P13.16.A MENINGIOMAS IN ADOLESCENTS AND YOUNG ADULTS: CLINICAL, HISTOPATHOLOGICAL, AND MOLECULAR CHARACTERIZATION.

Abstract BACKGROUND Meningiomas are the most common type of primary intracranial tumor, characterized by slow growth and predominantly benign nature. Although typically diagnosed in older adults (median age 66 years), their occurrence in younger patients is rare and poorly characterized. Limited studies in Adolescents and Young Adults (AYAs) have raised questions about potential differences in clinical behavior and histopathological features. Moreover, molecular drivers in this population remain insufficiently explored. We aimed to comprehensively characterize a cohort of young patients with meningiomas and compare their profiles to those of older adults. MATERIAL AND METHODS We retrospectively analyzed meningioma cases treated at our hospital between 2018-2025. Out of 201 patients, 15 were aged 15-40 years at diagnosis. Clinical data (age, sex, symptoms, status, tumor location, recurrence, overall survival [OS], recurrence-free survival [RFS]) and histopathological variables (WHO grade, subtype) were obtained from electronic medical records. Molecular analyses were conducted using targeted next-generation sequencing for mutations (SNVs, indels) and copy number variations (CNVs), and FISH for chromosomal/gene alterations (CDKN2A homozygous deletion). Results were compared with published data on older adults. RESULTS The mean age at diagnosis was 36.1 years (range 14-40), with a female-to-male ratio of 4: 1. Headache (40%) and seizures (33%) were the most common symptoms. Tumors were located in the skull base (40%), convexity (33%), midline (20%), and intraventricular region (7%). Median follow-up was 2.75 years. No deaths occurred, and two patients (13%) had recurrences, one with histological progression. OS at five years was 100%, with a mean RFS of 2.6 years; 87% of patients were disease-free at last follow-up. Histologically, 86% of tumors were WHO grade 1, 7% grade 2, and 7% grade 3. NF2 mutations were found in 45% of patients, all with 22q loss; four also showed 1p loss. AKT1 mutations were detected in two cases, and one tumor showed co-mutations in TRAF7 and KLF4. Variants of uncertain significance were detected in EGFR, ATRX, and SUFU. CNVs showed loss of 22q (64%), 1p (45%), and 19q (18%). One tumor initially grade 1 recurred with CDKN2A homozygous deletion and progressed to grade 3. CONCLUSION Meningiomas in AYA patients generally show a favorable clinical course and simpler molecular profile, primarily involving NF2 alterations and fewer aggressive biomarkers. Our findings highlight the value of molecular profiling in AYAs, as markers like CDKN2A deletions have key prognostic and therapeutic relevance. Larger cohorts are needed to validate these findings and better define molecular features of early-onset meningiomas.