• Lack of brain invasion or malignant molecular features.
• Includes Psammomatous, Meningothelial subtypes.
WHO Grade II (Atypical)
• Mitotic index 4-19 per 10 HPF.
• Brain invasion (macro/microscopic).
• Clear cell or Chordoid histotypes.
WHO Grade III (Anaplastic)
• Mitotic index ≥ 20 per 10 HPF.
• Papillary or Rhabdoid histotypes.
• TERT promoter mutation (Automatic Grade 3).
Pathological grading integrated with cIMPACT-NOW molecular requirements.
2021 Update
Molecular Upgrade Rules
Histologic appearances can be deceiving. Genetic markers now override morphology in the latest WHO standards.
TERT Promoter
Presence of TERT mutation upgrades a CNS WHO grade 1 or 2 meningioma to Grade 3.
CDKN2A/B Deletion
Homozygous deletion of CDKN2A and/or CDKN2B upgrades to Grade 3.
Surgical Margin
Correlation with Simpson Grade (Extent of Resection) is vital for recurrence prediction.
Recurrence Risk
Guidelines & Evidence
Clinical Details
Section 1
When to Use
When to Use
Interpreting pathology reports following meningioma resection.
Justifying adjuvant radiation therapy (typically mandated for Grade III and strongly considered for Grade II).
Section 2
Literature
Development
The WHO classification of Central Nervous System Tumors was radically overhauled in 2021 to integrate molecular pathways over pure histology. Previously, a meningioma could only be Grade III if it exhibited flagrant aggressive cellular features under the microscope. Now, genomic drivers define the grade.
Section 3
Pearls/Pitfalls
TERT and CDKN2A/B
Homozygous deletion of CDKN2A/B or mutation of the TERT promoter independently confers an aggressive clinical course identical to anaplastic meningioma (median survival significantly reduced, rapid local recurrence). If noted on a path report, the tumor is WHO Grade III regardless of the mitotic index.
Section 4
Evidence Appraisal
Primary Reference
The 2021 WHO Classification of Tumors of the Central Nervous System: a summary
Louis DN et al. • Neuro-oncology. 2021;23(8):1231-1251
