Case 10 -

Epithelioid Sarcoma Omar Sangueza

Clinical History: The patient is a 29-year-old male with a soft tissue mass involving his right arm. Diagnosis: Epithelioid Sarcoma. The histogenesis of epithelioid sarcoma (EPS) is uncertain. The morphologic and immunohistochemical profile of EPS suggests that it may represent a "carcinoma" of soft parts. EPS typically arises in adolescent and young adults, with a usual age range of 10-40 years. It predominantly occurs in the distal extremities and has a propensity, unlike most sarcomas, to involve the upper extremity, especially the hands and forearm. [1] Consequently, EPS often presents as a painless, soft tissue mass, superficially located within the dermis and subcutis. Radiologically, EPS are generally solitary but often multinodular masses that, similar to synovial sarcoma, frequently harbor calcifications, in approximately 20-30% of cases. [1] Histologically, EPS typically grow as multinodular proliferations composed of epithelioid to polygonal-appearing tumor cells with round to ovoid vesicular nuclei, inconspicuous to prominent nucleoli, and abundant eosinophilic cytoplasm. Nuclear pleomorphism generally ranges from slight to moderate with occasional bi-nucleated forms. Intracytoplasmic vacuoles may occasionally be observed, mimicking the appearance of epithelioid hemangioendothelioma. When abundant necrosis is present, the multinodular growth pattern exhibits a "granulomatous" appearance, reminiscent of rheumatoid nodule or granuloma annulare. Less commonly, focal areas of myxoid change may be observed. Rarely, multinucleated giant cells may be haphazardly scattered among the cellular regions, potentially causing confusion with giant cell tumor of tender sheath. Focal areas displaying spindle cell patterns and even storiform growth often occur. Dystrophic calcifications with or without osseous metaplasia are seen in up to one-fifth of cases. Surprisingly, mitotic activity is variable, ranging from <1 to >20 mitotic figures/10 high power fields. Recently, Guillou and others have described a "proximal-type" of EPS displaying marked cytologic atypia and rhabdoid features histologically and arising within more proximal anatomic sites, including the pelvis and perineal regions, buttocks and hip. [2] Limited follow-up data suggest that this unusual variant of EPS may behave more aggressively. Immunohistochemically, the vast majority of EPS express cytokeratin and epithelial membrane antigen. Likewise, vimentin is positive in >95% of cases. Up to 50% of tumors, at least focally, express CD34. [2, 3] As metastatic carcinomas are almost always negative for this marker, the use of CD34 may, in difficult cases, help distinguish these two entities. [3] Unlike epithelioid hemangioendothelioma, CD31 is uniformly negative in EPS. Although S-100 protein has also typically produced negative results, HMB45 has been rarely reported as positive. [2] Cytogenetic analysis has revealed no reproducible chromosomal abnormalities characteristic of EPS. Cordoba and colleagues reported a single case of epithelioid sarcoma with a t(8;22)(q22;11). [4] Local recurrence and metastatic rates in EPS are quite high ranging from 38-77% and 40-50%, respectively. [1, 5, 6] Prolonged follow-up is mandatory in these patients. Tumor-related death may be observed up to 20 years following initial presentation. A more aggressive clinical course has been associated with tumor size (>5 cm), proximal location, and histologic features such as necrosis, mitotic activity, and the presence of vascular invasion. Evans and Baer have emphasized the initial treatment has having a strong relationship with local recurrence but not affecting ultimate clinical outcome. [6] Indeed, regional lymph node metastasis appears to be strongly correlated with tumor size. Chase DR, Enzinger FM. Epithelioid sarcoma: diagnosis, prognostic indicators, and treatment. Am J Surg Pathol 1985;241-263. Guillou L, Wadden C, Coindre JM, et al. "Proximal-type" epithelioid sarcoma, a distinctive aggressive neoplasm showing rhabdoid features. Am J Surg Pathol 1997;21:130-146. Arber DA, Kandalaft PL, Mehta P, Battifora H. Vimentin-negative epithelioid sarcoma: the value of an immunohistochemical panel that includes CD34. Am J Surg Pathol 1993;17:302-307. Cordoba JC, Parham DM, Meyer WH, et al. A new cytogenetic finding in an epithelioid sarcoma, t(8;22)(q22;q11). Cancer Genet Cytogenet 1994;72:151-154. Halling AC, Wollan PC, Pritchard DJ, et al. Epithelioid sarcoma: a clinicopathologic review of 55 cases. Mayo Clin Proc 1996;71:636-642. Evans HL, Baer SC. Epithelioid sarcoma: a clinicopathologic and prognostic study of 26 cases. Semin Diagn Pathol 1993;10:286-291.