Diagnostic utility of PRAME immunohistochemistry in PEComa family of tumors and morphologic mimics with emphasis on the gynecologic tract

Perivascular epithelioid cell tumors (PEComas), rare mesenchymal tumors with myomelanocytic differentiation, can be a diagnostic challenge, often requiring a panel of immunohistochemical markers. Preferentially expressed antigen in melanoma (PRAME) is a relatively new antigen with utility in diagnosing melanomas. This study aimed to survey PRAME expression patterns in the PEComa family of tumors and morphologic mimics. Twenty cases of PEComas and 27 non-PEComas (10 leiomyosarcomas, 3 smooth muscle tumors of uncertain malignant potential [STUMPs], 11 leiomyomas, 1 uterine inflammatory myofibroblastic tumor [IMT], and 2 low-grade endometrial stromal sarcomas [LGESSs]) were stained with PRAME and compared to previously performed HMB45 and Melan-A stains, when available. Tumors showing no or barely perceptible PRAME staining at 10× were considered negative. Tumors were considered positive if there was full nuclear staining evident at 10× in at least one 10× field. Diffuse staining was defined as positivity in at least 80% of tumor nuclei. Overall, PRAME was expressed in 70% of PEComas, with diffuse positivity in 60%. However, PRAME was not specific for PEComas, with immunopositivity in the majority (70%) of uterine leiomyosarcoma cases, though negative in STUMP, leiomyoma, IMT, and LGESS cases. PRAME sensitivity was 70% and specificity was 74%, while HMB45 was more sensitive (90%) and specific (100%), but only 15% of PEComas showed diffuse staining. Melan-A staining was less common than HMB45 or PRAME, with only 18.8% sensitivity but 100% specificity. Among gynecologic PEComas, PRAME was expressed in 75% overall and enriched among malignant cases (85.7% positive). As part of an immunohistochemical panel, PRAME could be useful in the workup of PEComa cases. In the future, PRAME-specific immunotherapies may be beneficial in treating patients with malignant PEComas.