Epithelioid Sarcoma of the Oral Cavity: A Multi-institutional Clinicopathologic and Immunophenotypic Characterization of Five Cases and Comprehensive Literature Review

PURPOSE: Epithelioid sarcoma (ES) accounts for < 1% of all sarcomas and is characterized by predominantly epithelioid cytologic features together with epithelial immunophenotypic properties. Intraoral involvement is apparently rare with only 17 previously reported examples. Herein, the clinicopathologic and immunohistochemical features of 5 additional oral ES cases are presented with review of the literature. METHODS: The electronic databases of the authors' institutions were searched for archived, primary or metastatic, intraoral ES diagnoses. Five cases were identified. Clinicopathologic characteristics as well as information regarding treatment and outcome were collected. RESULTS: Among the 5 cases, 3 occurred in women and 2 in men (M: F ratio = 1:1.5, age mean = 42.8 years; range = 11-79 years); 3 were primary, proximal-type, and 2 metastatic. Two primary lesions involved the tongue and 1 the buccal mandibular vestibule, whereas both metastatic ES cases affected the mandibular gingiva/alveolar mucosa. Lesion size ranged between 0.4 and 3.8 cm (mean = 1.9 cm). Microscopically, all lesions featured sheets and lobules of variably pleomorphic, epithelioid-to-spindled and occasionally rhabdoid cells with enlarged round-to-oval nuclei, vesicular or coarse chromatin, and frequent acidophilic macronucleoli, together with abundant eosinophilic cytoplasm. Mitotic activity was overall low in primary oral ES lesions but frequent in metastatic tumors; necrosis was present in 3 cases. The stroma ranged from fibrous to fibromyxoid. By immunohistochemistry, all cases showed strong and diffuse positivity for cytokeratins and EMA, together with uniform loss of nuclear SMARCB1 expression. Molecular testing in a primary lingual ES revealed somatic biallelic loss on 22q11.22-q11.23 involving the SMARCB1 gene, together with loss of 12p. Among the 5 patients with oral ES, 1 remained disease free, 2 were alive with multifocal metastases, and 1 succumbed to the disease after a mean follow-up period of 19.7 months (range = 10-27 months). The remaining patient was lost to follow-up. CONCLUSIONS: Intraoral involvement by ES may infrequently occur either in the setting of primary or metastatic disease. The epithelioid, spindled, and, occasionally, rhabdoid cytomorphology of ES in conjunction with the aberrant immunoexpression of cytokeratins and EMA may cause a major diagnostic pitfall in oral biopsy specimens. A broad panel of epithelial and non-epithelial immunohistochemical markers, including SMARCB1, together with evaluation for surface dysplasia and a detailed clinical history, are necessary for exclusion of histologic mimics, establishing accurate diagnosis, and proper patient care.