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Uterine Tumor Resembling Ovarian Sex Cord Tumor

A Distinct Entity Characterized by Recurrent NCOA2/3 Gene Fusions

Dickson, Brendan C., MSc, MD*,†; Childs, Timothy J., MD; Colgan, Terrence J., MD*,†; Sung, Yun-Shao, MSc§; Swanson, David, BSc*,†; Zhang, Lei, MD§; Antonescu, Cristina R., MD§

The American Journal of Surgical Pathology: February 2019 - Volume 43 - Issue 2 - p 178–186
doi: 10.1097/PAS.0000000000001153
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Uterine tumor resembling ovarian sex-cord tumor (UTROSCT) is a rare and distinctive neoplasm of unclear histogenesis, and uncertain malignant potential. These neoplasms morphologically resemble sex-cord stromal tumors of the ovary, and possess a polyphenotypic immunophenotype. Their molecular pathogenesis has yet to be elucidated; notably, however, tumors lack alterations found in other uterine tumors bearing sex-cord–like differentiation, such as endometrial stromal sarcoma. Following identification of an index patient with an ESR1-NCOA3 fusion gene by RNA-sequencing, we undertook a retrospective review for additional cases of UTROSCT. We identified a total of 4 patients, with an average age of 53 years (range, 38 to 68 y). RNA-sequencing was performed in all cases, revealing an ESR1-NCOA3 fusion in 2 cases and one case each with related ESR1-NCOA2 and GREB1-NCOA2 fusions. Each of the tumors showed histologic and an immunophenotype features within the previously reported spectrum of UTROSCT; interestingly, one case contained prominent spindle cell fascicles and another was largely comprised of sheets of small round cells. Our results demonstrate UTROSCT are defined by recurrent fusions involving NCOA2 or NCOA3, a finding that is directly amenable to diagnostic evaluation. This study confirms UTROSCT is molecularly distinct from endometrial stromal sarcoma, and raises intriguing new questions into the pathogenesis of these neoplasms and possible relationship with other NCOA fusion-positive uterine tumors.

*Department of Pathology and Laboratory Medicine, Mount Sinai Hospital

Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto

Department of Pathology and Molecular Medicine, Kingston General Hospital, Queens University, Kingston, ON, Canada

§Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY

Conflicts of Interest and Source of Funding: Supported in part by: P50 CA140146-01 (C.R.A.); P30-CA008748 (C.R.A.); Kristen Ann Carr Foundation (C.R.A.); Cycle for Survival (C.R.A.). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Correspondence: Brendan C. Dickson, MSc, MD, Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Ave., Toronto, ON, Canada M5G 1X5 (e-mail: brendan.dickson@sinaihealthsystem.ca).

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