Original ArticlesOssifying Fibromyxoid Tumor of the Genitourinary Tract Report of 4 Molecularly Confirmed Cases of a Diagnostic PitfallArgani, Pedram MD*,†; Dickson, Brendan C. MD‡; Gross, John M. MD*,†; Matoso, Andres MD*,†,§; Baraban, Ezra MD*,†; Antonescu, Cristina R. MD∥ Author Information Departments of *Pathology †Oncology §Urology, The Johns Hopkins Medical Institutions, Baltimore, MD ‡Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, 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 CA217694 (C.R.A.), P30 CA008748 (C.R.A.), Kristin Ann Carr Foundation (C.R.A.), Dahan Translocation Carcinoma Fund and Joey’s Wings (P.A.). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. Correspondence: Pedram Argani, MD, The Johns Hopkins Hospital, Surgical Pathology, Weinberg Building, Room 2242, 401 North Broadway, Baltimore, MD 21231-2410 (e-mail: [email protected]); Cristina R. Antonescu, MD, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021 (e-mail: [email protected]). The American Journal of Surgical Pathology 47(6):p 709-716, June 2023. | DOI: 10.1097/PAS.0000000000002036 Buy Metrics Abstract Ossifying fibromyxoid tumors (OFMTs) are rare mesenchymal neoplasms which typically present in the superficial subcutaneous tissues and have not been reported to arise in visceral organs. We now report 4 molecularly confirmed cases of OFMT involving the genitourinary tract. All patients were males, ranging in age from 20 to 66 years (mean: 43 y). One case each arose in the kidney, ureter, perirenal soft tissue, and penis. All neoplasms demonstrated bland epithelioid to spindled cells set in a variably fibrous to fibromyxoid stroma, and only 1 had a peripheral shell of lamellar bone. All cases appeared well-circumscribed on gross/radiologic examination, though the primary renal neoplasm permeated between native renal tubules. By immunohistochemistry, S100 protein was negative in all 4 cases, while desmin was positive in 2 cases. In 2 cases, the Illumina TruSight RNA Fusion Panel demonstrated a PHF1::TFE3 and EP400::PHF1 fusion, respectively. In the remaining 2 cases, PHF1 gene rearrangement was confirmed by fluorescence in situ hybridization analysis. Due to unusual clinical presentation, lack of S100 positivity, and only occasional bone formation, the correct diagnosis was challenging in the absence of molecular testing. In summary, OFMT may rarely present primarily in the genitourinary tract. Given their nonspecific morphology and immunophenotype, molecular analysis is crucial to establish the correct diagnosis. Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.