Brain Tumours

Meet the patient

A 64-year-old smoker develops a thunderclap of new seizures over a fortnight, with a morning headache that eases as the day goes on and a creeping weakness of his left hand. His wife says his personality has flattened. The CT shows a ring-enhancing right frontal mass with surrounding oedema and midline shift; the MRI confirms a thick, irregularly enhancing ring crossing the corpus callosum.[1]

A 32-year-old otherwise well woman presents with a single first-ever generalised seizure. She has no focal deficit and the fundi are flat. The MRI shows a non-enhancing, T2/FLAIR-bright mass in the right frontal lobe. Two gliomas, two stories — and the molecular profile, not the histology alone, decides which is which. The two questions that drive the whole topic are primary or secondary? and what is the integrated molecular diagnosis?[1]

What a brain tumour is — and the split that decides everything

A brain tumour is any neoplasm arising within the cranial cavity — from the parenchyma, its coverings (meninges), the cranial nerves, the pituitary or pineal glands, or as a secondary deposit. The single most important first split, made at the bedside, is primary versus metastatic, because the implications for investigation, prognosis and treatment are entirely different. Metastases outnumber primary tumours by roughly five to ten times in adults, yet the public and many exam stems fixate on primary glioma — the examiner will test both directions.[7]

The second anchor is the WHO 2021 classification, which defines each tumour by integrated histology plus molecular marker rather than microscopy alone. Two gliomas that look identical down a microscope can have different diagnoses, treatments and prognoses once their IDH status and codeletion pattern are known. This molecular turn is the most important development in neuro-oncology in two decades and is examined explicitly.[1]

Whatever the histology, all brain tumours cause symptoms through a small set of shared mechanisms — mass effect and raised intracranial pressure, direct infiltration or destruction of functioning brain, peritumoural vasogenic oedema, seizure generation from cortical irritation, and CSF pathway obstruction producing hydrocephalus. Understanding these mechanisms unifies the presentation, the imaging and the medical management (steroids for oedema, anticonvulsants for seizures, shunts for hydrocephalus).[1]

Classification — the WHO 2021 molecular turn

The clinically useful first division is the primary or metastatic split. Among primaries, the WHO 2021 groups tumours by cell of origin and, increasingly, by defining molecular alteration.[1]

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The WHO 2021 adult-type diffuse gliomas — the single most examined classification

The WHO 2021 system replaced purely histological grading with adult-type diffuse gliomas defined by their molecular profile.[1][5]

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The logic is profound. A high-grade diffuse glioma in an adult is glioblastoma, IDH-wildtype unless it carries an IDH mutation — in which case, however aggressive the histology looks, it is astrocytoma, IDH-mutant (grade 4) with a substantially better prognosis. The old term 'glioblastoma multiforme' is obsolete; glioblastoma is by definition IDH-wildtype in the 2021 system. IDH-mutant gliomas tend to arise in younger adults (median age around 40) and run a more indolent course; IDH-wildtype glioblastoma strikes older adults (median around 65) and pursues a relentless course.[1][5]

Other primaries worth naming. Beyond diffuse gliomas, examiners expect a working knowledge of the paediatric and non-glial primaries: pilocytic astrocytoma (WHO grade 1, BRAF-altered, children, posterior fossa or optic pathway, often curable by resection); medulloblastoma (posterior fossa, children, four molecular subgroups — WNT, SHH, group 3, group 4); ependymoma (ZFTA fusion supratentorially, PF-EPN subgroups in the posterior fossa); diffuse midline glioma, H3 K27-altered (grade 4, brainstem in children, formerly DIPG, dismal prognosis); primary CNS lymphoma (diffuse large B-cell, deeply situated, periventricular, HIV-related or immunocompetent elderly).[1]

How common, and who

The CBTRUS statistical report is the authoritative epidemiological source. Primary brain and CNS tumours have an overall annual incidence of roughly 20 to 25 per 100,000, but incidence and tumour type vary dramatically with age.[7]

Brain tumours show a characteristic bimodal age distribution. In children (the leading cause of cancer death after leukaemia), the commonest tumours are pilocytic astrocytoma, medulloblastoma and ependymoma, predominantly in the posterior fossa. In older adults the dominant tumour is glioblastoma, IDH-wildtype, with meningioma the commonest overall primary at any age. The metastatic burden rises with the prevalence of systemic cancer and improved systemic control that lets patients live long enough to develop brain disease.[7]

The list of genuinely established risk factors is short and examiners test it precisely. High-dose ionising radiation to the head (historical scalp ringworm treatment, prior radiotherapy) increases the risk of meningioma, glioma and nerve-sheath tumours decades later. Inherited tumour syndromes account for a small but disproportionately examined fraction. Immunosuppression (HIV, transplant, congenital) markedly increases the risk of primary CNS lymphoma — an EBV-driven tumour.[1]

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What is not a risk factor matters as much: despite intense study, mobile-phone use, hair dyes, head trauma, aspartame and electromagnetic fields have not been convincingly linked to brain tumours. No modifiable risk factor explains the great majority of adult glioblastoma — these are sporadic, driven by somatic mutations.[1]

How a tumour produces symptoms — the Monro-Kellie box

The skull is a rigid box holding brain, blood and CSF. Adding a tumour (and its surrounding oedema) to a fixed-volume container raises the intracranial pressure and distorts brain tissue. The Monro-Kellie doctrine governs this: the volume of the three intracranial contents is constant, so an expanding mass can be accommodated only by displacing CSF and venous blood — a reserve that exhausts quickly, after which small increments in volume produce large rises in pressure. This is why a patient with a glioblastoma can be relatively well one week and comatose the next.[1]

The five symptom-generating mechanisms are mass effect (midline shift, herniation syndromes); vasogenic peritumoural oedema (blood-brain barrier disruption leaking protein-rich fluid — the target of dexamethasone); direct infiltration or destruction of functioning brain (focal deficits); seizure generation from cortical irritation (commoner with superficial, slow-growing, low-grade tumours); and CSF pathway obstruction producing hydrocephalus (posterior fossa, pineal and intraventricular tumours).[1]

The molecular pathogenesis of glioma

Isocitrate dehydrogenase (IDH1/2) mutation is the single most important alteration: the mutant enzyme produces the oncometabolite 2-hydroxyglutarate, which inhibits alpha-ketoglutarate-dependent dioxygenases, producing global epigenetic dysregulation (the glioma-CpG-island methylator phenotype, G-CIMP) and blocking differentiation. IDH-mutant gliomas arise in younger adults and carry a markedly better prognosis.[1]

1p/19q codeletion — whole-arm deletion of chromosome 1p and 19q — defines oligodendroglioma and is invariably associated with IDH mutation. It is a powerful favourable prognostic marker and predicts benefit from alkylating chemotherapy (PCV and temozolomide). MGMT promoter methylation silences the DNA-repair enzyme that would undo temozolomide's damage, so a methylated MGMT predicts a better response to temozolomide and is now a routine companion test in glioblastoma.[3]

In glioblastoma, IDH-wildtype, the dominant alterations are EGFR amplification and variant III mutation, PTEN loss, CDKN2A deletion, TERT promoter mutation, and the chromosome 7 gain plus chromosome 10 loss (+7/-10). These are not academic: TERT promoter mutation is one of the molecular features that can upgrade an IDH-wildtype diffuse astrocytoma to glioblastoma even when histology looks lower-grade.[1][5]

Meet the tumour at the bedside

Brain tumours announce themselves through three principal modes — raised intracranial pressure, focal neurological deficit, and seizure — often in combination, and occasionally as cognitive, personality or endocrine change, or as a stroke-like event from tumour haemorrhage. The tempo is usually progressive over weeks to months, which itself is a discriminator from vascular (sudden) and inflammatory (subacute relapsing) disease.[5]

The raised-ICP triad is headache, vomiting and papilloedema. The headache of raised ICP is characteristically worse in the morning, worse with Valsalva (coughing, straining, bending), often occipital or frontal, progressive, and may ease as the patient sits up. Vomiting may be effortless and projectile without preceding nausea, classically in the morning. Papilloedema — blurring of the optic disc margins, loss of venous pulsations, then elevation and haemorrhages — is the single most important bedside sign and demands fundoscopy in every patient with a progressive headache. A false-localising sixth-nerve palsy (bilateral lateral rectus weakness from raised ICP stretching the nerve) is not a brainstem lesion.[5]

The focal deficit maps onto the tumour's location, and examiners love the clinicopathological correlation.[1]

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Seizures occur in 30 to 50 percent of patients with brain tumours and are commoner with cortically based, slow-growing, low-grade tumours (ganglioglioma, DNET, low-grade glioma) than with deeply situated high-grade tumours. A new-onset seizure in an adult, with no immediate metabolic or vascular explanation, is a brain tumour until proven otherwise — one of the highest-yield exam statements and the trigger for urgent MRI with contrast.[5]

Atypical presentations the examiner tests deliberately. The elderly patient may present with progressive cognitive decline, apathy or gait disturbance mistaken for dementia. The pituitary tumour may declare itself with endocrine disturbance (galactorrhoea, acral enlargement, Cushingoid features) long before any mass effect. A haemorrhage into a tumour (melanoma, renal cell, choriocarcinoma, thyroid, glioblastoma) produces a stroke-like abrupt onset.[5]

The differential — read the imaging pattern, not the name

The differential of a brain mass on imaging is broad, and the imaging pattern — not the name — drives the work-up. A ring-enhancing lesion, a diffusely infiltrating non-enhancing mass, and a homogeneously enhancing extra-axial lesion each carry a different differential.[1]

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The can't-miss mimics are brain abscess (surgical emergency, source control, antibiotics) and primary CNS lymphoma (which dictates a fundamentally different management — biopsy only, no steroids before biopsy, high-dose methotrexate rather than resection).[5]

The bedside round — localise, gauge urgency, hunt the primary

A focused bedside assessment in suspected brain tumour has three aims: to localise the lesion, to gauge the urgency (raised ICP, herniation, hydrocephalus), and to hunt for a systemic primary if metastasis is plausible.[1]

History probes the headache (timing, progression, Valsalva, position), any seizures (focal versus generalised, post-ictal deficit), the tempo of any focal deficit (progressive over weeks is the hallmark of tumour), cognitive or personality change reported by family, visual symptoms, and endocrine change. A smoking history, prior cancer, weight loss, and family history of cancer or an inherited tumour syndrome are essential.[5]

Examination begins with vital signs and the Glasgow Coma Scale (eye opening E1 to E4, verbal V1 to V5, motor M1 to M6; maximum 15). A full neurological examination follows: cranial nerves including fundoscopy (papilloedema), visual fields (confrontation for bitemporal hemianopia), motor and sensory systems, coordination, gait and reflexes. A general examination hunts for a primary: skin (melanoma), breasts, lungs (clubbing, chest signs), thyroid, abdomen (hepatomegaly, masses), and lymph nodes.[5]

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Investigations — MRI with gadolinium is the gold standard

MRI brain with gadolinium contrast is the imaging modality of choice and the single most informative test. It defines the tumour's location (intra- versus extra-axial, supra- versus infratentorial), size, enhancement pattern (ring, nodular, homogeneous, none), peritumoural oedema, mass effect and midline shift, haemorrhage, calcification, and any CSF pathway obstruction. Glioblastoma classically shows a thick, irregularly enhancing ring with central necrosis crossing the corpus callosum (butterfly glioma); meningioma is a homogeneously enhancing extra-axial mass with a dural tail; oligodendroglioma is a cortically based, calcified mass.[5]

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Advanced MRI sequences add precision. MR spectroscopy shows elevated choline, reduced N-acetylaspartate and (in some tumours) a lactate or lipid peak, helping distinguish tumour from abscess, demyelination or radiation necrosis. MR perfusion measures relative cerebral blood volume: high rCBV suggests high-grade tumour or recurrence, low favours radiation necrosis. Diffusion-weighted imaging shows restricted diffusion in abscess and lymphoma. Functional MRI and diffusion tensor imaging map eloquent cortex and white-matter tracts for surgical planning.[5]

CT retains specific roles: faster and more available in the emergency department, detects acute haemorrhage and calcification superbly, and is first when MRI is contraindicated or the patient cannot tolerate it. A non-contrast CT showing acute hydrocephalus or midline shift is itself a neurosurgical emergency. CT chest, abdomen and pelvis is performed when metastasis is suspected and the primary is occult; whole-body PET-CT is increasingly used for the same purpose.[5]

Histology, molecular profiling, and the role of CSF

Definitive diagnosis requires tissue. Stereotactic biopsy obtains tissue when the tumour is unresectable or in eloquent or deep cortex; open biopsy or surgical resection provides more tissue. The histology is integrated with molecular profiling — IDH mutation, 1p/19q codeletion, MGMT promoter methylation, TERT promoter, EGFR, BRAF V600E, H3 K27, CDKN2A — to arrive at the WHO 2021 integrated diagnosis. MGMT promoter methylation is now a standard companion test because it predicts temozolomide benefit.[3][5]

Lumbar puncture and CSF analysis has a narrow but important role — cytology for leptomeningeal disease and primary CNS lymphoma, tumour markers (alpha-fetoprotein and beta-HCG for germ cell tumours), and oligoclonal bands when demyelination is in the differential. The cardinal rule: never perform lumbar puncture before imaging if a mass lesion is possible, because reducing the pressure below the tumour can precipitate tonsillar or uncal herniation.[5]

The immediate priority — recognise and treat raised ICP

The immediate priority in the patient with a brain tumour is to recognise and treat raised intracranial pressure, impending herniation, and seizures — these are the time-critical threats.[1]

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Dexamethasone is the specific therapy for the vasogenic oedema surrounding a brain tumour — it restores blood-brain barrier integrity — in contrast to cytotoxic oedema from stroke, where it is ineffective or harmful. The dose 4 to 16 mg a day is then weaned to the lowest effective dose, with PPI cover and monitoring for hyperglycaemia, myopathy and infection.[5]

Status epilepticus from a tumour-related seizure is treated as any status: lorazepam 4 mg IV (repeat once after 4 minutes), then levetiracetam 1500 to 3000 mg IV or fosphenytoin 18 mg phenytoin-equivalent per kg IV, with escalation to intubation, propofol or midazolam infusion and ICU care for refractory status.[5]

Herniation syndromes and hydrocephalus. Uncal herniation (ipsilateral dilated pupil from third-nerve compression, contralateral hemiparesis from cerebral peduncle compression, declining consciousness) demands the emergency bundle plus urgent neurosurgical decompression. Central herniation produces bilateral small pupils, decorticate then decerebrate posturing, and respiratory irregularity. Cerebellar tonsillar herniation causes neck stiffness, respiratory arrest and cardiorespiratory collapse — a posterior-fossa emergency. Obstructive hydrocephalus from a posterior fossa or intraventricular tumour is treated with an external ventricular drain acutely.[5]

Definitive treatment — histology- and molecular-specific

Definitive treatment is histology- and molecular-specific, delivered by a multidisciplinary team (neurosurgeon, neuro-oncologist, radiation oncologist, neurologist, specialist nurse, neuropsychologist, palliative care). The framework is: control symptoms, establish the diagnosis, resect what can be safely resected, then give adjuvant therapy according to the integrated diagnosis.[1]

Glioblastoma, IDH-wildtype — the Stupp protocol

The standard of care for fit adults with newly diagnosed glioblastoma is maximal safe surgical resection (the greater the extent of resection, the better the survival, while preserving eloquent function — awake craniotomy with direct cortical mapping for tumours in language, motor or sensory cortex) followed by the Stupp protocol.[2]

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This regimen more than doubled two-year survival compared with radiotherapy alone (27 percent versus 10 percent in the original EORTC/NCIC trial) and remains the global standard twenty years on. Tumour-treating fields (TTF) — low-intensity alternating electric fields delivered via scalp transducer arrays — added to maintenance temozolomide prolonged median survival to about 21 months in the EF-14 trial and are incorporated into many guidelines.[4] MGMT promoter methylation identifies the patients who benefit most from temozolomide — methylated tumours respond far better than unmethylated ones.[3]

For elderly or frail patients, the Perry trial showed that short-course radiotherapy (40 Gy in 15 fractions) with concomitant and adjuvant temozolomide outperformed short-course radiotherapy alone; in patients with MGMT-methylated tumours, temozolomide alone is a reasonable option.[6]

Astrocytoma and oligodendroglioma, IDH-mutant

For astrocytoma, IDH-mutant (grades 2 to 4) and oligodendroglioma, IDH-mutant, 1p/19q codeleted (grades 2 to 3), maximal safe resection is followed by risk-stratified adjuvant therapy. High-risk low-grade glioma and grade 3 to 4 IDH-mutant astrocytoma receive radiotherapy plus temozolomide or radiotherapy plus PCV chemotherapy (procarbazine, lomustine, vincristine). Oligodendroglioma with 1p/19q codeletion has the best prognosis of any diffuse glioma — median survival often exceeds 10 years — and responds well to radiotherapy plus PCV or temozolomide, the codeletion being a marker of chemosensitivity.[5]

Meningioma

The EANO meningioma guideline governs management. WHO grade 1 meningioma with complete Simpson grade I resection (tumour, dural attachment and involved bone) is often cured by surgery alone — observation with serial MRI follows. Subtotal resection, recurrent, atypical (grade 2) or anaplastic (grade 3) meningioma warrants adjuvant radiotherapy — fractionated external-beam or stereotactic radiosurgery (gamma knife) for small residual or recurrent disease. Small asymptomatic meningiomas in the elderly can simply be surveilled.[8]

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Pituitary adenoma

Pituitary macroadenomas causing visual field compromise (bitemporal hemianopia) or hormonal hypersecretion are managed by transsphenoidal surgery — the endoscopic endonasal approach is now standard. Prolactinoma is the exception: cabergoline 0.25 to 1 mg twice weekly (a dopamine agonist) is first-line and often shrinks the tumour, reserving surgery for those intolerant or resistant. Acromegaly is treated with transsphenoidal surgery followed, if not cured, by somatostatin analogues (octreotide, lanreotide), the GH-receptor antagonist pegvisomant, or dopamine agonists. Cushing disease is managed surgically with steroidogenesis inhibitors (ketoconazole, metyrapone) and radiotherapy as adjuncts.[5]

Primary CNS lymphoma — the one you manage completely differently

Primary CNS lymphoma is managed completely differently from other brain tumours, and this is heavily examined. The cardinal rules: stereotactic biopsy only (surgical resection confers no benefit and may harm), do NOT give steroids before biopsy (glucocorticoids lyse lymphoma cells and can abolish the diagnostic tissue within hours), and treat with high-dose methotrexate-based chemotherapy (methotrexate 3 to 8 g/m² every 2 to 4 weeks) — often with rituximab, cytarabine and, in younger fit patients, consolidation with autologous stem-cell transplant. Whole-brain radiotherapy is effective but neurotoxic, especially in older patients.[5]

Brain metastases

Management is guided by number, size, location, performance status and control of the primary. Single accessible metastasis with controlled primary and good performance status — surgical resection followed by stereotactic radiosurgery (SRS, gamma knife) to the cavity. Limited metastatic burden (typically up to 3 to 4 small lesions) — SRS alone, sparing the cognitive cost of whole-brain radiotherapy. Multiple or extensive metastases, poor performance status, uncontrolled primary — whole-brain radiotherapy (WBRT, 20 Gy in 5 fractions or 30 Gy in 10 fractions) for palliation, plus systemic therapy appropriate to the primary. Melanoma, non-small-cell lung cancer with EGFR or ALK mutations, and HER2-positive breast cancer increasingly respond to targeted agents and immunotherapy.[5]

Symptom control and supportive care

Beyond definitive therapy, several agents are near-universal. Dexamethasone 4 to 16 mg daily controls peritumoural oedema, weaned to the lowest effective dose with PPI cover. Anticonvulsants — levetiracetam 500 to 1500 mg twice daily is preferred (no enzyme induction, no interaction with chemotherapy) — are given only to patients who have had a seizure; routine prophylactic anticonvulsants are not recommended, a point examiners test. Venous thromboembolism is common in brain-tumour patients (especially glioma); prophylactic low-molecular-weight heparin is balanced against the small bleeding risk.[5]

The subtypes and scenarios that bite

Pilocytic astrocytoma (WHO grade 1, BRAF-altered) in children is often cured by complete surgical resection; BRAF inhibitors (dabrafenib plus trametinib) are emerging for unresectable disease. Medulloblastoma is treated with maximal safe resection, craniospinal irradiation, and chemotherapy (cisplatin, lomustine, vincristine); the molecular subgroup (WNT best, group 3 worst) now stratifies treatment intensity, and five-year survival is 70 to 80 percent overall. Diffuse midline glioma, H3 K27-altered (formerly DIPG) — biopsy for molecular confirmation is now standard where safe; focal radiotherapy provides transient symptomatic benefit; median survival remains under 12 months.[1]

Recurrent glioblastoma has limited options: re-resection if feasible, re-irradiation in selected cases, bevacizumab (anti-VEGF) for symptomatic oedema and radiographic response (without proven overall survival benefit), retreatment with temozolomide, and clinical trial enrolment — which every patient should be offered if eligible. Tumour-treating fields can be continued or started at recurrence.[4][5]

How brain tumours harm — complications and pitfalls

The complications span neurological, surgical, oncological and systemic. Progressive neurological deficit from tumour growth; seizures (including status epilepticus); hydrocephalus (obstructive from posterior fossa or intraventricular tumour); cerebral herniation; tumoural haemorrhage (melanoma, renal cell, choriocarcinoma, glioblastoma); leptomeningeal spread; and paraneoplastic syndromes. Venous thromboembolism is markedly more common in brain-tumour patients than in the general population, especially in glioma.[5]

Surgical complications include new focal deficit, haematoma, infection (wound, meningitis), CSF leak, and (with pituitary surgery) diabetes insipidus, CSF rhinorrhoea and hypopituitarism. Radiotherapy causes acute fatigue and skin reaction, early delayed somnolence syndrome (weeks), and late radiation necrosis (months to years — an enhancing mass that mimics recurrence, treated with bevacizumab or surgery). Whole-brain radiotherapy causes progressive cognitive decline, especially in survivors — a major reason SRS is preferred for limited metastases. Temozolomide causes myelosuppression (monitor FBC) and nausea.[5]

The classic errors an examiner will probe: giving steroids before biopsy in suspected primary CNS lymphoma (destroys diagnostic tissue); performing lumbar puncture before imaging in a patient with a mass (risk of herniation); routinely prescribing prophylactic anticonvulsants (no benefit, real harm, drug interactions); treating a tumoural haemorrhage as a stroke without an MRI (missing the underlying lesion); failing to search for a systemic primary in a brain metastasis; and treating an IDH-mutant astrocytoma as glioblastoma (worse prognosis assumed, wrong prognostic conversation).[5]

Prognosis and disposition

Prognosis varies more widely across brain tumours than in almost any other organ — from cure (pilocytic astrocytoma, grade 1 meningioma) to median survival measured in months (glioblastoma, DIPG). The key determinants are histology and integrated molecular diagnosis (IDH status and 1p/19q codeletion dominate glioma prognosis), age and performance status, extent of resection, MGMT promoter methylation (in glioblastoma), and the molecular subgroup in medulloblastoma.[2][5]

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Disposition after definitive treatment: inpatient for surgery and acute complications; outpatient with serial MRI surveillance (typically every 3 to 6 months for two years, then 6 to 12 months) for low-grade and resected tumours; neurorehabilitation (physiotherapy, occupational therapy, speech and language, neuropsychology) for residual deficits; and palliative care integrated early for advanced or progressive disease, addressing symptoms (headache, seizures, cognitive change, dysphagia), advance care planning and family support.[5]

Special populations

Pregnancy — brain tumours may grow rapidly in pregnancy (haemodynamic and hormonal changes, fluid shifts), and presentation can be confounded with pre-eclampsia (headache, visual disturbance, papilloedema, seizures). MRI without gadolinium is safe in pregnancy; gadolinium is avoided unless essential. Management is by a combined neurosurgical, obstetric and anaesthetic team, balancing gestational age, tumour type and urgency. Pituitary adenomas may enlarge in pregnancy (prolactinoma risk), and visual fields are monitored.[5]

Children — brain tumours are the commonest solid tumour and the leading cause of cancer death in children after leukaemia. The spectrum differs from adults: pilocytic astrocytoma, medulloblastoma, ependymoma, diffuse midline glioma (DIPG), craniopharyngioma. Children require paediatric neuro-oncology expertise, age-adapted treatment (craniospinal irradiation doses are reduced in the very young to spare neurocognition), and lifelong follow-up for late effects — endocrinopathy, cognitive decline, second malignancy, infertility.[1]

Elderly — glioblastoma is commonest in older adults, but age and performance status must temper therapy — the full Stupp protocol is demanding, and short-course radiotherapy with temozolomide (Perry) or temozolomide alone in MGMT-methylated tumours is appropriate for older or less fit patients. Meningioma is common and often indolent in the elderly, where observation is frequently the right choice for small asymptomatic tumours.[6]

Immunocompromised — in HIV and post-transplant immunosuppression, the differential of a brain mass shifts towards primary CNS lymphoma (EBV-driven) and cerebral toxoplasmosis. The classic approach to a solitary deep ring-enhancing lesion in HIV is to treat empirically for toxoplasmosis (sulfadiazine plus pyrimethamine) and reserve biopsy for non-responders; multiple lesions, a positive EBV CSF PCR, and SPECT thallium uptake favour lymphoma. Restoring immune function (antiretroviral therapy) is itself part of the lymphoma treatment.[5]

Inherited tumour syndromes — a new brain tumour in a young patient, a multifocal presentation, a family history of cancer, or a syndromic phenotype (cafe-au-lait patches, axillary freckling, Lisch nodules in NF1; bilateral acoustic neuromas in NF2; retinal and cerebellar haemangioblastomas in VHL) should prompt consideration of an inherited syndrome — see the FAMILIAL mnemonic. Surveillance of affected relatives is part of management.[1]

Evidence, guidelines and regional deltas

The framework rests on the WHO 2021 Classification of CNS Tumours (Louis 2021)[1] and the EANO guidelines on diffuse gliomas of adulthood (Weller 2021)[5] for glioma, the EANO meningioma guideline (Goldbrunner 2021) for meningioma[8], and the CBTRUS statistical report (Price 2025) for epidemiology.[7]

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Active controversies: the optimal management of IDH-mutant grade 2 glioma (observation versus early surgery and adjuvant therapy); the role and timing of temozolomide in elderly MGMT-unmethylated tumours; whether tumour-treating fields deliver enough benefit to justify the burden and cost outside trial settings; the place of targeted therapy and immunotherapy in primary brain tumours (largely disappointing to date, unlike in metastatic disease); and the integration of liquid biopsy (CSF and plasma cell-free tumour DNA) into surveillance.[5]

The mnemonic, and the mantra

The mantra: MRI with gadolinium, maximal safe resection, the Stupp protocol for glioblastoma; ask for the integrated molecular diagnosis — it changes everything; and never give steroids before biopsy in suspected primary CNS lymphoma, never LP before imaging if a mass is possible.[1]

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Ward-round test — three stems, thirty seconds each

Stem 1 — the man with the ring (answer)

A 64-year-old smoker presents with new seizures, a progressive left-hand weakness, and a morning headache. MRI shows a thick, irregularly enhancing ring with central necrosis in the right frontal lobe crossing the corpus callosum. What is the likely diagnosis, the molecular definition, and the standard of care? Model: This is glioblastoma, IDH-wildtype — the commonest primary malignant brain tumour in adults, defined in WHO 2021 by its IDH-wildtype status plus diagnostic molecular features (TERT promoter mutation, EGFR amplification, or +7/-10). The standard of care is maximal safe resection followed by the Stupp protocol — radiotherapy 60 Gy in 30 fractions plus concurrent temozolomide 75 mg per metre squared daily, then adjuvant temozolomide 150 to 200 mg per metre squared on days 1 to 5 of every 28-day cycle for 6 to 12 cycles — for a median survival of about 15 months. Check MGMT promoter methylation (predicts temozolomide benefit), and consider tumour-treating fields.[1][2]

Stem 2 — the periventricular mass (answer)

A 72-year-old with a periventricular homogeneously enhancing mass that restricts on diffusion-weighted imaging. The registrar wants to give dexamethasone for the surrounding oedema and then book resection. What is the likely diagnosis, and what is the rule that stops them? Model: The likely diagnosis is primary CNS lymphoma — a diffusely enhancing, periventricular mass that restricts on DWI, especially in an older or immunocompromised patient. The rule that stops them: do NOT give steroids before biopsy — glucocorticoids lyse lymphoma cells and can abolish the diagnostic tissue within hours, leaving the pathologist with nondiagnostic necrosis. Hold steroids, perform stereotactic biopsy only (resection confers no benefit), and only then commence high-dose methotrexate-based chemotherapy. The one exception is life-threatening mass effect with impending herniation.[5]

Stem 3 — the first seizure in an adult (answer)

A 45-year-old has a single first-ever generalised seizure, normal examination, and a non-enhancing T2/FLAIR-bright mass in the right frontal lobe that is IDH-mutant with ATRX loss and no 1p/19q codeletion. What is the integrated diagnosis, and what does it tell you about prognosis? Model: The integrated diagnosis is astrocytoma, IDH-mutant, WHO grade 2 (a low-grade diffuse glioma) — IDH-mutant, ATRX loss, no 1p/19q codeletion. This is a substantially better-prognosis tumour than IDH-wildtype glioblastoma: IDH-mutant gliomas arise in younger adults and run a more indolent course. Management is maximal safe resection with risk-stratified adjuvant therapy (radiotherapy plus temozolomide or PCV for high-risk disease). A new-onset seizure in an adult with no metabolic or vascular explanation is a brain tumour until proven otherwise — MRI with contrast is the first test, not CT or EEG.[1][5]

References

1. [1]Louis DN, Perry A, Wesseling P, et al. The 2021 WHO Classification of Tumors of the Central Nervous System: a summary Neuro Oncol, 2021.PMID 34185076
2. [2]Stupp R, Mason WP, van den Bent MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma N Engl J Med, 2005.PMID 15758009
3. [3]Hegi ME, Diserens AC, Gorlia T, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma N Engl J Med, 2005.PMID 15758010
4. [4]Stupp R, Taillibert S, Kanner A, et al. Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma: A Randomized Clinical Trial JAMA, 2017.PMID 29260225
5. [5]Weller M, van den Bent M, Preusser M, et al. EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood Nat Rev Clin Oncol, 2021.PMID 33293629
6. [6]Perry JR, Laperriere N, O'Callaghan CJ, et al. Short-Course Radiation plus Temozolomide in Elderly Patients with Glioblastoma N Engl J Med, 2017.PMID 28296618
7. [7]Price M, Ballard CAP, Benedetti JR, et al. CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2018-2022 Neuro Oncol, 2025.PMID 41092086
8. [8]Goldbrunner R, Minniti G, Preusser M, et al. EANO guideline on the diagnosis and management of meningiomas Neuro Oncol, 2021.PMID 34181733