Sclerosing epithelioid fibrosarcoma: cytologic characterization with histologic, immunohistologic, molecular, and clinical correlation of 8 cases

Abstract

Sclerosing epithelioid fibrosarcoma (SEF) is an uncommon malignant fibroblastic neoplasm. The diagnosis is typically made on core needle biopsy or resection specimens. Cytomorphologic characterization of SEF has been limited to rare case reports in the literature. The goal of this study was to review a series of cases of SEF and to determine the feasibility of cytologic diagnosis of this rare tumor. Eight SEF cases from 2009 to 2019 were identified in a retrospective review of 3 participating institutions. Cytomorphologic and corresponding histologic, immunophenotypic, molecular, and clinical data were examined and described. Patients were of median age 41 years old at diagnosis with a median follow-up of 35.5 months. These tumors, with a median greatest dimension of 13.4 cm, were located in the lower extremities, abdomen, retroperitoneum, head, groin, sacrum, and lung. The tumor cells ranged from small round, medium-sized ovoid/short spindle, to epithelioid/plasmacytoid cells. A sclerotic, fibrous to myxoid stroma was seen. Most samples revealed low-grade cytology. Two cases showed tumor necrosis. Only 3 cases with cell block/positive MUC4 immunostain were diagnostic. Corresponding molecular testing for EWSR1 gene rearrangement and/or EWSR1-CREB3L1 fusion were positive in 5 of 8 cases on biopsy or surgical samples. An additional case was positive for FUS-CREB3L2 fusion. Diagnosis of SEF based solely upon cytologic features remains challenging. Epithelioid or plasmacytoid morphology mimics common malignancies. A supportive clinical history, MUC4 immunohistochemistry, and characteristic molecular result should be used to aid the diagnosis.