Undifferentiated Sarcoma with EWSR1-POU5F1 Fusion: a new entity?

Document Type

Conference Proceeding

Publication Date

11-12-2025

Publication Title

Am J Clin Pathol

Keywords

Pathology

Abstract

Abstract: Introduction/Objective: EWSR1 rearranged sarcomas include Clear cell sarcoma of soft parts, Angiomatoid fibrous histiocytoma, Ewing sarcoma, Extraskeletal myxoid chondrosarcoma, Desmoplastic small round cell tumor, Myxoid liposarcoma, and Round cell sarcoma with EWSR1-non-ETS fusions. Here we describe a case of EWSR1-POU5F1 fusion in an undifferentiated sarcoma. This tumor does not belong to any known categories of soft-tissue tumors. EWSR1-POU5F1 fusion is well-established as a genetic alteration in myoepithelial tumors, but has been reported in an undifferentiated sarcoma only twice previously in literature. Methods/Case Report: A 12-year-old female presented with 11.5x7 cm mass on the right buttock, noticed 8 months ago, which was increasing in size. Histology showed a well delineated neoplasm consisting of cysts of varying sizes with neoplastic spindled and round cells in the septae. Few cells were mildly pleomorphic. The tumor cells showed vimentin, S100, and cyclin D1 immunoreactivity. No immunoreactivity with CD99, desmin, AE1/AE3, EMA, TLE1, BCL-2, CD68, NSE, GFAP, MyoD1, myogenin or CD34 was seen. lNl-1 was retained. Despite the relatively low mitotic count and small foci of coagulatlve necrosis, histologic impression of this neoplasm was that of an aggressive sarcoma, with infiltration of adipose tissue, tendon, and fascia. Solid tumor next generation sequencing comprehensive panel revealed EWSR1-POU5F1 fusion. A diagnosis of undifferentiated sarcoma with EWSR1 gene rearrangement, low grade was made. EWSR1-POU5F1 fusions have been previously described in soft tissue myoepithelial tumors, several of which have been described as having undifferentiated round cell morphology. Yet these cases showed evidence of epithelial differentiation, with EMA and/or pan-cytokeratin positivity. This case was uniformly negative tor EMA and pan- cytokeratin and was thus best classified as an undifferentiated sarcoma rather than a myoepithelial carcinoma. Results: NA. Conclusion: Herein we describe a case of undifferentiated sarcoma with EWSR1-POU5F1 fusion, which may represent a distinct entity.

Volume

164

Issue

Supplement_1

First Page

1

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