Meningioma
2023-09-02 Scott Ryall, PhD Affiliation1.Brigham and Women's Hospital, Harvard Medical School, Boston , MA (USA)
Classification
Definition
Meningiomas are the most common intracranial neoplasms, accounting for approximately a third of all central nervous system (CNS) tumors. 1 Traditionally, they are benign, slow-growing lesions likely derived from the meningothelial cells of the arachnoid mater. 2 Despite their benign reputation, meningioma may lead to significant morbidity, often dependent on the tumor's location.
In the 2021 edition of The World Health Organization (WHO) classification of CNS tumors, meningioma is considered a single tumor entity. However, its broad spectrum of morphological features is reflected in 15 subtypes. 3 These subtypes include i) meningothelial meningioma (grade 1), ii) fibrous meningioma (grade 1), iii) transitional meningioma (grade 1), iv) psammomatous meningioma (grade 1), v) angiomatous meningioma (grade 1), vi) microcystic meningioma (grade 1), vii) secretory meningioma (grade 1), viii) lymphoplasmacyte-rich meningioma (grade 1), ix) metaplastic meningioma (grade 1), x) chordoid meningioma (grade 2), xi) clear cell meningioma (grade 2), xii) atypical meningioma (grade 2), xiii) papillary meningioma (grade 3), xiv) rhabdoid meningioma (grade 3), and xv) anaplastic meningioma (grade 3). Importantly, the 2021 WHO classification emphasizes the need to evaluate the criteria defining atypical or anaplastic meningioma regardless of the tumor's subtype. 3
| Meningioma - Emerging Molecular Entities | Genetic Event(s) |
|---|---|
| Meningothelial Meningioma | Meningothelial meningioma often harbor co-occuring mutations in AKT1 (primarily as p.E17K) and TRAF7, or SMO and PIK3CA. 4-7 Meningothelial meningioma are often genomically stable and rarely harbor mutations in NF2 and/or deletions of chromosome 22q. DNA methylation analysis classifies meningiothelial meningioma as "Meningioma, subtype benign, subclass 2," which also includes secretory meningioma. 8 |
| Fibrous Meningioma | Fibrous meningioma, also referred to as fibroblasic meningioma, frequently harbor one-copy deletions of chromosome 22q and mutations in NF2 on the retained 22q allele. DNA methylation analysis classifies fibroblastic meningioma as "Meningioma, subtype benign, subclass 1," which also includes psammomatous and transitional meningioma. 8 |
| Transitional Meningioma | Transitional meningioma, like fibrous and psammomatous meningioma, frequently harbor one-copy deletions of chromosome 22q and mutations in NF2 on the retained 22q allele. DNA methylation analysis classifies transitional meningioma as "Meningioma, subtype benign, subclass 1," which also includes psammomatous and fibrous meningioma. 8 |
| Psammomatous Meningioma | Psammomatous meningioma, like fibrous and transitional meningioma, frequently harbor one-copy deletions of chromosome 22q and mutations in NF2 on the retained 22q allele. DNA methylation analysis classifies psammomatous meningioma as "Meningioma, subtype benign, subclass 1," which also includes transitional and fibrous meningioma. 8 |
| Angiomatous Meningioma | Angiomatous meningioma typically have trisomy of chromosome 5 in addition to several other less common polysomies including 20, 6, 12, 13, 7, 17, and 18 , in order of prevalence. 9,10 Infrequently, they harbor one-copy deletions of chromosome 22q and mutations in NF2 on the retained 22q allele. 9 DNA methylation analysis classifies angiomatous meningioma as "Meningioma, subtype benign, subclass 3," which also includes metaplastic and microcytic meningioma. 8 |
| Microcystic Meningioma | Microcystic meningioma, like angiomatous and metaplastic meningioma, typically have trisomy of chromosome 5 in addition to several other less common polysomies including 6, 12, 17, 18 and 20. 10 Infrequently, they harbor one-copy deletions of chromosome 22q and mutations in NF2 on the retained 22q allele. DNA methylation analysis classifies microcystic meningioma as "Meningioma, subtype benign, subclass 3," which also includes metaplastic and angiomatous meningioma. 8 |
| Secretory Meningioma | Secretory meningioma are defined by co-occurring mutations in KLF4 (primarily as p.K409Q) and TRAF7, with rare instances of KLF4 arising in isolation. 5,11 Secretory meningioma do not harbor mutations in NF2 and/or deletions of chromosome 22q. DNA methylation analysis classifies secretory meningioma as "Meningioma, subtype benign, subclass 2," which also includes meningothelial meningioma. 8 |
| Lymphoplasmacyte-rich Meningioma | Lymphoplasmacyte-rich meningioma is an extremely rare subtype of meningioma, characterized histologically by the presence of inflammatory infiltrates. Currently, the genetics of lymphoplasmacyte-rich meningioma are unknown. DNA methylation analysis has not been completed for these tumors due to the overwhelming amount of non-neoplastic DNA traditionally seen in these specimens. 8 |
| Metaplastic Meningioma | Metaplastic meningioma, like angiomatous and microystic meningioma, typically have trisomy of chromosome 5 in addition to several other less common polysomies: 6, 12, 17, 18 and 20. 10 Infrequently, they harbor one-copy deletions of chromosome 22q and mutations in NF2 on the retained 22q allele. DNA methylation analysis classifies metaplastic meningioma as "Meningioma, subtype benign, subclass 3," which also includes microcystic and angiomatous meningioma. 8 |
| Chordoid Meningioma | Chordoid meningiomas are considered grade 2 neoplasms due to their high rate of recurrence, despite lacking any high-grade histopathological features. 12 They harbor genetic abberrations including 1p, 2p, 6q, 14q, and 22q loss (the latter with co-ocurring mutations in NF2 on the retained 22q allele). Chromosome 2p deletions are more common in chordoid meningiomas than in other grade 2 meningiomas. Chordoid meningioma are not classified into a distinct DNA methylation group, but rather, segregate with other meningioma subtypes including those classified as benign (~60%), intermediate (~35%), and malignant (~5%). 13 |
| Clear cell Meningioma | Clear cell meningioma frequently harbor germline or somatic SMARCE1 mutations and/or deletions. Infrequently, they harbor one-copy deletions of chromosome 22q and mutations in NF2 on the retained 22q allele. DNA methylation analysis classifies clear cell meningioma as "Meningioma intermediate-A", 8 now further resolved into the distinct entity "Meningioma, clear cell subtype, SMARCE1-altered." |
| Atypical Meningioma | Atypical meningioma is recongized as an intermediate-grade meningioma with a heightened risk of recurrence post-surgery. Genetically, atypical meningiomas commonly harbor one-copy deletions of chromosome 22q and mutations in NF2 on the retained 22q allele. In addition, losses of chromosomes 1p, 14, 6q and 10q are common. 14 DNA methylation analysis does not segregate atypical meningiomas into their own distinct classification, but rather, assigns them across the benign, intermediate, or malignant subtypes. 8,14 This suggests that further stratification based on the inclusion of additional clinicopathological and genetic factors is possible. 15-17 |
| Papillary Meningioma | Papillary meningioma frequently harbor mutations or deletions of PBRM1. 18 Co-occuring mutations and/or deletions of BAP1, a gene more commonly altered in rhabdoid meningioma, have also been noted. 18 DNA methylation analysis does not segregate papillary meningioma into a unique classification, but rather, with tumors classifying as benign (subclass 3) or intermediate (subclass A or B). 8 |
| Rhabdoid meningioma | Rhabdoid meningioma commonly harbor mutations and/or deletions in BAP1, either somatically or in the context of BAP1 tumor predisposition syndrome OMIM:614327. 18,19 Rhabdoid meningiomas with papillary-like histologic features may also harbor mutations and/or deletions of PBRM1. 18,19 As with papillary meningioma, DNA methylation analysis does not segregate rhabdoid meningioma into a unique classification, but rather, with tumors classified as benign (subclass 3) or intermediate (subclass A or B). 8 |
| Anaplastic meningioma | Anaplastic meningioma often harbor TERT promoter mutations and/or homozygous deletions of CDKN2A/CDKN2B, both of which confer a high risk of recurrence and worse progression-free survival. 20-23 Loss of H3 p.K28me3 (K27me3), seen in ~10-20% of anaplastic meninigomas, is likewise associated with a worsened clinical course. 16,24 DNA methylation analysis primarily classifies anaplastic meningioma as "Meningioma, subtype malignant," although some may be classified as intermediate, depending on their underlying genetics. 8 |
Article Bibliography
| Reference Number | Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|---|
| 1 | 31675094 | 2019 | CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2012-2016. | Ostrom QT et al |
| 2 | 33194703 | 2020 | Meningioma: A Review of Clinicopathological and Molecular Aspects. | Huntoon K et al |
| 3 | 34185076 | 2021 | The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. | Louis DN et al |
| 4 | 23334667 | 2013 | Genomic sequencing of meningiomas identifies oncogenic SMO and AKT1 mutations. | Brastianos PK et al |
| 5 | 23348505 | 2013 | Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7, KLF4, AKT1, and SMO. | Clark VE et al |
| 6 | 24096618 | 2013 | AKT1E17K mutations cluster with meningothelial and transitional meningiomas and can be detected by SFRP1 immunohistochemistry. | Sahm F et al |
| 7 | 26826201 | 2016 | Oncogenic PI3K mutations are as common as AKT1 and SMO mutations in meningioma. | Abedalthagafi M et al |
| 8 | 28314689 | 2017 | DNA methylation-based classification and grading system for meningioma: a multicentre, retrospective analysis. | Sahm F et al |
| 9 | 25347344 | 2014 | Angiomatous meningiomas have a distinct genetic profile with multiple chromosomal polysomies including polysomy of chromosome 5. | Abedalthagafi MS et al |
| 10 | 32642661 | 2019 | Identification of shared genomic aberrations between angiomatous and microcystic meningiomas. | Kuroi Y et al |
| 11 | 23404370 | 2013 | Secretory meningiomas are defined by combined KLF4 K409Q and TRAF7 mutations. | Reuss DE et al |
| 12 | 10895812 | 2000 | Chordoid meningioma: a clinicopathologic study of 42 cases. | Couce ME et al |
| 13 | 30382370 | 2018 | Chordoid meningiomas can be sub-stratified into prognostically distinct DNA methylation classes and are enriched for heterozygous deletions of chromosomal arm 2p. | Sievers P et al |
| 14 | 36845294 | 2023 | Genomic markers of recurrence risk in atypical meningioma following gross total resection. | Vaubel RA et al |
| 15 | 24536048 | 2014 | Proposal for a new risk stratification classification for meningioma based on patient age, WHO tumor grade, size, localization, and karyotype. | Domingues PH et al |
| 16 | 29627952 | 2018 | Loss of histone H3K27me3 identifies a subset of meningiomas with increased risk of recurrence. | Katz LM et al |
| 17 | 32232472 | 2020 | A Risk Score Based on 5 Clinico-Pathological Variables Predicts Recurrence of Atypical Meningiomas. | Fioravanzo A et al |
| 18 | 32405805 | 2020 | Frequent inactivating mutations of the PBAF complex gene PBRM1 in meningioma with papillary features. | Williams EA et al |
| 19 | 28170043 | 2017 | Germline and somatic BAP1 mutations in high-grade rhabdoid meningiomas. | Shankar GM et al |
| 20 | 24261697 | 2014 | High incidence of activating TERT promoter mutations in meningiomas undergoing malignant progression. | Goutagny S et al |
| 21 | 26668184 | 2016 | TERT Promoter Mutations and Risk of Recurrence in Meningioma. | Sahm F et al |
| 22 | 29312603 | 2017 | Intratumoral heterogeneity and TERT promoter mutations in progressive/higher-grade meningiomas. | Juratli TA et al |
| 23 | 32642869 | 2020 | CDKN2A/B homozygous deletion is associated with early recurrence in meningiomas. | Sievers P et al |
| 24 | 32447376 | 2020 | Prognostic Value of Histopathological Features and Loss of H3K27me3 Immunolabeling in Anaplastic Meningioma: A Multicenter Retrospective Study. | Gauchotte G et al |
Citation
Scott Ryall, PhD
Meningioma
Atlas Genet Cytogenet Oncol Haematol. 2023-09-02
Online version: http://atlasgeneticsoncology.org/solid-tumor/209204/meningioma
