SMARCB1/INI1 Loss in Epithelioid Schwannoma

Abstract

The epithelioid variant of schwannoma is rare, and loss of SMARCB1/INI1 expression has been observed in a subset of cases. Our aim was to further define the clinicopathologic features and to evaluate SMARCB1/INI1 deficiency in a large cohort of 65 epithelioid schwannomas diagnosed between 2002 and 2015, which consisted of 32 men and 33 women with median age at diagnosis of 45 years (range, 13 to 75 y). Most tumors arose in the extremities (upper, 20, lower, 15) and trunk (17); 9 were visceral (8 gastrointestinal). Most somatic tumors were in dermis/subcutis (53/54) and encapsulated (53/54) with an epithelial membrane antigen-positive perineurial capsule in 46 cases; visceral tumors were unencapsulated. No patients were reported to have any neurocristopathy. Three patients had multiple lesions (2 each). Tumor size range was 0.4 to 22.7 cm (median, 1.2 cm). Tumors showed multilobulated growth of uniform epithelioid cells in sheets and nests or singly dispersed within a frequently myxoid or hyalinized stroma. Tumor cells had round vesicular nuclei and abundant palely eosinophilic cytoplasm, usually lacking significant pleomorphism or hyperchromasia. Some tumors showed foci resembling conventional schwannoma (spindled morphology, 29; Antoni B foci or Verocay bodies, 8; hyalinized thick-walled vessels, 16). Mitoses ranged from 0 to 9 per 10 high-power fields (median count, 1). No tumor had necrosis. Twenty-three cases showed degenerative nuclear atypia. Focally striking cytologic atypia was present in 7 tumors, 3 of which showed transformation to epithelioid malignant peripheral nerve sheath tumor. All tumors showed diffuse positivity for S-100 protein and consistent positivity for SOX10 (50/50), while INI1 expression was lost in 24 of 57. Other positive immunohistochemical results were: glial fibrillary acidic protein (15/37) and focal keratin (2/40); epithelial membrane antigen (0/53) and melanocytic markers were negative (Mart-1 0/29; HMB-45 0/23). Most patients underwent local excision (13 complete; 47 marginal/positive margins). Follow-up data available for 31 patients (range, 1 to 108 mo; median, 37) indicated that no patient had developed metastatic disease, including 3 cases with cytologic atypia, one of which showed malignant transformation. One tumor without atypia developed local recurrence 48 months after marginal excision; all other patients were alive with no evidence of disease. Epithelioid schwannoma most commonly occurs as a superficial tumor on the extremities or trunk in adults. Loss of SMARCB1/INI1 expression is seen in 42% of tumors. Tumors follow a generally benign clinical course, although recurrence and malignant transformation are infrequent. Some tumors are characterized by notable cytologic atypia, the significance of which is uncertain but which may indicate a morphologic continuum with low-grade epithelioid malignant peripheral nerve sheath tumor.