Original ArticlesOvarian Signet-ring Stromal Tumor A Morphologic, Immunohistochemical, and Molecular Study of 7 Cases With Discussion of the Differential DiagnosisTchrakian, Nairi FRCPath*; Oliva, Esther MD†,‡; Chong, Anne-Sophie MSc§; Rivera-Polo, Barbara PhD§,∥,¶; Bennett, Jennifer A. MD#; Nucci, Marisa R. MD**; Sah, Shatrughan FRCPath††; Schoolmeester, J. Kenneth MD‡‡; van der Griend, Rachael A. FRCPA§§; Foulkes, William D. MBBS, PhD§; Clarke, Blaise A. MBBCh, FRCPC*; Young, Robert H. MD, FRCPath†,‡; McCluggage, W. Glenn FRCPath∥∥ Author Information *Department of Laboratory Medicine and Pathobiology, University of Toronto, University Health Network, Toronto, ON §Cancer Research Program, Research Institute, McGill University Health Centre ∥Gerald Bronfman Institute of Oncology, McGill University, Montreal, QC, Canada †Pathology Division of Women’s and Perinatal Pathology, Department, Massachusetts General Hospital ‡Harvard Medical School **Department of Pathology, Brigham and Women’s Hospital, Boston, MA ¶Bellvitge Institute for Biomedical Research (IDIBELL), Barcelona, Spain #Department of Pathology, University of Chicago Medical Center, Chicago, IL ††Department of Histopathology, University Hospitals Coventry and Warwickshire NHS Trust, Walsgrave, Coventry ∥∥Department of Pathology, Belfast Health and Social Care Trust, Belfast, UK ‡‡Department of Laboratory Medicine and Pathology, Mayo Clinic, Jacksonville, FL §§Canterbury Health Labs, Christchurch, New Zealand 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: Nairi Tchrakian, FRCPath, Department of Laboratory Medicine and Pathobiology, University Health Network, Toronto General Hospital, 200 Elizabeth Street, Toronto, ON, Canada M5G 2C4 (e-mail: [email protected]). The American Journal of Surgical Pathology: December 2022 - Volume 46 - Issue 12 - p 1599-1610 doi: 10.1097/PAS.0000000000001954 Buy Metrics Abstract Signet-ring stromal tumor (SRST) is a rare ovarian stromal neoplasm characterized by a population of bland signet-ring cells, devoid of mucin or lipid, in a generally cellular fibromatous stroma. Previous reports have described heterogenous immunohistochemical and molecular genetic findings, including occasional nuclear β-catenin expression and/or CTNNB1 mutations. We report 10 ovarian stromal neoplasms originally diagnosed as SRST. All but 1 tumor underwent detailed immunohistochemical analysis (including β-catenin) and 5 of 10 had CTNNB1 mutation analysis performed. All tumors contained a population of morphologically bland signet-ring cells that ranged from 15% to 95% of the neoplasm, characterized by a single large empty intracytoplasmic vacuole, mostly with nuclear indentation. Six of the 10 tumors contained cellular fibroma-like areas, comprising from 10% to 85% of the neoplasm. Three of the 10 tumors were reclassified as microcystic stromal tumor with signet-ring cells on the basis of the microcyst formation and hyalinized stroma, beta-catenin and cyclin D1 nuclear expression and/or CTNNB1 mutation, CD10 staining and largely absent expression of inhibin and calretinin. In the remaining 7 tumors, the diagnosis of SRST remained, constituting the largest series of SRST reported in the literature to date. The results of our study suggest that a subset of tumors diagnosed as ovarian SRST, especially those which show β-catenin nuclear positivity and/or CTNNB1 mutation, likely represent microcystic stromal tumor with variant morphology. We also suggest that at least a subset of SRSTs without evidence of Wnt/β-catenin pathway abnormalities may be related to ovarian fibromas. We discuss the differential diagnosis of ovarian neoplasms containing signet-ring cells. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.