Unusual Variants of Endometrial Stromal Sarcoma

Endometrial stromal sarcoma (ESS) is traditionally classified into low-grade (LGESS) and high-grade (HGESS) categories based on morphology, immunophenotype, and specific molecular alterations. Some tumors, however, defy these patterns, displaying unusual features that complicate diagnosis and prognostication. We performed a retrospective review of ESS diagnosed from 2022 to 2025 at a single institution, obtaining 4 cases with highly uncommon pathologic findings, including 3 with available molecular data. Key histologic, immunohistochemical, molecular, and clinical findings were recorded. These cases broaden the known spectrum of ESS, demonstrating that tumors with genetic hallmarks of LGESS can exhibit unusual patterns of differentiation, high-grade features, unconventional immunohistochemical findings, and rare molecular profiles.