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35 Differentiating from

Oliver Kim and Thomas Krausz

Despite the abundant literature data on the topic, the diagnosis of malignant remains challenging. Its frequent phenotypic heterogeneity and diverse architectural patterns underline the capac- ity of mesothelioma to mimic other , notably adenocarci- noma and sarcomas. Immunohistochemical markers facilitate solving differential diagnostic problems; however, in some cases, a definitive diagnosis of malignant mesothelioma is still a challenge. The pleura or other serosal surfaces can be involved by a number of neoplastic conditions, ranging from benign to malignant. Furthermore, meta- static neoplasms commonly involve these sites. Although malignant mesothelioma is a relatively uncommon tumor, it is the most common primary of the pleura and can develop at other sites, including the peritoneum, pericardium, and tunica vaginalis (1). Histologically, the major subtypes of malignant mesothelioma are epithelioid, sarcomatoid, and mixed. Therefore, the differential diag- nosis varies according to histologic type. Correlation between clinical, radiographic, and pathologic findings is critical to make a correct diagnosis. Although distinguishing mesothelioma from an is the more common problem, differentiating either a metastatic or primary from a malignant mesothelioma can have important therapeutic consequences. Primary mesenchymal tumors, primarily solitary fibrous tumors and sarcomas, of the pleura and other serosal membranes are rare (1). Most sarcomatous tumors of the pleura are manifestations of either a metastatic sarcoma or a sarcomatoid mesothelioma. In addition, sarcomas arising from the chest wall or lung can also involve the pleura. Both primary and metastatic sarco- mas can mimic the characteristic clinical, radiologic, and pathologic findings of a malignant mesothelioma. Distinguishing sarcomatoid mesothelioma from morphologically similar sarcomas is a diagnostic challenge. This chapter outlines a practical approach in distinguishing mesothelioma from sarcomas.

527 528 Chapter 35 Differentiating Sarcomas from Mesotheliomas

Sarcoma Versus Malignant Mesothelioma: General Differential Diagnostic Considerations

The pathologic features of sarcomatoid mesothelioma are not entirely specific and often overlap with other primary and secondary serosal- based sarcomas and spindle . Furthermore, depending on the degree of deposition (desmoplastic mesothelioma), a more frequent problem is distinguishing sarcomatoid mesothelioma from benign fibrous pleurisy. The growth pattern of sarcomatoid mesothelioma is diverse. It may be storiform with similarity to the so- called malignant fibrous . The tumor cells may display a fibrosarcoma-like appearance with long fascicles exhibiting a herring- pattern. Leiomyoid differentiation has been described in which the cells have oval, elongated nuclei, eosinophilic cytoplasm, and coexpress and (2,3). In addition, heterologous elements, including osteoid (4), chondroid (4), and rhabdomyoblastic differenti- ation (5), rarely can be identified. Depending on the histologic features present, diagnostic considerations can include fibrosarcoma, so-called malignant fibrous histiocytoma, malignant peripheral (6), , (7), (8), (9–11), (12), malignant solitary fibrous tumor (13–15), and (16), all of which have been reported to arise primarily in the pleura. Metastatic neoplasms, includ- ing sarcomatoid , malignant , and thymoma, have all been documented and should be diagnostic considerations (17). Gastrointestinal stromal tumor (GIST), either as a or an extraintestinal primary, can also histologically resemble a sarcomatoid mesothelioma. C-KIT immunoreactivity defines this tumor, and is negative in mesotheliomas. expression is most useful in distinguishing most sarcomas from sarcomatoid mesothelioma. Characteristically, nearly all mesotheliomas of epithelioid, sarcomatoid, or mixed type exhibit strong cytokeratin expression (18,19). Both low and high molecular weight are detectable in most mesotheliomas, especially low molecular weight cytokeratins. Although cytokeratin can be utilized to distinguish sarcomatoid mesothelioma from most sarcomas, there are a few caveats. First, inves- tigators have reported variable immunoreactivity with cytokeratins. Although all epithelioid mesotheliomas express cytokeratin, the per- centage of sarcomatoid mesotheliomas reported in the literature to express cytokeratin is variable. Some investigators have detected cytokeratins in 100% of their sarcomatoid mesothelioma cases exam- ined (18,19). In contrast, others failed to detect cytokeratins in up to 40% of sarcomatoid mesotheliomas (4,5,13,20–24). In our experience, all cases of sarcomatoid mesothelioma exhibit immunoreactivity with cytokeratin antibody CAM 5.2. Thus, these results stress the importance of utilizing, in addition to cytokeratins, a panel of other immunomarkers. O. Kim and T. Krausz 529

Second, cytokeratin expression can also be occasionally seen in sar- comas (25,26), including monophasic synovial sarcoma, angiosarcoma, malignant peripheral nerve sheath tumor, and leiomyosarcoma. But cytokeratin immunoreactivity seen in these sarcomas is usually focal. Monophasic synovial sarcomas tend to express either or both cytoker- atins 7 and 19, whereas malignant peripheral nerve sheath tumors do not (27). Malignant melanoma can metastasize to the pleura and sim- ulate a mesothelioma. Rare are -positive (28,29) but typically express S-100 and HMB-45 antigen. Third, cytokeratin does not discriminate sarcomatoid mesothelioma from metastatic , primary pleural thymoma, pseudomesotheliomatous carcinoma of lung, or even metastatic epithe- lioid sarcoma. Cytokeratin immunoreactivity is typically strong in all of these tumors. In these cases, positivity with any of the mesothelial- specific markers or absence of carcinoma markers would favor sarcomatoid mesothelioma. However, many of the allegedly specific mesothelial markers have cross-reactivity with other tumors, especially metastatic carcinoma. Hence, the importance of utilizing a broad panel of carcinoma and mesothelial markers is emphasized, in addition to obtaining clinical history. Of important note, thymomas can rarely occur in the pleura without evidence of an associated mediastinal tumor (30). They may occur as a localized tumor or, more rarely, as a diffuse pleural thickening mimicking a mesothelioma (30–32). Histo- logically, they may be confused with a sarcomatoid mesothelioma with a lymphocytic infiltrate or a lymphohistiocytoid mesothelioma. The neoplastic cells exhibit strong cytokeratin immunoreactivity. As opposed to mesotheliomas, which can have a mixed population of plasma cells and T and B lymphocytes, thymomas contain a popula- tion of precursor T lymphocytes, commonly coexpressing CD1, CD2, CD3, CD99 (MIC-2) (33), bcl-2 (34), and terminal deoxynucleotidyl transferase (35) antigens. , both the conventional and proximal variant, can metastasize to the lung and pleura and be difficult to differentiate from the epithelioid mesothelioma. They typi- cally exhibit strong immunoreactivity to both low and high molecular weight . Although the conventional or distal variant of epithe- lioid sarcoma tends to occur in young adults, the proximal variant occurs in the older age group. Thus, epithelioid sarcoma should be con- sidered in the differential diagnosis. The differentiating factor would be the strong positivity for CD34 in a high percentage of epithelioid sarcomas, for which mesotheliomas are negative. Ultrastructural features of sarcomatoid mesothelioma are non- specific and overlap with those of fibroblasts (5,36). The tumor cells contain variable amounts of rough endoplasmic reticulum, Golgi appa- ratus, intermediate filaments, and extracellular collagen. Occasionally, the tumor cells exhibit actin filaments in the cell periphery, resembling myofibroblasts. Epithelial differentiation can also be identified on occa- sion, which includes the presence of intercellular junctions, rare surface microvilli, aggregates of tonofilaments, and incomplete formation of basal lamina. Differentiation of sarcomatoid mesotheliomas from other 530 Chapter 35 Differentiating Sarcomas from Mesotheliomas

sarcomatoid neoplasms can be made by the presence of specific ultra- structural components in other tumors that are typically lacking in mesotheliomas. Thus, the diagnosis continues to rely on a multimodal approach incorporating clinical history, gross and microscopic features, immunohistochemistry, and electron to arrive at a defini- tive diagnosis.

Synovial Sarcoma Versus Malignant Mesothelioma

Synovial sarcoma is a rare tumor most commonly found in the soft tissues of the extremities but other sites, including the head and neck (37–39), mediastinum (40–42), lung (43–48), heart (49), esophagus (50), and (51), have also been reported. There have been reports of synovial sarcoma arising in the pleural cavity (8,52,53). The rarity of this tumor at this site makes it a potentially overlooked diagnosis, espe- cially since the histologic characteristics of synovial sarcoma can closely resemble malignant mesothelioma. Both tumors can present with either purely sarcomatoid or mixed sarcomatoid/epithelioid components. Thus, monophasic synovial sarcoma must be distinguished from sar- comatoid malignant mesothelioma, and biphasic synovial sarcoma from mixed malignant mesothelioma. However, there are both clinical and histologic features that aid in making a diagnosis of synovial sarcoma arising within the pleural cavity. In contrast to malignant mesothelioma, the majority of pleural syn- ovial sarcomas tend to occur in children, adolescents, and young adults. Although presenting with effusions is common, as in mesothelioma cases, synovial sarcomas tend to be localized and relatively circum- scribed mass lesions with rapid growth, rather than a diffusely infil- trating mass, as is characteristic for mesothelioma. Pleural synovial sarcomas exhibit similar histomorphologic, immunohistologic, and ultrastructural features as synovial sarcomas occurring in other sites. Reported cases of primary pleural synovial sarcomas correspond to both the biphasic (52,53) and monophasic (44,54,55) variants of synovial sarcoma. Thus, synovial sarcoma can be confused with both the bipha- sic and sarcomatoid malignant mesothelioma (Figs. 35.1 and 35.2). In synovial sarcoma, the neoplastic epithelial cells tend to express “car- cinoma” markers, including keratins (Fig. 35.1), epithelial membrane antigen (EMA), (CEA), and BerEP4. The cytokeratin staining pattern of the glandular cells of synovial sarcoma is diffuse as opposed to the perinuclear keratin-staining pattern seen in mesothelioma. In addition, the secretions from the epithelial compo- nent are typically positive for neutral mucins, which are periodic acid-Schiff (PAS) positive and diastase-resistant, and Alcian blue posi- tive and hyaluronidase resistant. This histochemical and immuno- phenotypic reaction strongly argues against a malignant mesothelioma. Monophasic synovial sarcoma and the sarcomatoid component of biphasic synovial sarcoma characteristically express cytokeratins, focally differentiating it from the typically strong and diffuse cytoker- atin positivity seen in sarcomatoid mesothelioma (Fig. 35.2). Epithelial Figure 35.1. Biphasic synovial sarcoma [hematoxylin and eosin (H&E)] (A) exhibiting strong keratin immunoreactivity (B) of the epithelioid (glandular) component. Biphasic malignant mesothelioma (H&E) (C) showing both epithe- lioid and sarcomatoid components. 532 Chapter 35 Differentiating Sarcomas from Mesotheliomas

Figure 35.2. Monophasic synovial sarcoma (H&E) (A) expressing focal keratin immunoreactivity (B) in the spindle cells. In comparison, a sarcomatoid malig- nant mesothelioma (H&E) (C) exhibiting strong and diffuse keratin immunore- activity (D).

membrane antigen also reacts in a similar pattern as cytokeratins in syn- ovial sarcomas except it is expressed in a more prominent, often linear fashion. MIC-2 (CD99) and bcl-2 have been shown to be useful markers in the diagnosis of synovial sarcoma, exhibiting immunoreactivity in the majority of cases (24,56,57). However, a few reports have shown variable positivity for both markers in cases of mesothelioma (58,59). It is important to keep in mind when the differential diagnoses include malignant peripheral nerve sheath tumor and spindle cell melanoma that S-100 protein may be detected in approximately 30% of synovial sarcomas. Rare cells in malignant mesothelioma can also express S-100 antigen. Ultrastructurally, the epithelial component exhibits features similar to adenocarcinoma (60), including terminal bar and O. Kim and T. Krausz 533

Figure 35.2. Continued desmosomal junctional complexes, external lamina, and surface micro- villi protruding into the glandular lumen. In the monophasic synovial sarcoma, the ultrastructural features may be nonspecific, but occasional abortive lumina with projecting microvilli may be seen with thorough examination. Of course, t(X;18)(p11;q11) is the cytogenetic hallmark of synovial sarcoma, being present in nearly all cases (61,62).

Epithelioid /Angiosarcoma Versus Malignant Mesothelioma

Although primary malignant vascular tumors of the serous membranes are rare, both epithelioid hemangioendothelioma and angiosarcoma of the pleura have been described (10,11,63,64). Endothelial tumors arising near serous membranes can mimic an epithelioid malignant mesothelioma histologically and clinically (Fig. 35.3). Although these 534 Chapter 35 Differentiating Sarcomas from Mesotheliomas

are regarded as morphologically and biologically distinct entities, rep- resenting the low- and high-grade forms of malignant vascular tumors, it is increasingly recognized that it is difficult to distinguish between an epithelioid angiosarcoma and high-grade epithelioid hemangioen- dothelioma. In addition, both tumors, when arising within the pleura, have been associated with high morbidity and mortality (10). However, the diagnostic distinction may still be important as further studies determine which histologic features of epithelioid hemangioendothe-

Figure 35.3. Epithelioid hemangioendothelioma showing the typical myxo- hyaline matrix (H&E) (A) with aggregates of epithelioid tumor cells exhibiting intracytoplasmic lumina with entrapped red blood cells (H&E) (B). Strong CD31 immunoreactivity (C) reflects the endothelial nature of the epithelioid tumor cells. Note the cytohistologic similarities to an epithelioid malignant mesothelioma (H&E) (D). O. Kim and T. Krausz 535

Figure 35.3. Continued lioma have an impact on prognosis. We have seen a case of epithelioid hemangioendothelioma where the patient survived 8 years after pleurectomy. Epithelioid tumor cells with prominent nucleoli and cytoplasmic vacuoles characterize both tumors. The vacuoles do not contain hyaluronic acid, glycogen, lipid, or mucin, but may contain an entrapped red blood cell, reflecting primitive lumen formation (Fig. 35.3). Epithelioid angiosarcoma is histologically a more aggressive- looking tumor with large, vesicular nuclei and frequent mitotic figures. The myxohyaline matrix is typical for epithelioid hemangioendothe- lioma and not seen in epithelioid angiosarcoma. Both tumors may exhibit a tubulopapillary growth pattern with diffuse extension over the pleural surfaces similar to that seen in an epithelioid mesothelioma. Hence, the term pseudomesotheliomatous angiosarcoma or hemangio- endothelioma was coined. As opposed to epithelioid mesotheliomas, 536 Chapter 35 Differentiating Sarcomas from Mesotheliomas

epithelioid angiosarcoma or hemangioendothelioma shows only focal and inconsistent immunoreactivity to cytokeratin antibodies (63,65). The tumor cells also coexpress endothelial markers, including CD31 (Fig. 35.3), CD34, and von Willebrand factor. Ultrastructur- ally, the tumor cells demonstrate abundant intermediate filaments, micropinocytotic vesicles, abortive lumena, interrupted basal lamina, and Weibel-Palade bodies.

Solitary Fibrous Tumor Versus Malignant Mesothelioma

Solitary fibrous tumor is the most common benign mesenchymal pleural and must be distinguished from a sarcomatoid malignant mesothelioma. Although first described by Klemperer and Rabin (66) as a localized fibrous mesothelioma, subsequent studies demonstrated that the tumor cells did not exhibit features of mesothe- lial cells but showed fibroblastic differentiation (56,67,68). The tumor most often occurs in adults between the fifth and sixth decade of life. Extrapleural solitary fibrous tumors are also well recognized. Most patients are asymptomatic but may experience hypoglycemia, which is characteristically associated with some cases of solitary fibrous tumor (69). As opposed to mesotheliomas, solitary fibrous tumors are typi- cally well circumscribed and often partially encapsulated, or may be attached to the pleura by a short pedicle. Histologically, solitary fibrous tumors exhibit a so-called patternless architecture characterized by a combination of alternating hypocellular, collagenous, and hypercel- lular spindle cell areas with -like vasculature (Fig. 35.4). The tumor is composed of bland spindle cells with scant cytoplasm and vesicular nuclei. The spindle cell component can adopt a variety of growth patterns that may be mistaken for other tumors, including a storiform pattern reminiscent of fibrohistiocytic tumors; hemangioperi- cytic, angiofibromatous, herringbone, neural-type, and fascicular pat- terns similar to fibrosarcoma; and malignant peripheral nerve sheath tumor or monophasic synovial sarcoma. The hypocellular areas can exhibit prominent myxoid change, and, rarely, metaplastic bone for- mation, mature adipocytes, and multinucleated stromal giant cells. Mitotic activity is generally low. Malignant solitary fibrous tumors are usually hypercellular with cytologic atypia, necrosis, infiltrative margins, and increased mitotic activity (more than four mitoses per 10 high-power fields), although the cut-off point between a benign and malignant solitary fibrous tumor is not established. On a small , it can be extremely difficult to differentiate a solitary fibrous tumor from a mesothelioma or other mesenchymal tumors. Immunohisto- chemistry has an important diagnostic role in this differentiation. Tumor cells in solitary fibrous tumors are characteristically immunore- active with CD34 (70–73) (Fig. 35.4). In addition, MIC-2 (CD99) is present in a high percentage of cases (74). Variable positivity is seen with bcl-2 (56,75) and actin. Focal and limited reactiv- ity is occasionally seen for S-100, and desmin. Mesothelioma is O. Kim and T. Krausz 537

Figure 35.4. Solitary fibrous tumor showing a hypercellular focus of bland spindle cells with hemangiopericytoma-like vasculature (H&E) (A), intercellular collagen formation (H&E) (B), and strong immunoreactivity to CD34 (C). 538 Chapter 35 Differentiating Sarcomas from Mesotheliomas

typically CD34-negative and strongly positive for cytokeratin. A diag- nostic problem may arise when entrapped mesothelial cells in a soli- tary fibrous tumor immunoreact strongly with a cytokeratin immunostain. Ultrastructurally, solitary fibrous tumors are nonspecific and often demonstrate features of fibroblasts, myofibroblasts, or, arguably, pericytes (71). Electron microscopy is of limited use in dis- tinguishing solitary fibrous tumor from sarcomatoid mesothelioma.

References

1. Battifora H, McCaughey WTE. Tumor and pseudotumors of the serosal membrane. In: Rosai J, Sobin L, eds. Atlas of Tumor Pathology, 3rd ed. Washington DC: Armed Forces Institute of Pathology, 1995:37–47. 2. Hurlimann J. Desmin and neural marker expression in mesothelioma cells and mesothelioma. Hum Pathol 1994;25:753–757. 3. Mayall FG, Goddard H, Gibbs AR. Intermediate filament expression in mesotheliomas: leiomyoid mesotheliomas are not uncommon. Histopathology 1992;21:453–457. 4. Yousem SA, Hochholzer L. Malignant mesotheliomas with osseous and cartilaginous differentiation. Arch Pathol Lab Med 1987;111:62–66. 5. Roggli JL, Colbeck J, Sanfilipo F, et al. Pathology of human mesothelioma. Aetiologic and diagnostic consideration. Pathol Ann 1987;22:91–131. 6. Woodruff JM, Christiansen WN. Glandular peripheral nerve sheath tumors. 1993;72:3618–3628. 7. Moran CA, Suster S, Koss MN. Smooth muscle tumours presenting as pleural neoplasms. Histopathology 1995;27:227–234. 8. Nicholson AG, Goldstraw P, Fisher C. Synovial sarcoma of the pleura and its differentiation from other primary pleural tumours: a clinicopathologi- cal and immunohistochemical review of three cases. Histopathology 1998; 33:508–513. 9. Attanoos RL, Dallimore NS, Gibbs AR. Primary epithelioid haeman- gioendothelioma of the peritoneum: an unusual mimic of mesothelioma. Histopathology 1997;30:375–377. 10. Lin B, Colby T, Gown AM, et al. Malignant vascular tumors of the serous membranes mimicking mesothelioma. Am J Surg Pathol 1996;20:1431– 1439. 11. McCaughey WTE, Dardick I, Barr JR. Angiosarcoma of serous membranes. Arch Pathol Lab Med 1983;107:304–307. 12. Wong WW, Pluth JR, Grado GL, Schild SE, Sanderson DR. Liposarcoma of the pleura. Mayo Clin Proc 1994;69:882–885. 13. Carter D, Otis CN. Three types of spindle cell tumors of the pleura. , sarcoma, and sarcomatoid mesothelioma. Am J Surg Pathol 1988; 12:747–753. 14. England DM, Hochholzer L, McCarthy MJ. Localized benign and malig- nant fibrous tumors of the pleura. Am J Surg Pathol 1989;13:640–658. 15. Moran CA, Suster S, Koss MN. The spectrum of histologic growth patterns in benign and malignant fibrous tumors of the pleura. Semin Diagn Pathol 1992;9:169–180. 16. Luppi G, Cesinaro AM, Zoboli A, Morandi U, Piccinini L. Mesenchymal chondrosarcoma of the pleura. Eur Respir J 1996;9:840–843. 17. Chernow B, Sahn SA. Carcinomatous involvement of the pleura. An analy- sis of 96 patients. Am J Med 1977;63:695–702. O. Kim and T. Krausz 539

18. Battifora H. The pleura. In: Sternberg SS, ed. Diagnostic Surgical Pathol- ogy, vol 1. New York: Raven Press, 1989:829–855. 19. Montag AG, Pinkus GS, Corson JM. Keratin protein immunoreactivity of sarcomatoid and mixed types of diffuse malignant mesotheliomas: an immunoperoxidase study of 30 cases. Hum Pathol 1988;19:336–342. 20. Al-Izzi M, Thurlow NP, Corrin B. Pleural mesothelioma of type, localized fibrous tumour of the pleura, and reactive subme- sothelial : an immunohistochemical comparison. J Pathol 1989; 157:41–44. 21. Azumi N, Battifora H, Carlson G, et al. Sarcomatous mesothelioma of pleura: immunohistochemical study. Lab Invest 1989;60:4. 22. Blobel GA, Moll R, Franke WW, et al. The intermediate filament cytoskele- ton of malignant mesotheliomas and its diagnostic significance. Am J Pathol 1985;121:235–247. 23. Mayall FG, Goddard H, Gibbs AR. The diagnostic implications of variable cytokeratin expression in mesotheliomas. J Pathol 1993;170:165–168. 24. Wirth PR, Legler J, Wright GL. Immunohistochemical evaluation of seven monoclonal antibodies for differentiation of pleural mesothelioma from lung adenocarcinoma. Cancer 1991;67:655–662. 25. Brown DC, Theaker JM, Banks PM, et al. Cytokeratin expression in smooth muscle and smooth muscle tumours. Histopathology 1987;11:477–486. 26. Miettinen M, Lehto VP, Virtanen I. Keratin in the epithelial-like cells of classic biphasic synovial sarcoma. Virchow Arch 1982;40:157–161. 27. Smith TA, Machen SK, Fisher C, Goldblum JR. Usefulness of cytokeratin subsets for distinguishing monophasic synovial sarcoma from malignant peripheral nerve sheath tumor. Am J Clin Pathol 1999;112:641–648. 28. Bishop PW, Menasce LP, Yates AJ, et al. An immunophenotypic survey of malignant melanomas. Histopathology 1993;23:159–166. 29. Zarbo RJ, Gown AM, Nagle RB, et al. Anomalous cytokeratin expression in malignant melanoma: one- and two-dimensional Western blot analysis and immunohistochemical survey of 100 melanomas. Mod Pathol 1990;3: 494–501. 30. Moran CA, Travis WD, Rosado-de-Christenson ML, Koss ML, Rosai J. Thymomas presenting as pleural tumors: report of eight cases. Am J Surg Pathol 1992;16:138–144. 31. Payne CB, Morningstar WA, Chester EH. Thymoma of the pleura mas- querading as diffuse mesothelioma. Am Rev Respir Dis 1966;94:441–446. 32. Shih D, Wang J, Tseng H, et al. Primary pleural thymoma. Arch Pathol Lab Med 1997;121:79–82. 33. Chan JK, Tsang WY, Seneviratne S, Pau MY. The MIC2 antibody 013. Prac- tical application for the study of thymic epithelial tumors. Am J Surg Pathol 1995;10:1115–1123. 34. Brocheriou I, Carnot F, Briere J. Immunohistochemical detection of bcl-2 protein in thymoma. Histopathology 1995;27:251–255. 35. Robertson PB, Neiman RS, Worapongpaiboon S, John K, Orazi A. 013 (CD99) positivity in hematologic proliferations correlates with TdT posi- tivity. Mod Pathol 1997;10:277–282. 36. Oury TD, Hammar SP, Roggli VL. Ultrastructual features of diffuse malig- nant mesotheliomas. Hum Pathol 1998;29:1382–1392. 37. Amble FR, Olsen KD, Nascimento AG, Foote RL. Head and neck synovial sarcoma. Otolaryngol Head Neck Surg 1992;107:631–637. 38. Grayson W, Nayler SJ, Jena GP. Synovial sarcoma of the parotid gland. A case report with clinicopathologic analysis and review of the literature. A Afr J Surg 1998;36:32–34. 540 Chapter 35 Differentiating Sarcomas from Mesotheliomas

39. Shmookler BM, Enzinger FM, Brannon RB. Orofacial synovial sarcoma. A clinicopathologic study of 11 new cases and review of the literature. Cancer 1982;50:267–276. 40. Cataldi A, Orlassino R, Novero D. Synovial sarcoma of the mediastinum. Report of a case. Radiol Med 1994;87:719–721. 41. Peoch M, LeMarchardour F, Bost F, et al. Primary pulmonary sarcoma of the mediastinum. A case report with immunohistochemistry, ultrastruc- tural, and cytogenetic study. Ann Pathol 1995;15:203–206. 42. Witkin GB, Miettinen M, Rosai J. A biphasic tumor of the mediastinum with feature of synovial sarcoma. A report of four cases. Am J Surg Pathol 1989; 13:490–499. 43. Hisaoka M, Hashimoro H, Iwamasa T, Ishikawa K, Aoki T. Primary syn- ovial sarcoma of the lung: report of two cases confirmed by molecular detection of SYT-SSX transcripts. Histopathology 1999;34:205– 210. 44. Kaplan MA, Goodsman MD, Satish J, Bhagavan BS, Travis WD. Primary pulmonary sarcoma with morphologic features of monophasic synovial sarcoma and chromosome translocation t(X;18). Am J Clin Pathol 1996; 105:195–199. 45. Keel SB, Bacha E, Mark EJ, Nielsen SP, Rosenberg AE. Primary pulmonary sarcoma: a clinicopathologic study of 26 cases. Mod Pathol 1999;12:1124– 1131. 46. Koss M, Travis W, Moran C. Pulmonary sarcomas, blastoma, carcinosarco- mas, and . In: Hasleton PS, ed. Spencer’s Pathology of the Lung, 5th ed. New York: McGraw Hill, 1996:1065–1109. 47. Roberts CA, Seemayer TA, Neff JR, Alonso A, Nelson M, Bridge JA. Translocation (X;18) in primary synovial sarcoma of the lung. Cancer Genet Cytogenet 1996;88:49–52. 48. Yoon GS, Park SY, Kang GH, Kim OJ. Primary pulmonary sarcoma with morphologic features of biphasic synovial sarcoma: a case report. J Korean Med Sci 1998;13:71–76. 49. Nicholson AG, Rigby M, Lincoln C, Meller S, Fisher C. Synovial sarcoma of the heart. Histopathology 1997;30:349–352. 50. Billings SD, Meisner LF, Cummings DW, Tejada E. Synovial sarcoma of the upper digestive tract: a report of two cases with demonstration of the (X;18) translocation by fluorescence in situ hybridization. Mod Pathol 2000;13: 68–76. 51. Nielson GP, Shaw PA, Rosenberg AE, Dickersin GR, Young RH, Scully RE. Synovial sarcoma of the vulva: a report of two cases. Mod Pathol 1996;9: 970–974. 52. Gaertner E, Zeren H, Colby TV, et al. Biphasic synovial sarcomas arising in the pleural cavity: a clinicopathologic study of five cases. Am J Surg Pathol 1996;20:36–45. 53. Jawahar DA, Vuletin JC, Gorecki P, et al. Primary biphasic synovial sarcoma of the pleura. Respir Med 1997;91:568–570. 54. Essary LR, Vargas SO, Fletcher CDM. Primary pleuropulmonary synovial sarcoma: reappraisal of a recently described anatomic subset. Cancer 2002;94:459–469. 55. Zeren H, Moran CA, Suster S, Fishback NF, Koss MN. Primary pulmonary sarcomas with features of monophasic synovial sarcomas: a clinicopatho- logical, immunohistochemical, and ultrastructural study of 25 cases. Hum Pathol 1995;26:474–480. 56. Chilosi M, Facchetti F, Tos APD, et al. bcl-2 expression in pleural and extrapleural solitary fibrous tumours. J Pathol 1997;181:362–367. O. Kim and T. Krausz 541

57. Dei Tos AP, Wadden C, Calonje E, et al. Immunohistochemical demonstra- tion of glycoprotein p30/32MIC2 (CD99) in synovial sarcoma. A potential cause of diagnostic confusion. Appl Immunohistochem 1995;3:168– 173. 58. Segers K, Ramael M, Singh SK, et al. Immunoreactivity for bcl-2 protein in malignant mesothelioma and non-neoplastic mesothelium. Virchows Arch 1994;424:631–634. 59. Stevenson AJ, Chatten J, Bertoni F, Miettinen M. (p30/32MIC2) neuroecto- dermal/Ewing’s sarcoma antigen as an immunohistochemical marker: review of more than 600 tumors and the literature experience. Appl Immunohistochem 1994;2:231–240. 60. Fisher C. Synovial sarcoma: ultrastructural and immunohistochemical fea- tures of epithelial differentiation in monophasic and biphasic tumors. Hum Pathol 1986;17:996–1008. 61. Limon J, Mrozek K, Mandahl N, et al. Cytogenetics of synovial sarcoma. Presentation of 10 new cases and review of the literature. Genes Chromo- somes Cancer 1991;3:338–345. 62. Smith S, Reeves BR, Wong L, Fisher C. A consistent chromosome translo- cation in synovial sarcoma. Cancer Genet Cytogenet 1987;26:179–180. 63. Falconieri G, Bussani R, Mirra M, Zanella M. Pseudomesotheliomatous angiosarcoma: a pleuropulmonary lesion simulating malignant pleural mesothelioma. Histopathology 1997;30:419–424. 64. Zhang PJ, Livolsi VA, Brooks JJ. Malignant epithelioid vascular tumors of the pleura: a report of a series and literature review. Hum Pathol 2000;31: 29–34. 65. Gray MH, Rosenberg AE, Dickersin GR, et al. Cytokeratin expression in epithelioid vascular neoplasms. Hum Pathol 1990;21:212–217. 66. Klemperer P, Rabin CB. Primary neoplasms of the pleura. Report of five cases. Arch Pathol 1937;11:385–412. 67. Burrig KF, Kastendieck H. Ultrastructural observations on the histogenesis of localized fibrous tumors of the pleura (benign mesothelioma). Virchows Arch 1984;403:413–424. 68. Scharifker D, Kaneko M. Localized fibrous “mesothelioma” of pleura (sub- mesothelial fibroma): a clinicopathologic study of 18 cases. Cancer 1979;43: 627–635. 69. Dotan ZA, Mor Y, Olchovsky D, et al. Solitary fibrous tumor presenting as perirenal mass associated with hypoglycemia. J Urol 1999;162:2087– 2088. 70. Brunnemann RB, Ro JY, Ordonez NG, Mooney J, El Naggar AK, Ayala AG. Extrapleural solitary fibrous tumor: a clinicopathologic study of 24 cases. Mod Pathol 1999;12:1034–1042. 71. Mentzel T, Bainbridge TC, Katenkamp D. Solitary fibrous tumor: clinico- pathological, immunohistochemical, and ultrastructural analysis of 12 cases arising in soft tissues, nasal cavity and nasopharynx, urinary bladder and prostate. Virchows Arch 1997;430:445–453. 72. Nielson GP, O’Connell JX, Rosenberg AE. Solitary fibrous tumor of : a report of 15 cases, including 5 malignant examples with light microscopic, immunohistochemical, and ultrastructural data. Mod Pathol 1997;10:1028–1037. 73. Suster S, Nascimento AG, Mietinnen M, Sickel JZ, Moran CA. Solitary fibrous tumors of soft tissue. A clinicopathologic and immunohistochemi- cal study of 12 cases. Am J Surg Pathol 1995;19:1257–1266. 74. Renshaw AA. 013 (CD99) in spindle cell tumors. Reactivity with heman- giopericytoma, solitary fibrous tumor, synovial sarcoma, and 542 Chapter 35 Differentiating Sarcomas from Mesotheliomas

but rarely with sarcomatoid mesothelioma. Appl Immunohistochem 1995; 3:250–256. 75. Suster S, Fisher C, Moran CA. Expression of bcl2 oncoprotein in benign and malignant spindle cell tumors of soft tissue, skin, serosal surfaces, and gastrointestinal tract. Am J Surg Pathol 1998;22:863–872.