Glioblastoma Multiforme

Glioblastoma multiforme (GBM) is the most aggressive and most common primary malignant brain tumour in adults. It is classified as a WHO Grade 4 astrocytoma and is notorious for its rapid progression, resistance to therapy, and poor prognosis.

Pathophysiology

Origin: Arises from astrocytes, a type of glial cell in the central nervous system.

• Genetics:
• Primary GBM (de novo): Often seen in older adults; associated with EGFR amplification, PTEN mutations, and chromosome 10 loss.
• Secondary GBM (progresses from lower-grade gliomas): Seen in younger patients; associated with IDH1/2 mutations and TP53 mutations.
• Features:
• High cellularity with pleomorphic, hyperchromatic nuclei
• Pseudopalisading necrosis
• Microvascular proliferation (glomeruloid bodies)
• Diffuse infiltration beyond visible margins.

 Clinical Features

• Symptoms depend on location but may include:
• Headache (due to increased intracranial pressure)
• Seizures
• Neurological deficits (hemiparesis, aphasia, visual changes)
• Personality/memory changes if in frontal lobe
• Onset is typically rapid and progressive.

 Imaging

• MRI with contrast is the gold standard.
• Characteristic findings:
• Ring-enhancing lesion with central necrosis
• Surrounding edema and mass effect
• "Butterfly glioma" appearance if it crosses the corpus callosum

 Diagnosis

• Histopathological confirmation via stereotactic biopsy or resection.
• Molecular markers (IDH mutation, MGMT promoter methylation) are critical for prognosis and therapy decisions.

Treatment

GBM is not curable — treatment aims to prolong survival and maintain quality of life.

1. Surgical Resection:
• Maximal safe resection preferred
2. Radiation Therapy:
• Standard post-op treatment (60 Gy over 6 weeks)
3. Chemotherapy:
• Temozolomide (TMZ) is the drug of choice
• Better response if MGMT promoter is methylated
4. Tumor Treating Fields (TTF):
• An adjunct non-invasive therapy using alternating electric fields

Prognosis

• Median survival: 12–15 months with standard therapy
• 2-year survival: ~25%
• 5-year survival: <10%
• Poor prognostic factors: Age >60, unmethylated MGMT, IDH wild-type