    • enhanced T1WI:

      • strong initial enhancement

      • ring enhancement possible

      • postinitial plateau/wash-out

    • T2WI:

      • well-circumscribed lesion of intermediate intensity in signal-intense cyst

  Prognosis:	90% 5-year survival after simple mastectomy + axillary node dissection
  DDx:	solitary central duct papilloma; multiple peripheral benign papillomas

  P.560

  
  

  Paget Disease of the Nipple (5%)

  Inflammatory Breast Carcinoma

  • = tumor emboli within dermal lymphatics (angiolymphatic spread)

  Prevalence:	1 2 4% of breast cancers
  Age:	52 years (on average)
  Histo:	infiltrating ductal carcinoma
  Location:	L > R breast; bilaterality in 30 55%

  • rapid symptomatic development over 1/3 of breast surface:

    • palpable tumor (63%)

    • erythema of skin (13 64%)

    • peau d'orange edema of skin (13%)

    • nipple retraction (13%)

  • palpable axillary adenopathy (in up to 91%)

  • tumor mass malignant-type calcifications

  • diffusely increased breast density

  • stromal coarsening (50%)

  • thickening of Cooper ligaments

  • extensive skin thickening (71%)

  • MR:

    • T1WI:

      • skin thickening

    • enhanced T1WI:

      • strong increased uptake in thickened skin + tumor infiltrated parenchyma

      • occasionally delineation of primary tumor

    • T2WI:

      • diffuse increase in intensity compared to contralateral breast

      • sometimes hypovascular tumor surrounded by nontumoral edema

Dx:	skin biopsy
Prognosis:	2% 5-year survival; median survival time of 7 months (untreated) + 18 months (after radical mastectomy)
DDx:	mastitis (test treatment with macrolide antibiotic azithromycin, eg, Zithromax Z-pak )

Epidemiology of Breast Cancer

Incidence:

2 5 breast cancers/1,000 women; in USA >142,000 new cases per year (of which 25,000 are in situ); 25% of all female malignancies

• 12% lifetime risk of breast cancer = 1 in 9 women will develop breast cancer during her life!

Age:	0.3 2% in women <30 years of age; 15% in women <40 years of age;85% in women >30 years of age
Mortality:	43,000 deaths per year

• Death rate has remained stable for past 60 years!

Risk Factors (increasing risk):

Demographic Factors in Breast Cancer

• increasing age (66% of cancers in women >50 years):

  Age	Prevalence of Breast Cancer
  25	5:100,000	1:19,608
  40	80:100,000	1:1,250
  45	1075:100,000	1:93
  50	180:100,000	1:555
  55	3030:100,000	1:33
  60	240:100,00060	1:416

  Relative Risk Compared with Woman of Age 60
  30 years of age	0.07
  35 years of age	0.19
  40 years of age	0.35
  50 years of age	0.71
  60 years of age	1.00
  70 years of age	1.27
  80 years of age	1.45

• Ashkenazi Jewish women + nuns

• upper > lower social class

• unmarried > married women

• Whites > Blacks after age 40

REPRODUCTIVE VARIABLES IN BREAST CANCER

• nulliparous > parous:

  Relative Risk Compared with Nulliparous:
  age at 1st pregnancy	<19 years	0.5
  age at 1st pregnancy	20 30 years
  age at 1st pregnancy	30 34 years	1.0
  age at 1st pregnancy	>35 years	>1.0

• first full-term pregnancy after age 35: 2 risk

• low parity > high parity

• early age at menarche (<12 years):

  • relative risk compared with onset of regular ovulatory cycle:

  	Menarche <12	Menarche >12
  immediately	3.7	1.6
  1 4 years	2.3	1.6

• late age at menopause: relative risk compared with menopause before age 44 years:

  • natural menopause >55 years of age 2.0

• early bilateral oophorectomy: relative risk compared with menopause between ages 45 49 years:

  • artificial menopause at 50 54 years 1.34

  • artificial menopause before age 45 0.77

Multiple Primary Cancers in Breast Cancer

• 4 5 increase in risk for cancer in contralateral breast

• increased risk after ovarian + endometrial cancer

BRCA

= mutation of tumor suppressor gene

• BRCA 1 (breast cancer 1) on long arm of chromosome 17

• BRCA 2 (breast cancer 2) on chromosome 13 involved in 5 10% of all breast cancers

Family History of Breast Cancer

• breast cancer in first-degree relative: Relative risk compared with negative family Hx:

  • (+) for mother 1.8

  • (+) for sister 2.5

  • (+) for mother + sister 5.6

• 25% of patients with carcinoma have a positive family history

• carcinoma tends to affect successive generations approx. 10 years earlier

P.561

BENIGN BREAST DISEASE AND BREAST CANCER

• 2 4 increased risk with atypical hyperplasia relative risk compared with no biopsy:

  • benign breast disease in all patients 1.5

  • nonproliferative disease 0.9

  • proliferative disease without atypia 1.6

  • fibroadenoma + hyperplasia 3.5

  • atypical duct hyperplasia (ADH):

    • no family history of breast cancer 4.4

    • family history of breast cancer 8.9

PARENCHYMAL BREAST PATTERN AND BREAST CANCER

• prominent duct pattern + extremely dense breasts according to Wolfe classification N1 (0.14%), P1 (0.52%), P2 (1.95%), DY (5.22%)

RADIATION EXPOSURE AND BREAST CANCER

• excess risk of 3.5 6 cases per 1,000,000 women per year per rad after a minimum latent period of 10 years (atomic bomb, fluoroscopy during treatment of tuberculosis, irradiation for postpartum mastitis, Hodgkin disease)

GEOGRAPHY

• Western + industrialized nations (highest incidence)

• Asia, Latin America, Africa (decreased risk)

Breast Cancer Evaluation

Localizing Signs of Breast Cancer

• = PRIMARY SIGNS OF BREAST CANCER

• Dominant mass seen on two views with

  • Spiculation = stellate/star-burst appearance (= fine linear strands of tumor extension + desmoplastic response); scirrhus caused by:

    • infiltrating ductal carcinoma (75% of all invasive cancers)

    • invasive lobular carcinoma (occasionally)

    • mass feels larger than its mammographic/sonographic size

    DDx:

    prior biopsy/trauma/infection

    Predictive Value of radiographic signs of Malignancy related to Clinical Findings

    Mammographic Sign	Palpable Abnormality	PPV (%)
    Classic for malignancy	+	100
    Classic for malignancy	-	74
    Microcalcifications*	+	25
    Microcalcifications*	-	21
    Indeterminate mammogram	+	11
    Indeterminate mass	-	5
    Benign mass	+	2
    Asymmetric density (? mass)	+	4
    Asymmetric density (? mass)	-	0
    Dilated vein		0
    Skin thickening		0
    Dilated duct		0
    *(>3 punctate irregular microcalcifications in area <1 cm2)

  • Smooth border

    • intracystic carcinoma (rare): subareolar area; bloody aspiration

    • medullary carcinoma: soft tumor

    • mucinous/colloid carcinoma: soft tumor

    • papillary carcinoma

    • telltale signs: lobulation, small comet tail, flattening of one side of the lesion, slight irregularity

    • halo sign (= Mach band) may be present

    DDx:

    cyst (sonographic evaluation)

  • Lobulation

    • appearance similar to fibroadenoma (only characteristic calcifications may exclude malignancy)

    • The likelihood of malignancy increases with number of lobulations

    • clinical size of mass > radiographic size (Le Borgne's law)

• Asymmetric density = star-shaped lesion

  • distinct central tumor mass with volumetric rather than planar appearance (additional coned compression views!)

  • denser relative to other areas (= vessels + trabeculae cannot be seen within high-density lesion)

  • fat does not traverse density

  • corona of spicules

  • in any quadrant (but fatty replacement occurs last in upper outer quadrant)

  DDx:

  postsurgical fibrosis, traumatic fat necrosis, sclerosing duct hyperplasia

• Microcalcifications

  • associated with malignant mass by mammogram in 40%, pathologically with special stains in 60%, on specimen radiography in 86%

  • 20% of clustered microcalcifications represent a malignant process!

    • shape: fragmented, irregular contour, polymorphic, casting rod-shaped without polarity, Y-shaped branching pattern, granular salt and pepper pattern, reticular pattern

    • density: various densities

    • size: 100 300 m (usually); rarely up to 2 mm

    • distribution: tight cluster over an area of 1 cm² or less is most suggestive; coursing along ductal system seen in ductal carcinoma with comedo elements

• Architectural distortion

  Cause:

  desmoplastic reaction

  • ragged irregular border

  DDx:

  postsurgical fibrosis

• Interval change

  • neodensity = de novo developing density (in 6% malignant)

  • enlarging mass (malignant in 10 15%)

• Enlarged single duct

  • (low probability for cancer in asymptomatic woman with normal breast palpation)

  • solitary dilated duct >3 cm long

  DDx:

  inspissated debris/blood, papilloma

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• Diffuse increase in density (late finding)

  Cause:

  (1) plugging of dermal lymphatics with tumor cells
  (2) less flattening of sclerotic + fibrous elements of neoplasm in comparison with more compressible fibroglandular breast tissue

Nonlocalizing Signs of Breast Cancer

• = Secondary Signs Of Breast Cancer

• Asymmetric thickening

• Asymmetric ducts

  • especially if discontinuous with subareolar area

• Skin changes

  • skin retraction = dimpling of skin

    Cause:	desmoplastic reaction causes shortening of Cooper ligaments/direct extension of tumor to skin
    DDx:	trauma, biopsy, abscess, burns

  • skin thickening secondary to blocked lymphatic drainage/tumor in lymphatics

    • peau d'orange

  DDx:

  normal in inframammary region

• Nipple/areolar abnormalities

  • retraction/flattening of nipple

    DDx:

    normal variant

  • Paget disease = eczematoid appearance of nipple + areola in ductal carcinoma

    • associated with ductal calcifications toward the nipple

    DDx:

    nipple eczema

  • nipple discharge

    • spontaneous persistent discharge

    • need not be bloody

  DDx:

  lactational discharge

• Abnormal veins

  • venous diameter ratio of >1.4:1 in 75% of cancers; late sign + thus not very important

• Axillary nodes (sign of advanced/occult cancer)

  • >1.5 cm without fatty center

  DDx:

  reactive hyperplasia

Location of Breast Masses

• benign + malignant masses are of similar distribution

• @ upper outer quadrant (54%)

• @ upper inner quadrant (14%)

• @ lower outer quadrant (10%)

• @ lower inner quadrant (7%)

• @ retroareolar (15%)

• Mediolateral oblique view is important part of screening because it includes largest portion of breast tissue + considers most common location of cancers!

Metastatic Breast Cancer

• @ Axillary lymph adenopathy

  Incidence:	40 74%
  Risk for positive nodes:	30% if primary >1 cm, 15% if primary <1 cm

• @ Bone

• @ Liver

  Incidence:

  48 60%

• US:

  • hypoechoic (83%)/hyperechoic (17%) masses

Screening of Asymptomatic Patients

• Definition of screening (World Health Organization):

  • A screening test must

    • be adequately sensitive and specific

    • be reproducible in its results

    • identify previously undiagnosed disease

    • be affordable

    • be acceptable to the public

    • include follow-up services

• Guidelines of American Cancer Society, American College of Radiology, American Medical Association, National Cancer Institute:

  • Breast self-examination to begin at age 20

  • Breast examination by physician every 3 years between 20 40 years, in yearly intervals after age 40

  • Baseline mammogram between age 35 40; follow-up screening based upon parenchymal pattern + family Hx

  • Initial screening at 30 years if patient has first-degree relative with breast cancer in premenopausal years; follow-up screening based upon parenchymal pattern

  • Mammography at yearly intervals after age 40

  • All women who have had prior breast cancer require annual follow-up

  • Additional recommendations:

    • Screening at 2-year intervals for women >70 years

    • Baseline mammogram 10 years earlier than age of mother/sister when their cancer was diagnosed

• Rate of detected abnormalities:

  • 30 abnormalities in 1,000 screening mammograms:

    20 23	benign lesions
    7 10	cancers

• Acceptable recall rate for screening examination:

  • 10% for initial prevalence screening;

  • 5% for subsequent incidence screening

• Interval cancers:

  • 10 20% of cancers surface between annual screenings

Role of Mammography

• Overall detection rate:

  • 58 69%; 8% if <1 cm in size

• Mammographic accuracy:

  88%	correctly diagnosed by radiologist
  27%	detected only by mammography
  8%	misinterpretations
  4%	not detected
  15 30%	positive predictive value (national average): 25% PPV for women in 5th decade 50% PPV for women in 8th decade

Value of Screening Mammography

Indication:

• decrease in cancer mortality through earlier detection + intervention when tumor size small + lymph nodes negative; tumor grade of no prognostic significance in tumors <10 mm in size

• Health Insurance Plan (HIP) 1963 1969

  • randomized controlled study of 62,000 women aged 40 64

  P.563

  
  

  • 25 30% reduction in mortality in women >50 years (followed for 18 years)

  • 25% reduction in mortality in women 40 49 years (followed for 18 years); no significant effect at 5- and 10-year follow-up

  • 19% of cancers found by mammography alone

  • 61% of cancers found at physical examination

  • effectiveness of screening <50 years of age is uncertain

• Breast Cancer Detection Demonstration Project (BCDDP) 1973 1980

  • 4,443 cancers found in 283,000 asymptomatic volunteers

  • 41.6% of cancers found by mammography alone (77% with negative nodes)

  • 8.7% of cancers found by physical examination alone

  • 59% of noninfiltrating cancers found by mammography alone

  • 25% of cancers were intraductal (vs. 5% in previous series)

  • 21% of cancers found in women aged 40 49 years (mammography alone detected 35.4%)

  • 51% of cancers found with both mammography + physical examination

• Two-county Swedish trial 1977 1990

  • randomized controlled study of 78,000 women in study group + 56,700 in control group aged 40 74 years

  • single MLO mammogram at 2-year intervals for women <50 years of age

  • single MLO mammogram at 3-year intervals for women 50 years of age

  • 40% reduction in mortality at 7 years in women 50 74 years

  • 0% reduction in mortality at 7 years in women 40 49 years

• Metaanalysis of combined results of 5 Swedish trials for women aged 39 49

  • 29% reduction in breast cancer mortality with screening mammograms offered at intervals from 18 to 28 months

Occult versus Palpable Breast Cancer

• 27% are occult cancers (NO age difference)

• Positive axillary nodes:

  • occult cancers (19%); palpable cancers (44%)

• 10-year survival:

  • occult cancers (65%); palpable cancers (25%)

Mammographically Missed Cancers

• False-negative screening mammogram:

  • = pathologic diagnosis of breast cancer within 1 year after negative mammogram with the following types of misses:

    • lesion could not be seen in retrospect (25 33%) = acute cancer = cancer surfacing in screening interval

    • cancer undetected by first reader but correctly identified by second reader (14%)

    • cancer visible in retrospect on prior mammogram (61%)

    Incidence:

    approx. 4 15 34% of all cancers; approx. 3 cancers:2,000 mammograms; 5 15 22% of palpable breast cancers

  • A second reader will detect an additional 5 15% of cancers!

• Cause:

  • Interpretation error (52%):

    • benign appearance (18%): medullary carcinoma, colloid carcinoma, intracystic papillary carcinoma, some infiltrating ductal carcinomas

    • present on previous mammogram (17%)

    • seen on one view only (9%)

    • site of previous biopsy (8%)

  • Observer error (30 43%):

    • overlooked

    • presence of an obvious finding leads to overlooking of a more subtle lesion = satisfied search phenomenon

    • no knowledge of clinical finding

    • rushed interpretation

    • heavy caseload

    • extraneous distraction

    • eye fatigue

    • inexperience

  • Technical error (5%):

    • inadequate radiographic technique: improper positioning, inadequate compression, under- /overexposed image, poor screen-film contact, geometric motion blurring

    • failure to image region of interest

    • suboptimal viewing conditions: inadequate luminance of view boxes, extraneous view box light, high ambient room light

  • Tumor biology:

    • small tumor size

    • failure to incite desmoplastic reaction

    • (eg, invasive lobular carcinoma)

    • limitations of screen-film mammography in physically dense breasts

    • no associated microcalcifications

    • (approx. 50% of cancers)

    • developing soft-tissue radiopacity

    • stability of mammographic findings

      • Malignant calcifications may be stable for up to 63 months

      • A mass may not change for up to 4.5 years

• Location of missed cancers:

  • retroglandular area (33%), lateral parenchyma (31%), central (18%), medial (13%), subareolar (4%)

Radiation-induced Breast Carcinoma

• Lifetime risk with cumulative carcinogenic effect related to age!

  • women age <35: 7.5 additional cancers per 1 million irradiated women per year per rad

  • women age >35: 3.5 additional cancers per 1 million irradiated women per year per rad

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Role of Breast Ultrasound

Indications:

• Ultrasound is no screening tool!

• TARGETED EXAM

  • Initial study of palpable lump in patient <30 years of age/pregnant/lactating

    • Ultrasound will not add useful information in an area that contains only fatty tissue on a mammogram!

  • Characterization of mammographic/palpable mass as fluid-filled/solid

    • Ultrasound will add useful information if there is water-density tissue in the area of palpable abnormality!

    • Differentiation of cystic from solid lesion is the principal role of ultrasound!

  • additional evaluation of nonpalpable abnormality with uncertain mammographic diagnosis

  • search for focal lesion as cause for mammographic asymmetric density

  • confirmation of lesion seen in one mammographic projection only

• WHOLE-BREAST EXAM

  • Breast secretions

  • Suspected leaks from silicone implant

  • Follow-up of multiple known mammographic/sonographic lesions

  • Radiographically dense breast with strong family history of breast cancer

  • Metastases thought to be of breast origin, but with negative clinical + mammographic exam

  • Mammography not possible: radiophobic patient, bedridden patient, after mastectomy

• interventional PROCEDURE

  • Ultrasound-guided cyst aspiration

  • Ultrasound-guided core biopsy

  • Ultrasound-guided ductography, if

    • secretions cannot be expressed

    • duct cannot be cannulated

Accuracy:

98% accuracy for cysts; 99% accuracy for solid masses; small carcinomas have the least characteristic features

Role of Breast MRI

Indications:

• young patient with positive BCRCA screen

• dense breast + high-risk lesion of LCIS

• palpable mass + negative mammo- + sonogram

• axillary node malignancy + negative mammogram

• planning for biopsy to determine scar versus tumor

• staging:

  • tumor size: MRI more accurate in estimate of tumor size than mammography/ultrasound

  • detection of extensive intraductal component: MRI superior to mammography

  • multifocality (25 50%):

    • in 70% detected by MRI only

  • multicentricity(15 30%):

    • in 50% detected by MRI only

  • bilaterality (5%):

    • in 75% detected by MRI only

  • before + after 2nd cycle of neoadjuvant chemotherapy to separate responders from nonresponders

  • chest wall invasion

• status post lumpectomy with positive margins

• status post mastectomy + breast reconstruction with implant (yearly screening)

• implant imaging

• repeated indeterminate mammogram

Sensitivity:

72 93 100%

• A normal MR mammogram

  • correctly rules out malignancy in >96%

  • means no invasive cancer >3 mm

  • means no further exam for 2 years (for 1 year if BRCA positive)

  • may miss: DCIS, LCIS, lobular cancer, tubular cancer

Timing of MR:

7 20 days after beginning of cycle; 6 months after open biopsy; 12 months after radiation therapy

MR:

• Malignant morphology always trumps kinetics!

• reduced signal on T2WI

• irregular morphology

• lymphangitic bridges/streaks

• contrast enhancement:

  • rapid increase in signal intensity after contrast injection = rapid wash-in

    • 90/90 rule = cancers show an SI increase of >90% in the first 90 seconds!

  • markedly higher amplitude than normal parenchymal tissue

  • plateau/fast wash-out in postinitial phase

  • arterial feeder sign

  • intense early rim/peripheral enhancement ( central necrosis)

  • centripetal progression of enhancement

  • malignant mass margination

Slowly/Nonenhancing Breast Cancer on MRI

• Lobular carcinoma

• Tubular carcinoma

• Mucinous carcinoma

• Grade I invasive ductal carcinoma

Indication for Screening Breast Mri (if score > 2.0)

History	Score
BRCA 1 or	2 2.0
Personal history of breast/ovarian cancer	2.0
Breast cancer in mother <60 years	1.0
Breast cancer in sibling <60 years	0.5
Menstruation >35 years	0.5
Nulliparous	0.5
First pregnancy >30 years	0.5
Breast cancer in first-degree relative (nonsibling)	0.5
Ashkenazi Jew	0.5
Dense breast	0.5

P.565

BI-RADS Score for Breast MRI

	Descriptor	Score
Major feature
	Peak enhancement in 90-seconds	2.0
	Centripetal wash-in	2.0
	Spiculated lesion	2.0
	Rapid wash-out	2.0
	T2 isointense mass	1.0
	Initial contrast uptake >100%	1.0
Minor feature
	Perilesional edema (T2/STIR)	1.0
	Branching lesion	1.0
	Dendritic configuration adjacent to primary	1.0
	Heterogeneous lesion on T2	1.0
	Size of lesion >10 mm	0.5
	Lobulated margins of lesion	0.5
Interpretation
	Compatible with malignancy	>7
	Probably malignant	>5
	Indeterminate	3 5
	Probably benign	<3
	Compatible with benignity	<1

Role of Stereotactic Biopsy

Indications:	obviously malignant nonpalpable lesion, indeterminate likely benign lesion, anxiety over lesion
Targets:	well-defined solid mass, indistinct/spiculated mass, clustered microcalcifications
Advantage:	single-stage surgical procedure
Problematic:	3 5-mm small lesion, fine scattered microcalcifications, indistinct density, area of architectural distortion

Excision:

• radial scar suspected (in up to 28% associated with tubular carcinoma), lesion close to chest wall, lesion in axillary tail, very superficial lesion, atypia/atypical hyperplasia (in 49 61% associated with malignancy), carcinoma in situ (in 9 20% associated with invasion), branching microcalcifications suggestive of DCIS with comedo necrosis

Sensitivity:	85 99% with core needle biopsy (100% specific), 68 93% with fine-needle aspiration (88 100% specific)
Miss rate:	3 8% for stereotactic biopsy, 3% for surgery

Breast Cyst

Incidence:	most common single cause of breast lumps between 35 and 55 years of age
Age:	any; most common in later reproductive years + around menopause
Histo:	cyst wall lined by single layer of (a) flattened epithelial cells; cyst fluid with Na+/ K+ ratio 3 (b) epithelial cells with apocrine metaplasia (secretory function); cyst fluid with Na+/K+ ratio <3
Cause:	fluid cannot be absorbed due to obstruction of extralobular terminal duct by fibrosis/intraductal epithelial proliferation

• size changes over time

Simple Breast Cyst

• well-defined flattened oval/round (if under pressure) mammographic mass + surrounding halo (DDx: well-defined solid mass)

• solitary/multiple

• needle aspiration of fluid (proof) + postaspiration mammogram as new baseline

• US (98 100% accuracy):

  • Correlate with palpation/mammogram as to size, shape, location, surrounding tissue density!

  • spherical/ovoid lesion with anechoic center

  • well-circumscribed thin echogenic capsule

  • posterior acoustic enhancement (may be difficult to demonstrate in small/deeply situated cysts)

  • thin edge shadows

  • occasionally multilocular thin septations/cluster of cysts

• MR:

  • T1WI:

    • well-circumscribed hypointense lesion without discernible cyst wall; well seen within adipose parenchyma; poorly seen in normal parenchyma

  • enhanced T1WI:

    • no change in signal intensity; improved demarcation due to enhancement of surrounding parenchyma

  • T2WI:

    • well-circumscribed hyperintense lesion with homogeneous internal texture (detectable at a diameter of ~ 2 mm)

Pneumocystogram (for symptomatic cysts)

• air remains mammographically detectable for up to 3 weeks

• therapeutic effect of air insufflation (equal to 60 70% of aspirated fluid volume): no cyst recurrence in 85 94% (40 45% cyst recurrence without air insufflation)

Complex/Complicated Breast Cyst

• = any cyst that does not meet criteria of simple cyst

Cause:

fibrocystic changes (vast majority), infection, malignancy (extremely rare)
0.3% of all breast cancers are intracystic

• Patients with apocrine cysts are at greater risk to develop breast cancer!

• uniformly thick wall + tenderness = inflammation/infection

• diffuse low-level internal echoes (= foam cyst):

  • with mobility upon increase in power output

    • = subcellular material like protein globs, floating cholesterol crystals, cellular debris

  • without mobility upon increase in power output = cells like foamy macrophages, apocrine metaplasia, epithelial cells, pus, blood

• fluid-debris level

  Rx:

  aspiration to rule out blood/pus

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  Benign Disease of the Terminal Ductal Lobular Unit

• thick septation/eccentric wall thickening

  • further characterized by protruding ill-defined outer margin, convex microlobulated inner margin ( mural nodule ), nonmobile mass with coarse heterogeneous echotexture, CD flow within thickening

  Rx:

  treated like solid nodule

• spongelike cluster of microcysts

  Rx:

  treated like solid nodule

• MR:

  • T1WI:

    • hyper-/isointense cyst content (hemorrhage) sign of sedimentation

  • enhanced T1WI:

    • thick ring-enhancing cyst wall (inflammation)

    • slight contrast uptake in surrounding tissue (= reactive hyperemia)

Rx:	complete aspiration (assures benign cause), core needle biopsy (if partially/nonaspiratable)
DDx:	artifactual scatter in superficial/deep small cysts, fibroadenoma, papilloma, carcinoma

Cyst Aspiration

• inspection of cyst fluid:

  • normal: turbid greenish/grayish/black fluid

  • abnormal: straw-colored clear fluid/dark blood

• needle moves within nonaspiratable complex cyst

• fluid without blood should be discarded

• bloody fluid should be examined cytologically

Carcinoma Of Male Breast

Incidence:

0.2%; 1,400 new cases/year with 300 deaths
3.7% of male breast carcinomas occur in men with Klinefelter syndrome!

Peak age:	60 69 years
At risk:	(males with increased estrogen levels)

• Klinefelter syndrome (20-fold risk over normals):

  • XXY chromosomes

• Liver disease: cirrhosis, schistosomiasis, malnutrition

• Radiation therapy to chest (latent period of 12 35 years)

• Occupational heat exposure (diminished testicular function)

• Testicular atrophy: injury, mumps orchitis, undescended testes

• Jewish background

• Family history in male/female (in up to 30%)

• Gynecomastia is NOT a risk factor!

Histo:

same as in females; infiltrating ductal carcinoma (majority); invasive lobular carcinoma distinctly uncommon (tubular structures usually not found in male breast)

• firm painless retroareolar/upper-outer-quadrant mass

• breast swelling, bloody nipple discharge, retraction

Location:

L > R breast; bilaterality is uncommon

• resembles scirrhous carcinoma of female breast

• usually located eccentrically

• calcifications fewer + more scattered + more round + larger

• enlarged axillary nodes (in 50% at time of presentation)

• metastases to pleura, lung, bone, liver

Delay in diagnosis from onset of symptoms:	6 18 months
Rx:	surgery, hormonal manipulation (85% estrogen receptor and 75% progesterone receptor positive)
Prognosis:	5-year survival rate for stage 1 = 82 100%, for stage 2 = 44 77%, for stage 3 = 16 45%, for stage 4 = 4 8% (same as for women!)
DDx:	breast abscess, gynecomastia, epidermal inclusion cyst

Chronic Abscess of Breast

• COLD ABSCESS usually seen in lactating women

• fever, pain, increased WBC (clinical diagnosis)

• rapid response to antibiotics

Location:

most commonly in central/subareolar area

• ill-defined mass of increased density with flamelike contour

• secondary changes common: architectural distortion, nipple + areolar retraction, lymphedema, skin thickening, pathologic axillary nodes

• liquefied center can be aspirated

• US:

  • anechoic/nearly anechoic area with posterior enhancement

• MR:

  • T1WI:

    • hyperintense round/ovoid lesion (high protein content)

  • enhanced T1WI:

    • no contrast uptake centrally

    • strong enhancement of abscess wall

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  • T2WI:

    • hyperintense round/oval lesion

DDx:

seroma

Phyllodes tumor

Incidence:

1: 6,300 examinations; 0.3 1.5% of all breast tumors; 3% of all fibroadenomas

Age:	5th-6th decade (mean age of 45 years, occasionally in women >20 years of age
Histo:	similar to fibroadenoma but with increased cellularity + pleomorphism (wide variations in size, shape, differentiation) of its stromal elements; fibroepithelial tumor with leaflike (phylloides) growth pattern = branching projections of tissue into cystic cavities; cavernous structures contain mucus; cystic degeneration + hemorrhage

• sense of fullness

• rapidly enlarging breast mass; periods of remission

• huge, firm, mobile, discrete, lobulated, smooth mass

• thinning + livid discoloration of skin, wide veins, shining skin

• large homogeneous noncalcified mass with smooth

• polylobulated margins mimicking fibroadenoma

• rapid growth to large size (>6 10 cm), may fill entire breast

• occasional halo sign (due to compression of surrounding tissue)

US:

• round/lobulated tumor with well-demarcated border

• posterior acoustic shadow

• fluid-filled clefts in large tumors

• MR:

  • T1WI:

    • hypo-/isointense to parenchyma

    • hypointense regions of cystic/necrotic changes (occasionally)

  • enhanced T1WI:

    • strong initial uptake in solid tumor component

    • continuous increase/plateau in postinitial phase

    • increasing demarcation of nonenhancing cystic components (mass-in-mass morphology)

  • T2WI:

    • iso - to hyperintense to parenchyma

    • hyperintense regions of cystic/necrotic changes (occasionally)

DDx:

fibroadenoma

Benign Phyllodes tumor

• = FIBROADENOMA PHYLLODES = GIANT FIBROADENOMA

• = benign giant form of intracanalicular fibroadenoma

Histo:	low mitotic activity (0 4 mitoses/10 HPF)
Cx:	in 5 10% degeneration into malignant fibrous histiocytoma/fibrosarcoma/liposarcoma/chondrosarcoma/osteosarcoma with local invasion + hematogenous metastases to lung, pleura, bone (axillary metastases quite rare)
Prognosis:	15 20% recurrence rate if not completely excised

Malignant Phyllodes Tumor

• = CYSTOSARCOMA PHYLLODES = ADENOSARCOMA

Histo:	high mitotic activity (>5 mitoses/10 HPF) in a predominantly sarcomatous differentiation
Prognosis:	hematogenous spread in 20%

Dermatopathic Lymphadenopathy

• = benign reactive lymphadenopathy within breast associated with cutaneous rashes

Cause:	exfoliative dermatitis, erythroderma, psoriasis, atopic dermatitis, skin infection)
Histo:	follicular pattern retained, germinal centers enlarged, enlarged paracortical area with pale-staining cells (lymphocytes, Langerhans cells, interdigitating reticulum cells)

• mobile nontender firm subcutaneous nodules

Location:	often bilateral
Site:	predominantly upper outer quadrant

• regional subcentimeter masses with central/peripheral radiolucent notches

Epidermal Inclusion Cyst

• = benign cutaneous/subcutaneous lesion

Cause:	congenital, metaplasia, trauma (needle biopsy, reduction mammoplasty), obstructed hair follicle
Path:	cyst filled with keratin
Histo:	stratified squamous epithelium

• smooth round nodule attached to skin with blackened pore, movable against underlying tissue

• circumscribed round/oval iso-/high-density mass of 0.8 10.0 cm in diameter

• may contain heterogeneous microcalcifications

• US:

  • circumscribed hypoechoic solid mass extending into dermis

DDx:

sebaceous cyst (epithelial cysts containing sebaceous glands)

Fat Necrosis of Breast

• = TRAUMATIC LIPID CYST = OIL CYST

• = aseptic saponification of fat by tissue lipase after local destruction of fat cells with release of lipids + hemorrhage + fibrotic proliferation

Etiology:	direct external trauma (seat belt injury), breast biopsy, reduction mammoplasty, implant removal, breast reconstruction, irradiation, nodular panniculitis (Weber-Christian disease), ductal ectasia of chronic mastitis, foreign body reaction (silicone, paraffin)
Incidence:	0.5% of breast biopsies
At risk:	middle-aged obese women with fatty pendulous breasts
Histo:	cavity with oily material surrounded by foam cells (= lipid-laden macrophages)

• history of trauma in 40% (eg, prior surgery, radiation >6 months ago, reduction mammoplasty, lumpectomy)

• usually clinically occult

• firm, slightly fixed tender/painless mass

• skin retraction (50%)

• yellowish fatty fluid on aspiration

Location:

anywhere; more common in superficial periareolar region; near biopsy site/surgical scar

• early: ill-defined irregular spiculated dense mass (indistinguishable from carcinoma if associated with distortion, skin thickening, retraction)

• later:well-circumscribed mass with translucent areas at center (= homogeneous fat density of oil cyst) surrounded by thin pseudocapsule (in old lesions)

P.568




• calcifies in 4 7% (= liponecrosis macrocystica calcificans):

  • occasionally curvilinear/eggshell calcification in wall

• fine spicules of low density vary with projection

• localized skin thickening/retraction possible

US:

• hypo-/anechoic mass with ill-/well-defined margins acoustic shadowing

• complex cyst with mural nodules/echogenic bands

MR:

• T1WI:

  • signal intensity equal to parenchyma

  • round lesion with hyperintense fat signal (oil cyst)

  • signal loss with macrocalcifications

• enhanced T1WI:

  • localized ill-defined area of moderate enhancement + continuous postinitial increase (granulation tissue) within 6 months after trauma

  • no enhancement in late lesion/oil cyst

• T2WI:

  • ill-defined hyperintense area (reactive edema of fresh lesion)

  • round lesion with central signal intensity of fat (in oil cyst)

Weber-Christian Disease

• = nonsuppurative panniculitis with recurrent bouts of inflammation = areas of fat necrosis, involving subcutaneous fat + fat within internal organs

• accompanied by fever + nodules over trunk and limbs

Fibroadenoma

• = ADULT-TYPE FIBROADENOMA

• = estrogen-induced benign tumor originating from TDLU; forms during adolescence; pregnancy + lactation are growth stimulants; regression after menopause (mucoid degeneration, hyalinization, involution of epithelial components, calcification)

Incidence:	3rd most common type of breast lesion after fibrocystic disease + carcinoma; most common benign solid tumor in women of childbearing age (~10%)
Age:	mean age of 30 years (range 13 80 years); median age 25 years; most common breast tumor under age 25 years

Hormonal influence:

• slight enlargement at end of menstrual cycle + during pregnancy; regresses after menopause; may occur in postmenopausal women receiving estrogen replacement therapy

Histo:

mixture of proliferated fibrous stroma + epithelial ductal structures
(a) intracanalicular fibroadenoma compressing ducts
(b) pericanalicular fibroadenoma without duct compression
(c) combination
Cellular FA = predominantly epithelial elements in younger women
Fibrous FA = predominantly fibrotic elements in older women

• firm, smooth, sometimes lobulated, freely movable mass

• in 35% not palpable

• NO skin fixation

• rarely tender/painful

• clinical size = radiographic size

Size:	1 5 cm (in 60%)
Location:	multifocal in 15 25%; bilateral in 4%

• circular/oval-shaped lesion of low density

• nodular/lobulated contour when larger (areas with different growth rates)

• smooth, discrete margins (indistinguishable from cysts when small)

• often with halo sign

• smoothly contoured calcifications of high + fairly equal density in 3% due to necrosis from regressive changes in older patients:

  • peripheral subcapsular myxoid degeneration

    • peripheral marginal ringlike calcifications

  • central myxoid degeneration

    • popcorn type of calcification (PATHOGNOMONIC)

  • calcifications within ductal elements

    • pleomorphic linear branching pattern

  • Calcifications enlarge as soft-tissue component regresses!

US:

• round (3%)/oval mass (96%) with length-to-depth ratio of >1.4 (in carcinomas usually <1.4)

• hypoechoic similar to fat lobules (80 96%)/hyperechoic/mixed pattern/anechoic/isoechoic compared with adjacent fibroglandular tissue

• homogeneous (48 89%)/inhomogeneous (12 52%) texture

• regular (57%)/lobulated (15 31%)/irregular (6 58%) contour

• hump and dip sign = small focal contour bulge immediately contiguous with a small sulcus (57%)

• intratumoral bright echoes (10%) = macrocalcifications

• posterior acoustic enhancement (17 25%)/acoustic shadow without calcifications (9 11%)

• echogenic halo (capsule) with lateral shadowing

• slight compressibility of tumor

MR:

• T1WI:

  • iso-/mildly hypointense compared to parenchyma

  • more obvious in fatty tissue

  • endotumoral signal loss due to macrocalcifications

• enhanced T1WI:

  • very strong enhancement (with proportionately larger epithelial component)

  • postinitial continuous increase/plateau

  • endotumoral septa with mild contrast uptake

• T2WI:

  • high signal intensity (for tumor with proportionately larger epithelial component)

  • occasionally endotumoral septations (caused by fibrotic component)

  • iso-/slightly hypointense compared to breast parenchyma (for predominantly fibrotic tumor)

DDx:

adenosis tumor/florid adenosis

Juvenile/Giant/Cellular Fibroadenoma

• = fibroadenoma >5 cm in diameter/weighing >500 g

Cause:	hyperplasia + distortion of normal breast lobules secondary to hormonal imbalances between estradiol + progesterone levels
Age:	any (mostly in adolescent girls)
Histo:	more glandular + more stromal cellularity than adult type of fibroadenoma; ductal epithelial hyperplasia

P.569

• rapidly enlarging well-circumscribed nontender mass

• dilated superficial veins, stretched skin

• discrete mass with rounded borders

MR:

• T1WI:

  • iso- to slightly hypointense round/oval mass difficult to separate from normal breast parenchyma

• enhanced T1WI:

  • strong enhancement with sharp demarcation from surrounding tissue + endotumoral septations

• T2WI:

  • typically hyperintense

DDx:

medullary/mucinous/papillary carcinoma/carcinoma within fibroadenoma

Fibrocystic Changes

• MAZOPLASIA = MASTITIS FIBROSA CYSTICA = CHRONIC CYSTIC MASTITIS = CYSTIC DISEASE = GENERALIZED BREAST HYPERPLASIA = DESQUAMATED EPITHELIAL HYPERPLASIA = fibroadenomatosis = MAMMARY DYSPLASIA = Schimmelbusch DISEASE = FIBROUS MASTITIS = MAMMARY PROLIFERATIVE DISEASE

• Not a disease since found in 72% of screening population >55 years of age

• The College of American Pathologists suggests use of the term fibrocystic changes/condition in mammography reports!

Incidence:	most common diffuse breast disorder; in 51% of 3,000 autopsies
Age:	35 55 years
Etiology:	exaggeration of normal cyclical proliferation + involution of the breast with production + incomplete absorption of fluid by apocrine cells due to hormonal imbalance

• asymptomatic in macrocystic disease

• fullness, tenderness, pain in microcystic disease

• palpable nodules + thickening

• symptoms occur with ovulation; regression with pregnancy + menopause

Histo:

• overgrowth of fibrous connective tissue = stromal fibrosis, fibroadenoma

• cystic dilatation of ducts + cyst formation (in 100% microscopic, in 20% macroscopic)

• hyperplasia of ducts + lobules + acini = adenosis; ductal papillomatosis

• individual round/ovoid cysts with discrete smooth margins

• lobulated multilocular cyst

• enlarged nodular pattern (= fluid-distended lobules + extensive extralobular fibrous connective tissue overgrowth)

• teacup-like curvilinear thin calcifications with horizontal beam + low-density round calcifications in craniocaudal projection = milk of calcium (4%)

• oyster pearl like /psammoma-like calcifications

• involutional type calcifications = very fine punctate calcifications evenly distributed within one/more lobes against a fatty background (from mild degree of hyperplasia in subsequently atrophied glandular tissue)

US:

• ductal pattern, ductectasia, cysts, ill-defined focal lesions

MR:

• T1WI:

  • hypointense compared to intramammary adipose tissue

  • interspersed hypointense cysts of varying sizes

• enhanced T1WI:

  • patchy to diffuse increased enhancement (correlating with degree of adenosis)

    • Avoid scheduling patient during 1st and 4th week of menstrual cycle/under HRT

  • continuous rise after postinitial phase

• T2WI:

  • occasionally diffusely increased signal intensity (in 2nd half of menstrual cycle/under HRT)

  • interspersed hyperintense cysts of varying sizes

Risk for invasive breast carcinoma:

• NO INCREASED RISK (70%)

  • Nonproliferative lesions: adenosis, florid adenosis, apocrine metaplasia without atypia, macro-/microcysts, duct ectasia, fibrosis, mild hyperplasia (more than 2 but not more than 4 epithelial cells deep), mastitis, periductal mastitis, squamous metaplasia

  • Fibroadenoma

• SLIGHTLY INCREASED RISK (1.5 2 times):

  • Moderate + florid solid/papillary hyperplasia

  • Papilloma with fibrovascular core

  • Sclerosing adenosis

• MODERATELY INCREASED RISK (5 times):

  • Ductal/lobular atypical hyperplasia (borderline lesion with some features of carcinoma in situ)

• HIGH RISK (8 11 times):

  • Atypical hyperplasia + family history of breast cancer

  • Ductal/lobular carcinoma in situ

Adenosis

Age:	all
Path:	lobulocentric lesion derived from TDLU with distortion and effacement of underlying lobules
Histo:	epithelial and myoepithelial proliferation of ductules + lobules with nuclear pleomorphism + increase in cell size

• increase in size of TDLUs to 3 7 mm

• snowflake pattern of widespread ill-defined nodular densities

• often round intralobular microcalcifications/milk of calcium (less common + less extensive than in sclerosing adenosis)

US:

• adenosis lobules are sonographically iso- to mildly hypoechoic compared with fat

MR:

• no abnormalities on T1WI/T2WI

• usually strong, occasionally branching contrast uptake in focal areas of adenosis

DDx:

malignancy

Sclerosing Adenosis

Path:	myoepithelial proliferation + reactive stromal fibrosis
Histo:	stromal sclerosis involving >50% of all TDLUs, which become elongated + distorted + compressed by sclerosis
DDx:	tubular carcinoma (absence of basement membrane + myoepithelial cells); radial scar (more extensive fibrosis + central fibrocollagenous scar)

P.570

• palpable mass (rare) = adenosis tumor

Rarely associated with:

lobular carcinoma in situ > ductal carcinoma in situ

• Sclerosing adenosis is not a risk factor/precursor of breast cancer

• calcifications in 50%

  • focal form

    • focal cluster of microcalcifications

    • focally dense breast appearing as a nodule/spiculated lesion

  • diffuse form

    • adenosis + diffusely scattered calcifications (calcifications in cystically dilated acinar structure)

    • diffusely dense breast

DDx:

other spiculated lesions

Adenosis Tumor = Florid Adenosis

Average age:	30 years
Histo:	focal proliferation of ductules and lobular glands with hyperplasia of epithelial + myoepithelial cells

• firm clinically discrete/ill-defined mass

• nodular mass usually <2 cm in diameter

• microcalcifications

DDx:

fibroadenoma

Fibrosis

• round/oval clustered microcalcifications with smooth contours + associated fine granular calcifications filling lobules

Atypical Lobular Hyperplasia

• = proliferation of round cells of LCIS type growing along terminal ducts in permeative fashion (pagetoid growth) between benign epithelium + basal myoepithelium BUT NOT completely obliterating terminal ductal lumina/distending lobules (as in lobular carcinoma in situ)

• no mammographic correlate

Atypical Ductal Hyperplasia

• = low-grade intraductal proliferation with partial/incompletely developed features of noncomedo DCIS

• frequent calcifications

Classification of Fibrocystic Changes

Grade	Frequency	Histological Category	Breast Cancer Risk
I	70%	Nonproliferative lesion	0
II	25%	Proliferative lesion without atypia	2x
III	5%	Proliferative lesion with atypia	4 5x

Intraductal Papillomatosis

= hyperplastic polypoid lesions within a duct

Age:

perimenopausal

• spontaneous bloody/serous/serosanguinous nipple discharge (most common cause of nipple discharge)

• small retroareolar opacity (= dilated duct) extending 2 3 cm into breast

• intraluminal filling defect on galactography

Fibrous Nodule Of The Breast

= FIBROUS DISEASE OF THE BREAST = FIBROUS DISEASE = FIBROSIS OF THE BREAST = FIBROUS MASTOPATHY = FIBROUS TUMOR OF THE BREAST

Frequency:	3 4% of benign masses; 8% of surgical breast specimens
Histo:	focally dense collagenous stroma surrounding atrophic epithelium; NONSPECIFIC
Age:	20 50 years; only 8% postmenopausal

• palpable/nonpalpable mass: edge merges into surrounding dense tissue

Location:

unilateral (80 85%)/bilateral (15 20%)

• circumscribed (55%)/indistinct (32%) margin

• suggestive of malignancy (11%): irregular shape, spiculated margin, posterior acoustic shadowing

DDx:

fibroadenoma, malignancy

Galactocele

= retention of fatty material in areas of cystic duct dilatation appearing during/shortly after lactation

Cause:	? abrupt suppression of lactation/obstructed milk duct
Age:	occurs during/shortly after lactation

• thick inspissated milky fluid (colostrum)

Location:

retroareolar area

• large radiopaque lesion of water density (1st phase)

• smaller lesion of mixed density + fat-water level with horizontal beam (2nd phase)

• small radiolucent lesion resembling lipoma

• fluid-calcium level

• US:

• complex mass

Dx:

aspiration of milky fluid

Granular Cell Tumor

• = GRANULAR CELL MYOBLASTOMA (1926)

• = benign tumor, occasionally locally invasive + metastasizing

Origin:	Schwann cell (positive for S-100 marker protein)
Prevalence:	1:1,000 primary breast carcinomas
Age:	20 59 (mean 34) years; 76% for African-Americans
Histo:	rounded groups of large polygonal cells with small dark regular nuclei + abundant eosinophilic granular cytoplasm; immunoreactive to S-100 protein
DDx:	carcinoma, lymphoma, metastasis Fine-needle aspirate may be difficult to interpret!
Location:	tongue (most common), oropharynx, GI tract, skin, bronchial wall, subcutaneous tissue (6 8%), biliary tract (1%)
Site:	more commonly other than upper outer quadrant

• asymmetric lump with slow growth, hardness, skin fixation/retraction, ulceration

• often fixed to pectoralis fascia

• well-circumscribed spiculated mass 1 3 cm in diameter

P.571

Gynecomastia

• benign, usually reversible excessive development of the male breast

• NOT a risk factor for development of breast cancer!

Cause:

• Hormonal

  • Cause: excess estrogens or decreased androgens

  • neonate: influence from maternal estrogens crossing placenta

  • puberty: high estradiol levels

    Incidence:	in up to 60 75% of healthy boys
    Age:	1 year after onset of puberty (13 14 years)
    Prognosis:	subsides within 1 2 years

  • senescence: decline in serum testosterone levels

  • hypogonadism (Klinefelter syndrome, anorchism, acquired testicular failure (eg, testicular neoplasm)

  • tumors: adrenal carcinoma, pituitary adenoma, testicular tumor, hyperthyroidism

• Systemic disorders

  • advanced alcoholic cirrhosis, hemodialysis in chronic renal failure, chronic pulmonary disease (emphysema, TB), malnutrition

• Drug-induced

  • anabolic steroids, estrogen treatment for prostate cancer, digitalis, cimetidine, thiazide, spironolactone, reserpine, isoniazid, ergotamine, marijuana

• Neoplasm: hepatoma (with estrogen production)

• Idiopathic

mnemonic:

CODES

• Cirrhosis

• Obesity

• Digitalis

• Estrogen

• Spironolactone

Incidence:	85% of all male breast masses
Age:	neonatal period, adolescent boys (40%), men >50 years (32%)
Histo:	increased number of ducts, proliferation of duct epithelium, periductal edema, fibroplastic stroma, adipose tissue

• palpable firm mass >2 cm in subareolar region

Location:

bilateral (63%), left-sided (27%), right-sided (10%)

• mild prominence of subareolar ducts in flame-shaped distribution (focal type)

• homogeneously dense breast (diffuse type)

• MR:

  • hypointense retromamillary area

  • no/slight contrast enhancement

DDx:

pseudogynecomastia (= fatty proliferation in obesity)

Hamartoma Of Breast

• FIBROADENOLIPOMA = LIPOFIBROADENOMA = ADENOLIPOMA

Incidence:	2 16:10,000 mammograms
Mean age:	45 (27 88) years
Histo:	normal/dysplastic mammary tissue composed of dense fibrous tissue + variable amount of fat, delineated from surrounding tissue without a true capsule

• soft, often nonpalpable (60%)

Location:

retroareolar (30%), upper outer quadrant (35%)

• round/ovoid well-circumscribed mass usually > 3 cm

• mixed density with mottled center (secondary to fat) = slice of sausage pattern

• thin smooth pseudocapsule (= thin layer of surrounding fibrous tissue)

• halo sign = peripheral radiolucent zone due to compression of surrounding tissue

• may contain calcifications

MR:

• T1WI:

  • well-circumscribed round/oval/lobulated lesion with pseudocapsular demarcation:

    • intermediate intensity for parenchymal component

    • high intensity for lipomatous component

    • low intensity for cystic component

• enhanced T1WI:

  • no/strong enhancement in parenchymal component with continuous postinitial increase (dependent on vascularization)

T2WI:

• intermediate intensity for parenchymal + lipomatous components

• high intensity for cystic component

DDx:

liposarcoma, Cowden disease

Hematoma Of Breast

Cause:

(1) surgery/biopsy (most common)
(2) blunt trauma
(3) coagulopathy (leukemia, thrombocytopenia)
(4) anticoagulant therapy

• well-defined ovoid mass (= hemorrhagic cyst)

• ill-defined mass with diffuse increased density (edema + hemorrhage)

• adjacent skin thickening/prominence of reticular structures

• regression within several weeks leaving (a) no trace, (b) architectural distortion, (c) incomplete resolution

• calcifications (occasionally)

US:

• hypoechoic mass with internal echoes

MR:

• T1WI:

  • homogeneous high signal sedimentation (fresh)

  • low signal intensity + peripheral ring of high signal (deoxyhemoglobin of subacute hematoma)

• enhanced T1WI:

  • no uptake within hematoma

  • moderate diffuse reactive enhancement surrounding hematoma + continuous postinitial increase

• T2WI:

  • homogeneous low signal intensity (fresh)

  • low signal intensity + peripheral ring of low signal intensity

P.572

Juvenile Papillomatosis

Path:	many aggregated cysts with interspersed dense stroma
Histo:	cysts lined by flat duct epithelium/epithelium with apocrine metaplasia, sclerosing adenosis, duct stasis; marked papillary hyperplasia of duct epithelium with often extreme atypia
Mean age:	23 years (range of 12 48 years)

• localized palpable tumor

• family history of breast cancer in 28% (affected first-degree relative in 8%; in one/more relatives in 28%)

Prognosis:	development of synchronous (4%)/metachronous (4%) breast cancer after 8 9 years.
DDx:	fibroadenoma

Lactating Adenoma

newly discovered painless mass during 3rd trimester of pregnancy/in lactating woman

Etiology:	? variant of fibroadenoma/tubular adenoma/lobular hyperplasia or de novo neoplasm
Path:	well-circumscribed yellow spherical mass with lobulated surface + rubbery firm texture and without capsule
Histo:	secretory lobules lined by granular and foamy to vacuolated cytoplasm + separated by delicate connective tissue

• firm freely movable painless mass

• homogeneously hypoechoic/isoechoic mass

• posterior acoustic enhancement (most)/shadowing

• fibrous septa

Prognosis:	regression after completion of breast feeding
DDx:	breast carcinoma (1:1,300 1:6,200 pregnancies)

Lipoma Of Breast

usually solitary asymptomatic slow-growing lesion

Incidence:	extremely rare
Histo:	encapsulated tumor containing mature fat cells
Mean age:	45 years + post menopause

• clinically often occult

• soft, freely movable, well delineated

• usually >2 cm

• radiolucent tumor easily seen in dense breast; almost invisible in fatty breast

• discrete thin radiopaque line (= capsule), seen in most of its circumference

• displacement of adjacent breast parenchyma

• calcification with fat necrosis (extremely rare)

US:

• hypo- or hyperechoic lesion

MR:

• T1WI:

  • well-circumscribed hyperintense lesion

  • thin hypointense capsule

  • no contrast enhancement

• T2WI:

  • signal intensity equivalent to subcutaneous fat

DDx:

fat lobule surrounded by trabeculae/suspensory ligaments

Lymphoma Of Breast

• Primary Lymphoma

  • = extranodal lymphoma of the breast without prior history of lymphoma/leukemia

    Prevalence:

    0.12 0.53% of all breast malignancies; 2.2% of all extranodal lymphomas

  • asymptomatic

• Secondary Lymphoma

  • One of the most common type of metastatic lesions in the breast!

  • fever, pain

Histo:	B-cell NHL (majority), Hodgkin disease, leukemia (CLL), plasmacytoma
Age:	50 60 years; M < F
Location:	right-sided predominance; 13% bilateral

• well/incompletely circumscribed round/oval lobulated mass/masses

• infiltrate with poorly defined borders

• NO calcifications/spiculations

• skin thickening + trabecular edema

• bilateral axillary adenopathy in 30 50%

US:

• oval/round homo-/heterogeneously hypoechoic mass/masses

• sharply defined/poorly defined borders

• posterior acoustic shadowing/enhancement

Prognosis:	3.4% 5-year disease-free survival for all stages; 50% remission rate with aggressive chemotherapy
Recurrence:	mostly in contralateral breast/other distant sites
DDx:	circumscribed breast carcinoma, fibroadenoma, phylloides tumor, metastatic disease

Pseudolymphoma

= lymphoreticular lesion as an overwhelming response to trauma

Mammary Duct Ectasia

• = PLASMA CELL MASTITIS = VARICOCELE TUMOR OF BREAST = MASTITIS OBLITERANS = COMEDOMASTITIS= PERIDUCTAL MASTITIS = SECRETORY DISEASE OF BREAST

• = rare aseptic inflammation of subareolar area

Pathogenesis (speculative):

• Stasis of intraductal secretion leads to duct dilatation + leakage of inspissated material into parenchyma giving rise to an aseptic chemical mastitis (periductal mastitis); the extravasated material is rich in fatty acids = nontraumatic fat necrosis

• Periductal inflammation causes damage to elastic lamina of duct wall resulting in duct dilatation

Histo:	ductal ectasia, heavily calcified ductal secretions; infiltration of plasma cells + giant cells + eosinophils
Mean age:	54 years

• often asymptomatic

• breast pain, nipple discharge, nipple retraction, mamillary fistula, subareolar breast mass

Location:

subareolar, often bilateral + symmetric; may be unilateral + focal

• dense triangular mass with apex toward nipple

• distended ducts connecting to nipple

• periphery blending with normal tissue

P.573




• multiple often bilateral dense round/oval calcifications with lucent center + polarity (= orientation toward nipple)

  • periductal

    • oval/elongated calcified ring around dilated ducts with very dense periphery (surrounding deposits of fibrosis + fat necrosis)

  • intraductal

    • fairly uniform linear, often needle-shaped calcifications of wide caliber, occasionally branching (within ducts/confined to duct walls)

• nipple retraction/skin thickening may occur

Sequelae:	cholesterol granuloma
DDx:	breast cancer

Mammoplasty

= COSMETIC BREAST SURGERY

Augmentation Mammoplasty

Most frequently performed plastic surgery in USA

Frequency:

150,000 procedures in 1993 (70% for cosmetic reasons, 30% for reconstruction); 1.8 million American women have breast implants (estimate)

Methods:

• Injection augmentation (no longer practiced): paraffin, silicone, fat from liposuction

  Cx:

  tissue necrosis resulting in dense, hard, tender breast masses; lymphadenopathy; infection; granuloma formation (= siliconoma)

• Implants (prepectoral/subpectoral)

  • spongelike masses of Ivalon, Etheron, Teflon

  • Silicone elastomer (silastic) smooth/textured shell containing silicone oil/saline: >100 varieties of dimethyl polysiloxane

    • single lumen of polymerized methyl polysiloxane with smooth/textured outer silicone shell/polyurethane coating

    • double lumen with inner core of silicone + outer chamber of saline

    • reverse double-lumen = inner saline-filled lumen surrounded by silicone-filled envelope

    • triple lumen

  • expandable implant intraluminal valves = saline injection into port with gradual tissue expansion for breast reconstruction

    Location:

    retroglandular/subpectoral

• Autogenous tissue transplantation

  • (for breast reconstruction) with musculocutaneous flaps: transverse rectus abdominis muscle (TRAM), latissimus dorsi, tensor fasciae latae, gluteus maximus

Mammographic technique for implants:

• Two standard views (CC and MLO views) for most posterior breast tissue

  • 22 83% of fibroglandular breast tissue obscured by implant depending on size of breast + location of implant + degree of capsular contraction on standard views!

  • The false-negative rate of mammography increases from 10 20% to 41% in patients with implants!

• Two Eklund (= implant displacement) views (CC and 90 LAT views) for compression views of anterior breast tissue = push-back view = breast tissue pulled anteriorly in front of implant while implant is pushed posteriorly + superiorly thus excluding most of the implant

MR technique for implants:

• Physical principle: resonant frequencies of water, fat (~220 Hz lower than water) and silicone (~100 Hz lower than fat) differ

• Most effective sequence: inversion recovery (IR), which suppresses fat

  • with additional suppression of water = pure depiction of silicone

  • with additional suppression of silicone = pure depiction of saline component

• Orientation: axial + sagittal (2 angulations mandatory)

Cx of silicone-gel-filled implant:

• Capsular fibrosis (100%)

  • = normal host response to wall off foreign body

  • low-intensity implant shell + fibrous capsule cannot be differentiated on MRI

  • physiologic fluid may occupy space between implant shell + fibrous capsule

  • radial folds (normal) = hypointense lines emanating from the fibrous capsule-shell junction as wrinkle

  • gently undulating circumferential contour (normal)

• Contracture (12 20%): more frequent with retroglandular implants; increasing with time

  • distortion of breast contour

  • hardening of breast

  • tightness, pain

  • crenulated contour (US helpful)

  • capsular calcifications at periphery of prosthesis

  • focal bulge = herniation of a locally weakened fibrous capsule

  • fibrous capsule delineated by US (unleaked silicone is echolucent)

  • extensive periprosthetic calcifications

  • MR (low specificity):

    • rounded implants with transverse diameter < 2x the anteroposterior diameter

    • marked thickening of fibrous capsule

    • signal-free periprosthetic zone of macrocalcifications

    • complete absence of radial folds

    • contrast enhancement from granulomatous inflammation

    Rx:

    not health hazard; capsulotomy (release); capsulectomy (removal of scar tissue)

• Implant migration

  Cause:

  overdistension of implant pocket at surgery

• Rupture of prosthesis

  • = hole/tear in implant shell observed at surgery

  Frequency:	0.2 6.0%
  Prevalence:	>50% after 12 years
  Intact implant:	89% after 5 years, 51% after 12 years, 5% after 20 years
  Result:	total/partial/no collapse of shell

  P.574

  
  

  • change in contour/location of implant

  • flattening of implant

  • breast pain

• Gel bleed = silicone leaching (100% = normal condition as all implants bleed)

  • = leakage of microscopic quantities of silicone oil through semiporous but intact barrier shell made of silicone elastomer

  • silicone-equivalent signal within keyhole-shaped terminal bend of radial folds + between capsule and implant shell

  Dx:

  microscope

• Infection/hematoma formation

• Localized pain/paresthesia

Intracapsular Rupture

= broken implant casing, which swims within silicone gel contained by intact fibrous capsule

Incidence:

80 90% of all ruptures

• Mammo (11 23% sensitive, 89 98% specific):

  • bulging/peaking of implant contour (DDx: herniation through locally weakened capsule)

• US (59 70% sensitive, 57 92% specific, 49% accurate):

  • stepladder sign = series of parallel horizontal echogenic straight/curvilinear lines inside implant (= collapsed implant shell floating within silicone gel)

  • heterogeneous aggregates of low- to medium-level echogenicity (65% sensitive, 57% specific)

N.B.:

visualization of internal lumen within anechoic space in double-lumen implants can be confused on US with intracapsular rupture

MR (81 94% sensitive, 93 97% specific, 84% accurate):

• multiple curvilinear low signal-intensity lines often parallel to fibrous capsule (corresponding to collapsed prosthesis shell inside the silicone-filled fibrous capsule):

  • linguine sign = multiple hypointense wavy lines within implant (= pieces of free-floating collapsed envelope), 100% PPV

  • in incomplete rupture inverted teardrop / noose / keyhole / lariat (= lasso) sign = loop-shaped hypointense structure contiguous with implant envelope (= small focal invagination/fold of shell with silicone on either side)

  DDx:

  radial fold (extending from periphery perpendicular to surface directed toward center of implant)

• water droplet sign = salad-oil sign = appearance of multiple droplets of fluid of extracapsular origin/saline-containing envelope within lumen of silicone implant (DDx: 1 2 droplets may be normal; after injection of saline/Betadine/antibiotics/steroids)

Extracapsular Rupture

= extrusion + migration of silicone droplets through tear in both implant shell + fibrous capsule

Incidence:

up to 20% of all ruptures

• palpable breast masses

US:

• snowstorm / echogenic noise pattern = markedly hyperechoic nodule with well-defined anterior + indistinct echogenic noise posteriorly (= free silicone droplets mixed with breast tissue)

• highly echogenic area with acoustic shadowing

• hypoechoic masses almost indistinguishable from cysts + usually surrounded by echogenic noise (= large to medium-sized collections of free silicone) with low-level internal echoes

MR:

• discrete hypointense foci on fat-suppressed T1WI + hyperintense signal on water-suppressed T2WI in continuity with/separate from implant

• linguine sign = sign of associated intracapsular rupture

Mammography:

• lobular/spherical dense area of opacities adjacent to/separate from silicone implant

• rim calcifications

Extracapsular Spread of Silicone

Source:

gel bleed, implant rupture (11 23%) more common with thinner shell + older implants

• silicone lymphadenopathy

• paresthesia of arm (from nerve impingement secondary to fibrosis surrounding silicone migrated to axilla/brachial plexus)

• silicone nipple discharge (rare)

• migration to arm (+ constrictive neuropathy of radial nerve), subcutaneous tissue of lower abdominal wall, inguinal canal

• migration to ipsilateral chest wall + axillary nodes

• silicone droplets in breast in 11 23% (97% specific, 5% sensitive)

• granuloma formation (siliconoma) + fibrosis

  • = collection of silicone within breast parenchyma surrounded by a foreign-body granulomatous reaction

Reduction Mammoplasty

• swirled architectural distortion (in inferior breast best seen on mediolateral view)

• postsurgical distortion

• residual isolated islands of breast tissue

• fat necrosis

• dystrophic calcifications

• asymmetric tissue oriented in nonanatomic distribution

Mastitis

Acute Mastitis

= infection of the breast with primary ascending canalicular + secondary interstitial spread

Age:

any

• tender swollen red breast (DDx: inflammatory carcinoma)

• enlarged painful axillary lymph nodes

• febrile, elevated ESR, leukocytosis

• diffuse increased density

• diffuse skin thickening

• swelling of breast

P.575




• enlarged axillary lymph nodes

• rapid resolution under antibiotic therapy

MR:

• T1WI:

  • circumscribed area of low signal intensity

  • strong initial enhancement + postinitial plateau

Cx:

abscess, fistula

Puerperal Mastitis

• = LACTATIONAL MASTITIS

• = usually interstitial infection during lactational period

  • through infected nipple cracks

  • hematogenous

  • ascending via ducts = galactophoritis

Organism:	Staphylococcus, Streptococcus
Rx:	incision + drainage

Nonpuerperal Mastitis

• Infected cyst

• Purulent mastitis with abscess formation

• Plasma cell mastitis

• Nonspecific mastitis

Granulomatous Mastitis

• Foreign-body granuloma

• Specific disease (TB, sarcoidosis, leprosy, syphilis, actinomycosis, typhus)

• Parasitic disease (hydatid disease, cysticercosis, filariasis, schistosomiasis)

Metastasis to Breast

Incidence:	<1%
Mean age:	43 years

• Intramammary primary:

  • commonly located in contralateral breast

• Extramammary primary:

  • ?leukemia/lymphoma > malignant melanoma > ovarian carcinoma > lung cancer > sarcoma

  • In up to 40% no known history of primary cancer!

  • in children: rhabdomyosarcoma, leukemia, non-Hodgkin lymphoma

• round homogeneous mass with smooth margin

• solitary mass (85%), esp. in upper outer quadrant

• multiple masses; bilaterality in up to 30%

• skin adherence (25%) skin thickening

• axillary node involvement (40%)

Hemorrhagic Metastasis to Breast

• Malignant melanoma

• RCC

• Choriocarcinoma

• Kaposi sarcoma

Mondor disease

= rare usually self-limited thrombophlebitis of subcutaneous veins (mostly thoracoepigastric v.) of the breast/anterior chest wall

Cause:	unknown; trauma, physical exertion, surgery, breast cancer, inflammation, dehydration
May be associated with:	carcinoma (in up to 12%), deep venous thrombosis

• painful tender palpable cordlike structure

• skin dimpling, erythema

Location:

usually lateral aspect of breast

• linear ropelike tubular superficial structure beading

• rarely calcification of vein

• US:

  • superficial hypoechoic tubular structure containing low-level internal echoes (= thrombus)

Prognosis:

resolves spontaneously in 2 4 weeks

Paget Disease Of The Nipple

• [Sir James Paget (1814 1899), surgeon and pathologist at St. Bartholomew's Hospital, London, England; first described in 1874]

• uncommon manifestation of breast cancer characterized by infiltration of the nipple epidermis by adenocarcinoma

Prevalence:	2 3% of all breast cancers
Age:	all ages; peak between 40 and 60 years

• nipple changes (32%): erythema, scaling, erosion, ulceration, retraction of nipple and areola:

  • Median delay of correct diagnosis by 6 11 months as features suggest a benign diagnosis of eczema!

  • nipple changes + palpable mass/thickening of breast (45%)

• palpable mass/thickening of breast only (14%)

  • bloody nipple discharge + itching

  Histo:

  Paget cell = large pleomorphic cells with pale cytoplasm arising in main secretory ducts and migrating into epidermis; histologically and biologically similar to comedocarcinoma

  Associated with:

  • extensive invasive (30%)/in situ ductal carcinoma (60%) limited to one duct in subareolar area/remote + multicentric

  • negative mammogram in 50%

  • nipple/areolar/skin thickening

  • nipple retraction

  • dilated duct

  • linearly distributed subareolar/diffuse malignant microcalcifications

  • discrete retroareolar soft-tissue mass/masses

  • MR:

    • T1WI:

      • flattening/thickening of mamillary region

    • enhanced T1WI:

      • variably no to strong initial uptake

      • postinitial plateau/wash-out

      • asymmetric enhancement of nipple

      • retroareolar lymphatic enhancement

    • T2WI:

      • rarely asymmetric areolar hyperintensity

Dx:	cytologic smear of a weeping nipple secretion/excisional biopsy of a nipple lesion
Prognosis:	survival rate with palpable mass similar to infiltrating duct carcinoma; 85 90% 10-year survival rate without palpable mass; positive axillary nodes in 0 13%

Papilloma Of Breast

= usually benign proliferation of ductal epithelial tissue

P.576

Incidence:	rare; 1 2% of all benign tumors
Age:	30 77 years (juvenile papillomatosis = 20 26 years); may occur in men
Histo:	hyperplastic proliferation of ductal epithelium; lesion may be pedunculated/broad-based; connective tissue stalk covered by epithelial cells proliferating in the form of apocrine metaplasia/solid hyperplasia may cause duct obstruction + distension to form an intracystic papilloma

MR:

• T1WI:

  • round/oval tumor with signal isointense to parenchyma

  • homo-/heterogeneous contrast enhancement stronger than surrounding parenchyma

  • continuous postinitial increase/occasionally plateau

DDx:

invasive papillary carcinoma

Central Solitary Papilloma

Location:

subareolar within major duct

• NOT premalignant

• spontaneous usually bloody/serous (9 48%)/clear nipple discharge (52 88 100%):

  • Most common cause of serous/sanguineous nipple discharge!

• trigger point = nipple discharge produced upon compression of area with papilloma

• intermittent mass disappearing with discharge

• negative mammogram/intraductal nodules in subareolar area

• asymmetrically dilated single duct

• subareolar amorphous coarse calcifications

• dilated duct with obstructing/distorting intraluminal filling defect on ductography (= galactography)

• intraductal hypoechoic mass in isolated dilated duct

Cx:

0 5 14% frequency of carcinoma development

Peripheral Multiple Papillomas

Location:

within terminal ductal lobular unit; bilateral in up to 14%

• In 10 38% associated with:

  • atypical ductal hyperplasia, lobular carcinoma in situ, papillary + cribriform intraductal cancers, radial scar

• nipple discharge (20%)

• round/oval/slightly lobulated well-circumscribed nodules

• segmental distribution with dilated ducts extending from beneath the nipple (20%)

• may be associated with coarse microcalcifications

MR:

• usually not detectable on precontrast T1WI

Cx:	5% frequency of carcinoma development; increased risk dependent on degree of cellular atypia
Prognosis:	in 24% recurrence after surgical treatment

Pseudoangiomatous Stromal Hyperplasia

• = benign proliferative lesions of mammary stroma in a spectrum from focal incidental findings to clinically

• + mammographically evident breast masses

Histo:

(a) incidental focal microscopic finding in 23% of all breast specimens
(b) tumoral form (rare)

Tumoral Form Of Pseudoangiomatous Stromal Hyperplasia

Age:	4 5th decade (range 14 67 years)
Histo:	proliferating myofibroblasts creating slit-like spaces positive for CD34 + muscle actin; similar in appearance to low-grade angiosarcoma

• single circumscribed palpable mass

• well-circumscribed 5 6 (range, 1 12)-cm mass

• growth over time recurrence after excisional biopsy

• US:

  • hypoechoic solid mass with slightly heterogeneous echotexture

  • small cystic component

DDx:

fibroadenoma, phylloides tumor

Radial Scar

• = SCLEROSING DUCT HYPERPLASIA = INDURATIVE MASTOPATHY = FOCAL FIBROUS DISEASE = BENIGN SCLEROSING DUCTAL PROLIFERATION = INFILTRATING EPITHELIOSIS = NONENCAPSULATED SCLEROSING LESION

• = benign proliferative breast lesion (malignant potential is controversial) unrelated to prior surgery/trauma

Incidence:	0.1 2.0/1,000 screening mammograms; in 2 16% of mastectomy specimens
Cause:	? localized inflammatory reaction,? chronic ischemia with slow infarction
Path:	scar sclerotic center composed of acellular connective tissue (= fibrosis) and elastin deposits (= elastosis); entrapped ductules with intact myoepithelial layer in sclerotic core; corona of distorted ducts + lobules composed of benign proliferations (sclerosing adenosis, ductal hyperplasia, cyst formation, papillomatosis)

In up to 50% associated with:

• tubular carcinoma, comedo carcinoma, invasive lobular carcinoma + contralateral breast cancer

• Avoid frozen section, core needle biopsy, fine-needle aspiration!

• rarely palpable

• mean diameter of 0.33 cm (range, 0.1 0.6 cm)

• typically no central mass (BUT: irregular noncalcified mass often with architectural distortion)

• variable appearance in different projections (= radial scars are typically planar in configuration)

• oval/circular translucent areas at center

• very thin long spicules, clumped together centrally

• radiolucent linear structures (= fat) paralleling spicules ( black star appearance)

• no skin thickening/retraction

• MR:

  • T1WI:

    • stellate lesion with signal intensity equal to parenchyma (difficult/impossible to visualize within parenchyma; good in adipose tissue)

  • enhanced T1WI:

    • slight to moderate uptake with nonspecific curve

  • T2WI:

    • no characteristic finding

Rx:	surgical excision required for definite diagnosis
DDx:	carcinoma, postsurgical scar, fat necrosis, fibromatosis, granular cell myoblastoma

P.577

Sarcoma Of Breast

Incidence:	<1 % of malignant mammary lesions
Age:	45 55 years
Histo:	fibrosarcoma, rhabdomyosarcoma, osteogenic sarcoma, mixed malignant tumor of the breast, malignant fibrosarcoma and carcinoma, liposarcoma

• rapid growth (4 6 cm at time of detection)

• smooth/lobulated large dense mass

• well-defined outline

• palpated size similar to mammographic size

Angiosarcoma

= highly malignant vascular breast tumor

Incidence:	200 cases in world literature; 0.04% of all malignant breast tumors; 8% of all breast sarcomas
Age:	3rd 4th decade of life
Histo:	hyperchromatic endothelial cells; network of communicating vascular spaces
	stage I:	cells with large nucleoli
	stage II:	endothelial lining displaying tufting + intraluminal papillary projections
	stage III:	mitoses, necrosis, marked hemorrhage
Metastasis:	hematogenous spread to lung, skin, subcutaneous tissue, bone, liver, brain, ovary; NOT lymphatic

• rapidly enlarging painless immobile breast mass

• skin thickening + nipple retraction

• large solitary mass with ill-defined nonspiculated border

• US:

  • well-defined multilobulated hypoechoic mass with hyperechoic areas (from hemorrhage)

Prognosis:	1.9 2.1 years mean survival; 14% overall 3-year survival rate
Rx:	simple mastectomy without axillary lymph node dissection
DDx:	phylloides tumor, lactating breast, juvenile hypertrophy Frequently misdiagnosed as lymphangioma/hemangioma!

Seroma of breast

• localized collection of wound serum after surgery

• MR:

  • T1WI:

    • circumscribed area of mildly hypointense signal

  • enhanced T1WI:

    • contrast enhancement in surrounding parenchyma

  • T2WI:

    • hyperintense area of fluid retention