Adult Neuro-Oncology

Epidemiology

Incidence

Glioblastoma is the most common malignant primary CNS tumour in adults (incidence on the order of 3 per 100,000 per year).

Age peak

Glioblastoma peaks in the 6th–7th decades; IDH-mutant gliomas typically present in younger adults (3rd–5th decades).

Location

Supratentorial, within the cerebral hemispheres.

Clinical Presentation

• Progressive focal neurological deficit, new-onset seizures (a common presenting feature of lower-grade gliomas), headache, or features of raised intracranial pressure.
• Cognitive or personality change with frontal tumours; dysphasia with dominant-hemisphere lesions.

Imaging

• Contrast-enhanced MRI is the principal modality. Glioblastoma typically shows irregular, ring-like enhancement with central necrosis and surrounding non-enhancing infiltrative T2/FLAIR signal.
• IDH-mutant astrocytomas are often non-enhancing or only minimally enhancing; the T2–FLAIR mismatch sign favours IDH-mutant astrocytoma.
• Advanced sequences (perfusion, spectroscopy) and amino-acid PET can help, but tissue with molecular testing remains the diagnostic standard.

Pathology & Molecular

Histology. Diffusely infiltrating glioma. Glioblastoma additionally shows microvascular proliferation and/or necrosis.

Molecular. An IDH1/IDH2 mutation defines astrocytoma and oligodendroglioma; whole-arm 1p/19q codeletion defines oligodendroglioma. In an IDH-mutant astrocytoma, homozygous CDKN2A/B deletion denotes CNS WHO grade 4. An IDH-wildtype diffuse astrocytic glioma that carries a TERT promoter mutation, EGFR amplification, or combined gain of chromosome 7 and loss of chromosome 10 (+7/−10) meets the criteria for glioblastoma, IDH-wildtype, even without classic grade-4 histology.

Management

Surgery. Maximal safe resection improves survival and provides tissue for the integrated diagnosis. For glioblastoma, a greater extent of resection of contrast-enhancing tumour is associated with longer survival, with benefit demonstrated above a threshold of roughly 78% and continuing into the 95–100% range. Awake mapping and intra-operative adjuncts (neuronavigation, 5-ALA fluorescence, intra-operative neuromonitoring) support safe maximal resection.

Adjuvant therapy. For newly diagnosed glioblastoma, radiotherapy with concurrent and adjuvant temozolomide (the 'Stupp regimen') is standard; adding Tumour-Treating Fields to maintenance temozolomide further prolongs survival. MGMT promoter methylation predicts temozolomide benefit and helps guide treatment, particularly in elderly or frail patients. For 1p/19q-codeleted oligodendroglioma, radiotherapy followed by PCV (procarbazine, lomustine, vincristine) chemotherapy markedly prolongs survival.

Considerations. Treatment is individualised by molecular subtype, age, performance status and MGMT status, and is delivered through a neuro-oncology multidisciplinary team.

Outcomes

Prognosis tracks molecular type far more closely than histology alone. Glioblastoma, IDH-wildtype carries the poorest prognosis (with the Stupp regimen, median overall survival around 14–16 months and 2-year survival about 27%).

By molecular subgroup: IDH-mutant astrocytomas, and especially 1p/19q-codeleted oligodendrogliomas, have substantially longer survival. In long-term trial follow-up of codeleted anaplastic oligodendroglioma treated with radiotherapy plus PCV, median survival exceeded 14 years.

WHO CNS5 (2021) — adult-type diffuse gliomas

Epidemiology

Incidence

The most common primary CNS tumour; incidence rises with age.

Age peak

Middle-aged and older adults; more common in women.

Location

Convexity, parasagittal/falcine, sphenoid wing, olfactory groove, tuberculum sellae, posterior fossa, and spinal locations.

Clinical Presentation

• Often asymptomatic and found incidentally. When symptomatic, features depend on location — focal deficit, seizures, or cranial neuropathies.
• Slow growth means mass effect may become considerable before symptoms appear.

Imaging

• Contrast MRI: an avidly and homogeneously enhancing, extra-axial, dural-based mass, often with a dural tail and a CSF cleft separating it from brain.
• CT may show hyperostosis or calcification. A provisional diagnosis is frequently made on imaging alone.

Pathology & Molecular

Histology. Meningothelial, fibrous, transitional and other subtypes. Atypical (grade 2) and anaplastic/malignant (grade 3) tumours carry a higher recurrence risk; brain invasion qualifies a tumour as at least grade 2.

Molecular. Recurrent alterations include NF2, and (in non-NF2 tumours) TRAF7, KLF4, AKT1 and SMO. Molecular and DNA-methylation profiling increasingly refine recurrence-risk estimation.

Management

Surgery. Gross-total resection including the involved dura is often curative, and the Simpson grade of resection correlates with recurrence. Asymptomatic, small, or elderly patients are frequently managed with a watch-and-scan strategy.

Adjuvant therapy. Radiosurgery or fractionated radiotherapy is used for inoperable, residual or recurrent tumours and for higher-grade (grade 2–3) disease. No systemic therapy is established as standard of care.

Considerations. Management balances tumour location, growth on serial imaging, symptoms, age and comorbidity; many incidental meningiomas are simply observed.

Outcomes

Grade 1 meningiomas have excellent outcomes after complete resection; recurrence risk rises with incomplete resection and with higher grade.

By molecular subgroup: Grade 2–3 meningiomas recur more frequently and more often require adjuvant radiotherapy.

Epidemiology

Incidence

The most common intracranial tumour in adults overall.

Age peak

Reflects the underlying systemic-cancer population.

Location

Typically at the grey–white matter junction; often multiple.

Clinical Presentation

• Headache, focal deficit, seizures, or cognitive change; sometimes the presenting feature of a previously unknown primary cancer.
• Peritumoural vasogenic oedema often contributes to symptoms and responds to corticosteroids.

Imaging

• Contrast MRI: one or more enhancing lesions at the grey–white junction with disproportionate surrounding oedema.
• Systemic staging identifies the primary and the extracranial disease burden, which guide treatment intent.

Pathology & Molecular

Histology. Histology reflects the primary tumour; resection or biopsy confirms metastasis and can reveal an occult primary.

Molecular. Molecular characterisation of the metastasis (or the primary) increasingly directs targeted therapies and immunotherapy.

Management

Surgery. For a single accessible metastasis with controlled or limited systemic disease, surgical resection followed by radiotherapy prolongs survival and improves local control versus radiotherapy alone (Patchell, 1990). Surgery also relieves mass effect and secures a tissue diagnosis.

Adjuvant therapy. After complete resection of a single metastasis, post-operative radiotherapy (historically whole-brain; increasingly focal/cavity stereotactic radiosurgery) reduces intracranial recurrence and neurological death (Patchell, 1998). Stereotactic radiosurgery is widely used for a limited number of metastases.

Considerations. Decisions integrate the number and size of lesions, systemic disease control, performance status, primary histology and available systemic therapy, within a multidisciplinary team.

Outcomes

Outcomes depend heavily on systemic disease control and primary histology; local therapy improves intracranial control and can extend survival in selected patients.

By molecular subgroup: For a resectable single metastasis, surgery plus radiotherapy improves local control and reduces neurological death compared with single-modality treatment.

Epidemiology

Incidence

Common, with a reported prevalence on the order of 1 in 1,000 adults (range about 1 in 865 to 1 in 2,688). About half are microadenomas (<10 mm).

Age peak

Adults across a wide age range.

Location

Sella turcica; macroadenomas may extend suprasellar (to the chiasm) or laterally (into the cavernous sinus).

Clinical Presentation

• Mass effect: headache, bitemporal hemianopia from chiasmal compression, and hypopituitarism.
• Hypersecretion syndromes: prolactinoma (amenorrhoea/galactorrhoea, reduced libido, infertility), acromegaly (GH/IGF-1), Cushing disease (ACTH) and, rarely, TSH-secreting tumours.
• Pituitary apoplexy, an acute haemorrhage or infarction with sudden headache and visual loss, is a neurosurgical emergency.

Imaging

• Dedicated pituitary MRI with and without contrast (including dynamic sequences) defines size, chiasmal contact and cavernous-sinus invasion.
• Formal visual-field assessment is required whenever the chiasm is involved.

Pathology & Molecular

Histology. Adenohypophyseal neuroendocrine tumour; immunohistochemistry for pituitary hormones and transcription factors defines the lineage.

Molecular. Transcription-factor–based lineage classification (e.g. PIT1, TPIT, SF1) underpins the contemporary PitNET classification.

Management

Surgery. Transsphenoidal surgery (usually endoscopic endonasal) is the first-line treatment for most pituitary adenomas — all functioning tumours except prolactinoma, and symptomatic non-functioning macroadenomas causing mass effect.

Adjuvant therapy. Prolactinomas are the exception: first-line therapy is medical, with dopamine agonists (cabergoline, bromocriptine). Medical therapy (for example somatostatin analogues or pegvisomant for acromegaly) and radiotherapy are used for residual or recurrent disease.

Considerations. Endocrine assessment and hormone replacement, ophthalmology, and pituitary multidisciplinary input are integral. Incidental, asymptomatic non-functioning microadenomas can often be monitored.

Outcomes

Outcomes are generally favourable with appropriate, lineage- and function-specific treatment, and early diagnosis improves results.

By molecular subgroup: Prolactinomas are usually controlled medically; other adenomas are generally treated surgically first, with medical therapy reserved for those not cured by surgery.