Subtitle: Meningioma under WHO CNS5 (2021): the 15 subtypes, grade 2 and grade 3 criteria, IHC (SSTR2A, EMA, PR), and molecular markers (NF2, TRAF7, AKT1, KLF4, SMO, SMARCE1, BAP1, TERT, CDKN2A/B), with 10 MCQs.
Author: PathologyMCQ Editorial Board
Category: Neuropathology
Last Updated: October 2026
Read Time: 8 minutes
At-a-Glance
- Meningiomas are the commonest primary intracranial tumour (about one-third), arising from arachnoid cap cells.
- WHO CNS5 lists 15 subtypes as one tumour type; grade is set by mitoses, brain invasion, atypical features and molecular markers, not mainly by subtype.
- Grade 2: 4–19 mitoses/10 HPF, brain invasion, 3 of 5 atypical features, or chordoid/clear cell subtype.
- Grade 3: ≥20 mitoses/10 HPF, frank anaplasia, TERT promoter mutation or CDKN2A/B homozygous deletion.
- SSTR2A is the most useful IHC marker; NF2 and TRAF7 alterations are mutually exclusive.
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WHO CNS5 Grading
Meningioma grading (WHO CNS5, 2021)
| CNS WHO grade | Criteria |
|---|---|
| Grade 1 | Fewer than 4 mitoses/10 HPF; no brain invasion; no grade 2 or 3 features |
| Grade 2 (atypical) | 4–19 mitoses/10 HPF, or brain invasion, or 3 of 5: sheeting, small cells with high N:C ratio, prominent nucleoli, hypercellularity, spontaneous necrosis; chordoid and clear cell subtypes |
| Grade 3 (anaplastic) | ≥20 mitoses/10 HPF, or frank anaplasia, or TERT promoter mutation, or CDKN2A/B homozygous deletion |
HPF = 0.16 mm², so 10 HPF is about 1.6 mm². WHO CNS5 uses Arabic numerals for grades.
Subtypes
Meningioma subtypes
| Subtype | Key features |
|---|---|
| Meningothelial | Lobules of epithelioid cells, whorls, intranuclear pseudoinclusions |
| Fibrous | Spindle cells in fascicles with collagen |
| Transitional | Mixed meningothelial and fibrous, abundant whorls and psammoma bodies |
| Psammomatous | Numerous psammoma bodies; spinal, older women |
| Angiomatous | Many small, hyalinised vessels |
| Microcystic | Loose, cobweb-like background, pleomorphic cells |
| Secretory | CEA-positive pseudopsammoma bodies; KLF4 + TRAF7 |
| Lymphoplasmacyte-rich | Heavy chronic inflammatory infiltrate |
| Metaplastic | Bone, cartilage, fat or xanthomatous change |
| Chordoid (grade 2) | Cords of cells in myxoid stroma |
| Clear cell (grade 2) | Glycogen-rich clear cells; SMARCE1 loss; spine, cerebellopontine angle |
| Papillary | Perivascular pseudopapillae; graded by standard criteria |
| Rhabdoid | Rhabdoid cells; check BAP1; graded by standard criteria |
| Atypical (grade 2) | Defined by grade 2 criteria |
| Anaplastic (grade 3) | Defined by grade 3 criteria |
Immunohistochemistry
IHC in meningioma
| Marker | Use |
|---|---|
| SSTR2A | Most sensitive and specific; diffuse positivity |
| EMA | Positive in most, often membranous and patchy |
| PR | Positive in many grade 1 tumours; less in higher grades |
| Ki-67 | Supports grading; not a grading criterion on its own |
| STAT6 | Negative; excludes solitary fibrous tumour |
| BAP1 | Loss in rhabdoid meningiomas with BAP1 alteration |
| SMARCE1 | Loss in clear cell meningioma |
| H3K27me3 | Loss associated with shorter recurrence-free survival |
Molecular Findings
Key molecular alterations
| Alteration | Association |
|---|---|
| NF2 (22q loss) | Fibrous and transitional; convexity; NF2 syndrome |
| TRAF7 ± KLF4, AKT1 or PIK3CA | Skull base; secretory (KLF4), meningothelial (AKT1); mutually exclusive with NF2 |
| SMO | Meningothelial, anterior skull base (olfactory groove) |
| POLR2A | Meningothelial, skull base (tuberculum sellae) |
| SMARCE1 | Clear cell meningioma |
| BAP1 | Rhabdoid and papillary meningioma; aggressive |
| TERT promoter mutation | Grade 3, whatever the histology |
| CDKN2A/B homozygous deletion | Grade 3, whatever the histology |
Remember: TRAF7 and NF2 alterations are mutually exclusive. DNA methylation classes predict recurrence better than histology alone but are not yet a grading criterion.
Video: Meningioma Grading
Test Yourself: 10 MCQs
Meningioma: 10 MCQs
Grading, subtypes and molecular markers, with instant explanations.
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Exam Pearls
- Grade by mitoses, brain invasion, atypical features and TERT/CDKN2A/B, not by most subtypes.
- Grade 2 subtypes: chordoid and clear cell.
- Papillary and rhabdoid are no longer graded 3 on morphology alone.
- Secretory = KLF4 + TRAF7; clear cell = SMARCE1; rhabdoid = check BAP1.
- SSTR2A positive, STAT6 negative.
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References
- WHO Classification of Tumours Editorial Board. Central Nervous System Tumours. 5th ed. IARC; 2021.
- Louis DN, et al. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary. Neuro Oncol. 2021;23:1231–51.
- Sahm F, et al. DNA methylation-based classification and grading system for meningioma. Lancet Oncol. 2017;18:682–94.
- Clark VE, et al. Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7, KLF4, AKT1 and SMO. Science. 2013;339:1077–80.
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