PATH-41. Grade 3 Meningiomas based on the 2021 WHO CNS Tumor Classification: A Retrospective study on Clinical Characteristics and Prognosis

Abstract BACKGROUND The latest edition of the WHO (WHO) Classification of Tumours of the Central Nervous System (the 2021 WHO Classification) includes molecular markers in its diagnostic criteria for meningiomas for the first time. A TERT promoter (TERTp) mutation or CDKN2A/B homozygous deletion is now independently qualifies a meningioma as Grade 3. METHODS A total of 478 meningioma cases that underwent surgical resection at our institution between 2001 and 2024 were reviewed. DNA was extracted from tumors with histological malignancy of Grade 2 or higher, and molecular analysis was performed to detect TERTp mutation and CDKN2A homozygous deletion (CDKN2A-HD). We re-classified meningioma cases according to the 2021 WHO Classification and examined the clinical characteristics and prognosis of Grade 3 meningiomas. RESULTS Among the 478 meningioma cases, 83 (17.4%) were histologically classified as Grade 2 or higher. Following re-evaluation based on the 2021 WHO Classification, which incorporates TERTp mutation and CDKN2A-HD, 10 patients were diagnosed with Grade 3 meningioma. Seven of the 10 patients were female, and the median age at diagnosis of Grade 3 was 61 years (range 37-81 years). Malignant transformation from Grade 2 to Grade 3 was observed in 4 of these 10 cases. Of the 10 Grade 3 cases, 5 were diagnosed with Grade 3 based on histological criteria alone, 3 met histological criteria and exhibited CDKN2A-HD, and 2 were diagnosed with Grade 3 based on TERTp mutation alone. The median progression-free survival after diagnosis of Grade 3 meningioma was 1.2 years. CONCLUSION Most patients with Grade 3 meningiomas experienced multiple recurrences and had a poor prognosis. Notably, several cases were diagnosed based solely on molecular alterations without conventional histological features. This highlights the important role of molecular markers in accurately identifying Grade 3 meningiomas.