Adult diffuse gliomas
- Lesion
Diffuse gliomas grow into normal brain like roots; glioblastoma, the worst, shows dead zones lined by crowded tumour cells and new vessels.
What it is
Diffuse gliomas are the most frequent primary malignant brain tumours of adults. They infiltrate surrounding brain, so complete removal is impossible. Molecular features define the three main types: astrocytoma IDH-mutant (younger adults, slower), oligodendroglioma IDH-mutant with 1p/19q codeletion (best outlook, sensitive to chemotherapy), and glioblastoma IDH-wildtype (older adults, aggressive). The IDH mutation produces 2-hydroxyglutarate, an oncometabolite that changes DNA methylation.
Step by step
- A glial progenitor acquires an early driver: IDH mutation, or in glioblastoma, EGFR and TERT changes.
- IDH-mutant cells make 2-hydroxyglutarate, which blocks enzymes and causes a hypermethylated genome.
- Further hits (TP53, ATRX, or 1p/19q loss) define the lineage.
- Tumour cells migrate along white matter tracts and vessels.
- Hypoxia in fast growth causes necrosis; surviving cells palisade and secrete VEGF.
- VEGF drives glomeruloid microvascular proliferation and edema.
Adult diffuse gliomas compared
| Feature | Astrocytoma, IDH-mutant | Oligodendroglioma | Glioblastoma, IDH-wildtype |
|---|---|---|---|
| Age | Young adults | Adults, middle age | Older adults |
| Key genes | IDH1/2, ATRX loss, TP53 | IDH1/2, 1p/19q codeletion, TERT promoter | EGFR amplification, TERT promoter, +7/−10, PTEN |
| Histology | Infiltrating astrocytic cells, hyperchromatic nuclei | Round nuclei with halos, delicate branching capillaries, calcium | Pleomorphic cells, mitoses, pseudopalisading necrosis, microvascular proliferation |
| Grades | 2, 3 or 4 | 2 or 3 | 4 |
| Outlook | Years; can progress to grade 4 | Best of the three | Median survival about a year and a half with treatment |
Markers
- IDH1 R132H
- ATRX
- p53
- GFAP
- OLIG2
- Ki-67
- MGMT promoter methylation
- 1p/19q codeletion (FISH or sequencing)
Clinical notes
- New seizures in an adult, headaches or progressive focal deficit; MRI shows a ring-enhancing mass with necrosis in glioblastoma.
- Oligodendrogliomas often present with seizures and show calcification on CT.
Test yourself
Think of the answer, then tap the question to see it.
What two microscopic features define glioblastoma?
Necrosis with pseudopalisading tumour cells and microvascular (glomeruloid) proliferation.
Which molecular change defines oligodendroglioma together with IDH mutation?
Codeletion of chromosome arms 1p and 19q.
What does IDH-mutant protein produce?
The oncometabolite 2-hydroxyglutarate, which inhibits DNA and histone demethylases.
Why is MGMT promoter methylation tested in glioblastoma?
Methylation silences a DNA repair enzyme and predicts a better response to alkylating chemotherapy.
Elsewhere in DurgiPedia
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Glioblastoma Multiforme (StatPearls (NCBI Bookshelf), 2026); Central Nervous System Tumors Treatment (PDQ®)–Health Professional Version (National Cancer Institute, 2026).
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Representative model, for educational purposes only.