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Glioblastoma

Summary

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  • Glioblastoma (GBM) is an aggressive primary brain tumour arising from glial cells
  • Characterised by rapid growth, necrosis, and angiogenesis
  • Presents with neurological symptoms and has poor prognosis despite multimodal treatment1

Pathophysiology

  • Under WHO 2021, glioblastoma is by definition IDH-wildtype (IDH-mutant grade 4 tumours are now classified as astrocytoma)
  • Molecular criteria can define GBM even without necrosis/microvascular proliferation: TERT promoter mutation, EGFR amplification, or +7/−10 chromosome copy-number change
  • Highly invasive with marked angiogenesis and necrosis

Demographics

  • Most common primary malignant brain tumour in adults
  • Incidence: 3.2 per 100,000 person-years
  • Median age at diagnosis: 64 years
  • Male to female ratio: 1.6:1
  • Risk factors:
    • Ionizing radiation exposure
    • Rare genetic syndromes (e.g., Li-Fraumeni syndrome, neurofibromatosis type 1)

Diagnosis

  • Clinical presentation:
    • Headaches
    • Seizures
    • Focal neurological deficits
    • Cognitive changes
  • Histopathology:
    • WHO grade 4 astrocytoma
    • Microvascular proliferation
    • Pseudopalisading necrosis
    • High mitotic activity
  • Molecular markers:
    • MGMT promoter methylation status
    • IDH mutation status
    • 1p/19q codeletion (to rule out oligodendroglioma)

Imaging

  • MRI (preferred modality):
    • T1-weighted with contrast: Ring-enhancing mass with central necrosis
    • T2-weighted/FLAIR: Extensive peritumoural oedema
    • DWI: Restricted diffusion in cellular components
    • Perfusion imaging: Increased relative cerebral blood volume
  • CT:
    • Hypodense mass with irregular enhancement
    • Surrounding oedema and mass effect
  • Advanced imaging techniques:
    • MR spectroscopy: Elevated choline, reduced NAA, presence of lipid/lactate peak
    • PET: Increased FDG uptake in high-grade components

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  • 60-year-old patient, with a previous right MCA territory ischaemic stroke, presented with a left-sided homonymous hemianopia.
  • CT showed a hyperdense mass lesion posterior to the old infarct.
  • MRI showed a diffusion-restricting, peripherally enhancing mass lesion. SWI showed neovascularisation and microhaemorrhages within the lesion.

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  • A patient presented with a headache and on examination had a large right visual field defect.
  • CT showed a larger left occipital lesion with striking (neo)vascularity.
  • MRI showed a peripherally enhancing lesion causing diffusion restriction and containing small regions of blood product.

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  • 65-year-old patient presented with headache, nausea, vomiting and speech disturbance.
  • Imaging showed a peripherally enhancing, centrally necrotic, left cerebellar mass lesion.
  • ADC values were lower in the periphery of the tumour indicating hypercellularity.
  • Unusually for the cerebellum, histopathology revealed a glioblastoma.

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  • A 50-year-old patient presented following a seizure.
  • MRI showed a large right temporal peripherally enhancing lesion with areas of diffusion restriction (not shown).
  • Intra-operative MRI was used to guide a maximal safe resection.
  • Within 6 months, there was a large volume of disease progression. While obvious on structural imaging, this was confirmed on DSC perfusion (elevated CBV and abnormal K2) and DCE perfusion (elevated Ktrans and VE and a Type 2 curve).

Treatment

  • Maximal safe resection with concurrent/adjuvant temozolomide and radiotherapy (Stupp protocol); prognosis remains poor

Differential diagnosis

Differential Diagnosis Differentiating Feature
Metastatic brain tumour Multiple lesions at grey-white junction; surrounding vasogenic oedema disproportionate to lesion size; no corpus callosum crossing
Primary CNS lymphoma Homogeneous enhancement without central necrosis; restricted diffusion on DWI; hyperdense on non-contrast CT; periventricular location
Brain abscess Thin smooth ring enhancement; restricted DWI centrally; no irregular thickened wall; may have satellite lesions
Anaplastic astrocytoma Less necrosis; less enhancement or no enhancement; less vasogenic oedema
Oligodendroglioma Calcifications on CT; cortical-based; "chicken wire" vascular pattern; less necrosis
Meningioma Extra-axial location, dural tail sign
Demyelinating disease Incomplete ring enhancement, periventricular location
Radiation necrosis History of radiation therapy, more well-defined borders
Subacute stroke Follows vascular territory, diffusion restriction in acute phase
Tumefactive multiple sclerosis Incomplete ring enhancement, less mass effect

  1. Lim et al. Current state of immunotherapy for glioblastoma. 2018. Nature reviews. Clinical oncology - Open in new tab. ↩