Meningioma

Meningioma is the most common primary intracranial neoplasm and the most common benign brain tumor. Meningiomas arise from arachnoid cap cells of the meninges and are usually extra-axial, dura-based, well-circumscribed lesions. The 2021 WHO Classification preserved the three-grade system (1, 2, 3) but added molecular markers (TERT, CDKN2A/B) that can promote tumors to grade 3 regardless of histology. The vast majority of meningiomas are grade 1 (benign) but a minority behave aggressively, and the molecular era is beginning to refine prognostic stratification. This page covers meningioma pathology, grading, and clinical-pathologic features.

Pathology

Gross Features

  • Well-circumscribed, dura-based mass attached to the meninges.
  • “Dural tail” on imaging: extension along dura.
  • Often bossed surface.
  • Cut surface: pale, sometimes whorled, sometimes hemorrhagic.

Histologic Subtypes (WHO Grade 1)

  • Meningothelial: lobular pattern; meningothelial cells with oval nuclei and central clearing (“orphan annie eye”); intranuclear pseudoinclusions common.
  • Fibrous: spindle cells, collagen-rich stroma.
  • Transitional: mixed meningothelial and fibrous features.
  • Psammomatous: numerous psammoma bodies (concentric calcifications).
  • Angiomatous: numerous vessels.
  • Microcystic: extensive microcysts.
  • Secretory: PAS-positive intracytoplasmic hyaline inclusions (pseudopsammoma bodies).
  • Lymphoplasmacyte-rich: abundant inflammatory infiltrate.
  • Metaplastic: osseous, cartilaginous, or other metaplasia.

Atypical Meningioma (WHO Grade 2)

Defined by one of:

  • Mitoses ≥ 4 per 10 high-power fields.
  • Brain invasion (regardless of other features).
  • Three or more of: sheeting growth, increased cellularity, small cell change with high N:C ratio, prominent nucleoli, necrosis.
  • Specific subtypes: chordoid meningioma (chordoma-like) and clear cell meningioma are automatically grade 2.

Anaplastic / Malignant Meningioma (WHO Grade 3)

One or more of:

  • Mitoses ≥ 20 per 10 HPF.
  • Frank anaplasia (sarcoma- or carcinoma-like).
  • TERT promoter mutation or CDKN2A/B homozygous deletion (added in 2021): promotes to grade 3 regardless of histology.
  • Specific subtypes: rhabdoid meningioma and papillary meningioma — grade 3.

Characteristic Features

  • Whorls: spiraling arrangement of meningothelial cells; characteristic.
  • Psammoma bodies: concentric laminated calcifications; characteristic but not pathognomonic.
  • Intranuclear pseudoinclusions: invaginations of cytoplasm into nuclei.
  • Syncytial appearance: meningothelial cells with indistinct cell borders.

Immunohistochemistry

  • EMA: positive (membrane).
  • SSTR2A (somatostatin receptor 2A): highly sensitive meningioma marker.
  • Vimentin: positive.
  • Progesterone receptor: often positive.
  • S100, GFAP: usually negative.
  • STAT6: negative (positive in solitary fibrous tumor / hemangiopericytoma).
  • Cytokeratin: rare positivity.

Molecular Features

  • NF2 (Merlin/schwannomin) gene: deletion or mutation in ~60% of sporadic and all NF2-associated meningiomas.
  • TRAF7, KLF4, AKT1, SMO, PIK3CA mutations: in NF2-wildtype meningiomas; subgroup-specific.
  • TERT promoter mutation: in aggressive meningiomas; now grade 3 marker.
  • CDKN2A/B homozygous deletion: grade 3.
  • DNA methylation classification subgroups are emerging.

Anatomic Distribution

  • Parasagittal / falcine: most common.
  • Convexity: hemispheric surface.
  • Sphenoid wing: medial, middle, lateral subtypes.
  • Olfactory groove: anosmia, frontal symptoms.
  • Suprasellar / tuberculum sella: visual disturbance.
  • Cavernous sinus: cranial neuropathies III, IV, V, VI.
  • CPA: hearing loss, vestibular symptoms.
  • Foramen magnum: lower cranial nerves, long tract signs.
  • Spinal: typically thoracic; extramedullary intradural.
  • Intraventricular: choroid plexus origin.

Clinical Features

  • Often slow-growing; symptoms develop gradually.
  • Headache, focal deficits depending on location, seizures.
  • Often incidental in older patients.
  • Women > men (~2:1); hormone responsiveness in some.

Imaging

  • Dura-based, well-circumscribed mass.
  • Homogeneous strong enhancement.
  • Dural tail (extension along dura).
  • Often hyperostosis of adjacent bone.
  • Calcifications common.
  • Edema surrounding (variable).

Treatment

  • Observation for small, asymptomatic.
  • Surgical resection (Simpson grading of resection completeness: I-V; lower number = more complete).
  • Stereotactic radiosurgery for smaller lesions or residual.
  • Fractionated radiation for grade 2 or 3.
  • Hormonal: progesterone receptor antagonists used historically; limited efficacy.
  • For aggressive / refractory grade 3: bevacizumab, somatostatin analogs in trials; targeted therapy based on mutations (e.g., everolimus for AKT1-mutated) emerging.

Other Meningioma-Related Tumors

  • Solitary fibrous tumor (SFT, formerly hemangiopericytoma): dural-based; STAT6 nuclear positivity; NAB2-STAT6 fusion; aggressive; metastasis risk.
  • Hemangioblastoma: cerebellar, brainstem, spinal cord; cystic with mural nodule; inhibin positive; VHL syndrome.
  • Choroid plexus papilloma/carcinoma: intraventricular.

Genetic Predisposition

  • NF2 (Neurofibromatosis type 2): multiple meningiomas + vestibular schwannomas + ependymomas.
  • Schwannomatosis: rare; multiple schwannomas + sometimes meningiomas.
  • Familial multiple meningiomas: rare.
  • Therapeutic radiation: increased meningioma risk (latency years to decades).

🔍 Did You Know?

The 2021 WHO classification introduced a notable change to meningioma grading: TERT promoter mutation and CDKN2A/B homozygous deletion automatically promote a meningioma to grade 3 regardless of histologic features. This was based on accumulated evidence that meningiomas with these molecular alterations behave aggressively even when their histology appears low-grade. The change reflects the broader trend in CNS tumor classification: molecular features are now integrated with histology to provide a more accurate prognosis. The clinical implication is real: a meningioma that looks grade 1 by microscopy but harbors TERT promoter mutation has a substantially higher risk of recurrence and may warrant more aggressive treatment than the histology alone would suggest. The molecular workup for difficult-to-treat or recurrent meningiomas now routinely includes assessment of NF2, TERT promoter, CDKN2A/B, and other relevant molecular markers. DNA methylation classification is emerging as another tool that may further refine prognostication and may identify subgroups responsive to specific therapies. The lesson: even for meningiomas — a “benign” tumor in most cases — the modern integrated diagnosis combines location, histology, and molecular features to predict behavior and guide management. Meningioma is no longer the pure histologic tumor it was a decade ago.

Pitfalls and Pearls

  • Meningioma: dura-based; EMA positive; SSTR2A highly sensitive; PR often positive; whorls + psammoma bodies.
  • Grade 1: most meningiomas (~80%).
  • Grade 2 (atypical): mitoses ≥ 4, brain invasion, or 3+ atypical features; chordoid and clear cell subtypes auto-grade 2.
  • Grade 3: mitoses ≥ 20, frank anaplasia, OR TERT promoter mutation OR CDKN2A/B homozygous deletion; rhabdoid and papillary subtypes.
  • Brain invasion: automatic grade 2 even with otherwise grade 1 features.
  • NF2 mutation: most common driver in sporadic meningiomas.
  • TRAF7, KLF4, AKT1, SMO mutations: NF2-wildtype meningiomas; some targetable.
  • Dural tail + homogeneous enhancement + extra-axial: classic imaging.
  • Hyperostosis: bony reaction.
  • Simpson grading: surgical resection completeness predicts recurrence.
  • Solitary fibrous tumor (SFT): STAT6 nuclear; distinct from meningioma; metastasis risk.
  • NF2 syndrome: multiple meningiomas + vestibular schwannomas.
  • Radiation-induced meningioma: years to decades after therapy.
  • Hemangioblastoma: distinct entity; VHL syndrome.

References

  1. Louis DN, Perry A, Wesseling P, et al. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol. 2021;23(8):1231-1251.
  2. Sahm F, Schrimpf D, Stichel D, et al. DNA methylation-based classification and grading system for meningioma: a multicentre, retrospective analysis. Lancet Oncol. 2017;18(5):682-694.
  3. Brastianos PK, Horowitz PM, Santagata S, et al. Genomic sequencing of meningiomas identifies oncogenic SMO and AKT1 mutations. Nat Genet. 2013;45(3):285-289.
  4. Goldbrunner R, Stavrinou P, Jenkinson MD, et al. EANO guideline on the diagnosis and management of meningiomas. Neuro Oncol. 2021;23(11):1821-1834.
  5. Simpson D. The recurrence of intracranial meningiomas after surgical treatment. J Neurol Neurosurg Psychiatry. 1957;20(1):22-39.