Overview
This lecture covers the 2021 WHO CNS-5 classification of gliomas, glioneuronal tumors, neuronal tumors, and ependymomas with an emphasis on genetics, grading, and diagnostic criteria.
Classification of Gliomas and Related Tumors
- Gliomas are classified as adult type diffuse gliomas, pediatric type diffuse gliomas, and circumscribed gliomas.
- Adult type diffuse gliomas: astrocytoma (IDH mutant), oligodendroglioma (IDH mutant, 1p19q codeleted), glioblastoma (IDH wild type).
- Pediatric type diffuse gliomas: low grade (RAS/MAPK pathway mutations) and high grade (H3K27M/H3G34R/V mutations or RTK fusions).
- Circumscribed astrocytic gliomas include pilocytic astrocytoma, pleomorphic xanthoastrocytoma, subependymal giant cell astrocytoma, chordoid glioma, astroblastoma (MN1 altered).
Ependymomas
- Classified by location: supratentorial (ZFTA/YAP1 fusion), posterior fossa (PFA/PFB, H3K27me loss), spinal (MYCN amplification or NF2 loss).
- Mixopapillary ependymoma is now grade 2 due to higher recurrence risk.
- Subependymomas can occur in any CNS compartment.
Glioneuronal and Neuronal Tumors
- Includes ganglioglioma, desmoplastic infantile ganglioglioma, dysembryoplastic neuroepithelial tumor (DNET), central neurocytoma, and others.
- These tumors often cause epilepsy and are termed long-term epilepsy-associated tumors (LEATs).
- Glioneuronal tumors may be graded and classified based on genetic and histologic features.
Molecular and Diagnostic Criteria
- Adult gliomas: IDH mutations, ATRX/TP53 mutations (astrocytoma), 1p19q codeletion (oligodendroglioma).
- Pediatric gliomas: lack IDH mutations, frequently have MAPK or histone pathway alterations.
- Grading based on molecular and histological features; e.g., CDKN2A/B homozygous deletion or necrosis/microvascular proliferation upgrades to grade 4.
- Integrated/structured reporting includes histology, CNS WHO grade, and molecular features.
Key Terms & Definitions
- IDH mutation — Mutation in isocitrate dehydrogenase gene, key for glioma classification.
- 1p19q codeletion — Combined loss of chromosomal arms 1p and 19q, diagnostic for oligodendroglioma.
- WHO CNS-5 — 2021 World Health Organization classification of CNS tumors.
- LEATs — Long-term epilepsy-associated tumors, often glioneuronal.
- H3K27M/H3G34R/V mutations — Histone gene mutations common in pediatric high-grade gliomas.
- MAPK pathway — Genetic pathway often mutated in pediatric low-grade gliomas.
- NOS — Not otherwise specified; key diagnostic info unavailable.
- NEC — Not elsewhere classified; testing done but tumor doesn’t fit current categories.
Action Items / Next Steps
- Review the latest WHO CNS-5 classification charts and tumor grading protocols.
- Study the genetic markers and molecular pathways associated with each tumor type.
- Prepare diagrams summarizing glioma and ependymoma classification for quick revision.