141 - Esophageal Motility Disorders

Editors: Shields, Thomas W.; LoCicero, Joseph; Ponn, Ronald B.; Rusch, Valerie W.

Title: General Thoracic Surgery, 6th Edition

Copyright 2005 Lippincott Williams & Wilkins

> Table of Contents > Volume II > The Mediastinum > Section XXVIII - Mediastinal Infections, Overview of Mass Lesions in the Mediastinum, and Control of Vascular Obstructing Symptomatology > Chapter 166 - Overview of Primary Mediastinal Tumors and Cysts

Chapter 166

Overview of Primary Mediastinal Tumors and Cysts

Thomas W. Shields

Numerous tumors and cysts occur in the mediastinum. They affect people of all ages, although they are apparently more common in young and middle-aged adults. Most masses are discovered on routine radiographic examination of the chest in an asymptomatic person, but many of these lesions produce specific or nonspecific symptoms and signs. Generally, benign lesions, which previously comprised the majority of mediastinal tumors and cysts, are asymptomatic, although symptoms may be present as the result of the size or location of a benign lesion. Malignant lesions also may be asymptomatic; however, most produce clinical findings.

The precise nature of a lesion in the mediastinum, as elsewhere, cannot be determined without histologic examination of the tissue. Nonetheless, a reasonable, tentative, preoperative diagnosis for each lesion frequently can be made by considering its location in the mediastinum, the age of the patient, the presence or absence of local or constitutional symptoms and signs, and the association of a specific systemic disease state.

MEDIASTINAL COMPARTMENTS

Although the anteroposterior limits of the mediastinum are the undersurface of the sternum anteriorly and the anterior surface of the vertebral bodies posteriorly, the paravertebral (costovertebral) regions bilaterally are included as a portion of the mediastinum in any discussion of mediastinal masses.

It is most satisfactory to divide the mediastinum into three regions: (a) the anterior compartment, (b) the visceral compartment, and (c) the paravertebral sulci. At the level of the thoracic inlet, only the visceral compartment and the paravertebral sulci are present. The anterior compartment is limited superiorly by the innominate vessels, although thymic tissue of either lobe may proceed in front of these vessels up into the neck. Just below the superior edge of the sternum one may divide the visceral compartment into a potential pretracheal space, which may be referred to as the anterosuperior mediastinum, and the retrotracheal space. Below the innominate vessels, the prevascular space (i.e., the anterior compartment of the mediastinum) extends down to the diaphragm. The visceral compartment as well as the two paravertebral sulci extend from the thoracic inlet down to the diaphragm as well. The lateral limits bilaterally are the mediastinal surfaces of the parietal pleura. Lesions arising in one compartment, when they enlarge in an anteroposterior direction, may encroach on an adjacent compartment. Further anatomic details are discussed in Chapter 154. The term posterior mediastinum should not be used, because in the literature it has been and unfortunately continues to be used to refer to both a portion of the central space (the area posterior to the trachea and heart) and the paravertebral areas.

INCIDENCE

Primary tumors and cysts of the two mediastinal compartments and the paravertebral sulci are uncommon. A summary of selected major reports in the American, Japanese, and European literature revealed a total of 3,124 cases in children and adults recorded from 1956 to 1995. Other reviews have been cited by Davis and associates (1987), and these combined with the aforementioned summary report a total of 4,272 cases (see Reading References for reviews not included in Tables 166-2 and 166-3). Even so, many reviews of specific mediastinal tumors, such as those by Lewis (1983), Adkins (1984), Cohen (1984), Lack (1985), and Lewis (1987) and their associates, are not included in this number. In 1988, Zeng and colleagues in China reported a collected series of 4,357 cases, including 286 substernal thyroid lesions, diagnosed between the years 1963 and 1985. In Zeng's own institution, 307 lesions, including 15 thyroid cases, were seen during this period at a rate of approximately 12 cases per

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year. In the United States, Davis and associates (1987) reported 400 mediastinal lesions over a 50-year period at Duke University, a rate of approximately eight cases per year. Teixeria and Bibas (1989) reported a similar number of primary mediastinal tumors or cysts (eight per year) at the Hospital des Servidores de Estrado in Brazil during the 10-year period from 1975 to 1985. In Japan, Miura and associates (1994) reviewed three series that had appeared in the Japanese literature [Masaoka (1970), Teramatsu (1975), and Wada (1980) and their associates] and added their own experience, for a total of 7,294 cases. The number of cases per year was not stated for the earlier series, but in their own experience an average of eight cases per year were seen. Thus, it is evident that these lesions are only infrequently encountered, particularly when compared with new cases of carcinoma of the lung seen per year by the average practitioner of thoracic surgery. Nonetheless, familiarity with the clinical features and location of the various lesions is essential.

LOCATION OF COMMON TUMORS AND CYSTS

Characteristically, each variety of tumor or cyst arising in the mediastinum or paravertebral sulci has, as a rule, a predilection for one of the mediastinal compartments or the paravertebral sulci. However, migration or enlargement into an adjacent space is not uncommon. Also, lesions of specific tissues may originate in more than one space. This is especially true of lymphatic tumors, which may originate in either the anterior or visceral compartments and, rarely, even in the paravertebral sulcus, and is less often true of neurogenic lesions. Neurogenic lesions more commonly occur in one of the paravertebral sulci but may arise from the vagus or phrenic nerves or paraganglia in the visceral compartment. Rarely, a paraganglioma (five cases) occurs in the intraatrial septum of the heart, as noted by Meunier and associates (2001). Tumors of mesenchymal cell origin (lipomas, hemangiomas, lymphangiomas, and their malignant counterparts) may occur in any of the mediastinal locations.

The major lesions occurring in the anterior mediastinum are of thymic origin, lymphomas, and germ cell tumors. Less common masses are of vascular or mesenchymal origin. Rarely, true aberrant thyroid tissue is found. Displaced parathyroid tissue also is found in this compartment, and thymic cysts also occur here.

In the visceral compartment, foregut cysts (bronchogenic, esophageal, and gastric) and primary as well as secondary tumors of the lymph nodes constitute the majority of lesions. Pleuropericardial cysts, which most often occur in the anterior cardiophrenic angle, and cystic lymphangiomas arise posterior to the anterior surface of the heart and thus are properly assigned to this compartment. Neurenteric cysts and gastroenteric cysts are seen in the visceral compartment of children. Miscellaneous lesions of lymph nodes, thoracic duct cysts, and other rare cysts (parathyroid cysts) also occur in the visceral compartment.

Most lesions arising in the paravertebral sulci are tumors of neurogenic origin. Vascular tumors (e.g., hemangiomas) mesenchymal tumors, and lymphatic lesions also may be found here (Table 166-1). Fibromas, lipomas, and their malignant components are rare but may occur in any of the three compartments. In addition, many lesions arising outside the mediastinum may project into the various compartments and masquerade as primary mediastinal masses on a radiograph of the chest (see Chapter 168).

RELATIONSHIP OF AGE TO TYPE OF MEDIASTINAL LESION

The incidence and types of the many primary mediastinal tumors and cysts vary with the age of the patient group under consideration. In infants and children, the collected series reveal the lesions, in order of decreasing frequency, to be neurogenic tumors, enterogenous (foregut) cysts, germ cell tumors, lymphomas, angiomas and lymphangiomas, thymic tumors, and pericardial cysts (Table 166-2). Comparable series in adults are less readily obtainable, because most reports include lesions in both children and adults. In a collected series of 2,412 patients, however, which was probably made up mostly of adult patients, the lesions mentioned, in order of decreasing frequency, were neurogenic tumors, thymic tumors, lymphomas, germ cell tumors, enterogenous cysts, and pericardial cysts (Table 166-3). In my experience and in that of many of my colleagues, however, thymic epithelial tumors are now the most common mediastinal tumors in adult patients. Zeng and associates (1988) also noted the high incidence of thymoma in southern China (26.3%) as well as an increasing incidence in the Henan Province in northern China. Mullen and Richardson (1986) found that thymomas constituted 47% of all mediastinal tumors in the anterior compartment in adults (Table 166-4). However, it should be noted that in a review of mediastinal tumors in the files of the Walter Reed Army Medical Center and the Walter Reed Tumor Registry, Cohen and associates (1991)

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reported that lymphomas now constitute the largest number of mediastinal tumors seen.

Table 166-1. Usual Locations of the Common Primary Tumors and Cysts of the Mediastinum

Anterior Compartment	Visceral Compartment	Paravertebral Sulci
Thymoma	Enterogenous cyst	Neurilemoma (schwannoma)
Germ cell tumor	Lymphoma
Lymphoma	Pleuropericardial cyst	Neurofibroma
Lymphangioma		Malignant schwannoma
Hemangioma	Mediastinal granuloma
Lipoma	Lymphoid hamartoma	Ganglioneuroma
Fibroma	Mesothelial cyst	Ganglioneuroblastoma
Fibrosarcoma	Neuroenteric cyst	Neuroblastoma
Thymic cyst	Paraganglioma	Paraganglioma
Parathyroid adenoma	Parathyroid cyst	Pheochromocytoma
	Pheochromocytoma	Fibrosarcoma
Aberrant thyroid	Thoracic duct cyst	Lymphoma

Table 166-2. Incidence of Mediastinal Tumors and Cysts in Children

Lesion	Ellis and DuShane (1956)	Heimburger and Battersby (1965)	Jaubert de Beaujeu, et al (1968)	Haller, et al (1969)	Grosfeld, et al (1971)	Whittaker and Lynn (1973)	Pokorny and Sherman (1974)	Bower and Kieswetter (1977)	Azarow, et al (1993)	Akashi, et al (1995)	Total
Neurogenic tumors	19	9	22	18	35	37	35	41	22	47	245
Enterogenous cysts	10	10	15	10	0	12	14	17	11	7	106
Germ cell tumors	16	5	9	8	5	21	4	5	4	21	98
Lymphomas	0	6	0	8	13	9	27	12	4	14	93
Angiomas and lymphangiomas	9	5	1	4	1	6	7	5	3	6	47
Stem cell tumors	4	0	1	10	2	0	0	5	0	0	22
Thymic tumors and cysts	0	0	3	0	4	2	3	1	7	6	26
Pleuropericardial cysts	0	0	1	1	0	0	0	2	1	2	7
Miscellaneous	0	1	2	3	2	11	0	0	4	5	33
Total	58	36	54	62	62	98	90	88	56	108	712

SIGNS AND SYMPTOMS

In children, over one half to two thirds of mediastinal tumors and cysts are symptomatic, whereas in adults approximately one third to one half of the lesions produce symptoms. The signs and symptoms that occur depend on the benignity or malignancy of the lesion, its size, its location, the presence or absence of infection, the elaboration of specific endocrine or other biochemical products, and the presence of associated disease states.

In infants and children, respiratory symptoms such as cough, dyspnea, and stridor are prominent because even a small mass, because of its location, may compress the airway. Also, because of the relatively small size of the thorax, any mass may readily encroach on the volume of the lungs. In addition, septic complications with resultant pneumonitis and fever occur frequently. In children, lethargy, fever, and chest pain often occur with malignant lesions.

Table 166-3. Mediastinal Tumors and Cysts, Primarily in Adults

Lesion	Herlitzka and Gale (1958)	Morrison (1958)	Le Roux (1962)	Boyd and Midell (1968)	Wychulis, et al (1971)	Fontenelle, et al (1971)	Rubush, et al (1973)	Ovrum and Birkeland (1979)	Davis, et al (1987)	Cohen, et al (1991)	Total
Neurogenic tumors	35	101	30	11	212	7	36	19	57	39	547
Thymomas and thymic cysts	14	47	17	20	225	18	51	10	67	45	514
Lymphomas	12	33	0	20	107	14	14	9	62	36	307
Germ cell tumors	26	36	21	22	99	3	14	5	42	23	291
Enterogenous cysts	26	29	14	15	83	2	8	0	50	36	263
Pericardial cysts	17	13	20	6	72	3	10	7	36	8	192
Miscellaneous	29	30	3	2	118	17	24	6	40	29	298
Total	159	289	105	96	916	64	157	56	354	216	2,412
Note: Excluding substernal thyroid, mediastinal granuloma, and primary carcinoma of mediastinum.

Adults, although usually asymptomatic, may present with cough, dyspnea, vague chest pain, or local signs or symptoms related to infection or malignancy of the mediastinal mass.

Infection of benign cysts may cause symptoms in adults, although at present such inflammatory complications are noted infrequently. Symptoms and signs from compression of vital structures by benign lesions are also uncommon in the adult because most normal, mobile, mediastinal structures can conform to distortion from pressure. When malignant disease is present, however, not only does distortion occur, but fixation is noted as well. Obstruction and compression of vital structures are then common. Superior vena caval obstruction, dysphagia, cough, and dyspnea may be observed. Direct invasion of adjacent structures, such as the chest wall, pleura, and adjacent nerves, is common with malignant tumors. Specific findings of chest pain, pleural effusion, hoarseness, Horner's syndrome, superior vena cava syndrome (SVCS), upper extremity pain, back pain, paraplegia, and diaphragmatic paralysis may occur in the presence of a malignant tumor but also may occasionally accompany a benign lesion. In addition, constitutional evidence (i.e., weight loss, fever) of malignant disease is sometimes

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evident. Endocrinologic syndromes may occur in association with either a benign or malignant lesion.

Table 166-4. Relative Frequency of Common Primary Anterior Mediastinal Tumors in 702 Adults

Tumor	Wychulis, et al (1971)	Rubush, et al (1973)	Luosta (1978)	Ovrum and Birkeland (1979)	Nandi (1980)	Total	Incidence (%)
Thymic lesion	231	37	31	7	21	327	47
Lymphoma	107	7	37	9	0	160	23
Germ cell tumor	60	10	21	5	7	103	15
Endocrine tumor	61	13	11	21	6	112	16
Total	459	67	100	42	34	702
Percentage of series	43	58	48	62	50
From Mullen B, Richardson JD: Primary anterior mediastinal tumors in children and adults. Ann Thorac Surg 42:338, 1986. With permission.

Certain systemic disease states may be present with both malignant and benign mediastinal tumors in either children or adults. These, as well as other unique findings related to each type of tumor and cyst, are discussed separately in the chapters devoted to the various lesions. The diagnosis, treatment, and prognosis are also considered under the respective separate headings.

BENIGNITY VERSUS MALIGNANCY

The incidence of benignity versus malignancy varies with the lesion under consideration, the location of the mass, the age of the patient, and the hospital referral patterns. In Whooley and colleagues' (1999) report from the Roswell Park Cancer Institute, 70% of the mediastinal tumors were malignant in nature.

In the adult, probably less than 40% of the anterior mediastinal masses are malignant (20% 30% of all epithelial thymic tumors, approximately 100% of the lymphatic lesions, and 15% 20% of all germ cell tumors). In the visceral compartment, the lymphatic lesions may be benign or malignant, whereas almost all cysts (enterogenous, mesothelial, and other types) are benign. In the paravertebral sulci, Davidson (1978), Reed (1978), and Zeng (1988) and their colleagues reported an incidence of only 1% 3% malignancy in the neurogenic tumors, the most common type of tumor seen in these locations. Interestingly, in Whooley and associates' (1999) and Inci and Turgut's (1999) series the incidence of malignant neurogenic tumors was 60% and 5%, respectively. In Azarow and colleagues' (1993) series the incidence was 32%.

In children, the overall incidence of malignancy of mediastinal lesions is greater than that in the adult. In a series of 108 children with tumors of the mediastinum, Akashi and co-workers (1995) reported that most malignant tumors were identified in children 3 years of age or younger (86%), whereas 91% of the benign tumors were in older children. According to Mullen and Richardson (1986), 45% of the lesions in the anterior mediastinal compartment in children are malignant lymphomas. These would make up even a greater percentage of cases if cases of thymic hyperplasia were excluded. Only a small percentage of the germ cell tumors in children are malignant. In the visceral compartment, many of the lymph node lesions are malignant, both non-Hodgkin's lymphoma and Hodgkin's disease, whereas most other lesions are cysts and are benign. King and associates (1982) reported that of 136 malignant mediastinal lesions in children, 87 (64%) were lymphomas. Almost all were in either the anterior or visceral compartment, or in both. Of these lymphomas, 54 (62%) were non-Hodgkin's lymphoma, and 33 (38%) were Hodgkin's disease. In the paravertebral sulci, most lesions are neurogenic in origin. Reed and associates (1978) reported the incidence of malignancy in 50 children under 16 years of age to be 60%. The incidence recorded over a 25-year period at the Children's Memorial Hospital in Chicago was also 60% (Table 166-5). Moreover, in a smaller series of 20 patients seen during the 7-year period from 1980 to 1987 from the same hospital, as reported by the author and Reynolds (1988), the incidence of malignancy in these neurogenic tumors was 85%.

In contrast to these observations, Davis and colleagues (1987) reported a different age distribution of malignant lesions in their 400 patients with mediastinal masses. They found the lowest incidence of malignancy in children 10 years of age and younger, and the highest incidence in patients

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in the third and fourth decades of life. They attributed this to the large number of patients with lymphoma and malignant germ cell tumors in these age groups. Overall, in their patient groups they found that anterosuperior masses were more likely to be malignant (59%) than were masses in the other compartments (<30%). Differences in terminology and, again, patient referral both play a role in these varying data. Another observation relative to the incidence of malignancy is that, as reported in the aforementioned review of Cohen and associates (1991), there has been a highly statistically significant increase in the number of patients with malignant mediastinal tumors from the 1950s to the 1980s (Table 166-6). This observation is reinforced by the report of Whooley and colleagues in 1999.

Table 166-5. Neurogenic Tumors in Children

Tumor	Children's Memorial Hospitala	Armed Forces Institute of Pathologyb
Malignant
Neuroblastoma	12	16
Ganglioneuroblastoma	6	14
Neurogenic sarcoma	1	0
Askin tumor	6	0
Total	25 (60%)	30 (60%)
Benign
Ganglioneuroma	10	18
Neurofibroma	6	0
Neurolemoma	1	2
Total	17 (40%)	20 (40%)
a From Shields TW, Reynolds M: Neurogenic tumors of the thorax.
Surg Clin North Am 68:645, 1988. With permission.
b From Reed JC, Hallet KK, Feigin DS: Neural tumors of the thorax: subject review from the AFIP. Radiology 126:9, 1978. With permission.

Table 166-6. Incidence of Malignancy of Mediastinal Tumors from 1950 to 1989

Decade	No. of Patients	Malignant Tumors	Percentage
1950 1959	18	5	28
1960 1969	66	10	15
1970 1979	53	17	32
1980 1989	93	52	56
From Cohen A, et al: Statistics from the Walter Reed Army Medical Center and Walter Reed Tumor Registry. In Cohen AJ, et al: Primary cysts and tumors of the mediastinum. Ann Thorac Surg 51:378, 1991. With permission.

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Akashi A, et al: The results and prognoses of surgical treatment for primary mediastinal tumors in children. J Jpn Assoc Chest Surg 9:135, 1995.

Azarow KS, et al: Primary mediastinal masses. A comparison of adult and pediatric populations. J Thorac Cardiovasc Surg 106:67, 1993.

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Cohen AJ, et al: Primary cysts and tumors of the mediastinum. Ann Thorac Surg 51:378, 1991.

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Ellis FH Jr, DuShane JW: Primary mediastinal cysts and neoplasms in infants and children. Am Rev Tuberc 74:940, 1956.

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READING REFERENCES

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