[Ossifying fibromyxoid tumor with rare fusion subtypes: a clinicopathological analysis]

Objective: To investigate the clinicopathological characteristics of ossifying fibromyxoid tumor (OFMT) with rare fusion subtypes. Methods: Three cases of OFMT with rare fusion subtypes, diagnosed and consulted in the Zhejiang Hospital, Zhejiang Provincial People's Hospital, Hangzhou, China and Ningbo Clinical Pathology Diagnosis Center, Ningbo, China from January 2016 to December 2024 were collected. Immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and targeted RNA sequencing were performed to analyze the immunohistochemical and molecular genetic characteristics of these OFMT. Literature review was also conducted. Results: All three patients were male, with ages of 50, 74, and 58 years, respectively. The tumors were located in the left foot, left thigh, and left lumbar region, respectively, and all presented as slowly growing, painless masses in the skin or subcutaneous tissue. Grossly, the tumors measured 3.5 cm, 6.3 cm, and 5.0 cm in maximum diameter, respectively, with a grayish-white to grayish-yellow, solid, lobulated cut surface. One case exhibited a noticeable myxoid texture. Microscopically, one tumor was located in the superficial dermis, while the other two were in the subcutaneous tissue. The tumors were well-demarcated and showed a lobulated or multinodular growth pattern. None of the cases had a complete surrounding bony shell (only one case had very focal ossification). The tumor cells were monomorphic, short spindle-shaped, oval to epithelioid, and arranged in solid sheets, trabeculae, and small nests within a variably fibromyxoid stroma. Case 1 exhibited abundant pseudorosette-like structures formed by short spindle cells surrounding acellular fibrous stroma. Case 2 showed focal transition of epithelioid tumor cells into fasciculately arranged spindle cells, with extensive stromal hyalinization. Case 3 had a predominantly myxoid stroma with a rich network of thin-walled blood vessels. The tumor cells exhibited mild nuclear atypia with 1-3 mitotic figures per 50 high-power fields. All three cases showed diffuse and strong expression of CD10. Two of the three cases showed nuclear expression of TFE3, while one case showed diffuse and strong expression of desmin and S-100. Targeted RNA sequencing revealed PHF1 (ex12)::TFE3 (ex7) fusion in two cases and MEAF6 (ex5)::PHF1 (5'UTR) fusion in one case, which were further confirmed by FISH study. All three patients underwent tumor resection. Two showed no recurrence during follow-up periods of 98 months and 15 months, respectively, while one experienced local recurrence at 12 months postoperatively. Conclusions: OFMT with rare fusion subtypes often exhibits atypical histological and immunophenotypic features, and lacks a characteristic bony shell. Incorporating TFE3 into the diagnostic IHC panel greatly aids in screening for the cases with rare PHF1::TFE3 fusions. Familiarity with the histological and immunophenotypic characteristics, and differential diagnostic points of these rare OFMT subtypes, is essential for judicious use of molecular genetic tools in achieving a definitive diagnosis.