High frequency and unique subtypes of meningioma in patients with BAP1 tumor predisposition syndrome

PURPOSE: BAP1-tumor predisposition syndrome (BAP1-TPDS) is associated with four main cancers: uveal melanoma, cutaneous melanoma, malignant mesothelioma, and renal cell carcinoma. However, additional cancers are found more rarely in BAP1-TPDS patients. The aim of this study was to investigate the association, clinical, and pathologic characteristics of meningioma in BAP1-TPDS. METHODS: We conducted a retrospective chart review of meningiomas in two independent cohorts of patients with germline BAP1 pathogenic or likely pathogenic (P/LP) variants at The Ohio State University Wexner Medical Center and at the Memorial Sloan Kettering Cancer Center from October 1st, 2010 date to April 21st, 2025. Additionally, we conducted a literature review of meningioma case studies for individuals with germline BAP1 (P/LP) variants. RESULTS: In a cohort of 237 subjects with BAP1-TPDS, we identified 6.8% (16/237) with a history of meningiomas. The average age of diagnosis was 44.5 years (17–71). For patients with available pathology, 61.5% (8/13) of the tumors were grade 2/3. Patients with available tumor tissue 83.3% (5/6) showed evidence of BAP1 biallelic inactivation. Family history of meningioma was reported in 18.8% (3/16) of patients. Four cases of meningioma were identified during meningioma surveillance imaging, and five cases had recurrences after treatment. Published cases were consistent with the early age of onset, high-grade tumors, and clinical phenotype of tumors. CONCLUSION: This study provides additional evidence that high-grade brain and spinal meningiomas are part of the clinical spectrum of BAP1-TPDS. Craniospinal imaging surveillance in the BAP1-TPDS population should be considered starting around puberty, enabling early detection and management for individuals with BAP1-TPDS.