197 Integrating Histologic and Molecular Features in Meningiomas

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INTRODUCTION: Histologic findings are the primary determinant of meningioma prognosis and post-operative management. However, the relationship of specific pathologic features to molecular alterations has not yet been comprehensively investigated. METHODS: Detailed histological information was collected for 809 resected meningiomas, including cases with DNA methylation (n=380), copy number array (n=252), next-generation sequencing (n=52), RNA risk score (n=394), and/or TERT promoter profiling (n=238). Analyses were conducted on prognostic pathologic features, including WHO Grade, Ki-67, mitotic index (MI), brain invasion, and atypical histologic findings (necrosis, hypercellularity, prominent nucleoli, sheeting, and small cells). Correlation with molecular variables was performed using Fisher’s Exact Tests, including DNA methylation subgroup, RNA risk score, CNV profiles, and TERT promoter mutations. All statistics were corrected for multiple hypothesis testing. RESULTS: Nearly 65% of meningiomas exhibited at least one form of histologic atypia, most commonly increased cellularity or necrosis. Recurrent lesions were associated with sheeting and necrosis, elevated Ki-67/MI, and higher WHO grade. Aggressive histologic features, including increased cellularity, elevated Ki-67/mitotic index, and WHO grade, correlated with DNA methylation and RNA risk groups. Several chromosomal arm events were related to pathologic features (prominent nucleoli, Ki-67, MI, and grade), including chromosomes 1, 4, 10, 14, and 18. CONCLUSIONS: Our analysis highlights the continued value in screening for histologic markers of aggressive behavior in meningiomas, as they correlate with the presence of high-risk molecular features and may serve as proxy markers when advanced molecular testing is not available.

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