Original ArticlesInflammatory Myofibroblastic Tumor of the Uterus An Immunohistochemical Study of 23 CasesBennett, Jennifer A. MD*; Croce, Sabrina MD†; Pesci, Anna MD‡; Niu, Nifang PhD*; Van de Vijver, Koen MD, PhD§; Burks, Eric J. MD∥; Burandt, Eike MD¶; Zannoni, Gian Franco MD#; Rabban, Joseph T. MD, MPH**; Oliva, Esther MD††Author Information *University of Chicago Medical Center, Chicago, IL †Institut Bergonié, Comprehensive Cancer Center, Bordeaux, France ‡IRCCS Ospedale Sacro Cuore Don Calabria, Verona #Catholic University of Sacred Heart, Rome, Italy §Cancer Research Institute Ghent and University Hospital Ghent, Ghent, Belgium ∥Boston University School of Medicine ††Massachusetts General Hospital, Boston, MA ¶University Medical Center Hamburg-Eppendorf, Hamburg, Germany **University of California San Francisco, San Francisco, CA Conflicts of Interest and Source of Funding: Dr J.T.R. reports that his spouse receives salary and stock options from Merck & Co. The remaining authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Jennifer A. Bennett, MD, Department of Pathology, University of Chicago Medicine, 5841 South Maryland Avenue, Room J-607B, MC6101, Chicago, IL 60637 (e-mail: [email protected]). The American Journal of Surgical Pathology: November 2020 - Volume 44 - Issue 11 - p 1441-1449 doi: 10.1097/PAS.0000000000001525 Buy Metrics Abstract Inflammatory myofibroblastic tumors (IMT) of the uterus may be underrecognized as their morphology and immunophenotype may overlap with myxoid variants of uterine smooth muscle tumors and endometrial stromal tumors. Although ALK is a helpful biomarker, not all uterine IMTs are ALK-rearranged, and a small subset of myxoid leiomyosarcomas is ALK-positive. Herein, we evaluated a series of 23 IMTs for the novel endometrial stromal markers interferon-inducible transmembrane protein-1 (IFITM1) and BCOR, the novel myoid marker transgelin, and possible predictive markers p16 and p53 by immunohistochemistry to determine their expression profile and potential prognostic value. Patients’ ages ranged from 8 to 59 (mean 39) years and tumors from 2 to 20 (mean 8.2) cm. Follow-up was available for 12/23 (52%) patients; 9/12 (75%) without evidence of disease, 2/12 (17%) alive with disease, and 1/12 (8%) dead from disease. Four IMTs were classified as malignant due to extrauterine disease at diagnosis and/or recurrence. IFITM1 was positive (combined score>2) in 19/23 (83%), BCOR in 8/20 (40%), and transgelin in 22/23 (96%) of tumors. IFITM1 and BCOR were more often expressed in the myxoid component, and transgelin in the compact areas. p16 expression was absent in 5/23 (22%) of IMTs, while p53 was wildtype in all tumors. p16-negative IMTs included all 4 classified as malignant and one where the patient was lost to follow-up. Molecular data were available in 2 malignant IMTs, both of which harbored CDKN2A deletions. We conclude that caution is advised when using IFITM1, BCOR, and transgelin as markers for endometrial and smooth muscle tumors, as these are commonly expressed in IMTs. However, we did identify an association among lack of p16 staining, CKDN2A deletions, and aggressive behavior that merits corroboration by other studies. As a result of this finding, we recommend the use of p16 in the diagnostic work-up of uterine IMTs due to its potential prognostic significance. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.