Meningioma: Molecular Updates from the 2021 WHO Classification of CNS Tumors and Imaging Correlates

ABSTRACT

Meningiomas, the most common primary intracranial neoplasms, account for over a third of primary CNS tumors. While traditionally viewed as benign, meningiomas can be associated with considerable morbidity, and specific meningioma subgroups display more aggressive behavior with higher recurrence rates. The risk stratification for recurrence has been primarily associated with the World Health Organization (WHO) histopathological grade and extent of resection. However, a growing body of literature has highlighted the value of molecular characteristics in assessing recurrence risk. While maintaining the previous classification system, the 5th edition of the 2021 WHO CNS tumor (CNS5) book expands upon the molecular information in meningiomas to help guide management. The WHO CNS5 stratifies meningioma into three grades (1-3) based on histopathology criteria and molecular profile. pTERT mutations and CDKN2A/B deletions now signify a grade 3 meningioma with increased recurrence risk. Tumor location also correlates with underlying mutations. Convexity and most spinal meningiomas carry 22q deletion and/or NF2 mutations, while skull base meningiomas have AKT1, TRAF7, SMO, and/or PIK3CA mutations. MRI is the primary imaging modality for diagnosing and treatment planning of meningiomas, while DOTATATE-PET imaging offers supplementary information beyond anatomical imaging. Herein, we review the evolving molecular landscape of meningiomas, emphasizing imaging/genetic biomarkers, and treatment strategies relevant to neuroradiologists. ABBREVIATIONS: AKT1=AKT serine/threonine kinase 1; BAP1=BRCA1-associated protein 1; CDK4/6=Cyclin-dependent kinases 4 and 6; KLF4=Krüppel-like factor 4; NF2=Neurofibromatosis type 2; PIK3CA=Phosphatidylinositol-4,5-Bisphosphate 3-Kinase catalytic subunit alpha; POLR2A=RNA polymerase II subunit A; SMO: Smoothened, frizzled class receptor; SMARCB1=SWItch/sucrose non-fermentable related, matrix associated, actin dependent regulator of chromatin, subfamily b, member 1; TERT=Telomerase reverse transcriptase; TRAF7=TNF receptor-associated factor 7