Paper II
Question
Describe the types and grading of astrocytoma
Answer
Astrocytomas are the most common primary glial tumours of the central nervous system.
Types (WHO classification, incorporating molecular features)
- Diffuse (infiltrating) astrocytomas: The classic progressive spectrum
- Diffuse astrocytoma, IDH-mutant (WHO Grade 2)
- Anaplastic astrocytoma, IDH-mutant (WHO Grade 3)
- Glioblastoma, IDH-wildtype (WHO Grade 4) — most common and most aggressive primary brain tumour in adults
- Circumscribed astrocytomas (distinct, non-infiltrating, generally better prognosis):
- Pilocytic astrocytoma (WHO Grade 1) — common in children, often cerebellar
Grading
- Based on histological features: cellularity, nuclear atypia, mitotic activity, microvascular proliferation, and necrosis
- Grade 1 (Pilocytic astrocytoma): Low cellularity, biphasic pattern (compact and loose areas), Rosenthal fibres, eosinophilic granular bodies — well-circumscribed, low proliferative activity
- Grade 2 (Diffuse astrocytoma): Mild hypercellularity, mild nuclear atypia, no mitoses/necrosis/microvascular proliferation
- Grade 3 (Anaplastic astrocytoma): Increased cellularity, marked nuclear atypia, brisk mitotic activity, no necrosis
- Grade 4 (Glioblastoma): All features of grade 3, plus microvascular proliferation and/or necrosis (classically “pseudopalisading necrosis” — tumour cells arranged radially around necrotic foci) — the defining features that upgrade to grade 4
Molecular markers of prognostic significance
- IDH1/IDH2 mutation status — mutant tumours have significantly better prognosis than IDH-wildtype
- MGMT promoter methylation — predicts better response to temozolomide chemotherapy
- 1p/19q co-deletion — favours oligodendroglioma diagnosis over astrocytoma, better prognosis