Original ArticlesNovel High-grade Endometrial Stromal Sarcoma A Morphologic Mimicker of Myxoid LeiomyosarcomaHoang, Lien N. MD*; Aneja, Amandeep MD*; Conlon, Niamh MD†; Delair, Deborah F. MD*; Middha, Sumit PhD*; Benayed, Ryma PhD*; Hensley, Martee L. MD‡; Park, Kay J. MD*; Hollmann, Travis J. MD*; Hameed, Meera R. MD*; Antonescu, Cristina R. MD*; Soslow, Robert A. MD*; Chiang, Sarah MD*Author Information *Department of Pathology, Memorial Sloan Kettering Cancer Center ‡Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY †Department of Pathology, Cork University Hospital, Wilton, Cork, Ireland R.A.S. and S.C. are co-principal investigators. Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Robert A. Soslow, MD, Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Ave., New York, NY 10065 (e-mail: [email protected]). The American Journal of Surgical Pathology: January 2017 - Volume 41 - Issue 1 - p 12-24 doi: 10.1097/PAS.0000000000000721 Buy Metrics Abstract Endometrial stromal sarcomas (ESS) are often underpinned by recurrent chromosomal translocations resulting in the fusion of genes involved in epigenetic regulation. To date, only YWHAE-NUTM2 rearrangements are associated with distinctive high-grade morphology and aggressive clinical behavior. We identified 3 ESS morphologically mimicking myxoid leiomyosarcoma of the uterus and sought to describe their unique histopathologic features and identify genetic alterations using next-generation sequencing. All cases displayed predominantly spindled cells associated with abundant myxoid stroma and brisk mitotic activity. Tumors involved the endometrium and demonstrated tongue-like myometrial infiltration. All 3 were associated with an aggressive clinical course, including multisite bony metastases in 1 patient, progressive peritoneal disease after chemotherapy in another, and metastases to the lung and skin in the last patient. All 3 ESS were found to harbor ZC3H7B-BCOR gene fusions by targeted sequencing and fluorescence in situ hybridization. On the basis of the review of these cases, we find that ESS with ZC3H7B-BCOR fusion constitutes a novel type of high-grade ESS and shares significant morphologic overlap with myxoid leiomyosarcoma. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.