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NF2-schwannomatosis is the most common genetic predisposition syndrome associated with meningioma. Meningioma in NF2-schwannomatosis is a major source of morbidity and mortality. This is due to accumulative tumor burden in patients with synchronous schwannomas and ependymomas, sometimes including complex collision tumors. Balancing the impact of multiple interventions against the natural history of various index tumors, and the ongoing risk of de novo tumors over an individual's lifetime makes decision-making complex. The management of any given individual meningioma is often different from a comparable sporadic tumor. There is typically a greater emphasis on conservative management and tolerating growth until a risk boundary is reached, whereby symptomatic deterioration or higher risk from anticipated future treatment is threatened. Management by high-volume multidisciplinary teams improves quality of life and life expectancy. Surgery remains the mainstay treatment for symptomatic and rapidly enlarging meningioma. Radiotherapy has an important role but carries a higher risk compared to its use in sporadic disease. Whilst bevacizumab is effective in NF2-associated schwannoma and cystic ependymoma, it has no value in the management of meningioma. In this review, we describe the natural history of the disease, underlying genetic, molecular, and immune microenvironment changes, current management paradigms, and potential therapeutic targets., Competing Interests: G.E.G., A.P.J., K.C., D.B., and O.N.P. have received funding from NF2 BioSolutions UK. A.I.I. is supported by the NIHR Academic Clinical Fellowship Scheme. C.J.H., A.T.K., and O.N.P. are funded by Eleanor Peel Trust, the Royal College of Surgeons of Edinburgh, and the BMA Foundation. S. L. and D.G.E. are supported by the Manchester NIHR Biomedical Research Centre (IS-BRC-1215-20007). O.N.P. is UK Chief Investigator for Recursion Pharma Rec 2282 phase II/III RCT in NF2 mutated meningioma; A.I.I. is sub principal investigator. Supplement sponsorship. This supplement was sponsored by a generous donation from Mr. Paul Mielnik and his family to help raise awareness and advance the care of patients with meningiomas worldwide., (© The Author(s) 2023. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Vestibular schwannomas are tumors arising from the vestibulocochlear nerve at the cerebellopontine angle. Their proximity to eloquent brainstem structures means that the pathology itself and the treatment thereof can be associated with significant morbidity. The vast majority of these tumors are sporadic, with the remainder arising as a result of the genetic syndrome Neurofibromatosis Type 2 or, more rarely, LZTR1- related schwannomatosis. The natural history of these tumors is extremely variable, with some tumors not displaying any evidence of growth, others demonstrating early, persistent growth and a small number growing following an extended period of indolence. Emerging evidence now suggests that far from representing Schwann cell proliferation only, the tumor microenvironment is complex, with inflammation proposed to play a key role in their growth. In this review, we provide an overview of this new evidence, including the role played by immune cell infiltration, the underlying molecular pathways involved, and biomarkers for detecting this inflammation in vivo. Given the limitations of current treatments, there is a pressing need for novel therapies to aid in the management of this condition, and we conclude by proposing areas for future research that could lead to the development of therapies targeted toward inflammation in vestibular schwannoma., (© The Author(s) 2020. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)