Tumors of central and peripheral nervous system

1. CNS Tumors — Overview

• 50–75 % of CNS tumors are primary; rest are metastatic.
• Very frequent in children (20 % of all childhood tumors; 2nd most common pediatric malignancy after leukemia).
• Classical benign/malignant categories NOT used — GRADE is important:

Grade	Behavior
Grade 1	Surgery can be curative
Grade 2	Potential for transformation
Grade 3	Apparent malignancy (5–10 yr)
Grade 4	Rapid course (0.5–3 yr)

• Outcome depends on: histological subtype, grade, localization, molecular profile (“integrated diagnosis”).
• Even low-grade tumors can infiltrate huge areas → severe symptoms (e.g., benign meningioma at medulla → cardiorespiratory arrest).
• Extracranial metastases are extremely rare; subarachnoid space allows spread along brain + spinal cord.

2. Gliomas (from glial cells)

A) Astrocytomas (from astrocytes)

Fibrillary (Diffuse) Astrocytoma — IDH1/2 mutation

• 80 % of adult primary brain tumors.
• Age: 30–40 yr (lower grades), older for GBM.
• Presents with seizures, headaches, focal deficits.

Grades

• Grade 2 astrocytoma:
  • Diffusely infiltrating, astrocyte-like cells.
  • Sparse mitoses, minimal atypia.
  • > 10 yr median survival, eventual progression.
• Grade 3 (anaplastic) astrocytoma:
  • Marked atypia, ↑ mitoses.
  • 5–10 yr median survival.
• Grade 4 — Glioblastoma Multiforme (GBM):
  • Most frequent primary high-grade brain tumor in adults (60–80 yr).
  • Pseudopalisading necrosis + microvascular proliferation = diagnostic.
  • Highly cellular, markedly atypical astrocytic cells.
  • “Butterfly” lesion — crosses corpus callosum.
  • 15–18 months median survival even with surgery + chemo-radiotherapy (temozolomide).
  • Many patients present de novo as GBM rather than progressing from lower grade.

Pilocytic Astrocytoma (Grade 1)

• Relatively benign; children + young adults.
• Cystic tumor with bipolar cells, usually in cerebellum.
• BRAF mutation/fusion.
• Histology: Rosenthal fibers + eosinophilic granular bodies.
• Excellent prognosis after surgical resection.

B) Oligodendroglioma — IDH1/2 + 1p/19q co-deletion

• Arises from oligodendrocytes.
• 40–50 yr; 5–15 % of gliomas.
• Good response to chemo-radiotherapy → better prognosis than astrocytoma.
• Grade 2: clear cytoplasmic halo around nuclei = “fried egg” appearance; chicken-wire vasculature; calcifications.
• Grade 3 (anaplastic): higher mitotic activity, necrosis, microvascular proliferation.

C) Ependymoma

• From ependymal cells (radial glial cells) lining ventricular system.
• Adults: spinal cord.
• Young: 4th ventricle (→ hydrocephalus).
• Morphology: true ependymal rosettes + perivascular pseudorosettes; outpouching into ventricle.
• CSF dissemination common (supratentorial / posterior fossa / spinal forms).

3. Embryonal Tumor of CNS

Medulloblastoma

• Highly undifferentiated tumor.
• Children (1–5 yr); exclusively in cerebellum.
• CSF dissemination, high mitotic activity + apoptosis.
• Histology: immature anaplastic “small blue round cells” resembling neuronal progenitors; Homer-Wright pseudorosettes (focal neuronal differentiation).
• Poor prognosis but highly radiosensitive → 5-yr survival 75 % with surgery + chemo-radiotherapy.

Molecular Subgroups

Subgroup	Prognosis
WNT-activated	Best prognosis
SHH-activated (sonic hedgehog)	Favorable but aggressive course
Non-WNT / non-SHH	Poor prognosis

4. Meningioma

• Mostly benign tumors of meninges.
• Arise from meningothelial cells of arachnoid.
• Sites: external surfaces of brain (compress, do not infiltrate) or within ventricular system.
• More common in women (estrogen + progesterone receptors).
• Prognosis: size, location, surgical accessibility, histological grade.

Grading

• Grade 1 (typical meningioma): variants — psammoma bodies, meningothelial, fibrous, transitional (whorls).
• Grade 2 (atypical): ↑ mitotic activity, brain infiltration.
• Grade 3 (anaplastic): marked atypia, highly aggressive → brain infiltration + skull destruction.

5. Metastatic Tumors

• Most CNS metastases are carcinomas.
• Primary sites: lung (#1), breast, kidney, melanoma, GI tract.
• Sharply demarcated masses at gray-white matter junction, surrounded by edema.
• Paraneoplastic syndromes (no metastasis but neurological symptoms):
  • Subacute cerebellar degeneration.
  • Limbic encephalitis.
  • Subacute sensory neuropathy.
  • Rapidly developing psychosis, coma, catatonia.

6. Tumors of PNS

A) Schwannoma

• Encapsulated benign tumors from Schwann cells.
• Symptoms: local compression of adjacent structures.
• Often cerebellopontine angle, on vestibular branch of CN VIII → hearing loss = “acoustic neuroma”.
• Bilateral acoustic neuroma = neurofibromatosis type 2 (NF2).
• NF2 gene mutation in sporadic cases.
• Does NOT transform to malignancy (unlike neurofibroma).

Morphology

• Antoni A (elongated cells in fascicles — dense) + Antoni B (loose) growth patterns.
• Verocay bodies: nuclear palisading around fibrillary process (Antoni A).
• Frequently hyalinized vessels.
• IHC: S-100⁺.

B) Neurofibroma

• Sporadic or NF1 (neurofibromatosis type 1) association.

Three Types

Type	Features
Localized cutaneous	Dermis + subcutaneous fat; nodules with hyperpigmentation; only cosmetic concern
Plexiform	Thickens nerve fascicles; arises in NF1; potential for malignant transformation
Diffuse	Large deforming subcutaneous tumor; usually NF1

C) Malignant Peripheral Nerve Sheath Tumor (MPNST)

• Malignant mesenchymal tumor (sarcoma) from peripheral nerves.
• May develop from plexiform neurofibroma (NF1) or differentiate from Schwann cells (NOT from schwannoma!).
• Locally invasive → metastatic spread + multiple recurrences.

7. Summary Table

Tumor	Cell/Key features
Pilocytic astrocytoma (G1)	Children, cerebellum, cystic, Rosenthal fibers, BRAF
Fibrillary astrocytoma	IDH1/2; 80 % of adult brain tumors; infiltrative
Glioblastoma (G4)	Adults; pseudopalisading necrosis + microvascular proliferation; butterfly lesion; 15–18 mo survival
Oligodendroglioma	IDH1/2 + 1p/19q co-deletion; “fried egg” + chicken-wire vasculature + calcifications; chemo-sensitive
Ependymoma	4th ventricle in kids; spinal cord in adults; perivascular pseudorosettes
Medulloblastoma	Cerebellum in kids; small blue round cells; Homer-Wright rosettes; WNT (best) / SHH / non-WNT non-SHH
Meningioma	Arachnoid; psammoma bodies + whorls; women, ER/PR⁺
Metastases	Gray-white junction; lung > breast > kidney/melanoma
Schwannoma	CN VIII (acoustic); Antoni A/B, Verocay bodies, S-100⁺; NF2; no malignant transformation
Neurofibroma	NF1; plexiform can transform to MPNST

💡 High-yield: GBM (G4) = adults; pseudopalisading necrosis + microvascular proliferation; butterfly across corpus callosum; 15–18 mo survival. Pilocytic astrocytoma (G1) = children, cerebellum, Rosenthal fibers, BRAF. Oligodendroglioma = IDH + 1p/19q co-deletion → chemo-sensitive; “fried egg” + chicken-wire vasculature + calcifications. Ependymoma = 4th ventricle in kids → hydrocephalus; perivascular pseudorosettes. Medulloblastoma = cerebellum in kids; small blue round cells; Homer-Wright rosettes; WNT best prognosis. Meningioma = women, arachnoid, psammoma bodies + whorls, ER/PR⁺. Metastases at gray-white junction (lung #1). Schwannoma = CN VIII (acoustic neuroma), Antoni A/B, Verocay bodies, S-100⁺; bilateral = NF2. Neurofibroma = NF1; plexiform → MPNST risk.