Tumor Neuropathology
What You'll Learn
- The adult diffuse gliomas under WHO CNS5 — how IDH, 1p/19q, and molecular grade define astrocytoma vs oligodendroglioma vs glioblastoma
- Circumscribed, glioneuronal, ependymal and embryonal tumors and their signature histology
- Meningeal, nerve-sheath and sellar tumors
- The key other tumors — CNS lymphoma, metastases, hemangioblastoma
The neuropathology view — histology, IHC and molecular markers per tumor. Clinical neuro-oncology (management) lives in the Neuro-oncology notes.
- WHO CNS5 = integrated diagnosis: histology + molecular. IDH-mutant + 1p/19q codeletion = oligodendroglioma; IDH-mutant + ATRX loss = astrocytoma; IDH-wildtype adult diffuse glioma = glioblastoma if TERT-promoter mutation, EGFR amplification, or +7/−10 — even without necrosis or microvascular proliferation.
- CDKN2A/B homozygous deletion upgrades an IDH-mutant astrocytoma to CNS WHO grade 4.
- Glioblastoma buzzwords: pseudopalisading necrosis + microvascular (glomeruloid) proliferation.
- Pilocytic astrocytoma: biphasic, Rosenthal fibers + eosinophilic granular bodies, KIAA1549::BRAF fusion — grade 1, cerebellar child.
- Ependymoma: perivascular pseudorosettes + dot/ring EMA; Meningioma: whorls + psammoma bodies, EMA/PR/SSTR2a; Schwannoma: Antoni A/B + Verocay bodies, diffuse S100.
Adult Diffuse Gliomas (WHO CNS5)
| Tumor | Histology | Molecular / grade |
|---|
| Astrocytoma, IDH-mutant | Infiltrating fibrillary astrocytes; grade by mitoses/MVP/necrosis | IDH1/2 mut, ATRX loss, p53; CDKN2A/B homozygous deletion → grade 4 |
| Oligodendroglioma, IDH-mutant & 1p/19q-codeleted | “Fried-egg” clear halos, chicken-wire capillaries, microcalcification | IDH mut + whole-arm 1p/19q codeletion (defining); TERT; grade 2/3 |
| Glioblastoma, IDH-wildtype | Pleomorphic astrocytic tumor with pseudopalisading necrosis and/or microvascular proliferation | IDH-wt plus ≥1 of: TERT promoter mut, EGFR amplification, +7/−10 (= grade 4 even without necrosis/MVP) |
Circumscribed & Pediatric Gliomas
| Tumor | Histology | Marker / clue |
|---|
| Pilocytic astrocytoma (grade 1) | Biphasic compact/loose; Rosenthal fibers + eosinophilic granular bodies; piloid cells | KIAA1549::BRAF fusion; cerebellum, child; cyst + enhancing mural nodule |
| Pleomorphic xanthoastrocytoma | Pleomorphic + lipidized (xanthomatous) cells, EGBs, reticulin network | BRAF V600E; superficial temporal, young; CD34 |
| Diffuse midline glioma, H3 K27-altered (grade 4) | Infiltrating; pons/thalamus/cord of children | H3 K27M (or EZHIP overexpression / EGFR-altered); loss of H3K27me3 |
Glioneuronal & Neuronal Tumors
| Tumor | Histology | Clue |
|---|
| Ganglioglioma | Dysplastic ganglion cells + neoplastic glia; EGBs, CD34, perivascular lymphocytes | BRAF V600E; temporal lobe epilepsy, young |
| DNET | “Specific glioneuronal element” — columns of axons lined by oligodendrocyte-like cells with floating neurons in mucin | Cortical, drug-resistant epilepsy; grade 1 |
| Central neurocytoma | Uniform round cells, neuropil islands (“fibrillary”), calcification | Intraventricular (foramen of Monro); synaptophysin+ |
Ependymal Tumors
| Tumor | Histology | Molecular / site |
|---|
| Ependymoma | Perivascular pseudorosettes (constant) ± true ependymal rosettes; dot-like/ring EMA, GFAP | Supratentorial ZFTA-fusion; posterior-fossa PFA (H3K27me3 loss, worse) / PFB |
| Subependymoma (grade 1) | Clusters of bland nuclei in dense fibrillary matrix + microcysts | 4th/lateral ventricle, older adult; often incidental |
| Myxopapillary ependymoma (grade 2) | Papillae with myxoid/vascular cores | Filum terminale / conus |
Embryonal Tumors
| Tumor | Histology | Molecular |
|---|
| Medulloblastoma (grade 4) | Small round blue cells, high N:C, Homer-Wright rosettes; desmoplastic/nodular variant | Groups: WNT (best), SHH, group 3 (MYC, worst), group 4; cerebellar vermis, child |
| Atypical teratoid/rhabdoid (ATRT) | Rhabdoid cells (eccentric nucleus, inclusion-like cytoplasm) + embryonal areas | SMARCB1 (INI1) loss; infant |
Meningeal & Nerve-Sheath Tumors
| Tumor | Histology | Marker |
|---|
| Meningioma | Whorls + psammoma bodies, syncytial nuclei, intranuclear pseudoinclusions; grade 2 (atypical: ≥4 mitoses or brain invasion), grade 3 (anaplastic morphology, or TERT-promoter mutation / CDKN2A/B homozygous deletion) | EMA, PR, SSTR2a; NF2/22q |
| Schwannoma | Antoni A (compact, Verocay bodies) + Antoni B (loose); hyalinized vessels | Diffuse S100; NF2; vestibular (CPA) |
| Neurofibroma | Wavy spindle cells, “shredded carrot” collagen, mast cells; intermixed axons | Mixed S100/CD34/neurofilament; NF1 |
| MPNST | Hypercellular fascicles, geographic necrosis, high mitoses | H3K27me3 loss; NF1; S100 patchy |
Sellar Region
| Tumor | Histology | Clue |
|---|
| Pituitary adenoma / PitNET | Monomorphic cells, loss of acinar reticulin network | Hormone IHC + transcription factors (PIT1/TPIT/SF1) |
| Craniopharyngioma, adamantinomatous | Palisading epithelium, stellate reticulum, “wet keratin”, calcification, cholesterol clefts | Child; CTNNB1 (β-catenin) |
| Craniopharyngioma, papillary | Papillae of squamous epithelium, no wet keratin | Adult; BRAF V600E |
Other Tumors
| Tumor | Histology | Clue |
|---|
| Primary CNS lymphoma | Angiocentric sheets of large atypical B-cells (DLBCL); “hoops” of reticulin around vessels | CD20+; EBV+ if immunosuppressed; melts with steroids |
| Metastasis | Well-demarcated, at grey-white junction; morphology of primary; peritumoral edema | Lung/breast/melanoma/renal/GI; IHC to source |
| Hemangioblastoma (grade 1) | Rich capillary network + vacuolated stromal cells | Cerebellum; VHL; inhibin+; EPO → polycythemia |
| Choroid plexus papilloma | Fronds of cuboidal/columnar epithelium on fibrovascular cores | Ventricle, child; transthyretin+ |
| Finding | Tumor |
|---|
| 1p/19q codeletion + IDH mut | Oligodendroglioma |
| Pseudopalisading necrosis + MVP | Glioblastoma |
| Rosenthal fibers + EGBs, KIAA1549::BRAF | Pilocytic astrocytoma |
| Perivascular pseudorosettes, dot EMA | Ependymoma |
| Homer-Wright rosettes, small blue cells | Medulloblastoma |
| Whorls + psammoma bodies, EMA/PR | Meningioma |
| Verocay bodies, S100 diffuse | Schwannoma |
| Wet keratin + calcification | Adamantinomatous craniopharyngioma |
| Vacuolated stromal cells + capillaries | Hemangioblastoma (VHL) |
References
- WHO Classification of Tumours of the CNS, 5th ed. IARC; 2021.
- Louis DN, et al. cIMPACT-NOW updates. Acta Neuropathol. 2018–2020.
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