Neuro-oncology: Gliomas
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Direct answer
Glioma classification changed fundamentally in 2021: adult diffuse gliomas are now defined by molecular markers first — IDH-mutant astrocytoma (grades 2-4, with CDKN2A/B homozygous deletion upstaging to grade 4), IDH-mutant and 1p/19q-codeleted oligodendroglioma, and IDH-wildtype glioblastoma, which can be diagnosed even from a low-grade-looking biopsy if it carries TERT promoter mutation, EGFR amplification or the combined +7/-10 chromosome signature. Glioblastoma treatment is the Stupp protocol: maximal safe resection followed by concomitant radiotherapy (60 Gy in 30 fractions) with daily temozolomide 75 mg/m², then six adjuvant cycles of 150-200 mg/m² on 5 days per 28-day cycle. MGMT promoter methylation predicts chemotherapy benefit and longer survival; IDH mutation is the strongest favourable prognostic marker in diffuse gliomas. The neurologist's job spans seizure control, steroid stewardship, recognising pseudoprogression on post-radiotherapy MRI, and honest survival conversations.
What you must remember
- The 2021 WHO map: adult-type diffuse gliomas divide into astrocytoma, IDH-mutant (grades 2-4); oligodendroglioma, IDH-mutant and 1p/19q-codeleted (grades 2-3); glioblastoma, IDH-wildtype (grade 4) — plus paediatric-type entities such as diffuse midline glioma, H3 K27-altered.
- Molecular upstaging rules: CDKN2A/B homozygous deletion makes an IDH-mutant astrocytoma grade 4 regardless of histology; TERT promoter mutation, EGFR amplification or +7/-10 makes an IDH-wildtype tumour behave as glioblastoma.
- Stupp dosing verbatim: radiotherapy 60 Gy in 30 fractions with temozolomide 75 mg/m² daily throughout, then adjuvant temozolomide starting 150 mg/m² escalating to 200 mg/m², days 1-5 of each 28-day cycle for six cycles.
- Prognostic hierarchy: IDH mutation most favourable; MGMT promoter methylation predicts temozolomide responsiveness; 1p/19q codeletion adds chemosensitivity and the best outcomes among diffuse gliomas; age and extent of resection remain clinical anchors.
- Radiology anchors: glioblastoma as an enhancing rim-and-necrosis lesion with vasogenic oedema, often crossing the corpus callosum ("butterfly"); lower-grade gliomas as non-enhancing T2/FLAIR lesions, frequently frontal in IDH-mutant disease; perfusion rCBV elevation flags high-grade transformation.
- Pseudoprogression: new enhancement within 3-6 months after chemoradiotherapy, especially in MGMT-methylated tumours, mimics progression but stabilises or improves — clinicoradiological judgement, sometimes methionine-PET or biopsy, before changing therapy.
- Seizure pragmatics: low-grade gliomas seize frequently — antiseizure drug selection with enzyme-inhibiting interactions in mind (levetiracetam preferred alongside chemotherapy); prophylactic antiepileptics for unreformed seizures are not indicated; steroid (dexamethasone) only for symptomatic oedema, tapered to the lowest dose.
A pathway from biopsy to adjuvant cycles
A 46-year-old presents with a first generalised seizure; MRI shows a non-enhancing FLAIR lesion in the right frontal lobe with low perfusion. Maximal safe resection returns an IDH-mutant, 1p/19q-intact astrocytoma without CDKN2A/B deletion — grade 2 — and management is observation with serial imaging versus radiotherapy-plus-temozolomide decided by risk factors (age over 40, incomplete resection push toward treatment), because low-grade does not mean benign. Contrast the 62-year-old whose left temporal enhancing ring lesion resects as IDH-wildtype glioblastoma, MGMT-methylated: Stupp protocol begins, and at the three-month post-radiotherapy scan the enhancement has grown — but the patient is clinically better, and methionine-PET shows low uptake: pseudoprogression, so adjuvant cycles continue, and the next scan plateaus. The skills being exercised are the exam's actual questions: naming the molecular diagnosis from the marker panel, writing the Stupp doses from memory, and refusing to call progression without weighing pseudoprogression, radionecrosis and steroid effect.
Where candidates slip
The recurring gaps: quoting histology-only grades (a "grade 2" IDH-wildtype tumour with +7/-10 is glioblastoma — the molecular rule overrides); forgetting that oligodendroglioma requires both IDH mutation and 1p/19q codeletion (1p/19q loss alone means nothing without IDH); and mismanaging the post-treatment scan by starting second-line chemotherapy for pseudoprogression. The Indian practice note: generic temozolomide is widely available and affordable, but comprehensive molecular panels (IDH, ATRX, TERT, EGFR, 1p/19q, MGMT) are variable in cost and turnaround outside metropolitan centres — the examinable corollary is knowing the minimum viable panel: IDH mutation and 1p/19q status change the diagnosis, MGMT changes the conversation.
Frequently asked questions
Which molecular markers define glioblastoma, IDH-wildtype?
TERT promoter mutation, EGFR amplification, or combined chromosome +7/-10 — any one in an IDH-wildtype diffuse astrocytic tumour establishes glioblastoma even without grade 4 histology.
What is the complete Stupp regimen?
Maximal safe resection, then 60 Gy radiotherapy in 30 fractions with concomitant temozolomide 75 mg/m² daily, followed by six adjuvant 5-day cycles at 150-200 mg/m² every 28 days.
What does MGMT promoter methylation predict?
Better response to temozolomide and longer survival, because methylation silences the repair enzyme that removes temozolomide-induced DNA damage.
Which genetic combination defines oligodendroglioma?
IDH mutation plus 1p/19q codeletion — the combination that confers chemosensitivity and the best prognosis among diffuse gliomas.
What is pseudoprogression and how is it recognised?
New or increased enhancement within months of chemoradiotherapy that stabilises or improves without treatment change, more frequent with MGMT-methylated tumours — a clinicoradiological or PET-supported judgement.