Subtitle: WHO CNS5 (2021) updates for gliomas and ependymomas: adult diffuse gliomas (IDH, 1p/19q, CDKN2A/B, TERT/EGFR/+7−10), paediatric-type gliomas, circumscribed astrocytic gliomas and the site-plus-molecular ependymoma classification, with 10 MCQs.
Author: PathologyMCQ Editorial Board
Category: Neuropathology
Last Updated: October 2026
Read Time: 8 minutes
At-a-Glance
- Grades are now within tumour types and written in Arabic numerals (CNS WHO grade 1–4).
- Adult diffuse gliomas are just three: astrocytoma, IDH-mutant; oligodendroglioma, IDH-mutant and 1p/19q-codeleted; glioblastoma, IDH-wildtype.
- Molecular grading: CDKN2A/B homozygous deletion makes IDH-mutant astrocytoma grade 4; TERT promoter, EGFR amplification or +7/−10 makes an IDH-wildtype adult glioma a glioblastoma.
- Paediatric-type diffuse gliomas are separate families (H3 K27-altered, H3 G34-mutant, MYB/MYBL1, MAPK).
- Ependymomas are classified by site plus molecular group (ZFTA, YAP1, PFA, PFB, MYCN).
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Adult-Type Diffuse Gliomas
Adult-type diffuse gliomas (WHO CNS5)
| Tumour type | Defining molecular features | CNS WHO grade |
|---|---|---|
| Astrocytoma, IDH-mutant | IDH1/2 mutation; ATRX loss, TP53 mutation; no 1p/19q codeletion | 2, 3 or 4 (grade 4 if CDKN2A/B homozygous deletion, necrosis or MVP) |
| Oligodendroglioma, IDH-mutant and 1p/19q-codeleted | IDH1/2 mutation + whole-arm 1p/19q codeletion; TERT promoter; ATRX retained | 2 or 3 |
| Glioblastoma, IDH-wildtype | IDH and H3 wildtype + necrosis/MVP, or TERT promoter mutation, EGFR amplification or +7/−10 | 4 |
The terms anaplastic and glioblastoma, IDH-mutant are retired; these are now astrocytoma, IDH-mutant, grade 3 or 4.
Diagnostic Algorithm
- Step 1: IDH1 R132H IHC (sequence IDH1/2 if negative in patients under 55).
- Step 2: ATRX and p53 IHC; if ATRX retained, test 1p/19q.
- Step 3: CDKN2A/B for IDH-mutant astrocytoma; TERT, EGFR and +7/−10 for IDH-wildtype tumours.
- Midline or young patient: H3 K27M / H3 K27me3 and H3 G34 before calling an adult-type glioma.
Paediatric-Type Diffuse Gliomas
Paediatric-type diffuse gliomas
| Group | Examples | Key alteration |
|---|---|---|
| Low grade | Diffuse astrocytoma, MYB- or MYBL1-altered; angiocentric glioma; PLNTY; diffuse LGG, MAPK-altered | MYB/MYBL1, BRAF, FGFR |
| High grade | Diffuse midline glioma, H3 K27-altered (grade 4) | H3 K27M or EZHIP; H3 K27me3 loss |
| High grade | Diffuse hemispheric glioma, H3 G34-mutant (grade 4) | H3F3A G34R/V |
| High grade | Diffuse paediatric-type HGG, H3-wildtype and IDH-wildtype | PDGFRA, EGFR, MYCN |
| High grade | Infant-type hemispheric glioma | ALK, ROS1, NTRK, MET fusions |
Circumscribed Astrocytic Gliomas
Circumscribed astrocytic gliomas
| Tumour | Key features |
|---|---|
| Pilocytic astrocytoma | Biphasic, Rosenthal fibres, EGBs; KIAA1549::BRAF fusion; grade 1 |
| High-grade astrocytoma with piliform features | Piloid, anaplastic; MAPK alteration, CDKN2A/B deletion, ATRX loss; methylation-defined |
| Pleomorphic xanthoastrocytoma | Pleomorphic, xanthomatous cells, EGBs; BRAF V600E + CDKN2A/B; grade 2 or 3 |
| Subependymal giant cell astrocytoma | Tuberous sclerosis (TSC1/TSC2); grade 1 |
| Chordoid glioma | Third ventricle; PRKCA D463H |
| Astroblastoma, MN1-altered | Perivascular astroblastic pseudorosettes; MN1 fusion |
Ependymoma: Molecular Classification
Ependymoma types by site
| Site | Types | Notes |
|---|---|---|
| Supratentorial | ZFTA fusion-positive; YAP1 fusion-positive | ZFTA (formerly RELA) worse; YAP1 in infants, better |
| Posterior fossa | PFA; PFB | PFA: infants, H3 K27me3 loss, worse; PFB: older, better |
| Spinal | Spinal ependymoma; spinal ependymoma, MYCN-amplified | MYCN-amplified is aggressive |
| Any site | Myxopapillary ependymoma (grade 2); subependymoma (grade 1) | Myxopapillary upgraded to grade 2 |
Full detail: ependymoma molecular types → · Practise: ependymoma case-based MCQs → · astrocytoma MCQs →
Test Yourself: 10 MCQs
WHO CNS5 gliomas and ependymomas: 10 MCQs
Grading, molecular criteria and new entities, with instant explanations.
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More practice: the CNS tumours MCQ bank →
Exam Pearls
- IDH-mutant astrocytoma + CDKN2A/B homozygous deletion = grade 4.
- Adult IDH-wildtype + TERT, EGFR or +7/−10 = glioblastoma, even without necrosis.
- Oligodendroglioma needs IDH mutation and 1p/19q codeletion.
- H3 K27-altered midline glioma = grade 4 regardless of histology.
- Myxopapillary ependymoma is now grade 2.
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Related reads: Ependymoma molecular types → · Gliosis vs glioma →
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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.
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