Subtitle: Ependymoma in WHO CNS5 (2021): site-based molecular types (ZFTA and YAP1 supratentorial, PFA and PFB posterior fossa, spinal and MYCN-amplified), IHC surrogates (L1CAM, p65, H3K27me3), grading and 10 MCQs.
Author: PathologyMCQ Editorial Board
Category: Neuropathology
Last Updated: October 2026
Read Time: 6 minutes
At-a-Glance
- WHO CNS5 classifies ependymomas by site plus molecular group.
- Supratentorial: ZFTA fusion (L1CAM+, nuclear p65) and YAP1 fusion.
- Posterior fossa: PFA (H3K27me3 loss, young children, worse) and PFB (H3K27me3 retained, older patients, better).
- Spinal: classic spinal ependymoma (NF2), MYCN-amplified (aggressive), myxopapillary (now grade 2).
- Hallmark histology: perivascular pseudorosettes; EMA dot-like; GFAP and Olig2-negative/weak.
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Molecular Types (WHO CNS5)
| Type | Age | IHC / genetics | Behaviour |
|---|---|---|---|
| Supratentorial, ZFTA fusion-positive | Children and adults | L1CAM+, nuclear p65; ZFTA::RELA (formerly C11orf95) | Aggressive; grade 2 or 3 |
| Supratentorial, YAP1 fusion-positive | Infants, young children | YAP1::MAMLD1; L1CAM– | Relatively good |
| Posterior fossa group A (PFA) | Infants, young children | H3K27me3 loss, EZHIP overexpression; 1q gain adverse | Worse |
| Posterior fossa group B (PFB) | Adolescents, adults | H3K27me3 retained; chromosomal instability | Better |
| Spinal ependymoma | Adults | NF2 alterations; NF2 syndrome | Good |
| Spinal, MYCN-amplified | Adolescents, young adults | MYCN amplification | Aggressive, disseminates |
| Myxopapillary ependymoma | Adults | Filum terminale, conus | Grade 2 (upgraded) |
| Subependymoma | Older adults | Fourth or lateral ventricle | Grade 1 |
Histology and IHC
- Perivascular pseudorosettes: nuclear-free zones of fibrillary processes around vessels.
- True ependymal rosettes and canals: less common but specific.
- EMA: dot-like and ring-like (microlumina). GFAP: positive in pseudorosettes. Olig2: negative or weak (useful against oligodendroglial and astrocytic tumours).
- Grade 2 vs 3 is based on mitoses, microvascular proliferation and cellularity, though grading reproducibility is limited.
Summary Chart
Case MCQs
Q1. A supratentorial ependymoma shows cytoplasmic L1CAM. Which is true? Answer: the IHC is a surrogate for ZFTA fusion and is usually confirmed by FISH or RNA sequencing. ZFTA-fused tumours are supratentorial (not posterior fossa), graded 2 or 3, and L1CAM is not specific: it is also seen in central neurocytoma, olfactory neuroblastoma and embryonal tumours.
Q2. Which pairing is correct? Answer: supratentorial ZFTA (formerly RELA) fusion ependymoma, children, poor prognosis.
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Exam Pearls
- ZFTA = L1CAM + nuclear p65; YAP1 = infants, good outcome.
- PFA = H3K27me3 loss, young children, worse; PFB = retained, older, better.
- Spinal = NF2; MYCN-amplified spinal = aggressive.
- Myxopapillary ependymoma is now grade 2.
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Related reads: WHO CNS5 updates → · Ependymoma case-based MCQs →
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References
- WHO Classification of Tumours Editorial Board. Central Nervous System Tumours. 5th ed. IARC; 2021.
- Pajtler KW, et al. Molecular classification of ependymal tumors across all CNS compartments, histopathological grades and age groups. Cancer Cell. 2015;27:728–43.
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