Pathology and Molecular Pathology of Meningioma

Abstract

Meningiomas are the most common primary brain tumors occurring primarily in elderly adults with a female preponderance. Meningiomas are classified into 15 histopathological subtypes occurring across three WHO grades (1–3). Majority meningiomas are benign grade 1 meningiomas. Up to 25% are of grade 2 histology and rarely are of grade 3 histology. They are postulated to arise from the arachnoid cap cells and can be classified broadly into two molecular subgroups that correlate with the sites of occurrence, histopathology, and outcome. The cerebral/cerebellar convexity and spinal meningiomas are driven by NF2 gene inactivation (22q monosomy and NF2 mutations) and commonly progress to higher grades (atypical and anaplastic meningiomas) with accumulation of additional cytogenetic (1p deletion, 14q deletion) and molecular alterations (CDKN2A/B deletions, TERT promoter mutations). Skull base meningiomas typically lack NF2 mutations and instead harbor mutations in TRAF7, AKT1, KLF4, SMO, SUFU, PIK3CA, and POLR2A genes, show Grade 1 histology, and do not usually progress to higher grades. However, they show higher rates of subtotal resection leading to frequent recurrences. Rarer aggressive histological subtypes such as clear cell meningiomas, rhabdoid meningiomas, and papillary meningiomas harbor germline or somatic mutations in SMARCE1, BAP1, and PBRM1 genes, respectively, and occur in younger age groups, and as part of familial tumor syndromes. Extent of resection and WHO grade are the most important prognostic variables. TERT promoter mutations, CDKN2A deletions, 1p deletion, and 14q deletion are molecular and cytogenetic alterations that correlate with poor prognosis.