Sarcomatoid mesothelioma

Henderson DW, Attwood HD, Constance TJ, et al. 1988. Lymphohistiocytoid mesothelioma A rare lymphomatoid variant of predominantly sarcomatoid mesothelioma. Ultrastruct Pathol 12 367-384. 

Renshaw AA. 013 (CD99) in spindle cell tumors Reactivity with hemangiopericytoma, solitary fibrous tumor, synovial sarcoma, and meningioma, but rarely with sarcomatoid mesothelioma. Appl Immunohistochem. 1995 3 250-256. 

Epithelial and sarcomatoid mesotheliomas are usually vimentin positive... 

An especially troublesome differential diagnosis is the separation of primary mediastinal synovial sarcoma and PTC. This is because their clinical, electron microscopic, and immunophenotypic features are quite similar. The demonstration of t(X 18) chromosomal translocations in synovial sarcoma—by fluorescence in situ hybridization or traditional cytogenetic analyses—has now made this tumor consistently identifiable. Mesothelioma also enters consideration in this context notably, this tumor type shares possible reactivity for keratin and calretinin with sarcomatoid PTC and synovial sarcoma. However, only mesothelioma commonly expresses the WT-1 protein among these possibilities, and, unlike sarcomatoid PTC or synovial sarcoma, mesothelial tumors do not label for CD99. ... 

Aside from its exclusive composition by fusiform and pleomorphic tumor cells, sarcomatoid mediastinal mesothelioma also is dissimilar from its epithelioid... 

Hintetbetget M, Reineke T, Stotz M, et al. D2-40 and cal-tetinin A tissue mictoattay analysis of 341 malignant mesotheliomas with emphasis on sarcomatoid differentiation. Mod Pathol. 2007 20 248-255. 

Padgett DM, Cathto HP, Wick MR, et al. Podoplanin is a bettet immunohistochemical marker for sarcomatoid mesothelioma than caltetinin. Am J Surg Pathol. 2008 32 123-127. 

Pleural mesotheliomas show a wide range of histologic differentiation, although they can be divided into four major subtypes 1) epithelial 2) sarcomatoid [fibrous, sarcomatous] 3) biphasic and 4) desmoplastic [a variant of a sarcomatoid mesothelioma]. 

Although 100% of epithelial mesotheliomas express keratin, the percentage of sarcomatoid mesotheliomas reported in the literature to express keratin is variable. 

Lucas and colleagues immunostained 20 mesotheliomas with sarcomatoid components (10 biphasic and 10 sarcomatoid) for pan cytokeratin, CK5/6, cal-retinin, WTl, thrombomodulin, and smooth muscle actin. They compared the immunophenotypic profile of these tumors with 24 high-grade sarcomas, 10 pulmonary sarcomatoid carcinomas, and 16 epithelioid mesotheliomas. The 10 pulmonary sarcomatoid carcinomas were also immunostained for TTF-1. Their results are shown in Table 12.24. They concluded that 1) there was a decrease in epithelial and mesothelial epitopes in sarcomatoid mesothelioma 2) there was a wide immunophenotypic overlap among sarcomatoid... 

Reprinted from Lucas DR, Pass HI, Madan SK, et al. Sarcomatoid mesothelioma and its histological mimics A comparative immunohistochemical study. Histopathology. 2003 42 270-279. 

Attanoos and associates evaluated 31 sarcomatoid mesotheliomas and a spectrum of other spindle cell neoplasms with antibodies directed against cytokeratin, thrombomodulin, calretinin, and CK5/6. Twenty-four of 31 (77%) sarcomatoid mesotheliomas expressed cytokeratin, 9 of 31 (29%) expressed thrombomodulin, 12 of 31 (39%) expressed calretinin, and 9 of 31 (29%) expressed CK5/6. Two of 9 (22%) sarcomas not otherwise specified expressed broad-spectrum cytokeratin and thrombomodulin, and 1 of 9 (11%) expressed CK5/6. As might be expected, 100% of synovial sarcomas expressed broad-spectrum keratin but showed no immu-nostaining for thrombomodulin, calretinin, and CK5/6. Two of 3 (67%) angiosarcomas expressed thrombomodulin, which is not surprising since thrombomodulin... 

We have not found the expression of broad-spectrum keratin (AE1/AE3 keratin) in sarcomas or the degree of calretinin expression in sarcomatoid mesotheliomas, sarcomas, or sarcomatoid carcinomas noted by Lucas and coworkers.In our experience, broad-spectrum keratin is rarely found (<1% of cases) in sarcomas. Calretinin expression is found in a maximum of 20% of sarcomatoid mesotheliomas and is not seen in sarcomas or sarcomatoid carcinomas. Others have found similar immunoreactions (see the paragraphs that follow). 

FIGURE 12.48 Most well and moderately well differentiated epithelial mesotheliomas and a few sarcomatoid mesotheliomas show cytoplasmic and nuclear immunostaining for calretinin. X 400. 

Azumi and associates used immunohistochemistry to study 33 mesotheliomas (32 pleural, 1 peritoneal, 18 epithelial, 10 biphasic, 4 sarcomatoid, 1 desmoplastic) and 37 adenocarcinomas for hyaluronate. Three of 37 (8.1%) adenocarcinomas and all mesotheliomas immunostained for hyaluronate. The location of the staining reaction in the mesotheliomas was membranous in 30 cases, cytoplasmic in 21 cases, and membranous and cytoplasmic in 19 cases. The staining reaction in mesotheliomas was classified as moderate or greater in 27 of 33 (81.8%) cases. The authors concluded that the demonstration of hyaluronate should be considered an important adjunct to other immunohistochemical tests and electron microscopy in diagnosing epithelial mesotheliomas. 

Marchevsky evaluated sarcomatoid mesotheliomas and correctly pointed out that the diagnosis of sarcomatoid mesothelioma was particularly difficult as the sensitivity and specificity of mesothelial markers was considerably lower in these lesions than in malignant epithelial mesothelioma. Marchevsky correctly stated that immunostains for calretinin, thrombomodulin, and WTl were positive in fewer than 20% of sarcomatoid mesotheliomas. Marchevsky stated that immunostain-ing for AE1/AE3 keratin was the most helpful in that it showed staining in almost all cases of sarcomatoid... 

Most sarcomatoid mesotheliomas express keratin (usually low molecular weight keratin), vimentin, and frequently muscle-specihc/alpha actin. In our experience, a relatively small percent (10% to 20%) of sarcomatoid mesotheliomas express calretinin, and most sarcomatoid mesotheliomas do not express cytokeratin 5/6. Most sarcomatoid mesotheliomas express CK7, often intensely. In our experience, sarcomatoid mesotheliomas (and tumors with which they may be confused) do not express the negative markers used to evaluate potential epithelial mesotheliomas, including CEA, LeuMl, B72.3, BerEP4, BG8, and TTF-1. Therefore, we would not include these antibodies in a screen of a malignant spindle cell proliferative lesion of the pleura. 

Klebe and associates reported 27 cases of malignant mesothelioma that had heterologous elements.Of 27 cases, 16 (59%) were sarcomatoid, 10 (37%) were... 

Rare sarcomatoid mesotheliomas show heterologous differentiation composed of fat (Figs. 12.52 and 12.53). The immunohistogram of a sarcomatoid mesothelioma is shown in Figure 12.54. The most important immunohistochemical finding in sarcomatoid mesothelioma is coexpression of keratin and vimentin. 

Pleomorphic mesotheliomas exist and are composed of pleomorphic epithelioid and sarcomatoid cells. Occasional multinucleated macrophage giant cells are associated with the tumor cells. Pleomorphic mesotheliomas need to be differentiated from pleomorphic carcinomas of the lung. In most instances, pleomorphic mesotheliomas express pan cytokeratin and vimentin. 

Localized fibrous tumors of the pleura are contrasted to sarcomatoid mesotheliomas and sarcomas in Table 12.34. 

TABLE 12.34 Comparison of Immunohistochemical Features of Localized Fibrous Tumors of the Pleura, Sarcomatoid Mesothelioma, and Soft Tissue Sarcomas ... 

Thymomas may occur in the pleura and can be confused with mesothelioma. These neoplasms may be confused with a sarcomatoid mesothelioma with a heavy lymphoid infiltrate or with a lymphohistiocytoid mesothelioma. None of the cases presented by Moran and coworkers showed radiographic evidence of a mediastinal tumor, however 6 cases showed histologic features of a mixed (lymphocyte-epithelial) thymoma. The neoplastic thymic epithelial cells express keratin and CD5. 

---