Reappraisal of novel molecular parameters for meningioma grading by cIMPACT-NOW update 8 proposals

Meningiomas boast the most common central nervous system (CNS) tumors and could thus affect the quality of life for the general population. Particularly, identification of CNS WHO grade 2 and 3 meningiomas (formerly known as atypical and anaplastic meningiomas, respectively) is important, considering their prognostic impact on meningioma patients. The 5th edition of the WHO Classification of Central Nervous System Tumors (CNS5) incorporated molecular biomarkers, including TERT promoter mutation (TERTp mt) and homozygous deletion of CDKN2A (CDKN2A HD) as independent diagnostic criteria for meningioma, CNS WHO grade 3 [4, 6]. Additionally, the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy-Not Official WHO (cIMPACT-NOW), which provides practical recommendations for the improvement of the WHO classification of CNS tumors, has been working on the clarification and assessment of possible novel molecular criteria for meningioma grading [10]. A representative example by cIMPACT-NOW update 8 is chromosomes 1p and 22q losses to assign CNS WHO grade 2 for meningioma cases with CNS WHO grade 1 morphology [7, 10]. Since 22q loss is detected in grade 1 to grade 3 meningiomas including all the 1p loss cases [6, 10], we herein validated the status of 1p loss in our CNS WHO grade 2 and grade 3 meningioma cases, in combination with other established molecular biomarkers including TERTp mt and CDKN2A HD, in order to clarify the practical impact of 1p deletion in meningioma grading. We found that over 60% of histological grade 2 meningiomas did not possess chromosome 1p loss, and their downgrading would be thus advisable based upon molecular criteria to avoid unnecessary overtreatment. …