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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 treatment

Pathophysiology

  • Originates from astrocytes or neural stem cells
  • Key molecular alterations:
    • EGFR amplification (40-50% of cases)
    • PTEN mutations (30-40%)
    • TP53 mutations (30-40%)
    • IDH1/2 mutations (10% in primary GBM, 80% in secondary GBM)
  • Exhibits extensive intratumoural heterogeneity
  • Highly invasive, with infiltrative growth pattern
  • Marked angiogenesis and areas of 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 indiciating 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 surgical resection
  • Adjuvant therapy:
    • Radiation therapy (60 Gy in 30 fractions)
    • Concurrent and adjuvant temozolomide chemotherapy
  • Tumour-treating fields (TTFields) for newly diagnosed GBM
  • Bevacizumab for recurrent GBM
  • Experimental approaches:
    • Immunotherapy (e.g., checkpoint inhibitors, CAR-T cell therapy)
    • Targeted therapies (e.g., EGFR inhibitors)
    • Gene therapy
  • Supportive care:
    • Anticonvulsants for seizure control
    • Corticosteroids for oedema management
    • Rehabilitation and palliative care

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