CNS tumor

Meningeal tumors

Meningioma


Editorial Board Member: Maria Martinez-Lage, M.D.
Chunyu Cai, M.D., Ph.D.

Topic Completed: 10 November 2021

Minor changes: 11 November 2021

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PubMed Search: Meningioma[title] CNS pathology

Chunyu Cai, M.D., Ph.D.
Page views in 2020: 64,781
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Cite this page: Cai C. Meningioma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cnstumormeningiomageneral.html. Accessed December 7th, 2021.
Definition / general
  • Most common primary CNS tumor, arising from arachnoid cap cells associated with dura mater or choroid plexus, accounting for 36% all CNS tumors (Neuro Oncol 2015;17:iv1)
  • Growing along external surface of brain, spinal cord or rarely, within the ventricular system
Essential features
  • 3 grades exist based on WHO criteria:
    • Most are slow growing WHO grade 1 (benign)
    • 20 - 25% are WHO grade 2 (increased likelihood of recurrence)
    • 1 - 6% are WHO grade 3 (malignant with metastatic potential)
  • While there are 15 WHO recognized morphological meningioma variants, this topic focuses more on WHO grade 1 variants
    • WHO grade 1 meningiomas have low mitotic index (< 4/10 high power field), no brain invasion and < 3 atypical features (necrosis, small cell change, sheeted architecture, macronuclei and hypercellularity)
ICD coding
  • ICD-10:
    • D32.9 - benign neoplasm of meninges, unspecified
    • D32.0 - benign neoplasm of cerebral meninges
    • D32.1 - benign neoplasm of spinal meninges
    • C70 - malignant neoplasm of meninges
    • C70.0 - malignant neoplasm of cerebral meninges
    • C70.1 - malignant neoplasm of spinal meninges
    • C70.9 - malignant neoplasm of meninges, unspecified
    • D42 - neoplasm of uncertain behavior of meninges
    • D42.0 - neoplasm of uncertain behavior of cerebral meninges
    • D42.1 - neoplasm of uncertain behavior of spinal meninges
    • D42.9 - neoplasm of uncertain behavior of meninges, unspecified
Epidemiology
  • Mainly adults, mean age of 65
  • F > M
    • 66% of cerebral meningiomas occur in women; 90% of spinal cord meningiomas occur in women (Neuro Oncol 2012;14:v1)
  • Rare cases may occur in pediatric population, which are typically associated with genetic syndromes or childhood radiation (Acta Neuropathol 2021;142:873)
Sites
  • Extra-axial mass growing along external surface of brain, spinal cord, rarely within the ventricular system or outside of the CNS (ectopic)
    • Common CNS sites:
      • Convexity
      • Skull base
      • Falx and tentorium
      • Spinal cord
  • Ectopic:
Pathophysiology
  • Meningiomas driven by chromosome 22q alterations (e.g. NF2, SMARCB1) arise in neural crest cell derived meninges, including convexities, falx, tentorium and spinal cord
  • Meningiomas driven by hedgehog signaling pathway, PI3K signaling, TRAF7, KLF4 and POLR2A arise in the mesodermal derived meninges of the midline and paramedian anterior, central and ventral posterior skull base (Oncogene 2021;40:875)
Etiology
Clinical features
Grading
  • Grade 1 variants
    • Angiomatous:
      • Vascular component should exceed 50% of total tumor area
      • Can further divide into microvascular and macrovascular variants
      • Mean Ki67 index is ~2%
      • Does not recur if entirely resected
      • Differential diagnosis includes hemangioblastoma for the microvascular variant and vascular malformations for the macrovascular variant (Am J Surg Pathol 2004;28:390)
      • Genetically characterized by polysomy of chromosome 5, 13 and 20 (Oncotarget 2014;5:10596)
    • Fibroblastic:
      • Spindle cell neoplasm with few or no meningothelial nests or whorls; often has thick bundles of collagen
      • Resembles schwannoma or solitary fibrous tumor but is positive for meningothelial markers SSTR2A and EMA and negative for STAT6
      • NF2 mutated meningiomas are predominantly fibroblastic or transitional and more commonly located in convexity, falx or tentorium (Nat Genet 2013;45:285, Oncogene 2021;40:875)
    • Lymphoplasmacyte rich:
    • Meningothelial:
      • Most common variant
      • Lobulated architecture, often contains meningothelial whorls
      • Syncytial cells with indistinct cell membranes, eosinophilic cytoplasm
      • Round uniform nuclei, intranuclear pseudoinclusions common
      • May have sparse psammoma bodies
      • Meningiomas with SMO or AKT1 mutations are predominantly meningothelial and more commonly located in the midline or paramedian skull base (Nat Genet 2013;45:285, Oncogene 2021;40:875)
    • Metaplastic:
    • Microcystic:
      • Cells have elongated processes and vacuolated cytoplasm that resembles microcysts
      • May have prominent nuclear pleomorphism but usually low mitotic index
      • Often rich in vasculature and overlaps with angiomatous meningioma
      • Small areas of classic meningothelial nests may be present
      • Microcystic areas are weakly but diffusely positive for hypoxic marker carbonic anhydrase IX (J Neuropathol Exp Neurol 2019;78:1081)
    • Psammomatous:
      • Found in spinal region
      • Numerous psammoma bodies, intervening meningothelial cells hard to find
    • Secretory:
      • Eosinophilic round secretions (pseudopsammoma bodies) positive for CEA and PAS
      • Genetically characterized by combined KLF4 and TRAF7 mutations (Acta Neuropathol 2013;125:351)
    • Transitional:
      • Mixed meningothelial and fibroblastic features
      • Usually prominent whorls, psammoma bodies and clusters of syncytial cells
      • NF2 mutated meningiomas are predominantly fibroblastic or transitional (Nat Genet 2013;45:285)
  • Grade 2 variants
  • Grade 3 variants
  • Upcoming 2021 WHO CNS tumor classification emphasizes that the criteria defining atypical or anaplastic (i.e. grade 2 and 3) meningioma should be applied regardless of the underlying subtype (Neuro Oncol 2021;23:1231)
Diagnosis
  • Diagnose by imaging and pathology of biopsy / resection specimen
Radiology description
  • Extra-axial mass with dural tail
  • Uniformly contrast enhancing
  • Extensive peritumoral edema is usually associated with brain invasion (Neuro Oncol 2021;23:324)
    • With the caveat that several special grade I variants (angiomatous, microcystic, secretory and lymphoplasmacyte rich) can have prominent peritumoral edema (J Neurooncol 2013;111:49)
Radiology images

Contributed by Chunyu Cai, M.D., Ph.D.

MRI benign meningioma

MRI atypical meningioma

MRI en plaque meningioma

MRI secretory meningioma

Prognostic factors
Case reports
Treatment
  • Observation, if asymptomatic
  • Gross total resection is usually curative
  • Postoperative radiation if incompletely excised or WHO grade 2 or 3 (Neurosurg Focus 2015;38:E3)
Gross description
Gross images

Images hosted on other servers:
Missing Image

Tumor displaces brain without invading

Compression of underlying cortex

Resected tumor

Adherent to falx cerebri

Microscopic (histologic) description
  • Arachnoid plane exists between meningioma and CNS parenchyma
  • Histology varies by variant (see Grading)
Microscopic (histologic) images

Contributed by Chunyu Cai, M.D., Ph.D.

Meningothelial meningioma:

Meningothelial meningioma

Meningothelial meningioma syncycial

Meningothelial meningioma SSTR2


Fibrous meningioma:

Fibrous meningioma

Fibrous meningioma SSTR2a



Transitional meningioma:

Transitional meningioma


Angiomatous meningioma:

Angiomatous meningioma macrovascular

Angiomatous meningioma microvascular


Microcystic meningioma:

Microcystic meningioma vacuolated cytoplasm

Microcystic meningioma nuclear pleomorphism



Clear cell meningioma:

Clear cell meningioma

Clear cell meningioma SMARCE1


Lymphoplasmacyte rich meningioma:

Lymphoplasmacyte
rich meningioma

Lymphoplasmacyte
rich meningioma
CD3

Lymphoplasmacyte
rich meningioma
SSTR2


Secretory meningioma:

Secretory meningioma

Secretory meningioma pCEA

Secretory meningioma EMA


Other meningioma:

Metaplastic meningioma

Chordoid meningioma

Psammomatous meningioma

Cytology description
Cytology images

Contributed by Chunyu Cai, M.D., Ph.D.

Streaked cytoplasm

Psammoma body

Cellular whorls



Images hosted on other servers:

Meningothelial tumor

Positive stains
Negative stains
Molecular / cytogenetics description
  • Fibrous, transitional and psammomatous morphologies are associated with NF2 mutation, while meningothelial, secretory and microcystic variants are non-NF2 (Oncogene 2021;40:875)
  • Majority of atypical meningiomas have loss of NF2 combined with either genome instability (large scale chromosomal alterations) or loss of SMARCB1 (Nat Commun 2017;8:14433)
  • Non-NF2 meningiomas are enriched in mutations in TRAF2, KLF4, AKT1 and SMO, most of which are benign and preferentially located in the skull base (Science 2013;339:1077)
  • Clear cell meningioma has been linked to SMARCE1 mutation (J Pathol 2014;234:436)
  • Nearly 100% of secretory meningioma contain TRAF7 / KLF4 comutations, mutually exclusive to NF2 (Science 2013;339:1077)
  • Angiomatous meningiomas contain multiple chromosome alterations, particularly gains of 5 and 20 (100% and 89%); blood vessels are nonneoplastic in origin (Oncotarget 2014;5:10596)
  • DNA methylation profiling of meningioma distinguished 6 methylation classes (MCs) in adults, benign (ben) 1 - 3, intermediate (int) A and B and malignant (mal)
    • DNA methylation based meningioma classification is reported to better predict tumor recurrence and prognosis than the WHO histological classification (Lancet Oncol 2017;18:682)
  • Pediatric meningiomas are mostly associated with genetic syndromes or childhood radiation
    • Global DNA methylation profile grouped separately from adult meningiomas and forms 3 groups: group 1 (clear cell and papillary meningiomas), 2A (enriched in NF2 driven high grade meningiomas) and 2B (enriched for rhabdoid, chordoid and other non-NF2 driven high grade meningiomas)
Sample pathology report
  • Brain, inferior skull base mass (resection):
    • Meningioma, transitional (WHO grade 1) (see comment)
    • Comment: The tumor is a transitional meningioma. There is no evidence of necrosis, brain invasion, sheet-like growth or increased cellularity. There are no prominent nucleoli or small cells with a high nuclear to cytoplasmic ratio. Mitotic figures are not identified (0/10 high power fields). No brain is present for evaluation of brain invasion.
Differential diagnosis
Board review style question #1

A 57 year old man presented with an intracranial convexity based tumor with histology shown in the above image. What is the best set of immunostains to determine the diagnosis?

  1. p53 and EMA
  2. S100 and CD34
  3. SMA and SOX10
  4. SSTR2a and STAT6
Board review style answer #1
D. SSTR2a and STAT6. The image shows a low grade spindle cell neoplasm. Within the CNS, the main differential considerations are fibrous meningioma, solitary fibrous tumor / hemangiopericytoma and schwannoma. Schwannomas are more common in the cerebellopontine angle and spinal cord but not convexity, so the main differential diagnosis in this case is meningioma versus solitary fibrous tumor. Among the choices, SSTR2a is the most sensitive and specific marker for meningioma and STAT6 is the most sensitive and specific marker for solitary fibrous tumor.

Comment Here

Reference: Meningioma
Board review style question #2
Which of the following typically low grade meningioma variants can have prominent peritumoral edema?

  1. Angiomatous, microcystic, meningothelial
  2. Psammomatous, secretory, fibrous
  3. Secretory, angiomatous, metaplastic
  4. Secretory, microcystic, lymphoplasmacyte rich
  5. Transitional, microcystic, meningothelial
Board review style answer #2
D. Secretory, microcystic, lymphoplasmacyte rich. The low grade meningioma variants that may have prominent peritumoral edema are secretory, angiomatous, microcystic and lymphoplasmacyte rich.

Comment Here

Reference: Meningioma
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