PRAME Immunostaining in BAP-1-Inactivated Melanocytic Tumors: Unraveling Diagnostic Complexity and Exploring Germline Mutation Associations.
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BACKGROUND: Cutaneous melanocytic tumors with BAP-1 inactivation (BIMTs), linked to mutations in the BAP-1 gene, present diagnostic challenges due to their morphological similarities with other melanocytic lesions. The search for reliable diagnostic markers, including PRAME, holds potential to significantly improve the accuracy of differential diagnoses. METHODS: A retrospective analysis of 32 BIMTs from 25 patients, collected between 2018 and 2022, involved histologic examination and immunostaining for BAP-1 and PRAME. RESULTS: Positive PRAME expression, defined as diffuse staining in at least 75% of nevic cells, was observed in 19% of cases. Variations in PRAME expression patterns were noted, particularly in biphasic lesions and those associated with germline BAP-1 mutations. CONCLUSIONS: The diagnostic complexities of BIMTs necessitate a comprehensive diagnostic strategy. While BAP-1 immunostaining remains pivotal, this study explored PRAME as a potential adjunctive diagnostic tool. PRAME antibody shows highly variable expression in BIMTs, limiting its utility as a supportive tool for the differential diagnosis with melanomas, especially in patients with biphasic lesions and germline mutations in BAP-1.