Choroidal melanoma and polydactylous onychopapilloma leading to diagnosis of BAP1 tumor predisposition syndrome

Introduction BAP1 tumor predisposition syndrome (BAP1-TPDS) is an autosomal dominant syndrome associated with uveal melanoma and multiple systemic malignancies, which is believed to be underreported. Recently, the presence of polydactylous onychopapillomas were deemed an associated phenotype of BAP1-TPDS. Here we describe a case of choroidal melanoma in a patient with polydactylous onychopapilloma, as well as extensive family history of both BAP1-TPDS and relevant nail findings.Methods A retrospective chart review was conducted.Results A 62-year-old man presented with choroidal melanoma of the left eye. Tumor genetic expression profiling demonstrated Class 2, PRAME-negative status, and next-generation sequencing identified variants in GNAQ and BAP1 (c.123-12_127delTACTTCCCCCAGCCCTG), with the BAP1 splice-site variant present at a high variant allele frequency (91.3%). Physical examination revealed onychopapillomas affecting multiple digits and a family history of malignancy among first-degree relatives. Germline multi-cancer panel testing confirmed a hereditary BAP1 variant, establishing the diagnosis of BAP1-TPDS. The patient underwent plaque brachytherapy with continued tumor regression and is enrolled in multidisciplinary surveillance for BAP1-associated malignancies; genetic testing was recommended for close relatives.Discussion This case underscores the importance of combining tumor sequencing with careful phenotypic assessment and family history review. Recognition of polydactylous onychopapillomas may serve as a valuable clinical clue prompting germline testing for BAP1-TPDS in uveal melanoma patients.