High-grade Endometrial Stromal Sarcoma With a Novel ING3::BCOR Fusion.

High-grade endometrial stromal sarcoma (HGESS) is a rare tumor that typically occurs over a wide age range, from 14 to 71 yr, often presenting with nonspecific clinical symptoms. This tumor group displays heterogeneous tumor morphology and a growing number of molecular alterations. The most common alterations are YWHAE::NUTM2 fusion and BCOR gene alterations, including fusions and internal tandem duplications. Here, we report a HGESS with a novel ING3::BCOR fusion. A 74-yr-old female presented with vaginal bleeding and underwent myomectomy. Hematoxylin & eosin (H&E) sections revealed a spindle cell proliferation with both hypocellular and hypercellular areas. Cytologic atypia was mild to moderate, with a mitotic count of 5/10 high-power fields; the background stroma had focal myxoid and collagenous changes. Focal necrosis and pleomorphism were observed. Ancillary studies showed CD10 and diffuse cyclin D1 positivity by immunohistochemistry (IHC). Estrogen receptor (ER), progesterone receptor (PR), ALK1​, S100​, HMB45,​ and CD34​ were negative and p53 showed a wild-type staining pattern​. RNA-based next-generation sequencing showed an ING3::BCOR fusion, confirming the diagnosis of HGESS with ING3::BCOR fusion. HGESS is an evolving entity with an increasing number of genetic alterations, including genetic fusion involving the BCOR gene. HGESS with BCOR fusion should be considered in tumors with a combination of spindle cell growth, myxoid background, foci of coagulative necrosis, diffuse cyclin D1 positivity, and a negative hormone receptor status. Accurate diagnosis requires an integrated approach that combines histopathologic evaluation, IHC, and molecular testing.