Pediatric and AYA meningiomas constitute a molecularly distinct entity not captured by adult-based risk strategies

We analyzed 293 tumors from patients aged 0–39 years using integrated histopathological and molecular profiling. Youth-onset meningiomas were enriched for NF2 and SMARCE1 alterations and exhibited a gain-dominated copy-number landscape, including recurrent chr17q gain, whereas canonical adult high-risk features, such as chr1p loss, lacked prognostic significance.

Adult-derived prognostic frameworks—including WHO grade, methylation-based stratification, and integrated risk scores—failed to predict progression in patients ≤21 years. Tumors segregated into age-enriched epigenetic clusters defined by SMARCE1, NF2, and BAP1 alterations. Among NF2-altered tumors, patterns of Merlin inactivation shaped by germline status and co-occurring copy-number variations delineated biologically divergent subsets.