CNS Tumours

Central nervous system tumours are a perennial NEET PG favourite, tested heavily through histology images, immunohistochemistry markers, and "most common" associations. This note organises the high-yield primary CNS tumours by cell of origin, location, classic morphology, grade, and management — with the buzzwords examiners love.

Overview & classification

CNS tumours are classified by the WHO classification of tumours of the CNS (now integrating histology + molecular markers, "integrated diagnosis"). Broadly, they arise from neuroepithelial cells (gliomas), meninges (meningioma), nerve sheath (schwannoma), embryonal cells (medulloblastoma), or are metastatic.

Key epidemiological anchors that get asked repeatedly:

Category	Most common example
Most common CNS tumour overall	Metastasis (lung, breast, melanoma, renal, GI)
Most common primary CNS tumour (adult)	Meningioma (overall); Glioblastoma is the most common malignant primary
Most common primary malignant adult brain tumour	Glioblastoma (GBM), grade 4
Most common glioma	Astrocytoma
Most common paediatric CNS tumour overall	Pilocytic astrocytoma (most common solid childhood CNS tumour)
Most common malignant paediatric CNS tumour	Medulloblastoma
Most common intraventricular tumour (child)	Ependymoma / choroid plexus papilloma

High-yield: Overall the most common intracranial tumour is metastasis; the most common primary is meningioma; the most common primary malignant is glioblastoma. Distinguish "overall vs primary vs malignant" — examiners exploit this.

Location rule of thumb: In adults, brain tumours are supratentorial. In children, they are predominantly infratentorial (posterior fossa — cerebellum/brainstem), explaining the frequent presentation with cerebellar signs and obstructive hydrocephalus.

Gliomas — astrocytic tumours

Astrocytomas are graded by features such as nuclear atypia, mitoses, microvascular (endothelial) proliferation, and necrosis.

WHO grade	Tumour	Defining histology
Grade 1	Pilocytic astrocytoma	Biphasic; Rosenthal fibres + eosinophilic granular bodies; cystic with mural nodule
Grade 2	Diffuse astrocytoma	Increased cellularity, mild atypia, no mitoses
Grade 3	Anaplastic astrocytoma	Atypia + mitoses
Grade 4	Glioblastoma (GBM)	Microvascular proliferation + pseudopalisading necrosis

Glial cells stain GFAP positive — the single most testable IHC marker for gliomas.

Glioblastoma multiforme (GBM)

• WHO grade 4 astrocytoma; most common primary malignant brain tumour in adults; peak 45–70 yrs.
• Hemispheric (frontal/temporal); can cross corpus callosum → "butterfly glioma."
• Histology buzzwords: pseudopalisading necrosis (tumour cells crowding around serpentine necrotic foci) and microvascular/glomeruloid endothelial proliferation. GFAP positive.
• Molecular: IDH-wildtype GBM (primary, older patients, poor prognosis) vs IDH-mutant (now classed as astrocytoma grade 4). EGFR amplification, TERT promoter mutation, +7/−10, MGMT promoter methylation (predicts temozolomide response).
• Prognosis dismal — median survival ~12–15 months even with treatment.

High-yield: Pseudopalisading necrosis = glioblastoma. GFAP positive. "Butterfly glioma" crossing the corpus callosum. MGMT methylation → better temozolomide response.

Management flow: maximal safe surgical resection → radiotherapy + concurrent and adjuvant temozolomide (Stupp protocol). Tumour-treating fields may be added.

Pilocytic astrocytoma

• Most common CNS tumour of childhood; cerebellum is the classic site (also optic pathway — associated with NF1).
• Cystic lesion with an enhancing mural nodule on imaging.
• Histology: bipolar cells with long "hair-like" (pilocytic) processes; Rosenthal fibres and eosinophilic granular bodies. BRAF (KIAA1549) fusion.
• WHO grade 1 — excellent prognosis, often cured by resection.

Oligodendroglioma

• Adults, frontal lobe; slow-growing, often calcified and presents with seizures.
• Histology: "fried-egg" cells (perinuclear halo, artefact) and "chicken-wire" capillary pattern.
• Molecular hallmark: IDH mutation + 1p/19q co-deletion — defines the entity and predicts good chemo (PCV) response.

High-yield: 1p/19q co-deletion + IDH mutation = oligodendroglioma, chemosensitive, better prognosis. "Fried-egg" cells and calcification.

Ependymoma

• Arises from ependymal lining; children — 4th ventricle (→ hydrocephalus); adults — spinal cord (commonest spinal glioma, esp. myxopapillary type at filum terminale/conus).
• Histology: perivascular pseudorosettes (tumour cells around vessels) and true ependymal rosettes (around a central lumen). GFAP +, EMA shows dot-like/ring positivity.

Meningioma

• Arises from meningothelial (arachnoid cap) cells, not from dura itself.
• Most common primary intracranial tumour overall; adults, female predominance (express progesterone receptors; may enlarge in pregnancy).
• Risk: prior radiation; associated with NF2 (chromosome 22q loss).
• Locations (classic exam item): parasagittal/falx (commonest), convexity, sphenoid wing, olfactory groove (→ anosmia, Foster–Kennedy syndrome), tuberculum sellae, cerebellopontine angle, spinal.
• Imaging: dural-based, well-circumscribed, homogeneous enhancement with a "dural tail."
• Histology: whorls/syncytial nests of meningothelial cells and psammoma bodies (laminated calcified concretions). EMA positive, and may be progesterone-receptor positive. Mostly WHO grade 1, benign.

High-yield: Meningioma = EMA positive, psammoma bodies, dural tail, progesterone-receptor positive, NF2-associated. Other psammoma-body tumours: papillary thyroid carcinoma, serous papillary ovarian carcinoma, mesothelioma ("PSaMMoma" — Papillary thyroid, Serous ovarian, Meningioma, Mesothelioma).

Management: observation if small/asymptomatic; surgical excision for symptomatic; radiotherapy/radiosurgery for residual or inaccessible lesions.

Medulloblastoma

• Embryonal tumour (PNET) of the cerebellum (classically midline vermis in young children), WHO grade 4.
• Most common malignant paediatric brain tumour; presents with cerebellar ataxia, raised ICP, obstructive hydrocephalus.
• Histology: small round blue cells; Homer-Wright (neuroblastic) rosettes (cells around a central neuropil tangle, no lumen). Highly cellular, frequent mitoses.
• Tendency to seed via CSF → "drop metastases" along the spinal cord; stage with whole neuraxis MRI + CSF cytology.
• Molecular subgroups: WNT (best prognosis), SHH, Group 3 (MYC amplified, worst), Group 4.

High-yield: Homer-Wright rosettes + midline cerebellum + child = medulloblastoma, radiosensitive, CSF seeding ("drop mets"). WNT subgroup = best prognosis.

Management: surgical resection → craniospinal radiotherapy (radiosensitive tumour) + chemotherapy. Radiotherapy is limited/avoided under age 3.

Rosette pearl: Homer-Wright (neuroblastoma, medulloblastoma — central neuropil), Flexner-Wintersteiner (retinoblastoma, pineoblastoma — central lumen), perivascular pseudorosette (ependymoma — around vessel), Verocay body (schwannoma).

Acoustic neuroma (vestibular schwannoma)

• A schwannoma arising from the vestibular portion of CN VIII, at the cerebellopontine (CP) angle / internal acoustic meatus.
• Presents with sensorineural hearing loss, tinnitus, imbalance; large lesions compress CN V (corneal reflex loss) and VII.
• Bilateral acoustic neuromas are pathognomonic of NF2.
• Histology: Antoni A (compact, cellular, palisading nuclei forming Verocay bodies) and Antoni B (loose, hypocellular, myxoid) areas. S100 positive (neural crest origin).

High-yield: Schwannoma = S100 positive, Antoni A & B, Verocay bodies, CP-angle mass; bilateral → NF2.

Management: observation (small), stereotactic radiosurgery, or microsurgical excision with hearing/facial-nerve preservation.

Other named CNS lesions worth a line

• CNS lymphoma (primary): diffuse large B-cell; periventricular, in immunocompromised/HIV (EBV-driven). Steroid-responsive ("ghost tumour"). Stereotactic biopsy + high-dose methotrexate (avoid debulking).
• Haemangioblastoma: cerebellum; associated with von Hippel–Lindau; may cause polycythaemia (EPO); foamy stromal cells + rich capillary network.
• Craniopharyngioma: suprasellar, from Rathke pouch remnant; child or bimodal adult; calcification, "motor-oil" cyst fluid, wet keratin; bitemporal hemianopia. Adamantinomatous type → CTNNB1/β-catenin.
• Pituitary adenoma: sella; prolactinoma commonest; bitemporal hemianopia.
• Central neurocytoma: young adult, intraventricular near foramen of Monro; synaptophysin positive.

Genetic syndromes (frequently tested)

Syndrome	Gene	CNS tumours
NF1	NF1 (neurofibromin, ch17)	Optic glioma (pilocytic), neurofibromas, plexiform
NF2	NF2 (merlin, ch22)	Bilateral vestibular schwannomas, meningiomas, ependymomas
Von Hippel–Lindau	VHL (ch3)	Cerebellar/retinal haemangioblastoma
Tuberous sclerosis	TSC1/TSC2	Subependymal giant cell astrocytoma (SEGA)
Li-Fraumeni	TP53	Gliomas, medulloblastoma
Turcot	APC / MMR	Medulloblastoma / glioblastoma

Clinical features & general approach

CNS tumours present via three mechanisms:

1. Raised intracranial pressure → morning headache (worse on lying/straining), projectile vomiting, papilloedema, CN VI palsy (false-localising).
2. Focal deficit / seizures depending on location.
3. Endocrine / visual effects for sellar lesions.

Diagnostic flow: Clinical suspicion → Contrast-enhanced MRI brain (investigation of choice) → characterise (advanced: MR spectroscopy, perfusion) → stereotactic / open biopsy for histological + molecular diagnosis → integrated WHO grading → treatment.

High-yield: MRI with contrast is the investigation of choice for CNS tumours. Tissue/molecular diagnosis is definitive. Avoid lumbar puncture if raised ICP/posterior-fossa mass (risk of coning/herniation) — except staging medulloblastoma after the mass is addressed.

IHC marker quick map

Marker	Tumour
GFAP	Astrocytoma, GBM, ependymoma (glial origin)
EMA	Meningioma (membranous), ependymoma (dot-like)
S100	Schwannoma, melanoma, nerve sheath
Synaptophysin / NeuN	Neuronal tumours (neurocytoma), medulloblastoma
Progesterone receptor	Meningioma
Reticulin / Antoni	Schwannoma pattern

Complications

• Obstructive hydrocephalus (posterior fossa/intraventricular tumours) → may need CSF diversion/shunt.
• Herniation syndromes (uncal, central, tonsillar) from mass effect — neurosurgical emergency.
• Seizures, focal neurological deficits, cognitive decline.
• CSF seeding (medulloblastoma, ependymoma, germinoma, CNS lymphoma).
• Treatment-related: radiation necrosis, secondary tumours, endocrine deficits (cranial RT).

Key differentials

• Ring-enhancing lesion on MRI: GBM, metastasis, brain abscess, toxoplasmosis, tuberculoma, lymphoma (in HIV), demyelination. Multiple lesions favour metastasis/abscess; single butterfly favours GBM.
• CP-angle mass: vestibular schwannoma (commonest), meningioma, epidermoid, facial nerve schwannoma.
• Suprasellar mass: pituitary adenoma, craniopharyngioma, meningioma, germinoma.
• Posterior fossa child tumours: medulloblastoma (midline), pilocytic astrocytoma (cystic + nodule), ependymoma (4th ventricle), brainstem glioma.

Recently asked / exam angle

• "Pseudopalisading necrosis" image → glioblastoma; identify GFAP as the marker.
• "Most common location of meningioma" → parasagittal/falx; recognise psammoma bodies and EMA positivity; dural tail sign.
• Child with midline cerebellar tumour + small blue cells in rosettes → medulloblastoma (Homer-Wright); note radiosensitivity and CSF drop metastases.
• Bilateral acoustic neuromas → NF2; schwannoma is S100 positive with Antoni A/B and Verocay bodies.
• 1p/19q co-deletion + IDH mutation → oligodendroglioma (fried-egg cells, calcification, chemosensitive).
• Cerebellar haemangioblastoma + polycythaemia → VHL.
• "Investigation of choice for brain tumour" → contrast MRI; "definitive" → biopsy/histology.
• Most common CNS tumour overall (metastasis) vs primary (meningioma) vs malignant primary (GBM) — classic distractor set.
• Rosette matching: Flexner-Wintersteiner (retinoblastoma) vs Homer-Wright (medulloblastoma/neuroblastoma) vs perivascular pseudorosette (ependymoma).

Rapid revision

1. Pseudopalisading necrosis + microvascular proliferation = glioblastoma, WHO grade 4, GFAP+, IDH-wildtype.
2. Meningioma — commonest primary CNS tumour, EMA+, psammoma bodies, progesterone-R+, dural tail, NF2.
3. Medulloblastoma — midline cerebellum in children, Homer-Wright rosettes, radiosensitive, CSF "drop mets," WNT subtype best.
4. Pilocytic astrocytoma — commonest childhood CNS tumour, cyst + mural nodule, Rosenthal fibres, BRAF fusion, grade 1, curable.
5. Oligodendroglioma — fried-egg cells, calcification, IDH mut + 1p/19q co-deletion, chemosensitive.
6. Ependymoma — 4th ventricle in kids / spine in adults, perivascular pseudorosettes, EMA dot positivity.
7. Vestibular schwannoma — CP angle, S100+, Antoni A/B, Verocay bodies; bilateral = NF2.
8. Haemangioblastoma — cerebellum, VHL, polycythaemia from EPO.
9. Craniopharyngioma — suprasellar, calcified, "motor-oil" cyst, wet keratin, bitemporal hemianopia.
10. Overall commonest intracranial tumour = metastasis; commonest primary = meningioma; commonest malignant primary = GBM.
11. Adults supratentorial, children infratentorial.
12. Investigation of choice = contrast-enhanced MRI; definitive = histology + molecular (integrated WHO diagnosis); avoid LP with posterior-fossa mass.