Grade 3 Meningiomas Following 2021 WHO Guidelines—A Dual Center Retrospective Study on Clinical Characteristics and Outcomes

INTRODUCTION: In their updated 2021 guidelines, the World Health Organization (WHO) for the first time included molecular markers in the classification of Grade 3 meningiomas (G3Ms). Now, homozygous deletion of CDKN2A/B or TERT Promoter (TERTp) mutations independently qualify a meningioma as Grade 3 [1]. METHODS: We performed a dual-center retrospective review from 2005 to 2021 on primary G3Ms. To adhere to guidelines, tumors were regraded when RNA sequencing, methylation profiling, or DNA microarray was available. Tumor recurrence was the outcome metric. RESULTS: A total of 1358 patients were reviewed with 31 (2.3%) primary tumors meeting criteria for Grade 3 and 4/31 (13%) meeting only molecular criteria. Among the 31 patients, 16 (52%) were female with a median age of 65. Upon regrading, 25 (81%) met only histological criteria, 3 (9.7%) had only TERTp mutations, 1 (3.1%) had only CDKN2A deletion, 1 (3.1%) met histological criteria and had TERT mutation, and 1 (3.1%) met histological criteria and had CDKN2A deletion. Molecular profiling of 18 G3Ms demonstrated chromosomal deletions in 1p (16/18, 89%), 14q (10/18, 56%), and 22q (16/18, 89%). Common locations were frontal (11/31, 35%) and parietal convexity (6/31, 23%). Histological findings included necrosis (24/31, 77%), hypercellularity (23/31, 74%), and prominent nucleoli (21/31, 68%). Tumors recurred in 9/31 (29%) and 8/31 (26%) recurred multiple times. CONCLUSIONS: Here we present the first description of G3Ms following the updated 2021 WHO guidelines.