Metastatic Meningioma with Systemic Involvement: Discussion of Molecular, Genomic, and Radiological Features

Meningiomas are typically benign, slow-growing tumors localized to the cranial or spinal regions, with less than 1% metastasizing systemically, posing a serious clinical challenge. This case series adds critically needed data to broaden existing knowledge and demonstrates that early molecular profiling may identify patients at risk for systemic metastasis, informing surveillance strategies and treatment decisions. Between 2012-2024, we retrospectively reviewed patients with meningiomas from our institution’s electronic medical record. Clinical data, including imaging, biopsy results, and surgical outcomes, were reviewed, focusing on genomic details, histopathology, disease progression, and treatment. We found 2,888 patients with meningiomas, five of whom developed metastatic features, one Grade 2 atypical meningioma, and four Grade 3 anaplastic meningiomas. Metastases occurred to the scalp (1 case), parotid gland (1 case), vertebra (3 cases), liver (1 case), lungs (1 case), and neck (1 case). Imaging (CT, MRI, PET-CT) and biopsies confirmed origin of metastases. These patients received multiple surgical resections, chemotherapy, targeted therapy (everolimus, ixazomib, and tazemetostat), and localized radiation. Mutations in MTAP, BRCA-1-associated protein-1, CDKN2A/B, and H3K27me3 were identified. Despite aggressive treatment, 3 patients experienced disease progression and died, while the others showed partial response to therapy. Survival averaged 107 months from diagnosis, dropping to 24 months post-metastasis. Extra-CNS metastatic meningiomas pose significant diagnostic and therapeutic challenges. High-grade meningiomas are more likely to metastasize; early detection of metastatic spread is challenging. Our findings highlight the need for a multidisciplinary approach with close follow-up, especially in recurrent or high-grade meningiomas with distinct mutations. • Metastatic meningioma represents a rare but molecularly aggressive disease subset. • CDKN2A, TERT, and BAP1 alterations were associated with distinct metastatic patterns. • Metastatic timing ranged from early systemic spread to delayed progression over years. • Molecular profiling may inform surveillance and management in high-risk meningiomas.