162 - Sternotomy and Thoracotomy for Mediastinal Disease

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 XXIX - Primary Mediastinal Tumors and Syndromes Associated with Mediastinal Lesions > Chapter 192 - Mesenchymal Tumors of the Mediastinum

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Chapter 192

Mesenchymal Tumors of the Mediastinum

Thomas W. Shields

Philip G. Robinson

Primary mesenchymal tumors of the mediastinum are encountered infrequently. Wychulis (1971), Luosto (1978), and Davis (1987) and their colleagues, as well as Teixeira and Bibas (1989), reported an incidence of generally less than 6% of all mediastinal masses. King and associates (1982) reported a somewhat higher incidence in children of 10.7%. Of these mesenchymal tumors, Wychulis and colleagues (1971) from the Mayo Clinic reported about 55% to be malignant; from the same institution, King and associates (1982) reported an 85% incidence of malignancy in soft tissue mediastinal tumors in children. Signs and symptoms of these lesions vary with their location, size, and benignity or malignancy. These tumors are more often symptomatic in children than in adults.

Burt and colleagues (1998) reviewed the records at Memorial Sloan-Kettering Cancer Center from January 1, 1990 to December 31, 1991. They found 47 patients with primary mediastinal sarcomas. The patients ranged in age from 2.5 to 69.0 years, with a median age of 39 years. The ratio of men to women was 1:6. Forty-two (89%) of the patients were symptomatic, and their presenting complaints included chest or shoulder pain (38%), dyspnea (23%), cough (9%), paresthesias (9%), hemoptysis (6%), and various other complaints. The medical history of these patients was significant for von Recklinghausen's disease in three patients, irradiation to the chest for lymphoma in five patients, and radiation therapy for retinoblastoma in one patient. The mediastinal distribution of the tumors was 49% in the posterior compartment, 41% in the anterior compartment, and 10% in the visceral compartment. The most common tumors were malignant peripheral nerve tumor (26%), spindle cell sarcoma (15%), leiomyosarcoma (9%), and liposarcoma (9%).

Many classifications have been suggested, none of which is completely satisfactory because they frequently include generalized mesenchymal lesions within the thorax involving the lungs and mediastinum as well as the mediastinum, aorta, and pulmonary vessels. Examples of these are lymphangiomatosis, lymphangiomyoma, and hemangiomatosis. Tumors arising from the thoracic skeletal tissues and lesions, such as histiocytosis X, extramedullary hematopoiesis, and, possibly, benign xanthogranuloma, should be considered separately from mediastinal mesenchymal tumors. Also, we believe malignant neurogenic sarcomas should be excluded from the global category of mesenchymal tumors.

Our working classification for this group of lesions is presented in Table 192-1.

TUMORS OF ADIPOSE TISSUE

Lipomas

Incidence

Benjamin and associates (1972) reported an incidence of 1% of lipomas in a collected series of 1,064 mediastinal neoplasms. Strug and colleagues (1968) reported an incidence of 1.8% in 106 patients, and Teixeira and Bibas (1989) recorded an incidence of 1.7% in 179 patients in their series, excluding the 14 substernal thyroid goiters and 6 leiomyomas of the esophagus that they listed in their total of 199 solid mediastinal masses. Moigneteau and associates (1967) noted that mediastinal lipomas of nonthymic origin are more common than are thymolipomas.

Clinical Features

Lipomas occur most commonly in adults. Kleinhaus and Ducharmre (1969) noted that of the 120 cases in the literature at the time, fewer than 10 were recorded in children younger than the age of 10 years. According to Staub and colleagues (1965), men appear to be affected twice as often as women.

More than one half of the mediastinal lipomas produce few, if any, symptoms. When the lesion is large, respiratory symptoms, such as dyspnea, may occur because of compression

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of adjacent lung. Most are located in the anterior compartment, but they may develop in either the visceral compartment or in one of the paravertebral sulci. The lesion is most often solitary, but multiple lesions are occasionally seen.

Table 192-1. Primary Mesenchymal Tumors of the Mediastinum

  1. Tumors of adipose tissue
    1. Lipoma
    2. Lipomatosis
    3. Benign lipoblastoma, lipoblastomatosis
    4. Hibernoma
    5. Liposarcoma
  2. Tumors of blood vessel origin
    1. Hemangioma
    2. Angiosarcoma
    3. Benign and malignant epithelioid hemangioendothelioma
    4. Benign and malignant hemangiopericytoma
    5. Glomus tumor
  3. Tumors of lymph vessel origin
    1. Lymphangioma, cystic hygroma
    2. Lymphangiohemangioma
  4. Tumors of fibrous tissue
    1. Fibromatosis
    2. Fibrosarcoma
    3. Malignant fibrous histiocytoma
    4. Angiomatoid fibrous histiocytoma of low-grade malignancy
  5. Tumors of smooth muscle origin
    1. Leiomyoma
    2. Leiomyosarcoma
  6. Tumors of striated muscle origin
    1. Rhabdomyoma
    2. Rhabdomyosarcoma
  7. Tumors of pluripotential mesenchyme and other rare tumors of the mediastinum
    1. Benign and malignant mesenchymoma
    2. Localized fibrous tumor
    3. Calcifying fibrous pseudotumor
    4. Xanthoma
    5. Amyloid pseudotumor
    6. Elastofibrolipoma
    7. Follicular dendritic cell tumor
    8. Meningioma
    9. Ependymoma
    10. Synovial sarcoma
  8. Extraskeletal sarcomas
    1. Extraskeletal chondrosarcoma
    2. Extraskeletal osteosarcoma

Keeley and Vana (1956) classified the mediastinal lipomas as totally intrathoracic (the more common type) and as hourglass (i.e., the cervicomediastinal or transmural type). In the transmural variety, the fatty tumor may extend through an intercostal space or spaces into the chest wall or even may extend through an intervertebral foramen into the spinal canal, as reported by Quinn and associates (1983). Negri and colleagues (2000) reported a similar occurrence in a patient with an angiolipoma in the paravertebral region. A one-stage neurosurgical and video-assisted thoracic surgery (VATS) removal was carried out successfully.

Radiographic and Computed Tomographic Features

Radiographic features are not diagnostic, but occasionally the lesion may appear less dense, especially at its periphery, than other solid tumors (Fig. 192-1). Penetrated Bucky radiographs are best suited to demonstrate the lesser density of these tumors as compared with the surrounding structures. The examination of the patient in different positions may reveal different contours of the mass because of the effect of gravity on the soft, pliable fatty tissue. With the patient in an upright position, an hourglass or teardrop configuration is noted occasionally. Pure mediastinal lipomas can be distinguished from thymolipomas because they usually lack the characteristic bilobate shape of the latter lesions. A lipoma has a lower characteristic coefficient of density on computed tomography (CT) scans, which allows its identification (Fig. 192-2). The CT density of lipoma is in the range of 70 to 130 Hounsfield units.

Pathology

A lipoma is a well-circumscribed, encapsulated, soft, yellow mass that may readily be excised. Histologically, the tumor is composed of lobules of mature fat.

Treatment

Surgical excision through the appropriate thoracic incision or a VATS approach is curative. With a paravertebral

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lipoma, intraspinal canal extension must be looked for by preoperative CT or magnetic resonance (MR) imaging examination. If intraspinal canal extension is identified, single-stage excision, as described in Chapter 190, is indicated.

Fig. 192-1. Radiograph of small lipoma located in the anterior cardiophrenic angle. Lesser density of the tumor than the adjacent cardiac shadow is apparent so that the normally present silhouette sign of a mass adjacent to the heart is absent. From Shields TW, Lees WM, Fox RT: Anterior cardiophrenic angle tumors. Q Bull Northwestern Med School 36:363, 1962. With permission.

Fig. 192-2. CT scan of benign lipoma (M) adjacent to right side of the heart and arising from the right cardiophrenic angle. From Lau LS: Computed tomography of the mediastinum and lungs. In Martini N, Vogt-Moykopf I (eds): Thoracic Surgery: Frontiers and Uncommon Neoplasms. St. Louis: Mosby, 1989. With permission.

Variants of Mediastinal Lipomas

A number of lipomas contain significant amounts of additional mesenchymal tissues; thus, a number of lipomatous lesions have been recorded by different terms to denote the presence of the other cell types. Kline and associates (1990) reported the occurrence of an angiolipoma in the visceral mediastinal compartment, and, as noted, Negri and colleagues (2000) recorded one occurring in the paravertebral space. A mediastinal angiomyolipoma was recorded by Fukuzawa and colleagues (1992). Lim (1980) reported a patient who had a chondrolipoma located in the superior region of a paravertebral sulcus. Excision is the treatment of choice for all the aforementioned tumors. Kim and colleagues (1984) reported a primary myelolipoma of the mediastinum, and an earlier report was recorded by Foster (1958), according to the review of Sabate and Shahian (2002). Suzuki (1988) and Gao (2002) and their associates presented additional cases. The latter authors noted that only 12 cases of mediastinal myelolipoma had been reported in the Japanese literature. These tumors in the mediastinum are most commonly located in the posterior compartment. These myelolipomas are more common than the primary myelolipomas located in the lung. The radiographic, CT, and MR features, as noted by Kawanami and associates (2000), are the same as those described for the pulmonary myelolipomas in Chapter 118. The essential diagnostic feature is the presence of ectopic megakaryocytes within the lipomatous tumor. The diagnosis is most often established by examining the tissue obtained by fine-needle aspiration (FNA) of the mass. The treatment is surgical excision if the tumor is large or is symptomatic.

Lipomatosis

Lipomatosis is a poorly circumscribed overgrowth of mature adipose tissue. It occurs in different forms. Diffuse lipomatosis usually is localized to an extremity or the trunk. Pelvic lipomatosis is localized to the pericolonic and perivesicular areas. Other types of lipomatosis are symmetric lipomatosis, adiposis dolorosa (Dercum's disease), and corticosteroid lipomatosis. Pathologically, in lipomatosis, the adipose tissue is composed of mature fat cells with no cytologic evidence of malignancy.

Symmetric lipomatosis may be a cause of mediastinal widening. Homer and colleagues (1978) reported the value of CT examination for the condition's identification. In about half of the patients with this infrequent condition, lipomatosis results from exogenous obesity, corticosteroid ingestion, as noted by Shukla and colleagues (1988), or Cushing's syndrome. Once the lesion is identified by CT scanning, no further intervention or treatment is necessary.

Benign Mediastinal Lipoblastoma

A lipoblastoma, a benign fatty tumor that occurs in young children, usually younger than the age of 3 years, was first described by Vellios and associates (1958). It most often occurs in one of the extremities but can occur in the neck, chest wall, and paravertebral soft tissues. The tumor is composed of adipocytes arranged in lobules. The lipoblastoma usually is circumscribed, but a diffuse form may be infiltrative and is referred to as lipoblastomatosis. One case of lipoblastoma in the mediastinum was reported by Tabrisky and colleagues (1974); the tumor arose posteriorly at the level of the azygos, extended to the apex, and spread to fill the right hemithorax. Surgical excision of a circumscribed lesion is curative, but the diffuse form may recur.

Hibernoma

Hibernoma is an uncommon tumor that arises from remnants of brown fat. Less than 100 cases have been described, and of these, seven have occurred in the thorax. These intrathoracic hibernomas were reviewed by Ahn and Harvey (1990). In five patients, the hibernoma was located in the subpleural space, one was intrapericardial, and one was located in the anterior mediastinum. A cervicomediastinal hibernoma was reported by Santambrogio and co-workers (1997). This lesion, although described as extending into the

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anterior mediastinum, actually extended down into the pretracheal portion of the visceral compartment, as do most substernal goiters (see Chapter 168). The mass was large and distorted the trachea and splayed the vessels laterally. CT revealed a mixed density but mainly of fat. These tumors are benign and surgical resection is curative.

Liposarcoma

Incidence

Standerfer and colleagues (1981) added two cases to the 51 cases reviewed by Schweitzer and Aguam in 1977. Teixeira and Bibas (1989) added an additional case, and numerous single case reports have been added to the literature since that report. The greatest number of additional cases have been reported in a review of the Japanese literature by Minamoto and colleagues in 1996. Men and women are affected equally. Two thirds of the patients are older than the age of 40 years; the average age is approximately 45 years. Less than 5% of patients are younger than 16 years of age, and only two patients, one reported by Kauffman and Stout (1959) and one by Wilson and Bartly (1964), have been younger than the age of 3 years. Castleberry and associates (1984) report that in children, only 11% of all liposarcomas arise in the mediastinum.

Clinical Features

According to Mendez and associates (1979), liposarcomas are most common in the posterior mediastinum (i.e., the paravertebral sulcus and posterior portion of the visceral compartment) but may occur in any location within the mediastinum. Schweitzer and Aguam (1977) reported that 85% of patients with a liposarcoma are symptomatic, whereas only 15% have an asymptomatic lesion only discovered on routine chest radiography. Most patients present with respiratory symptoms of dyspnea, tachypnea, wheezing, and cough. One half of the patients present with pain or pressure within the thorax or shoulder region. Significant weight loss is seen in 25% of the patients, and the signs and symptoms of superior vena cava obstruction are seen in 15%.

Radiographic and Computed Tomographic Features

Liposarcomas are large lobulated masses with ill-defined borders on radiography of the chest. Adjacent structures may be compressed and infiltrated. Mendez and associates (1979) reported that liposarcomas have a density intermediate between those of water and fat. The density of these lesions is greater than that of a benign lipoma. The more poorly differentiated tumor with a greater number of abnormal cells may have a Hounsfield unit number as high as 15 to 20. The aforementioned authors suggest that this finding is useful in distinguishing lipomas from liposarcomas. However, the clinical features in most patients readily permit this differentiation.

Pathology

Liposarcomas are usually large. The cases of Klimstra and associates (1995) ranged from 6 to 40 cm, with an average size of 15.7 cm and a mean weight of 1,500 g. They appear circumscribed but are not encapsulated. They may arise in any of the mediastinal divisions and extend into either or both hemithoraces or even into the neck. On cut section, the surface of the tumor may have a gelatinous appearance. It may be pale yellow, bright orange, white, or gray-white. In other areas, it may show focal necrosis, hemorrhage, or cyst formation. Enzinger and Weiss (1995a) divided these tumors into five types: (a) well-differentiated, (b) myxoid, (c) round cell, (d) dedifferentiated, and (e) pleomorphic. Myxoid liposarcomas account for 40% to 50% of these tumors. Evans (1990) described an atypical lipomatous tumor of the mediastinum with bundles of smooth muscle. The patient developed several recurrences, which suggests that this lesion represented a low-grade liposarcoma. In 44 cases of primary mediastinal liposarcoma in the Japanese literature reviewed by Minamoto and colleagues (1996), the myxoid type represented 34.4% of the tumors, and the well-differentiated type made up 28.1%. Ten percent were either of the pleomorphic or round cell types; the remaining 27% of the tumors could not be classified specifically. Histologically, the myxoid subtype is composed of lipoblasts set in a myxoid matrix with a background network of delicate capillaries. All of the tumors contain varying numbers of malignant lipoblasts with enlarged round to oval hyperchromatic nuclei and foamy cytoplasm (Fig. 192-3). A characteristic chromosomal

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translocation t(12;16)(q13;p11) has been described by Knight and associates (1995) in these tumors. According to Kindblom and colleagues (1975), about one half of the patients with myxoid liposarcomas develop local recurrences, whereas only a small percentage of patients develop metastases. Well-differentiated liposarcomas are less aggressive neoplasms than myxoid ones. In contrast, the round cell, dedifferentiated, and pleomorphic liposarcomas are aggressive neoplasms. They can produce widespread metastases to the lungs, bones, and other organs.

Fig. 192-3. Photomicrograph of a myxoid liposarcoma. The tumor is composed of lipoblasts set in a myxoid background with a delicate capillary network running through the tumor.

Treatment

Complete surgical excision, when possible, is the preferred therapeutic choice. A standard open operation is indicated if the mass is thought to be malignant. Aubert and colleagues (2000) reported intrapleural metastases and implantation of a low-grade myxoid liposarcoma after its initial removal by a VATS technique. Unfortunately, contamination of these sites occurred during the removal of the tumor. These authors point out that VATS probably is not indicated for the removal of possible malignant tumors of the mediastinum. We concur with their opinion. Subtotal resection is often used but is only of short-term palliative benefit with early recurrence despite postoperative adjuvant therapy. Radiation therapy is of little avail in the dosage that can be used in most cases with the disease located in the chest. However, Grewal and associates (1993) reported a 75-year-old patient who had survived longer than 5 years after a partial excision and adjuvant radiation of a nonencapsulated liposarcoma of the anterior mediastinum. Castleberry and colleagues (1984) suggested the judicious use of radiation therapy and chemotherapy (i.e., vincristine, dactinomycin, and cyclophosphamide) to reduce the size of an initially inoperable tumor. They reported some success with this approach in a child.

Prognosis

The pseudoencapsulated lesions that can be completely removed have a better prognosis than the nonencapsulated, infiltrative tumors. Standerfer and colleagues (1981) reported a few cases of patients surviving 3 to 17 years after resection of pseudoencapsulated lesions. The patients with nonencapsulated lesions or one of the less well-differentiated tumor types have a poor prognosis and as a rule die within 2 years. Follow-up of the cases presented by Klimstra and associates (1995) was available in 23 of 28 patients for between 1 month and 6 years. They reported seven (31.8%) of the patients died of their tumors after a mean interval of 2.6 years. Eleven (47.8%) of their patients were free of disease after a mean interval of 1.6 years. The patients with myxoid liposarcomas died after a shorter interval. They did not have many of the higher-grade, round cell, and pleomorphic liposarcomas in their series. Patients presenting with a superior vena cava syndrome have an extremely poor prognosis, as noted by McLean and co-workers (1989). Two such patients, one reported by Kozonis and associates (1951) and one reported by Schweitzer and Aguam (1977), died within a short time of presentation.

TUMORS OF BLOOD VESSEL ORIGIN

Vascular tumors of the mediastinum are encountered infrequently. In the reviews of Wychulus (1971) and Benjamin (1972) and their associates, these tumors accounted for less than 0.5% of all mediastinal tumors. They may occur at any age and show no predilection for either gender. The anterior compartment is most often the initial site of origin, but neither the middle compartment nor the paravertebral sulci are spared the presence of these lesions. Balbaa and Chesterman (1957) reviewed more than 60 cases. With the data then available, benign lesions were more than twice as common as malignant ones. This figure for benign lesions is too low; the benign tumors probably account for almost 90% of the vascular mediastinal lesions.

According to Cohen and colleagues (1987) about one half of the benign lesions are asymptomatic. In contrast, almost all of the malignant lesions reported in the literature are symptomatic. Conceptually, according to Bedros and co-workers (1980), the vascular tumors can be divided into two basic types: the first type consists of vascular proliferations and includes both benign hemangiomas and angiosarcomas. The second type consists of a group of lesions formed by the proliferation of predominant cell types found in the adventitia, media, or intima of a blood vessel. Examples of these are the benign or malignant hemangiopericytomas arising from the pericytes of Zimmerman found in the adventitia, the leiomyomas and leiomyosarcomas thought to arise from the smooth muscle cells of media (see Tumors of Smooth Muscle Origin, later in this chapter), and the benign hemangioendothelioma (juvenile hemangioma) and epithelioid hemangioendothelioma of intimal cell derivation.

Hemangiomas

Incidence

Cohen and associates (1987) reported 88 mediastinal hemangiomas that had been described in the literature and added 15 patients of their own. Rodriguez Paniagua and associates (1988), in a discussion of the aforementioned report, added four more cases. Hemangiomas constitute about 90% of all vascular mediastinal tumors. As noted, these can be observed in any age group, but Gindhart and colleagues (1979) believe that the cavernous type is seen more often in children.

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Clinical Features

One third to almost one half of patients are asymptomatic. The remaining patients present with symptoms or signs that are the result of infiltration of adjacent structures or fullness in the neck, which is often present with anteriorly situated tumors. Chest pain, dyspnea, and hemoptysis are common complaints. Superior vena cava obstruction, Horner's syndrome, and other neurologic findings, as well as spinal cord compression, also have been described in these patients. Kissel and associates (1976) noted the occasional association of mediastinal hemangiomas in patients with Osler-Weber-Rendu disease, and Kings (1975) noted its association with multiple hemangiomas elsewhere in the body.

Radiologic Features

Radiography of the chest reveals the lesion but as a rule is of no help in suggesting the correct diagnosis (Fig. 192-4A). Phleboliths may be present in as many as 10% of the

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patients, but in the 15 patients described by Cohen and colleagues (1987), none were found. Angiography has not been helpful in the diagnosis of these lesions because they are not opacified by the contrast material (see Fig. 192-4B). In Cohen and associates' (1987) series, a venogram was successful in visualizing an anterior mediastinal hemangioma in one patient (see Fig. 192-4C). CT scanning is excellent for delineating the lesion and its relationship to adjacent structures (see Fig. 192-4D) and may suggest the presence of infiltration. The density of the lesion is the same as that of the surrounding vascular structures. Cohen and associates (1993) reported that CT scans of hemangiomas are characteristic. The masses have an attenuation of approximately 30 Hounsfield units. Phleboliths can usually be demonstrated on CT, but not on chest radiography. Contrast material enhancement is useful in making the diagnosis, if the bolus is followed by sequential scans. The contrast material gradually collects in the tumor, with the enhancement appearing at the periphery and gradually filling up the center. In addition, CT may suggest the best operative approach to the mediastinal lesion. Schurawitzki and colleagues (1991) described the MR findings of two mediastinal hemangiomas. In the first patient, the T1-weighted images showed a lesion with irregular contours that was homogenous and hypointense when compared with fat. The T2-weighted images showed an inhomogeneous increase in signal intensity. After gadolinium-diethylenetriaminepentaacetic acid was injected, moderate inhomogeneous enhancement was seen. The second patient showed multiple circumscribed, hyperintense areas on T1- and T2-weighted images that were caused by intratumoral hemorrhage (hemosiderin).

Fig. 192-4. A. Radiograph of hemangioma of the anterior mediastinum in a 43-year-old woman. No characteristic features are present. B. Normal aortogram. C. Anteroposterior subtraction venogram demonstrates the vascular nature of the lesion. D. CT scan delineates the extent and relationship of the hemangioma to the adjacent structures. From Cohen AJ, et al: Mediastinal hemangioma. Ann Thorac Surg 43:656, 1987. With permission.

Pathology

Grossly, the hemangioma may appear as a soft, compressible, purplish encapsulated mass or may appear to be an amorphous soft mass that insinuates itself among the various vascular or neurogenic structures adjacent to it. This is particularly true in the visceral compartment, and the tumor may be adherent to or even appear to be infiltrating the superior vena cava or other structures. In a paravertebral sulcus, it may involve the sympathetic chain or may rarely extend into the spinal canal through an enlarged intervertebral foramen. Rarely in the anterior compartment, a hemangioma may arise in the thymus, as noted by Cohen and co-workers (1987). On cut section, blood is contained within the lumina of the hemangioma.

Histologically, Enzinger and Weiss (1988) divided the hemangiomas into three types: (a) capillary, (b) cavernous, and (c) venous. Capillary hemangiomas are composed of a mass of capillaries with somewhat prominent endothelial cells. A cavernous hemangioma is composed of large dilatated blood vessels lined by flattened endothelial cells. The walls may show some fibrosis and focal chronic inflammation (Fig. 192-5). A cavernous hemangioma may simply be a dilatated version of a capillary hemangioma. A venous hemangioma is identified by its thick walls, which contain smooth muscle cells. Because the blood flow is slow through these vessels, they frequently thrombose and develop dystrophic calcifications (phleboliths).

Fig. 192-5. Photomicrograph of a cavernous hemangioma. Interconnecting vascular spaces contain red blood cells and are lined by flattened endothelial cells.

According to Davis and colleagues (1978), cavernous and capillary hemangiomas are the most common type, accounting for 90% of hemangiomas. Pachter and Lattes (1963b) have described a variant with a prominent smooth muscle component and have suggested that these be classified as angiomyomas or hamartomatous hemangiomas. The remaining 10% of the mediastinal hemangiomas have been designated with such terms as angiomas, hemangiofibromas, fibroangiomas, angiolipomas, fibrolipohemangiomas, venous hemangiomas, and arteriovenous malformations.

All varieties, despite their gross infiltrative nature at times and their adherence to adjacent structures, are benign lesions. No microscopic invasion of adjacent tissues has been described.

Treatment

Surgical excision is the treatment of choice. Radiation therapy is of no benefit in the management of these lesions. The tumor may be approached either through a standard posterolateral thoracotomy or median sternotomy incision, or even a transsternal (clamshell) incision. All of the patients reported by Cohen and associates (1987) had the surgical procedure carried out through a standard posterolateral approach. However, Rodriguez Paniagua and colleagues (1988) recommend the use of a median sternotomy. The choice of incision should be determined by the tumor's location and extent as defined by CT examination. When

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possible, total excision of the hemangioma should be carried out. At times, because of infiltration of adjacent vital or bony structures, only partial excision or even only a biopsy of the lesion can be accomplished. Cohen and associates (1987) were able to excise 6 of 12 tumors completely. A subtotal resection was carried out in five patients, and only biopsy could be accomplished in one. Despite the subtotal resection or biopsy only, major hemorrhage was not a problem in any of these patients. Rodriguez Paniagua and colleagues (1988), however, reported fatal postoperative exsanguination in a patient after partial excision of a mediastinal hemangioma. As a result, these authors suggest that only total resection of the vascular tumor should be done. In two of their patients, resection of the superior vena cava with the tumor and the replacement of this vein by a prosthetic graft led to excellent results. Cohen and colleagues (1988), from their previously reported experience, continue to support the concept of partial resection when total excision appears impossible or excessively hazardous.

Results

The prognosis after total or partial excision is excellent. Cohen and colleagues (1987) reported only one suspected radiologic recurrence in the patients undergoing total excision and one symptomatic recurrence that required reoperation after partial excision. The remaining patients, including the one patient with a biopsy only, did not have progression of their disease on long-term follow-up. Likewise, no evidence of malignant transformation has been observed.

Angiosarcomas

Angiosarcomas are malignant vascular tumors. They have been called by a variety of names, such as malignant hemangioendothelioma, angiofibrosarcoma, angiosarcoma, hemangioblastoma, hemangioendothelioblastoma, and hemangioendotheliosarcoma. They usually occur in the subcutaneous tissues of the skin and breast as well as in the deep soft tissues.

They have been rarely reported in the mediastinum. Kardamakis and colleagues (1996) reported a case of a primary hemangiosarcoma of the mediastinum that we interpret from the photomicrographs to be an angiosarcoma. The patient was a 44-year-old woman who complained of vague, retrosternal chest pain. A chest radiograph revealed a round mass in the right retrosternal area. A CT scan showed a well-circumscribed 6-cm mass. At the time of surgery, the mass displaced the right middle and lower lobes without invading them and was attached to the right hemidiaphragm. Grossly, the tumor was hemorrhagic with a spongy appearance. On microscopic examination, it was composed of spindle cells arranged in a diffuse pattern merging with vasoformative areas. The cells lining the vascular channels had pleomorphic nuclei and a high mitotic rate. The immunostains were positive for factor VIII related antigen. Twelve months after surgery, no signs of recurrence had occurred.

In reviewing the literature since 1963, Kardamakis and associates (1996) could only find 20 cases of mediastinal angiosarcoma. The patients ranged in age from 18 to 66 years, with retrosternal pain being the most common presenting complaint. Most of the tumors were located in the anterior mediastinum. The treatment was surgical excision. The prognosis is poor. The value of adjuvant therapy is difficult to assess, because of the small number of cases reported.

Mediastinal angiosarcomas also originate from the heart, pericardium, and great vessels. Angiosarcomas of the mediastinum and pericardium have been reported by Lee (1995) and Killion (1996) and associates as a complication of mediastinal radiation for seminomas. Both of the patients described were men; one was 35 years old and the other was 54 years old. One presented with a small pleural effusion 10 years after radiation therapy, and the other presented with dyspnea and pleuritic chest pains 15 years after irradiation. The first patient had a paravertebral mass at the level of the tenth thoracic vertebra, and the other had a thickened pericardium and pericardial fluid. On microscopic examination, the tissues showed spindled to epithelial cells. Both specimens eventually immunostained for factor VIII related antigens. Both patients died despite aggressive surgery and chemotherapy. These two cases point out the importance of considering angiosarcoma in postirradiation patients.

Of some interest are two cases in which the tumor originated in a great vein and successful resections were carried out. In one, the site of origin was the superior vena cava but without obstruction of the vessel. Abratt and associates (1983) resected the tumor and the cava and successfully reconstructed the venous flow with two Dacron grafts, one from each innominate vein to the right atrium. The patient received irradiation to the area postoperatively, and a survival of 40 months without recurrence was reported. In the second patient, the angiosarcoma originated in the left innominate vein, and symptoms of venous obstruction were evident clinically. The vein and contained tumor were excised, but blood flow was not reconstructed. Miller and colleagues (1985) reported an 8-year survival in this patient. A recent patient with an angiosarcoma of the left innominate vein was diagnosed and treated with radiation therapy. The case report was initially published by B rger and associates in 1990. Before the published report, the patient underwent a standard thoracotomy in 1989, but the tumor appeared to be nonresectable. At another hospital, the patient subsequently had the tumor radically resected, and venous continuity was reestablished by a prosthetic graft. R ckert and associates (2000) reported an 11-year survival of this patient after the radical resection and reconstruction of the left innominate vein involved by the primary angiosarcoma. This latter patient is the longest survivor to date.

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Epithelioid Hemangioendothelioma

Enzinger and Weiss (1988) used the term hemangioendotheliomas to designate a group of vascular tumors that have a histologic appearance between hemangiomas and angiosarcomas. In the past, this term, hemangioendothelioma, may have been used synonymously with angioma and hemangioma, thus making the older literature difficult to understand. At present, the term epithelioid hemangioendothelioma is preferred and designates a low-grade malignant neoplasm derived from endothelial cells. These are uncommon mediastinal tumors.

Grossly, the cut surface of these tumors appears red to white if it arises from a vessel, and white-gray if it does not. Microscopically, if the tumor arises from a vessel, the lumen may be filled with organizing thrombus, tumor cells, necrotic debris, or collagen. Around the periphery of the tumor in those that do not arise from a vessel, the endothelial cells form short cords or small nests of cells that may be embedded in a hyalinized or myxoid matrix (Fig. 192-6). Metaplastic bone formation or the presence of osteoclastic-type giant cells are not uncommon findings, according to Weidner (1991) and Suster and associates (1994).

Fig. 192-6. A. Photomicrograph of an epithelioid hemangioendothelioma arising from a blood vessel. In the upper left corner is a slitlike remnant of the vessel lumen. The neoplastic cells are present throughout the wall, forming small clear intracellular lumina or vacuoles. B. Higher magnification shows the intracellular lumina of the neoplastic cells.

Enzinger and Weiss (1988) describe three subtypes of hemangioendotheliomas: (a) epithelioid hemangioendothelioma, (b) spindle cell hemangioendothelioma, and (c) the so-called Dabska tumor. These heterogeneous groups of vascular tumors are intermediate in behavior between the benign hemangiomas and the frankly malignant angiosarcomas. The endothelial nature of these tumors can be confirmed by immunohistochemical studies. Mentzel and colleagues (1997) reported that the tumor cells usually stain positive for factor VIII related antigen and CD34 and are focally lectin binding for Ulex europaeus antigen. Some of these tumors may immunostain for CD31, which is considered the most specific and sensitive endothelial marker. Stain results for keratins, S-100 protein, actin, and desmin are negative when the tumor is in the thorax. Intracellular Weibel-Palade bodies, characteristic of endothelium-derived cells, may be demonstrated in these tumor cells by electron microscopy (Fig. 192-7).

Weiss and colleagues (1986) reported 46 patients with this tumor who were followed for an average period of 48 months. Six patients (13%) developed a local recurrence, 14 patients (31%) developed metastases, and 6 patients (13%) died of their disease. These tumors have been reported in the liver, lung, and soft tissues. In the lung, they were called intravascular

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bronchiolar tumors. Although Toursarkissian and associates (1990) reported 19 cases, including one of their own, of this tumor located in the mediastinum, only three of these tumors were specifically stated to be epithelioid hemangioendothelioma. Two of these three tumors, those reported by Toursarkissian and colleagues (1990) and Yousem and Hochholzer (1987), were located in the anterior compartment; the location of the third tumor, reported by Weiss and Enzinger (1982), was unspecified. Of the other hemangioendotheliomas reported, those in young children were located in one of the paravertebral sulci. At least one of these tumors, reported by Bedros and associates (1980), was most likely a juvenile hemangioma and should not be included in the group of tumors now designated as epithelioid hemangioendotheliomas. Some of the other cases in Toursarkissian and associates' review also may not meet the present criteria for an epithelioid hemangioendothelioma. Suster and associates (1994), on the other hand, have reviewed 12 cases that meet the criteria of epithelioid hemangioendotheliomas. All the tumors were located in the anterior compartment of the mediastinum. Men were affected more commonly than women, and the tumors occurred in adults of any age. About one half of the patients presented with symptoms of compression of surrounding structures, and the remainder were asymptomatic. The tumor grossly was either encapsulated or invasive, but in all, the microscopic features were of low to high grades of malignancy. Clinically, however, these tumors in the mediastinum behaved as low-grade malignant lesions. Mentzel and associates (1997) described two mediastinal cases as part of a series of 30 cases. Begbie and colleagues (1997) described one case occurring in a 50-year-old man with type IV Ehlers-Danlos syndrome. Their patient presented with multiple mediastinal nerve palsies and chest pain. MR imaging showed an anterior mediastinal mass that on biopsy was an epithelioid hemangioendothelioma. Ferretti and co-workers (1998) reviewed 20 cases of mediastinal epithelioid hemangioendotheliomas, and all but one, in which the location was not noted, were present in the anterior mediastinal compartment. These patients presented with a superior vena cava syndrome.

Fig. 192-7. Electron microscopic photograph of an epithelioid hemangioendothelioma demonstrates the so-called Weibel-Pallade bodies (arrows). Courtesy of W. B. Laskin, Department of Pathology, Northwestern University Medical School.

Complete surgical resection alone usually results in long-term survival. Isowa and associates (2002) have discussed the various surgical approaches to these anterosuperior tumors and described a novel approach by the use of a hemiplastron window technique. Removal of regional lymph nodes is indicated. In those patients in whom recurrence or a metastasis occurs, a second resection is recommended if applicable. Radiation therapy or chemotherapy may be used, but the efficacy of either modality is unknown. The patient reported by Begbie and associates (1997) was managed by initial irradiation and subsequent chemotherapy but eventually died of his disease.

Hemangiopericytoma

Benign and malignant hemangiopericytomas rarely are encountered in the mediastinum. These tumors may be located in any compartment, but the paravertebral sulci are among the more frequent sites. Of the less than 20 cases reported, some arising from an intercostal space, as noted by Biagi and associates (1990), about one fourth were benign, and the remainder were malignant. These tumors arise from cells (pericytes) that are wrapped around the pericapillary arterioles. Examples of this tumor have been reported by Balbaa and Chesterman (1957), Pachter and Lattes (1963b), and Galvin (1988), Chong (1993), and Mori (1994) and their colleagues. Symptoms and signs are protean (e.g., dysphagia, Pancoastlike syndrome, and the occurrence of a spontaneous hemothorax).

Grossly, the tumor appears as a solitary, apparently well-circumscribed, soft gray-white mass. Focal hemorrhages, cystic degeneration, and necrosis may be present and are suggestive of a malignant lesion. Microscopically, the tumor, as described by Marchevsky and Kaneko (1992), is composed of densely packed oval, round, or spindle cells arranged in a perivascular pattern around vascular, endothelial-lined spaces (Fig. 192-8). Reticulin stains demonstrate that the tumor cells are located outside the wall of the anastomosing vascular channels. Lesions with four or more mitoses per 10

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high-power microscopic fields, prominent cellular pleomorphism, increased cellularity, and areas of hemorrhage and necrosis usually are malignant and can metastasize. Kornstein (1995a) notes that immunohistochemistry with endothelial cell markers readily distinguishes the endothelial cells from the pericytes. Reactivity of the pericytes for actin, vimentin, and S-100 has been described.

Fig. 192-8. A. CT scan of the chest of an asymptomatic middle-aged woman reveals a moderate-sized mass in the anterior mediastinum just to the left of the sternum. On excision, the mass was shown to be a hemangiopericytoma. B. Photomicrograph of a hemangiopericytoma. A small vessel is surrounded by tightly packed tumor cells.

Treatment is surgical excision. These tumors are quite vascular, and bleeding may be hard to control during the procedure. Morandi and colleagues (2000) have suggested the use of angiography to identify the major supplying vessels, after which preoperative embolization is carried out. The subsequent surgical procedure is then more safely accomplished. The clinical course unfortunately is unpredictable. Radiation therapy as an adjunct is not thought to be useful, however. Chong and associates (1993) reported a patient with a longer than 2-year survival after partial resection and irradiation of a highly invasive tumor. The value of doxorubicin (Adriamycin) as a therapeutic modality in the management of these tumors, as suggested by Morris and colleagues (1981), lacks confirmation.

Glomus Tumor

Glomus tumors are found most often in the soft tissues of the body. These tumors are rarely identified in the trachea and lung (see Chapters 78 and 118). Fujinaga and colleagues (1996) reported the occurrence of a glomus tumor in the left costovertebral sulcus. These tumors are benign epithelial tumors of specialized arteriovenous shunts, the Sucquet-Hoyer canals. The treatment is surgical resection, which was carried out successfully in the aforementioned case. To our knowledge, this case is the first glomus tumor to be reported occurring in the mediastinum.

TUMORS OF LYMPH VESSEL ORIGIN

Mediastinal Lymphangioma

Incidence

Fewer than 1% of lymphangiomas are confined to the mediastinum. Most of those occurring in the mediastinum arise in the neck and extend into the mediastinum (cervicomediastinal cystic hygromas, which are discussed in detail in Chapter 168). Rarely, the lesion is associated with a generalized process such as lymphangiomatosis, Gorham's disease, lymphangiomyomatosis, Klippel-Trenaunay syndrome, or lymphatic varices (see Reading References).

Of the isolated mediastinal lymphangiomas, Ricci and associates (1964) stated that 48% are identified in the anterior compartment, 34% in the visceral compartment, and 9% in the paravertebral sulci. However, these figures may be unreliable because of differences in terminology for the mediastinal divisions used in the literature. In 14 patients with intrathoracic lymphangiomas reported by Brown and colleagues (1986) from the Mayo Clinic, only seven tumors were confined to the thorax. By our terminology, three (43%) were located in the anterior compartment, two (28%) in the visceral compartment, and two (28%) in a paravertebral sulcus. Of their seven other patients, two lesions were located in a paravertebral sulcus and extended into the retroperitoneum, four superiorly located lymphangiomas extended into or arose from the cervical region, and one patient had Gorham's disease with extensive lymphangiomatosis. Six of the seven patients with isolated lesions were adults, and the remaining one was an adolescent. Isolated mediastinal lymphangiomas only infrequently occur in children. Feutz and associates (1973) reported that of all isolated mediastinal lymphangiomas, about 25% occurred in children, but fewer than 5% were seen in infants younger than 1 year of age. However, Perkes and colleagues (1979) reported their occurrence in two infants younger than the age of 22 months. Ionescu and associates (1976) reported one occurring in a 20-month-old infant. There appears to be no gender predilection.

Clinical Features

Patients with an isolated tumor are generally asymptomatic. Symptoms of compression of adjacent structures, dyspnea, or a symptomatic chylothorax, such as that described by Johnson and co-workers (1986), may be present infrequently.

Radiographic and Computed Tomographic Features

On standard films, the lymphangioma appears as a smooth, rounded, or lobulated mass. It is of uniform density. Depending on its location, it may deviate the trachea or compress or distort other adjacent structures such as the esophagus. With a lesion located in a paravertebral sulcus, erosion of one or more vertebral bodies may be noted. A lymphangiogram may occasionally fill the lesion with contrast material or demonstrate the egress of the material into the pleural space when a chylothorax is present. The CT features of mediastinal lymphangioma have been described by Pilla and associates (1982). These consist of: (a) a well-circumscribed lesion without invasive characteristics, (b) normal structures that have been enveloped or displaced, (c) absence of calcifications, and (d) varied attenuation values within the lesion. Shaffer and associates (1994) described both the CT and MR findings of mediastinal lymphangiomas. Their most common CT finding was a well-circumscribed, uniformly cystic mass in the anterior or superior mediastinum. MR images parallel those of the CT scan with cystic components. The T1-weighted images showed a signal greater than muscle, and one case showed a T2-weighted image with a decreased signal. The advantages of MR imaging are (a) demonstration of cystic components,

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(b) lack of demonstration of invasion, and (c) improved surgical planning with coronal and sagittal images. They concluded that the CT and MR images of lymphangiomas were variable but that the diagnosis could not be suggested on the basis of the radiologic studies alone.

Pathology

The lymphangioma may either appear encapsulated or have ill-defined margins with envelopment or insinuation of the tumor between adjacent structures. It may be adherent to adjacent vessels, nerves, or the pericardium. Erosion of adjacent bony structures, rather than invasion, is seen with lesions that abut the rib cage or the vertebral column. The lesion is soft, spongy, and grayish. The cystic structures of the mass may be macroscopic or microscopic. The lymphangioma contains chyle, which grossly differentiates the lesion from a hemangioma, which contains blood. Morphologically, the lesion may be classified according to the size of the lymphatic spaces into cystic hygromas, composed of large cystic spaces, or cavernous lymphangiomas, composed of a spongelike mass of smaller spaces. Microscopically, the spaces in both these lesions are lined by attenuated endothelial cells similar to those of normal lymphatics. The spaces may be filled with chyle or a pink proteinaceous fluid. Unilocular cysts also have been described, but in the report of 18 such cases by Childress and associates (1956), many of these lesions most likely represented simple mesenchymal cysts.

Differentiation of a lymphangioma from a vascular lesion may be difficult. Marchevsky and Kaneko (1984) suggest that immunohistochemical techniques may be useful because the endothelial cells lining lymphatic spaces usually lack intracytoplasmic factor VIII immunoreactivity, which is characteristic of vascular endothelial cells.

Treatment

Surgical excision, preferably complete when possible, is the treatment of choice. The principles of management are essentially those enumerated in the surgical treatment of hemangiomas. Treatment with sclerosing agents is ineffective, as is radiation therapy of the lesion.

A few patients, usually those with lesions situated in a paravertebral sulcus, may develop a chylothorax either spontaneously, as reported by Johnson and associates (1986), or as a postoperative complication. The postoperative complication of a chylothorax is most likely to occur in the management of those lesions that extend below the diaphragm into the retroperitoneal area. Conservative management with closed-tube thoracostomy may be sufficient. In the patient reported by Johnson and associates (1986), neither conservative management nor multiple attempted surgical ligations were successful in treating the chylothorax. Finally, the drainage ceased after a course of radiation therapy. If all of these therapies should fail, the use of pleuroperitoneal shunting with a double-valve Denver peritoneal shunt should be considered. Milsom and associates (1985) and Miller (1989) have recorded successful use of this approach in a number of patients with unresolved chylothorax of varying causes. Murphy and colleagues (1989) used this technique in 16 patients, all but one of whom were infants, with satisfactory results in resolving persistent chylothoraces of varying causes in 75% of the cases. Two of the patients had acquired lymphangiomas, and the result was successful in both. These authors described the technique of placement and management of these shunts in excellent detail.

Prognosis

The isolated mediastinal lymphangioma is a benign lesion, and excellent results are obtained with complete or even partial excision. Progression is infrequent, and spontaneous malignant transformation is unrecorded.

Lymphangiohemangioma

The lymphangiohemangioma is a subset of lymphangiomas. The tumor consists of both lymphatic and vascular structures. It was first described by Angtuaco and associates (1983) as a lymphatic venous malformation occurring in the mediastinum. Toye and associates (1991) reported an additional case of a lymphangiohemangioma in the mediastinum. Riquet and colleagues (1997) described three more cases arising in the mediastinum. Two were associated with the presence of a left superior vena cava. The pathogenesis of these tumors is unknown, but Riquet and associates (1997) noted that many of these lesions are associated with venous malformations. Many questions remain as to the exact classification of this tumor. Treatment consists of surgical excision.

TUMORS OF FIBROUS TISSUE

Tumors of fibrous tissue origin are rare in the mediastinum. Strug and colleagues (1968), in an analysis of 106 patients with mediastinal tumors, observed three lesions, an incidence of 2.8%, derived from fibrous tissue origin. One of the tumors was benign, and the other two were malignant. At present, it is customary to categorize these tumors as fibromatoses, fibrosarcomas, and malignant fibrous histiocytomas.

Fibromatosis (Extraabdominal Desmoid)

According to Enzinger and Weiss (1988), fibromatosis can be divided into the superficial and deep types. The superficial types include such lesions as palmar fibromatosis

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(Dupuytren's contracture). Of the deep types of fibromatoses, the one that would affect the mediastinum is extraabdominal fibromatosis (extraabdominal desmoid). Desmoid tumors of the mediastinum are uncommon. Pachter and Lattes (1963a) described three cases in the mediastinum, but these tumors have been described mostly as single case reports. Tam (1994) and Ko (1996) and their colleagues have both described mediastinal desmoid tumors. Tam and associates (1994) described the case of an asymptomatic 35-year-old man who was incidentally found to have an anterior mediastinal mass. A chest radiograph showed a smooth marginated mass in the anterior mediastinum at the left cardiophrenic angle. The tumor infiltrated into the adjacent skeletal muscle and fat.

The radiographic findings of desmoids are variable. CT usually shows either a well-circumscribed or an ill-defined soft tissue density of variable attenuation when compared with muscle. After the administration of contrast, the attenuation may be higher than adjacent muscle. MR images are more consistent. The T1-weighted image shows low signal intensity relative to muscle, but the T2-weighted image demonstrates variable signal intensity.

This lesion originates from fibroblasts. It forms a firm tumor with indistinct gross margins. On cut section, the tumor is white to gray and resembles scar tissue. Microscopically, the tumor is composed of spindle-shaped cells of uniform size separated from one another by abundant collagen. The cells infiltrate into the surrounding connective tissue. These tumors do not metastasize, but they do recur locally if they are not completely excised. They should be treated by complete excision. Antiestrogen therapy may be used if estrogen receptors are demonstrated within the tumor.

The term fibroma, which is used in the older literature, should probably be discarded and a more specific histologic diagnosis made. It is possible that mediastinal fibromas described in the older literature represent benign localized fibrous tumors (i.e., benign fibrous mesotheliomas) (see Chapter 64). Another possible disease entity that the older literature could be referring to is sclerosing mediastinitis. This mediastinal fibrosis is probably secondary to a granulomatous disease, such as tuberculosis or histoplasmosis (see Chapter 165). Grossly, the fibrosis involves the visceral mediastinal compartment diffusely rather than as a well-circumscribed solitary lesion. Microscopically, the lesion is composed of abundant dense hyalinized collagen separating a few spindle cells with an occasional focus of lymphocytes.

Fibrosarcoma

Fibrosarcomas are generally symptomatic, with cough, chest pain, dyspnea, and dysphagia often being one or more of the chief complaints. These lesions may grow to great size, and some of these large tumors have been associated with hypoglycemia. Baldwin (1964) and Walsh and associates (1975) have reported such an occurrence. The mechanism of the resultant hypoglycemia has been discussed in Chapter 64.

Grossly, fibrosarcomas have a soft to firm consistency; their cut surfaces are gray-white to tan-yellow. On microscopic examinations, most tumors appear similar. They have a fascicular growth pattern composed of uniform spindle-shaped cells, which can be separated by collagen fibers. Sometimes, the fascicles interlace with each other and form a herringbone pattern. Mitotic figures should be present, but giant cells and multinucleated giant cells should not. A reticulin stain can show a collagen network among the cells. Pescarmona and colleagues (1991) reported the immunohistochemical features of one fibrosarcoma; the site of origin was in the anterior mediastinum. The tumor cells had positive results for vimentin and negative results for cytokeratins and S-100 protein.

Fibrosarcomas spread locally within the mediastinum and infiltrate into vital structures. Complete excision is rarely possible. The efficacy of irradiation or chemotherapy is unproved. Continued growth within the thorax is the rule, but distant metastases are uncommon. Barua and associates (1979) and Ringertz and Lidholm (1956) noted rare examples of distant metastases in these patients. The prognosis is poor, and most patients die within a few years of its discovery because of diffuse tumor spread within the thorax.

Malignant Fibrous Histiocytoma

Malignant fibrous histiocytoma, according to Enzinger and Weiss (1988), is the most frequent soft tissue sarcoma of late adult life. It is most commonly located in an extremity or in the retroperitoneum. It only rarely occurs as a primary mediastinal tumor. Malignant fibrous histiocytomas are divided into five subtypes: (a) storiform-pleomorphic, (b) myxoid, (c) giant cell, (d) inflammatory, and (e) angiomatoid.

Few cases of primary malignant fibrous histiocytomas have been recorded in the mediastinum. They are usually reported as single case reports rather than as series. Three of these cases, one reported by Chen and associates (1982), one of the two cases reported by Mills (1982), and the case reported by Paterson (1989) and their colleagues, were intimately associated with the aorta. In the patient reported by Paterson and associates (1989), the tumor was associated with a Dacron prosthesis in the aorta. It is likely that these cases represent tumors of the aorta rather than primary tumors of the mediastinum. The other recorded cases were found to originate in both mediastinal compartments as well as in the paravertebral sulci. Stark (1983) and Venn (1986) and their associates, as well as Marchevsky and Kaneko (1984), reported the anterior mediastinum to be the location in each of their cases. Natsuaki and colleagues (1986) noted one arising from a pedicle from the esophagus in the visceral compartment; the second case reported by Mills and associates (1982), as well as the ones reported by Besznyak (1985), Morshuis (1990), and Muneta (1992) and

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their colleagues, occurred in a paravertebral sulcus. Misonov (1990), Thippanna (1994), Shimizu (1994), and Davies (1995) and their colleagues have all reported mediastinal malignant fibrous histiocytomas. The case reported by Davies and associates (1995) is remarkable because the patient had systemic symptoms (i.e., fever, malaise, night sweats, and generalized arthralgia and myalgia) that were attributed to cytokine production by the angiomatoid malignant fibrous histiocytoma. After removal of the tumor, the systemic symptoms disappeared. Asakura and colleagues (2001) recorded an angiomatoid histiocytoma of intermediate malignancy in the mediastinum. The tumor cells were immunoreactive to vimentin as well as to CD68; they were negative for keratin, desmin, factor VIII related antigen, CD31, and CD34. A 5-year survival was obtained after resection and postoperative irradiation. This is unusual for the more malignant varieties. Enzinger and Weiss (1995b) have suggested that these tumors are of fibrohistiocytic origin.

Grossly, the malignant fibrous histiocytomas are flesh-colored multilobulated masses. On cut section, they have a gray to white surface. Microscopically, the tumors contain a mixture of fibroblastlike and histiocytelike cells. They also can contain pleomorphic giant cells and inflammatory cells. The fibroblastic cells are immunoreactive to vimentin. These tumors frequently recur after they have been excised, and they can metastasize to the lung and the lymph nodes. Weiss and Enzinger (1978) reported a local recurrence rate of 44% and an incidence of distant metastases of 42%.

The treatment of choice is complete excision when possible. Postoperative radiation therapy may be of benefit in these patients. Venn and associates (1986) suggested the use of intensive multidrug chemotherapy as well as radiation therapy preoperatively to reduce the bulk of the tumor. Muneta and colleagues (1992) obtained a marked clinical and radiographic response with the use of interferon- 2a in a 16-year-old girl who had failed to respond to either chemotherapy or irradiation. These authors believed the response possibly to be the result of augmentation of cell-mediated immunity. The advantages of these preoperative or postoperative adjuvant therapies remain unproved.

TUMORS OF SMOOTH MUSCLE ORIGIN

These smooth muscle tumors may be included with the tumors of blood vessel origin because it is thought that most, albeit these are rare primary tumors of the mediastinum, may arise from the smooth muscle cells of the media of mediastinal vascular structures. However, we have elected to present them separately.

Leiomyomas

Leiomyomas are separated into four categories: (a) multiple piloleiomyoma, (b) solitary piloleiomyoma, (c) solitary genital leiomyoma, and (d) angioleiomyoma. Any variety is uncommon in the mediastinum. Of course, type 3 is never seen in this location. Pachter and Lattes (1963a) described a leiomyoma arising in what we have classified as the visceral compartment. Rasaretnam and Panabokke (1975) stated that seven such lesions had been recorded up to the time of their report. Most were found in the visceral compartment near the esophagus but with no discernible connection to it. None were associated with any large vascular structure, but the tumor's origin from a small vessel could not be excluded.

Uno and colleagues (1988) reported a giant mediastinal leiomyoma located in the posterior compartment and summarized five additional cases in the Japanese literature. Shaffer and associates (1990) reported one leiomyoma adjacent but not attached to the aortic arch in the visceral compartment. The latter authors stated that, in their review of the literature, a primary mediastinal leiomyoma was five times more common in women than in men. They noted that the age range of the patients with these tumors was 22 to 67 years of age. Baldo and colleagues (1997) reported a vascular leiomyoma in the anterosuperior mediastinum causing a superior vena cava syndrome. Also, Matsuoka and colleagues (2002) have described a patient with an angioleiomyoma in the anterior compartment of the mediastinum. Microscopic examination revealed a highly vascular lesion with a proliferation of smooth muscle cells without cellular dysplasia or mitotic figures. Surgical resection was curative.

Grossly, these latter tumors are firm, well-circumscribed, gray-white lesions. Microscopically, they are composed of mature smooth muscle cells set in a collagenous stroma. These tumors are benign, and simple excision is curative. If the blood supply seems excessive, preoperative embolization of the vessel may be carried out, as suggested by Baldo and colleagues (1997).

Leiomyosarcoma

Leiomyosarcomas of the mediastinum are rare. They may arise in the soft tissue of the mediastinum or from the great vessels. Rasaretnam and Panabokke (1975) added one case to the two previously described in the literature. All three were in the visceral compartment, and no definitive site of origin could be identified in any of these tumors. Sunderrajan (1984) and Steen (1993) and their associates each described an additional case of a primary leiomyosarcoma that also was located in the visceral mediastinal compartment. The latter authors briefly reviewed the previously reported cases. Subsequently, Moran and colleagues (1994) reported 10 cases of leiomyosarcoma in the mediastinum. Their patients ranged in age from 26 to 71 years, with a mean of 56 years. Three of the patients were women, and seven were men. The patients complained of chest pain and cough, and one had a pleural effusion. All three of the patients with

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anterior mediastinal lesions were symptomatic, but only one of the seven patients with a middle mediastinal lesion was symptomatic. The asymptomatic tumors were found incidentally on routine chest radiographs or during evaluation for unrelated diseases. The chest radiographs showed widening of the mediastinum. The CT scans showed a soft tissue mass with displacement of adjacent structures. At the time of surgery, none of these lesions arose from either the aorta or the esophagus. On gross examination, the tumors ranged from 6 to 16 cm in greatest dimension. They were well circumscribed, firm, and rubbery with a nodular outer surface. On cut section, they had myxoid and cystic areas that resembled schwannian neoplasms. On microscopic examination, all of the tumors were composed of a proliferation of spindle cells in fascicles with varying degrees of nuclear pleomorphism, cellularity, and mitotic figures. The grade of the tumors varied from low grade to high grade (I to III). Immunohistochemically, the cells stained for vimentin, smooth muscle actin, and focally for desmin. None of the tumors stained for S-100, keratin, or myoglobin. On electron microscopy, the cytoplasm contained abundant cytoplasmic filaments with focal condensations. Treatment is surgical excision. Two patients were alive and well at 4 and 6 years. Three patients died of their disease between 2 and 7 years after the disease was diagnosed. One patient developed recurrences at 2 and 4 years and was eventually lost to follow-up. An additional patient was lost to follow-up, and three patients were reported too recently to have any meaningful length of follow-up. In addition, Hioki and colleagues (1997) reported a primary leiomyosarcoma arising in the anterior compartment and listed seven other cases that had been reported in the Japanese literature. Five of the total of eight cases were in the anterosuperior compartment, two in the middle compartment, and one in the paravertebral area. Gomez-Roman and Val-Bernal (1997) reported a 76-year-old man with a tumor in the anterosuperior mediastinum that was composed of both liposarcoma and leiomyosarcoma. Two additional cases of primary leiomyosarcoma of the mediastinum have been recorded one by Auliac (1999) and one by Eroglu (2002) and their associates, respectively.

In addition to these few cases of primary mediastinal leiomyosarcomas, however, numerous reports of leiomyosarcomas of the great vessels, primarily of the pulmonary artery, have been recorded. Kevorkian and Cento (1973) collected 11 cases of these large vessel sarcomas, of which 10 arose in the pulmonary artery and 1 arose from either the ascending aorta or proximal aortic root. Grossly, the cut surface of these tumors has a gray-white, whorled appearance. There may be areas of hemorrhage and necrosis. Henrichs (1979) and Wick (1982) and their associates described the characteristic light and electron microscopic features of the leiomyosarcomas of the pulmonary artery. Histologically, the cells are spindle-shaped with elongated blunt-ended nuclei and an eosinophilic cytoplasm. Immunohistochemically, the cells of these tumors stain with desmin and muscle-specific actin. On electron microscopy, the cells contain myofilaments, pinocytotic vesicles, intercellular connections, and a basal lamina.

These aforementioned lesions, however, are not true mediastinal tumors and should be classified as sarcomas of large vessel origin. Baker and Goodwin (1985) published an extensive review of pulmonary artery sarcomas. Numerous case reports of leiomyosarcoma of the pulmonary artery have appeared since this report. A typical example is the report of Eng and Murday (1992).

Of more interest relative to diseases of the mediastinum is the case report of a leiomyosarcoma of the superior vena cava by Davis and associates (1976) (Fig. 192-9). As a rule, such tumors most frequently involve the inferior vena cava or less commonly a peripheral vein. Kevorkian and Cento (1973), in an extensive review, could not find any examples of the occurrence of this tumor in the superior vena cava. However, Davis and associates (1976) identified a previously recorded autopsy case by Ehrenberg (1911) of an extensive, fatal leiomyosarcoma apparently arising from the superior vena cava. The patient reported by Davis and associates (1976) had a mass arising from the lateral wall of the superior

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vena cava. The mass, along with a portion of the wall of the vessel, was excised, and simple lateral repair of the wall of the vessel was carried out. The tumor recurred, and at a subsequent resection, a portion of the wall of the superior vena cava was excised and closed with a vein patch. Irradiation was given postoperatively. At long-term follow-up of 6.5 years, the patient was free of disease. Spaggiari and colleagues (1996) reported the removal and reconstruction of the superior vena cava and the right atrium in a patient with an extensive leiomyosarcoma arising from the aforementioned vessel. In their comments, they recorded seven previously reported cases of a leiomyosarcoma of the superior vena cava. In addition to the two aforementioned reports, the five other cases had been published by Stefanini (1971), Vogel (1981), Lupetin (1986), Courtin (1991), and Marini (1992) and their associates.

Fig. 192-9. Radiograph of the chest shows a mass adjacent to the right side of the midlevel of the mediastinum (arrows) that proved to be a leiomyosarcoma of the superior vena cava. From Davis GL, et al: Leiomyosarcoma of the superior vena cava, a first case with resection. J Thorac Cardiovasc Surg 72:408, 1976. With permission.

Because successful replacement of the vena cava by either a vein graft or a prosthetic graft, as in cases of involvement by a thymoma or a hemangioma (the technique is described in Chapter 172), can be carried out, it would now appear to be prudent to replace the superior vena cava initially when a primary tumor of the vein is present. The role of adjuvant radiation therapy is unsettled.

For completeness, the notation by Kornstein (1995b) of the occurrence of a leiomyosarcoma that arose as a nodule in an otherwise typical seminoma is worthy of note. To his knowledge, such mediastinal nongerm cell malignancies have been reported only in nonseminomatous germ cell tumors.

TUMORS OF STRIATED MUSCLE ORIGIN

Rhabdomyoma

The rhabdomyoma is a benign tumor of striated muscle cells. Rhabdomyomas are usually found in the head and neck regions of children and adults, as well as in the vulva and vagina of middle-aged women. This is a pathologic curiosity as a primary mediastinal tumor. Miller and colleagues (1978) reported one instance of this tumor occurring in the anterior mediastinum. They postulated that it arose from thymic myoid cells. Box and associates (1995) reported a rhabdomyoma occurring in the mediastinum of an adult and reviewed the subject. Their patient was a 52-year-old man who developed pneumonia and was found to have a mediastinal mass on chest radiography. The CT scan showed a posterior mediastinal mass extending to the neck. The lesion was surgically excised. On gross examination, it was a reddish tan, lobulated tumor with a thin capsule. On microscopic examination, it was composed of eosinophilic vacuolated polygonal cells with small peripheral nuclei. The cells immunostained for myoglobin. The patient had an uneventful recovery and was well 8 months after surgery.

Rhabdomyosarcoma

Donaldson (1989) noted that only 2% of all rhabdomyosarcomas are intrathoracic; these may be pulmonary or mediastinal in location. The tumor is rubbery and has a gray-white to pink-tan cut surface. Focal areas of necrosis and cystic degeneration may be present. Microscopically, four subtypes exist: (a) embryonal, (b) botryoid, (c) alveolar, and (d) pleomorphic. Infrequently, a rhabdomyosarcoma may be associated with a mediastinal nonseminomatous germ cell tumor in young adult men, as noted by Kornstein (1995b), as well as by Ritchey (1985) and Caballero (1992) and their associates. As noted by the senior editor (TWS) in Chapter 167, -fetoprotein and human chorionic gonadotropin levels should be obtained routinely in all young men with anterior mediastinal masses, regardless of any biopsy specimen diagnosis. Pachter and Lattes (1963a) reported three examples of primary mediastinal rhabdomyosarcomas, one embryonal and two pleomorphic. King and associates (1982) reported five such tumors in children; the average age was 9.2 years. Sartelet and colleagues (1998) reported a 9-year-old boy with a mediastinal solid alveolar rhabdomyosarcoma. The patient was treated with chemotherapy and radiation but died of his disease 19 months after the diagnosis. B gin and associates (1994) reported a glycogen-rich clear cell rhabdomyosarcoma located in the anterior compartment. The diagnosis was established by ultrastructural recognition of areas of rhabdomyogenesis. Immunohistochemically, the tumor was positive for vimentin and muscle-specific actin but was negative for myoglobin, cytokeratin, S-100 protein, placental alkaline phosphatase, and -fetoprotein. Deep-seated rhabdomyosarcomas infiltrate the adjacent connective tissue and other structures. The role of surgical intervention is probably limited to biopsy only. Radiation therapy with or without chemotherapy may be attempted. The most effective chemotherapeutic agents are considered to be doxorubicin, cyclophosphamide, dactinomycin (Actinomycin D), and vincristine. Maurer and associates (1983) reported patients with localized rhabdomyosarcomas at other sites to have a complete response rate of 80%. With chemotherapy, the disease-free survival is improved. Actuarial survival rates of 52% to 83% at 10 years, depending on the initial stage and the absence of hematogenous metastasis, have been reported by Maurer and associates (1988). In the presence of hematogenous metastatic disease, the survival rate is only 20%.

TUMORS OF PLURIPOTENTIAL MESENCHYME AND OTHER RARE TUMORS OF THE MEDIASTINUM

Benign and Malignant Mesenchymoma

Enzinger and Weiss (1988) characterize benign and malignant mesenchymomas as consisting of two or more soft tissue components in the same neoplasm. Examples these authors noted were of a tumor of coexisting rhabdomyosarcoma and liposarcomatous elements and a specific type of sarcoma together with more or less prominent foci of malignant cartilaginous or osseous tissue. They also noted

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small groups of lesions composed of malignant schwannoma with a rhabdomyoblastic component (malignant triton tumor) and rhabdomyosarcomalike tumors with scattered ganglionic elements (ectomesenchymoma) that may qualify as malignant mesenchymomas. Most of these tumors occur in older adults and rarely affect young adults or children. Pachter and Lattes (1963a) reported the occurrence of a few of these lesions, both benign and malignant, in the mediastinum. Boke (1997) and Ohara (1993) and their colleagues, as well as Hsieh and Tseng (1996), have all described benign mesenchymomas in the mediastinum that were cured by resection. Al-Kana and associates (1992) reported a malignant mesenchymoma of the mediastinum.

Solitary Fibrous Tumor: Localized Fibrous Tumor and Fibrous Mesothelioma

Solitary fibrous tumors, both benign and malignant, also have been called solitary mesotheliomas, benign fibrous mesotheliomas, and solitary fibrous tumors of the pleura. Of all these terms, England and associates (1989) advocated the use of the term localized fibrous tumor, which can be designated as either benign or malignant. The term solitary fibrous tumor is the most accepted term for this lesion. Pachter and Lattes (1963a) reported an isolated benign fibrous mesothelioma (localized fibrous tumor) in the mediastinum. Of interest was that in the same series, these authors noted 76 similar lesions in the pleural cavity and 36 in the pericardial cavity. Thus, in their series, a mediastinal location represented less than 1% of such intrathoracic tumors. England and colleagues (1989), however, reported that about 8% of 230 localized fibrous tumors of the thorax originated in the mediastinum. Witkin and Rosai (1989) reported 14 cases of fibrous mesothelioma, which they called solitary fibrous tumors, in the mediastinum. In both of these last two series, the tumors were divided into benign and malignant varieties. Khalifa and associates (1997) reported 10 cases, of which 4 were in the mediastinum. All the tumors occurred in adults and were predominantly found in men. In those patients in whom the clinical history was available, all but one of the malignant lesions were symptomatic, whereas about half of the benign tumors were asymptomatic. Dyspnea and cough were common, and pleural effusion was present with several malignant lesions. One patient, who died of the disease, presented with signs and symptoms of hypoglycemia as well as osteoarthropathy and clubbing; a second patient with a recurrent lesion died of uncontrolled hypoglycemia.

In Witkin and Rosai's (1989) series, all but three of these tumors arose in the anterior compartment in the region of the thymus; two occurred in the visceral compartment, and one was in a paravertebral sulcus. The tumors ranged in size from 4.5 to 24 cm and had a median weight of 600 g. In the pleural spaces, these tumors were usually on a pedicle. In the mediastinum, only two of the tumors reported by Witkin and Rosai (1989) had pedicles. Grossly, the tumors appear as encapsulated, firm, lobulated masses. On cut section, the surface is tan to gray with a whorled appearance. Cystic changes may be present. On microscopic examination, two patterns may be present. The more common one is the patternless pattern described by Stout (1971). This pattern shows round to spindle cells set between dense bundles of collagen. The second pattern is described as being hemangiopericytomalike. The malignant tumors show increased cellularity with overlapping and pleomorphic nuclei, increased mitotic activity, hemorrhage, and necrosis. England and colleagues (1989) described the malignant tumors as having more than four mitotic figures in each of 10 high-power ( 400) microscopic fields. The localized benign fibrous tumors may be misinterpreted as spindle cell variants of thymomas. Witkin and Rosai (1989) have listed the differential features between these two tumors (Table 192-2).

The immunohistochemical studies performed by Witkin and Rosai (1989) showed positive staining for vimentin and negative staining for S-100 and cytokeratin in these tumors. England and colleagues (1989) in their series, stained 35 benign and 29 malignant localized fibrous tumors. They found variable staining from tumor to tumor and from one microscopic field to another. Vimentin was expressed by

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the cells in 80% of the tumors stained, but cytokeratin was not. Van de Rijn and colleagues (1994) and Hanau and Miettinen (1995) have reported the positive reactivity of these tumor cells to CD34 antigen. CD34 reactivity is characteristically found in hematopoietic stem cells (see Chapter 64 for further details). This reactivity is absent in mesothelioma cells. On electron microscopy, the malignant tumors displayed greater nuclear size and prominent nucleoli. Otherwise, there was nothing to differentiate them from benign tumors. The tumor cells had features of fibroblasts with collagen in the background.

Table 192-2. Differential Diagnosis between Solitary Fibrous Tumor and Spindle Cell Thymoma

Characteristic Solitary Fibrous Tumor Spindle Cell Thymoma
Clinical associations Hypoglycemia, clubbing, hypertrophic osteo-arthropathy Red cell aplasia, hypogammaglobulinemia
Light microscopy Collagen between cells Collagen in trabeculae dividing tumor into lobules
Immunohistochemistry Keratin negative; variably vimentin and actin positive; CD34 positive Keratin positive; vimentin and actin negative
Ultrastucture Mesenchymal, lacking epithelial features Epithelial cells with tonofilaments
Adapted from Witkin GB, Rossi J: Solitary fibrous tumor of the mediastinum, a report of 14 cases. Am J Surg Pathol 13:547, 1989. With permission.

The cell of origin of solitary fibrous tumors is unclear. Most likely, these tumors originate from a submesothelial connective tissue cell rather than from a mesothelial cell. The immunohistochemical and electron microscopic findings are consistent with a submesothelial cell origin. The features that differentiate them from pleural mesotheliomas are listed in Table 192-3.

The treatment of solitary fibrous tumors is surgical excision, which is curative for benign lesions. Malignant ones, however, often recur and progress locally despite irradiation or chemotherapy. England and colleagues (1989) found that, in general, malignant localized fibrous tumors of the pleura do not always behave aggressively. When the entire tumor could be excised at the initial operation, the patient generally did well. The course of the disease may be prolonged for years before death. Distant metastasis is uncommon but has occurred to the lung.

Calcifying Fibrous Pseudotumor

Calcifying fibrous pseudotumors were reported by Fetsch and colleagues (1993) in the soft tissues and in the pleura by Pinkard and associates (1996) (see Chapter 67). These benign lesions are characterized by the abundant hyalinized collagen with psammomatous or dystrophic calcifications and lymphoplasmacytic infiltrates. Dumont and colleagues (1997) reported one of these lesions occurring in the anterior mediastinum with extension into the visceral compartment. Complete resection was accomplished through a median sternotomy. The prognosis of patients with these tumors is excellent.

Mediastinal Xanthoma

Rossi and associates (1973) reported a mediastinal xanthoma and noted that about 12 similar cases had been recorded in the literature. The lesion was located in the visceral compartment, and the adjacent lymph nodes were involved in the same process. At that time, they believed the lesion to be benign and reactive in nature. With additional information, as discussed by Enzinger and Weiss (1988), however, the malignant potential of all such lesions should be remembered.

Pseudotumor of the Mediastinum in Primary Amyloidosis

In patients with primary amyloidosis, the lung and associated lymph nodes may occasionally be involved. Infrequently, a pseudotumor in the mediastinum may occur when pulmonary involvement is present, but its occurrence in the absence of pulmonary involvement is rare. Hiller and associates (1995), however, described a middle-aged man with an isolated, irregular mediastinal mass in the visceral compartment above the right pulmonary hilus. Lymph nodes were enlarged, but no pulmonary involvement could be discerned. CT of the mass revealed a relatively dense homogenous mass without calcifications present, although in

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a previous report, Jenkins and Potter (1991) noted that two of four patients with pseudotumoral mediastinal amyloidosis had calcifications within the mass. The diagnosis in Hiller and colleagues' (1995) report was established by a positive Congo red test of aspirated material from the mass. Characteristic green birefringence of amyloid was also present. The patient's amyloidosis was treated medically.

Table 192-3. Differentiation of Solitary Fibrous Tumor and Mesothelioma of the Mediastinum

Characteristic Solitary Fibrous Tumor Mesothelioma
Light microscopy Patternless plump to spindled cells in collagenous background Tubulopapillary pattern, spindle cell, in hyaline background
Ultrastructure Spindled mesenchymal cells Microvilli, blunt cytoplasmic processes
Immunoreactivity Vimentin (+)a Vimentin ++
EMA (-) EMA (+)
Actin (+)  
Keratin (-) Keratin ++
CEA (-) CEA (+)
CD34 + CD34 (-)
Note: England and associates (1989) reported that 38 of 43 previously studied cases of solitary fibrous tumors of pleura, as well as 25 of the 31 cases they studied, were positive for vimentin immunoreactivity, a combined average of 85%. Therefore, this antigen is probably of little value in differentiating this tumor from a mesothelioma.
a Variably positive.
CEA, carcinoembryonic antigen; EMA, epithelial membrane antigen.

Elastofibrolipoma

An elastofibrolipoma of the mediastinum was described by De Nictolis and colleagues (1995a). The tumor occurred in the anterior compartment in a middle-aged woman and was successfully surgically excised. This lesion has not been described previously and is believed to be a variant of a fibrolipoma that contained abnormal elastic fibers. It is considered a benign tumor.

Follicular Dendritic Cell Tumor

Follicular dendritic cell tumors are extremely rare neoplasms that behave more like low-grade soft tissue sarcomas than malignant lymphomas. They have been identified mainly in the lymph nodes of the neck and axilla. Their identification is based on their histologic and immunohistochemical features. Perez-Ordonez and associates (1996) reported the occurrence of a follicular dendritic cell tumor in the mediastinum of three patients, as well as 10 other of these tumors located elsewhere. In addition, they extensively reviewed 17 other cases that had been reported in the literature. Surgical resection appears to be the treatment of choice, although radiation therapy and chemotherapy have been used as therapeutic adjuncts. The ultimate prognosis of these patients is as yet unknown.

Meningioma

A meningioma located in a paravertebral sulcus has been described by Wilson and associates (1979). It was believed to have arisen from a stellate ganglion. Histologically, the lesion was identical to meningiomas seen in the central nervous system. Such lesions do occur in extracranial locations, but the mediastinum is an unusual location.

Ependymoma

Two ependymomas have been reported to have occurred in the paravertebral sulci one by Doglioni (1988) and the other by Nobles (1991) and their colleagues. In neither case was the tumor attached to the spinal cord. The origin of this tumor is unknown, but it has been postulated that it arises from ependymal cell rests (neural tube remnants) or from ectopic germ cells (a monodermal teratoma). Both Marchevsky and Kaneko (1992) and Kornstein (1995c) summarized the microscopic and immunohistologic features of this tumor. It is composed of solid and papillary areas, elongated tubules, and rosettes of ependymal type. Rare psammoma bodies may be present. Elongated fibrillary cytoplasmic processes are readily identified. The tumor cells exhibit intracytoplasmic glial-fibrillary acidic protein reactivity.

One of the reported tumors had metastasized to an adjacent lymph node. Thus, these tumors must be considered malignant, as are ependymomas of the lung. Surgical excision is the therapy of choice.

Synovial Sarcoma

Witkin and associates (1989) described a biphasic tumor of the mediastinum with features of a synovial sarcoma. There are four varieties of synovial sarcomas described in the literature: (a) biphasic type, (b) monophasic type, (c) monophasic epithelial type, and (d) poorly differentiated (round cell) type. The cases described by the aforementioned authors were of the biphasic type. They reported four cases and added another as an addendum to their report. All but one were in middle-aged men; the exception was in an older man in the eighth decade of life. All were symptomatic. The lesions were identified as typical of a synovial sarcoma and had a biphasic pattern of malignant epithelial and spindle cells. All were composed of an intimate admixture of keratin-positive epithelial cells and vimentin-positive spindle cells with areas of transition, as well as hyalinization and calcification. All arose within the visceral compartment of the mediastinum. Surgical removal was attempted in all the patients, with subsequent radiation therapy and chemotherapy in two. Of the three patients in whom follow-up was available, all died of the disease, with local recurrence and pulmonary metastases documented in two. Two patients died within 10 and 14 months, respectively, and the third survived 4 years. Trupiano and colleagues (2002) have reported two additional cases of synovial sarcoma of the mediastinum. In one patient, immunochemical features were studied, and the the tumor tissue showed variable reactivity for cytokeratins (AE 1/3, CAM 5.2, and cytokeratins 7 and 19 of Moles catalogue) as well as to the epithelial membrane antigen. The tumor tissue revealed no reactivity to Leu M1, B 72.3, BER-EP4, or CEA. Genetic analysis by fluorescent in situ hybridization in one case and by the reverse transcriptase polymerase chain reaction in the other case was carried out. Both studies revealed evidence of an SSX1-SYT fusion transcript indicative of a t(X;18) characteristic of synovial sarcoma. Identification of t(X;18) is found in more than 90% of synovial sarcomas, as reported by Witkin and associates (1989). This genetic translocation involves the SYT gene on chromosome 18 and either the SSX1 or SSX2 gene on the X chromosome as identified by Clark and coinvestigators (1994).

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Mesothelioma

Malignant, diffuse mesotheliomas may arise from the mediastinal pleura, but these should not be considered primary tumors of the mediastinum. Bierhoff and Pfeifer (1996) described a biphasic malignant mesothelioma that originated in the visceral compartment of the mediastinum. The patient was a 50-year-old man who presented with a metastasis to a cervical lymph node. He was thought to have bronchial carcinoma. Four weeks later, he died, and at autopsy, he had a well-defined cystic mesothelioma in the mediastinum. It was thought to originate from a pericardial cyst. Crotty and associates (1992) described a 48-year-old woman who presented with dyspnea, chest discomfort, and left vocal cord paralysis. On chest radiograph, she had a prominent mediastinal shadow. A biopsy showed sclerosing mediastinitis. Over the course of the next year, the patient deteriorated. She had a second thoracotomy but died postoperatively. At autopsy, she had a sclerotic mass in the mediastinum, which was composed of malignant spindle cells as well as sclerotic connective tissue. Her final diagnosis was desmoplastic malignant mesothelioma. The course and behavior of these tumors are those of malignant mesotheliomas arising elsewhere in the thorax. This subject is well covered by Enzinger and Weiss (1988) and Roth and associates (1989).

EXTRASKELETAL SARCOMAS

Extraskeletal sarcomas are composed of osteogenic sarcomas and chondrosarcomas. These rare tumors may occur in the thorax, but a mediastinal origin of such tumors has only been recorded on a few occasions.

Extraskeletal Chondrosarcomas of the Mediastinum

Mediastinal extraskeletal chondrosarcomas are extremely rare neoplasms. Chetty (1990) reported one case that appears to have been a primary extraskeletal chondrosarcoma. It occurred in the right paravertebral space in a young man. The tumor was excised, but early recurrence with pulmonary invasion was fatal. Suster and Moran (1997) reported six cases and reviewed the literature. Their patients ranged in age from 11 to 63 years, with a median age of 32 years. Five of the patients were women, and one was a man. Two of the patients were asymptomatic, and the other four complained of backache, chest pain, respiratory difficulties, and dysphagia. All of the tumors were located in the posterior mediastinum. The radiologic findings varied somewhat depending on the type of chondrosarcoma. The chest radiographs showed well-circumscribed soft tissue densities that did not appear to be arising from bone. In one patient, a suggestion of cortical flaring of the vertebral body was seen at the level of T10. The CT scans, in four cases with contrast enhancement, showed well-delineated soft tissue masses with central areas of calcification. In an additional patient, the CT scan showed partial encasement of the trachea and aorta by the tumor. At the time of surgery, all the tumors were completely excised. None of these tumors appeared to have arisen from bone. On gross examination, the tumors ranged from 5 to 12 cm in greatest dimension. The tumors in four patients were well circumscribed and covered by a thin fibrous capsule. On cut section, they were tan-white with a soft, lobulated surface. In two patients, the tumors appeared well circumscribed and unencapsulated with a soft mucoid, gelatinous cut surface. On microscopic examination in the first four cases, the tumors were mesenchymal chondrosarcomas. In the other two patients, one tumor was a moderately to poorly differentiated chondrosarcoma, and in the second, the lesion was a myxoid chondrosarcoma. Immunohistochemical stains were performed on three of the mesenchymal chondrosarcomas and also on the myxoid chondrosarcoma. The stain results for keratin, epithelial membrane antigen, carcinoembryonic antigen, desmin, actin, and CD34 were negative. The cells in all of the cases stained strongly for vimentin. The stains for S-100 were positive in the cartilaginous areas of the mesenchymal chondrosarcomas but did not stain the cells in the myxoid chondrosarcoma.

The differential diagnosis for these lesions includes solitary fibrous tumor, monophasic synovial sarcoma, and chordoma. The treatment is complete surgical excision with postoperative radiation therapy if indicated. Of the four patients with mesenchymal chondrosarcomas, one patient died 8 years later, one was alive after 6 years, and two had recurrences after 3 and 7 years. The patient with the moderately well to poorly differentiated chondrosarcoma was lost to follow-up. The patient with the myxoid chondrosarcoma developed lung metastases 10 months after surgery but was lost to follow-up. As a rule, the other so-called chondrosarcomas of the mediastinum and elsewhere in the thorax have arisen from the tracheobronchial tree, as reported by Daniels and associates (1967), or more often from the vertebral bodies. Either of the latter types, however, must be considered as a lesion masquerading as a mediastinal tumor. Chondrosarcomas of the spine have been briefly discussed in Chapter 168.

Extraskeletal Osteogenic Sarcoma of the Mediastinum

An extraskeletal osteogenic sarcoma of the mediastinum was described initially by Wilson (1941), but this case is now thought to have arisen from the pericardium. Valderrama and colleagues (1983) described a case in an 11-year-old girl, but the site of origin, in ectopic hamartomatous thymic tissue within the left pulmonary ligament, can be debated as to whether the lesion was pleural or mediastinal in location. However, Ikeda and associates (1974) did report an extraskeletal osteogenic sarcoma arising in the

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visceral compartment of the mediastinum. Although the lesion recurred after the initial resection, the patient was still alive 5 years later after a second resection and postoperative irradiation. De Nictolis and colleagues (1995b) reported a 68-year-old man with an extraskeletal osteosarcoma of the anterior mediastinum. The patient underwent complete excision of the tumor but refused further treatment. He was alive and well 38 months after surgery. Venuta and associates (1993) described a case of a 22-year-old woman with a posterior mediastinal extraskeletal osteosarcoma and summarized the literature. Their patient underwent an incomplete resection but was treated with postoperative chemotherapy and radiation. The tumor recurred, however, and the patient died 7 months after surgery.

Tarr and colleagues (1988) reported an additional case located in the anterior mediastinal compartment. CT of the lesion revealed an extensive area of calcification within the mass (Fig. 192-10). The authors suggested that this finding should raise the index of suspicion as to the possibly extraskeletal osteogenic nature of the tumor. Greenwood and Meschter (1989) likewise reported an extraskeletal osteogenic sarcoma in the anterior mediastinum that was closely adherent to the anterior aspect of the pulmonary artery and arch of the aorta. The exact site of origin could not be discerned.

The prognosis of these lesions is unknown but probably is similar to that of extraosseous osteogenic sarcoma occurring elsewhere in the body, which has less than a 25% long-term survival probability. An interesting feature, as also mentioned for malignant schwannomas (see Chapter 189), is that extraskeletal osteogenic sarcoma may occur as a late complication of radiation therapy. This was noted by Boyer and Navin (1977), and the subject was reviewed by Varela-Duran and Dehner (1980). The possible late occurrence of such a tumor after irradiation of mediastinal lymphomas or seminomas should be remembered. The possibility of this event was confirmed by the report of Yoshitake and colleagues (1991). The authors reported the late development of an osteogenic sarcoma in a man after initially successful irradiation and chemotherapy for a primary mediastinal seminoma. Likewise, Catanese and associates (1988) reported such an occurrence in a patient treated for Hodgkin's disease.

RARE EPITHELIAL MEDIASTINAL TUMORS

Malignant Melanoma

Although a malignant melanoma is not of mesenchymal origin, the occurrence of a primary malignant melanoma in the mediastinum is so rare that we have arbitrarily included it with the rare mesenchymal tumors of this region. A small number of case reports have appeared in the literature. The first case was reported by Feldman and Kricun (1979), but the validity may be questioned as to its true origin, primary or secondary. A second case was reported by Shishido and associates (1997)

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and presented as a mass causing a superior vena cava obstruction. An additional case was published by Lau and colleagues (1999). In this last patient, no extrathoracic site could be identified, and the tumor that was present in the visceral compartment was confirmed to be a melanoma by the presence of melanin pigment by Fontana histologic staining, the expression of HMB-45 and S-100 positive results on immunohistochemical staining, and the presence of abundant melanosomes on electron microscopy. In discussing the subject, Moran and Suster (2000) noted that most primary melanomas located in the mediastinum occur in older adults, however, Vlodarsky and associates (2000) reported a primary mediastinal melanoma, as proved by the appropriate immunohistochemical studies, to have occurred in the anterior mediastinal compartment in a 12-year-old boy.

Fig. 192-10. A. Posteroanterior radiograph of the chest of an adult man with a large anterior mediastinal mass. B. CT scan revealed a nonhomogeneous mass with a large area of calcification (arrows). Tumor was an extraosseous osteogenic sarcoma on histologic examination. From Tarr RW, et al: Primary extraosseous osteogenic sarcoma of the mediastinum: clinical, pathologic and radiologic correlation. South Med J 81:1317, 1988. With permission.

Treatment is surgical excision, when possible, plus chemotherapy. The prognosis is guarded. Finally, it is to be noted that any time a melanoma is found in the mediastinum, it is far more likely to be a metastatic lesion than a primary tumor.

Sclerosing Hemangioma

Sakamoto and colleagues (2003) described a typical sclerosing hemangioma present in the visceral compartment of the mediastinum extending into the right paravertebral space. The cells were interstitial epithelioid cells, and hyperplastic type II pneumocytes lined the surface of papillary cystic structures present in the solid and sclerotic areas within the tumor. No lung nor lymphatic tissue was identified. The interstitial epithelioid cells were immunoreactive to EMA, vimentin, chromogranin, and thyroid transcription factor-1 (TTF-1). The expression of the latter is believed to support the origin of sclerosing hemangioma from primitive respiratory epithelium by Devouassoux-Shisheboran and colleagues (2000). The epithelial origin is also supported by the study of Rodriguez-Soto and associates (2000). How this tumor arose within the mediastinum remains unknown, and to the knowledge of the authors, the present case is the only one that has been identified in the mediastinum. These tumors are benign with a few exceptions in the lung (see Chapter 118), and there is no reason to believe that the lesion in the mediastinum would behave differently. Simple excision should be curative.

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General Thoracic Surgery. Two Volume Set. 6th Edition
General Thoracic Surgery (General Thoracic Surgery (Shields)) [2 VOLUME SET]
ISBN: 0781779820
EAN: 2147483647
Year: 2004
Pages: 203

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