01Core principlesThe concepts and mechanisms needed to understand the subject.
Gliomas arise within the central nervous system and include biologically diverse entities. A diffuse glioma infiltrates beyond the visible margin, whereas circumscribed astrocytic gliomas form a different glioma family and glioneuronal tumours are a distinct WHO category with different behaviour and age distributions. The term glioma therefore should not be used as a shorthand for glioblastoma or for one treatment regimen. Clinical symptoms localise the affected network but cannot establish tumour type or grade.
Presentation varies with location and speed. Cortical tumours often cause focal seizures; frontal disease may produce executive or personality change; dominant-hemisphere lesions can impair language; motor, sensory, visual and cerebellar networks generate corresponding deficits. High-grade lesions may progress over weeks with oedema and pressure symptoms, whereas lower-grade disease can present after a single seizure in an otherwise well adult. Imaging suggests infiltration, necrosis, enhancement and perfusion, but radiological appearance is not a complete molecular diagnosis.
The 2021 WHO fifth edition organises adult-type diffuse gliomas into three principal types: astrocytoma, IDH-mutant; oligodendroglioma, IDH-mutant and 1p/19q-codeleted; and glioblastoma, IDH-wildtype. This replaces a morphology-only approach. It also places paediatric-type diffuse low-grade and high-grade gliomas in separate families, including H3-altered and other molecularly defined tumours. NICE NG99 predates parts of this taxonomy but explicitly instructs laboratories to use the latest WHO classification, so modern integrated names should be used rather than preserving superseded labels from older treatment tables.
Key points
- Glioma is a broad family of CNS tumours; presentation reflects location and growth rate, while definitive type and grade require integrated pathological assessment. Glioneuronal tumours are a distinct WHO category, not a glioma subtype.
- Current WHO fifth-edition taxonomy separates adult-type diffuse gliomas into astrocytoma, IDH-mutant; oligodendroglioma, IDH-mutant and 1p/19q-codeleted; and glioblastoma, IDH-wildtype.
- Paediatric-type diffuse low-grade and high-grade gliomas are separate molecular families; patient age alone does not justify assigning an adult treatment pathway.
- At presentation, stabilise emergencies first, then characterise onset, seizures, focal function, cognition and pressure symptoms before interpreting MRI.
- Obtain standard structural MRI and refer at first radiological diagnosis to a specialist multidisciplinary team; tissue planning must balance diagnostic value against eloquent location and procedural risk.
- Neuropathology integrates morphology with molecular tests such as IDH status and 1p/19q codeletion; the final diagnosis then informs prognosis, treatment selection and the appropriate surveillance plan.
02Mechanisms and patternsImportant relationships and how to distinguish them.
Ask whether the event began with speech arrest, sensory change, visual symptoms, head or eye deviation, unilateral jerking or automatisms. A focal onset supports a cortical network but does not distinguish lower-grade from higher-grade glioma.
Map weakness, sensory loss, field defect, dysphasia, neglect, apraxia or ataxia and document progression. Sudden onset still requires a vascular and haemorrhagic differential, including bleeding into tumour.
Seek collateral history about work errors, disinhibition, apathy, memory loss, unsafe decisions or loss of initiative. These changes may precede obvious motor findings and affect consent and support needs.
Progressive headache, vomiting, papilloedema, sixth-nerve palsy or drowsiness may reflect oedema, tumour volume or hydrocephalus. Pupil change and declining consciousness require emergency action before molecular work-up.
After surgery, radiotherapy or systemic treatment, new symptoms can represent recurrence, seizure, infection, haemorrhage, radiation effect, treatment toxicity or steroid complications. Timing and imaging comparison matter.
A child or young person may harbour a paediatric-type diffuse or circumscribed tumour with distinct biology. Location, especially midline structures or posterior fossa, also changes procedural feasibility and emergency hydrocephalus risk.
03Interpreting evidenceInformation, measurements and their limitations.
Consider the information, its meaning and its limitations before deciding what follows.
- 01
Standard structural MRI brain - Why
- Define tumour location, infiltration, enhancement, diffusion, oedema and relation to eloquent cortex and CSF pathways.
- Interpretation and limitations
- NICE NG99 defines the standard series as T2, FLAIR, DWI and T1 pre- and post-contrast volume imaging. Enhancement can support suspicion of higher-grade biology but neither enhancement nor its absence supplies an integrated diagnosis.
- 02
Advanced MRI techniques - Why
- Assess possible high-grade transformation or clarify uncertain recurrence using perfusion, spectroscopy or other specialist sequences.
- Interpretation and limitations
- NICE advises considering advanced imaging when a lesion appearing low grade may have transformed and when standard follow-up imaging is unclear. These techniques guide sampling and interpretation but do not replace pathology.
- 03
Neuropathology with WHO integrated diagnosis - Why
- Combine morphology, immunohistochemistry and molecular findings into a current entity and CNS WHO grade.
- Interpretation and limitations
- For adult-type diffuse glioma, IDH status separates the principal pathways; oligodendroglioma requires both an IDH mutation and 1p/19q codeletion, while glioblastoma is IDH-wildtype in the current adult-type taxonomy.
- 04
Molecular marker panel - Why
- Resolve lineage, grade-relevant biology, prognosis and treatment-predictive information from adequate tumour tissue.
- Interpretation and limitations
- NICE NG99 specifically names IDH1/2, ATRX, 1p/19q, histone H3.3 and BRAF testing in appropriate contexts, and MGMT promoter methylation to inform temozolomide decisions. The exact panel follows age, site, morphology and current WHO criteria.
- 05
Systemic and baseline assessment - Why
- Exclude important mimics and establish fitness for surgery and adjuvant therapy through targeted laboratory, functional and anaesthetic review.
- Interpretation and limitations
- Infection, inflammation, demyelination, metastasis and lymphoma can mimic glioma. Steroid exposure before a diagnosis of possible lymphoma can reduce biopsy yield, so treatment decisions require specialist context.
04Applied reasoningWorked examples connecting principles to decisions.
01Worked case: first focal seizureNon-enhancing frontal lesion in an adultAn adult recovers from a first focal seizure and MRI shows a diffuse non-enhancing frontal lesion without acute mass effect.+
- 1Confirm seizure recovery, document focal neurological and cognitive baseline, treat any ongoing seizure as an emergency and avoid inferring low grade solely from current alertness.
- 2Review the complete standard structural MRI with the specialist team, considering advanced imaging when sampling a potentially transformed focus would change the diagnostic plan.
- 3Refer at first radiological diagnosis to the neuro-oncology multidisciplinary team, which balances resection or biopsy against eloquent location, tumour extent, age, performance and the need for tissue.
- 4Request an integrated WHO diagnosis from representative tissue, using morphology with IDH and lineage-defining molecular tests rather than reporting “oligoastrocytoma” from mixed appearance alone.
- 5Verify the final entity, grade and key predictive markers at MDT, then explain the treatment and surveillance implications while acknowledging sampling and imaging uncertainty.
02Emergency pathwayGlioma with rapid deteriorationA patient with suspected or known glioma develops falling consciousness, new pupil asymmetry, seizure without recovery or rapidly worsening weakness.+
- 1Resuscitate, treat active seizure and obtain urgent CT while involving anaesthesia and neurosurgery; do not wait for a complete MRI protocol or final pathology.
- 2Identify haemorrhage, hydrocephalus, oedema and shift, then begin cause-specific pressure control and operative planning with the neuroscience team.
- 3After stabilisation, obtain the imaging and tissue information needed for integrated diagnosis without allowing an emergency radiological impression to become the permanent tumour label.
03Classification pathwayAdult versus paediatric-type diffuse gliomaHistology suggests diffuse glioma but age, midline location or initial molecular tests do not fit a routine adult-type entity.+
- 1Use the current WHO family structure and interpret IDH, histone, 1p/19q and other tests in the context of site and age.
- 2Seek specialist neuropathology review and additional molecular testing when the integrated entity remains uncertain or the result would redirect therapy.
- 3Apply adult diffuse-glioma management guidance only after confirming that its biological and population scope fits the patient.
05Checking understandingVerify the reasoning, revisit uncertainties and apply feedback.
- Record a postoperative or pretreatment neurological, seizure, cognitive and functional baseline against which future change can be judged.
- Use the tumour-specific clinical review and MRI schedule agreed by the multidisciplinary team; frequency varies by integrated type, grade, treatment and residual disease.
- When standard MRI is equivocal for recurrence, correlate symptoms, treatment timing and serial change and consider advanced imaging before declaring progression.
- Monitor antiseizure-treatment effectiveness and toxicity when prescribed, but do not use symptom control as evidence that tumour biology is stable.
- Revisit rehabilitation, work, driving, psychological and caregiver needs at diagnosis and each major transition because cognition and behaviour may change independently of scan size.
06Special situationsVariants, exceptions and circumstances that change the usual approach.
Integrated means combined
An integrated diagnosis incorporates histology and molecular data; it is not a molecular result pasted beside an old morphological name. Discordant results require neuropathology review rather than forced categorisation.
Grade is entity-specific
CNS WHO grade describes expected biological behaviour within the diagnosed entity. The same numeral should not be interpreted as identical prognosis across unrelated tumour families.
Sampling has limits
A small biopsy may miss heterogeneous high-grade regions. Imaging, trajectory and pathology must be reconciled, especially when enhancement or perfusion suggests a more aggressive focus.
MGMT has a different role
MGMT promoter methylation is principally a treatment-predictive and prognostic marker in glioblastoma contexts; it does not define oligodendroglioma or replace IDH and 1p/19q classification.
Age label is biological
“Adult-type” and “paediatric-type” denote molecular families with typical age distributions, not absolute birthday cut-offs. Unusual age or site should prompt careful classification rather than automatic pathway transfer.
07Common pitfallsFrequent interpretation and management errors.
- 01
Calling every glial tumour glioblastoma or treating the broad word “glioma” as a complete pathological diagnosis.
- 02
Diagnosing tumour type or grade from enhancement alone without representative tissue and integrated molecular assessment when tissue is feasible.
- 03
Using the obsolete mixed label oligoastrocytoma when IDH and 1p/19q testing can resolve adult-type diffuse lineage.
- 04
Applying an adult diffuse-glioma treatment pathway to a child or to a molecularly defined paediatric-type tumour without specialist review.
- 05
Allowing classification work-up to delay emergency treatment of seizure, haemorrhage, hydrocephalus or herniation.