Clinical and Molecular Features of BAP1-Mutated Meningiomas: Case Series.

BRCA1-associated protein 1 (BAP1)-deficient meningiomas represent a clinically and molecularly distinct subgroup with variable histology and aggressive behavior that may not be fully captured by current grading criteria. The clinical spectrum of BAP1 alterations in meningiomas, including both somatic and germline contexts, remains incompletely characterized. We report three cases of BAP1-deficient meningiomas with divergent clinical trajectories. Case 1 was a 44-year-old woman with a somatic BAP1 nonsense mutation (Q392*) presenting as recurrent spinal meningiomatosis. Despite WHO grade 1 histology with rhabdoid features and no high-grade criteria, she experienced rapid recurrence and required multiple resections, radiation, and systemic therapy, illustrating that truncating somatic mutations may drive aggressive behavior independent of histological grade. Case 2 was a 22-year-old man harboring a germline BAP1 truncating mutation (R385*) with a family history of meningioma, who presented with a WHO grade 3 papillary meningioma and remained progression-free 24 months after resection and adjuvant radiotherapy. His family pedigree represents a rare phenotype within the BAP1 tumor predisposition syndrome. Case 3 was a 57-year-old man with a low-variant-allele-frequency BAP1 missense mutation (Y173C) and WHO grade 2 meningioma who demonstrated a favorable course at 26 months following gross total resection without adjuvant therapy. These cases illustrate the phenotypic heterogeneity of BAP1-deficient meningiomas and underscore that truncating mutations, particularly somatic ones, may confer aggressive behavior regardless of histological grade. Variant allele frequency and mutation type should inform risk stratification alongside traditional pathological features. Consideration of BAP1 as a defining molecular feature in future WHO classification iterations is likely warranted.