Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare mesenchymal neoplasm, of uncertain biological potential, that was recently reported to exhibit recurrent gene fusions involving NCOA2-3. The purpose of this study was to, using a larger sample size, better characterize the histopathologic and molecular diversity of UTROSCT. Twenty-six cases of UTROSCT from 5 institutions were selected for further study. Fluorescence in situ hybridization for NCOA1, NCOA2, NCOA3, ESR1 and GREB1, and targeted RNA sequencing was performed on 17 and 8 UTROSCTs, respectively. Eight cases underwent massively parallel sequencing to detect single nucleotide variants (SNV), copy number variations, and structural variants using a targeted hybrid-capture based assay. NCOA1-3 rearrangement was identified in 81.8% (18/22) of cases. The most common fusion was ESR1-NCOA3, occurring in 40.9% (9/22). GREB1-NCOA1 (n=4), ESR1-NCOA2 (n=3), and GREB1-NCOA2 (n=1) rearrangements were also identified. No recurrent SNVs were identified and no tumor had SNVs in FOXL2, DICER1, STK11, or AKT1, which can be seen in ovarian sex cord-stromal tumors. Copy number variations were infrequent. Clinical follow-up was available for 11 cases with a mean follow-up interval of 94.4 (range, 1 to 319) months. Only one case had a recurrence 66 months after the initial diagnosis and this was the single case with a GREB1-NCOA2 fusion. This study reports the morphologic spectrum of UTROSCT and confirms the recently reported recurrent NCOA2-3 gene fusions, in addition to identifying novel rearrangements involving NCOA1 in these tumors.
*Division of Women’s and Perinatal Pathology
†Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
‡Department of Pathology, La Paz University Hospital, IdiPAZ and Autonomous University of Madrid Medical School, Madrid, Spain
§Department of Pathology and Laboratory Medicine, Mount Sinai Hospital
∥Department of Laboratory Medicine and Pathobiology, University of Toronto
**Department of Laboratory Medicine and Molecular Diagnostics, Sunnybrook Health Sciences Center, Toronto, ON
¶Department of Pathology, Vancouver General Hospital, Vancouver, BC, Canada
#Department of Anatomical and Cellular Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong
††Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY
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: David L. Kolin, MD, PhD, Women’s and Perinatal Pathology, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115 (e-mail: email@example.com).