Original ArticlesMicrocystic Stromal Tumor A Distinctive Ovarian Sex Cord-Stromal Neoplasm Characterized by FOXL2, SF-1, WT-1, Cyclin D1, and β-catenin Nuclear Expression and CTNNB1 MutationsIrving, Julie A. MD, FRCPC*,†; Lee, Cheng-Han MD, PhD, FRCPC‡; Yip, Stephen MD, FRCPC§; Oliva, Esther MD∥; McCluggage, W. Glenn FRCPath¶; Young, Robert H. MD∥Author Information *Department of Laboratory Medicine, Pathology, and Medical Genetics, Royal Jubilee Hospital, Victoria †Department of Pathology, University of British Columbia §Department of Pathology and Laboratory Medicine, Vancouver General Hospital, Vancouver, BC ‡Department of Laboratory Medicine and Pathology, University of Alberta and Royal Alexandra Hospital, Edmonton, AB, Canada ∥James Homer Wright Pathology Laboratories of the Massachusetts General Hospital, and the Department of Pathology, Harvard Medical School, Boston, MA ¶Department of Pathology, Belfast Health and Social Care Trust, Belfast, Northern Ireland, United Kingdom Presented in part at the United States and Canadian Academy of Pathology Annual Meeting, 2014. 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: Julie A. Irving, MD, FRCPC, Department of Laboratory Medicine, Pathology, and Medical Genetics, Royal Jubilee Hospital, 1952 Bay Street, Victoria, BC, Canada V8R 1J8 (e-mail: [email protected]). The American Journal of Surgical Pathology: October 2015 - Volume 39 - Issue 10 - p 1420-1426 doi: 10.1097/PAS.0000000000000482 Buy Metrics Abstract Since our first description of the microcystic stromal tumor (MST) of the ovary, a rare and distinctive neoplasm with a definitional, usually striking microcystic pattern and a CD10+/vimentin+/inhibin−/calretinin− immunophenotype, 3 examples with β-catenin nuclear localization, and CTNNB1 mutation have been reported. We undertook a detailed immunohistochemical study and molecular analysis of CTNNB1 and FOXL2 of 15 cases of MST to further characterize this neoplasm and establish its histogenesis. Diffuse nuclear staining for FOXL2, WT-1, cyclin D1, and β-catenin was present in all tumors tested, and 12/15 were positive for steroidogenic factor-1 (SF-1). Heterozygous missense point mutations in exon 3 of CTNNB1 were detected in 8 of 14 cases, resulting in amino acid changes at codons 32, 34, 35, and 37. There was no correlation between CTNNB1 exon 3 mutation status and tumor immunophenotype. All 14 cases tested showed wild-type FOXL2. Our study establishes that MST of the ovary exhibits a characteristic FOXL2/SF-1/WT-1/cyclin D1/nuclear β-catenin–positive immunohistochemical profile, which may be useful in diagnosis and in the exclusion of histologic mimics. The presence of diffuse nuclear FOXL2 and WT-1 immunostaining in all cases and SF-1 in most supports the classification of MST within the sex cord-stromal category. Aberrant nuclear β-catenin expression, detected in all MSTs, appears to be the result of stabilizing CTNNB1 mutations in 57% of cases, providing further evidence that dysregulation of the Wnt/B-catenin pathway is involved in the tumorigenesis of MST and may involve activation of β-catenin with upregulation of cyclin D1. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.