CNS Tumors
CNS Tumors
What You'll Learn
- Most common brain tumor overall = metastasis; most common primary malignant brain tumor = glioblastoma (IDH-wildtype, grade 4); most common primary brain tumor (benign + malignant) = meningioma
- Most common pediatric brain tumor = pilocytic astrocytoma (grade 1, cerebellar, BRAF fusion, excellent prognosis); most common malignant pediatric brain tumor = medulloblastoma
- 2021 WHO CNS5 classification integrates molecular markers into tumor diagnosis — key classification-defining markers include IDH mutation status, 1p/19q codeletion, H3 K27-altered status, CDKN2A/B, TERT/EGFR/+7/−10, BRAF, and INI1/SMARCB1. MGMT promoter methylation is a key predictive marker for temozolomide response in glioblastoma but is NOT itself a WHO CNS5 classification-defining marker.
- IDH mutation = better prognosis in diffuse gliomas; IDH-wildtype diffuse astrocytic tumor in adults is classified as glioblastoma regardless of histologic grade if molecular criteria are met
- 1p/19q codeletion defines oligodendroglioma and predicts chemosensitivity (PCV regimen); MGMT promoter methylation predicts temozolomide response in glioblastoma
- Hemorrhagic metastases mnemonic “MR CT”: Melanoma, Renal cell carcinoma, Choriocarcinoma, Thyroid — gray-white junction predilection
- Genetic syndromes: NF1 → optic glioma; NF2 → bilateral vestibular schwannomas + meningiomas; VHL → hemangioblastoma; TSC → SEGA
- Pseudopalisading necrosis + microvascular proliferation = glioblastoma; psammoma bodies = meningioma; Rosenthal fibers = pilocytic astrocytoma; Homer Wright rosettes = medulloblastoma
HighYield Pearls
- WHO 2021 = molecular > histology: integrated molecular-histologic diagnosis — IDH, 1p/19q, H3 K27-altered (includes K27M and non-K27M mechanisms in diffuse midline glioma), CDKN2A/B, TERT/EGFR/+7−10, BRAF, and INI1/SMARCB1 drive classification, not microscope alone. MGMT methylation is predictive (TMZ response) rather than classification-defining.
- CDKN2A/B homozygous deletion in IDH-mutant astrocytoma → grade 4 even without necrosis or microvascular proliferation; IDH-WT diffuse astrocytic tumor + TERT promoter mutation OR EGFR amplification OR +7/−10 → glioblastoma grade 4 regardless of histology
- Oligodendroglioma requires BOTH IDH-mutant AND 1p/19q codeletion (ATRX retained); 1p/19q codeletion predicts chemosensitivity to PCV; frontal predominance, fried-egg cells, chicken-wire vasculature
- Medulloblastoma 4 molecular groups: WNT (best prognosis, β-catenin nuclear, monosomy 6) > SHH (PTCH1/SUFU; TP53-WT better than TP53-mut) > Group 4 (most common) > Group 3 (MYC amp, worst); all get craniospinal RT + chemo
- Ependymoma molecular subgroups: supratentorial ZFTA (RELA) fusion (worse) vs YAP1 fusion; posterior fossa Group A (high methylation, infants, worse) vs Group B (older, better); perivascular pseudorosettes + true ependymal rosettes
- AT/RT = SMARCB1 (INI1) loss on IHC — pediatric, rhabdoid cells, highly aggressive; germline INI1 = rhabdoid predisposition syndrome; ETMR = LIN28A+ with C19MC alteration (infantile)
- Pilocytic astrocytoma: KIAA1549-BRAF fusion (NOT V600E); cerebellar cyst + enhancing mural nodule; Rosenthal fibers + eosinophilic granular bodies; grade 1, excellent prognosis. PXA, ganglioglioma, papillary craniopharyngioma = BRAF V600E
- NF2-related schwannomatosis (merlin/22q) → bilateral vestibular schwannomas + meningiomas + ependymomas; meningioma brain invasion alone OR atypical histologic features (including necrosis) upgrades to grade 2; grade 3 (anaplastic) requires frank anaplasia, very high mitotic activity, OR molecular criteria (TERT promoter mutation or CDKN2A/B homozygous deletion)
- Hemorrhagic mets mnemonic “MR CT”: Melanoma, RCC, Choriocarcinoma, Thyroid (+ lung) — gray-white junction; PCNSL = periventricular, homogeneously enhancing, restricted diffusion, CD20+ large B-cell, HD-MTX
- Bifocal pineal + suprasellar mass = synchronous germinomas; germinoma is PLAP+/OCT3/4+ and radiosensitive; NGGCTs use serum/CSF AFP (yolk sac) and β-hCG (choriocarcinoma) markers
🔍 Quick ReferenceHistology · Molecular · Imaging / location
Histology / immunohistochemistry
- Pseudopalisading necrosis + microvascular proliferation → Glioblastoma (astrocytoma grade 4, IDH-wildtype)
- Fried-egg cells + chicken-wire vasculature → Oligodendroglioma
- Perivascular pseudorosettes (radial tumor cells around vessel) + true ependymal rosettes → Ependymoma
- Rosenthal fibers + eosinophilic granular bodies (EGB) → Pilocytic astrocytoma (also PXA, ganglioglioma)
- Homer Wright pseudorosettes + small blue round cells → Medulloblastoma
- Rhabdoid cells with eccentric nuclei + INI1/SMARCB1 loss on IHC → AT/RT (atypical teratoid/rhabdoid tumor)
- Psammoma bodies + whorls + spindle/syncytial cells + EMA+ → Meningioma
- Antoni A (Verocay bodies — palisading nuclei around acellular zone) + Antoni B (loose myxoid) + S100+ → Schwannoma
- Schwann cells + axons + fibroblasts + mast cells (admixed) → Neurofibroma (plexiform variant pathognomonic for NF1)
- Stromal cells with foamy/vacuolated cytoplasm + rich capillary network + inhibin+ → Hemangioblastoma
- Wet keratin nodules + “machine oil” cyst fluid → Adamantinomatous craniopharyngioma
- Lymphocyte-rich infiltrate + PLAP+ + OCT3/4+ large cells → Germinoma
- CD20+ large B-cell perivascular infiltrate → PCNSL
- Reticulin loss (vs normal acinar pattern) + monomorphic cells → Pituitary adenoma
- Brachyury (T)+ physaliphorous (bubbly) cells → Chordoma
- Floating neurons in mucin pools + cortical bubbly nodules → DNET (dysembryoplastic neuroepithelial tumor)
- Pleomorphic + xanthomatous (lipid-laden) cells + reticulin + EGB → PXA (pleomorphic xanthoastrocytoma)
Molecular markers
- IDH-wildtype + TERT promoter mutation / EGFR amplification / +7/−10 → Glioblastoma grade 4 (regardless of histology)
- CDKN2A/B homozygous deletion (in IDH-mutant astrocytoma) → Grade 4 upgrade even without histologic features
- IDH-mutant + 1p/19q codeletion + ATRX-retained (both required) → Oligodendroglioma (PCV-chemosensitive)
- MGMT promoter methylation → Temozolomide response in glioblastoma
- H3K27M / H3 K27-altered → Diffuse midline glioma, grade 4 (DIPG, thalamus, spinal cord)
- KIAA1549-BRAF fusion → Pilocytic astrocytoma (NOT V600E)
- BRAF V600E → PXA, ganglioglioma, papillary craniopharyngioma (adamantinomatous = NOT V600E)
- ZFTA (RELA) fusion → Supratentorial ependymoma (worse) vs YAP1 fusion (better)
- WNT-activated (nuclear β-catenin, monosomy 6) → Medulloblastoma WNT (best prognosis); MYC amplification → Group 3 (worst); PTCH1/SUFU → SHH
- SMARCB1 (INI1) loss → AT/RT; germline = rhabdoid predisposition syndrome
- LIN28A+ with C19MC alteration → ETMR (embryonal tumor with multilayered rosettes)
- NF2 / merlin (22q) loss → Schwannoma, meningioma, ependymoma
- VHL (3p) inactivation → Hemangioblastoma (cerebellum + spinal) + RCC + pheo
- AFP elevation → Yolk sac tumor; β-hCG elevation → Choriocarcinoma (NGGCTs)
Imaging / location / clinical
- Cystic cerebellar mass with enhancing mural nodule (child) → Pilocytic astrocytoma
- Cystic mass with enhancing mural nodule (adult, cerebellum/spinal) → Hemangioblastoma (VHL; polycythemia from EPO)
- Midline posterior fossa mass in child + hydrocephalus → Medulloblastoma
- 4th ventricle mass in child / spinal cord mass in adult → Ependymoma
- Butterfly lesion crossing corpus callosum → Glioblastoma (or PCNSL)
- Extra-axial dural-based mass + dural tail + intense homogeneous enhancement → Meningioma
- Bilateral CN VIII (cerebellopontine angle) masses → NF2 vestibular schwannomas
- Calcified suprasellar mass with cysts (child) → Adamantinomatous craniopharyngioma
- Periventricular homogeneously enhancing mass + restricted diffusion (immunocompromised) → PCNSL
- Multiple gray-white junction lesions → Brain metastases (lung, breast, melanoma, RCC, colon)
- Bifocal pineal + suprasellar enhancing mass → Synchronous germinomas
- Clival or sacral midline destructive mass → Chordoma (notochordal remnant; brachyury+)
- Superficial temporal cystic mass + epilepsy (young adult) → PXA or ganglioglioma
- Drug-resistant focal epilepsy + cortical bubbly multinodular lesion → DNET
- Olfactory groove mass with intracranial + sinonasal extension → Esthesioneuroblastoma
- Frontal lobe tumor with calcifications (adult) → Oligodendroglioma
- Cardiac myxomas + spotty pigmentation + pigmented schwannoma → Carney complex
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