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Diffuse Hemispheric Glioma

Summary

  • Rare, aggressive glioma of adolescents/young adults with diffuse infiltration of a cerebral hemisphere
  • Typically presents with seizures, focal neurological deficits, and raised intracranial pressure
  • MRI shows unilateral hemispheric involvement with T2/FLAIR hyperintensity and variable enhancement1

Pathophysiology

  • WHO grade 4 glioma defined by the H3 G34 mutation (H3.3 G34R/V) — distinct from the H3 K27M of diffuse midline glioma
  • Arises in the cerebral hemispheres of adolescents/young adults, with diffuse infiltration and poor prognosis

Demographics

  • Adolescents and young adults (typically ~15–25 years)
  • Rare; recently defined as a distinct WHO 2021 entity

Diagnosis

  • Clinical presentation:
    • Seizures (focal or generalised)
    • Progressive focal neurological deficits
    • Signs of raised intracranial pressure (headache, vomiting, papilledema)
  • Neuroimaging (MRI) is crucial for initial diagnosis
  • Definitive diagnosis requires histopathological examination and molecular testing

Imaging

  • MRI is the imaging modality of choice:
    • T2/FLAIR: Diffuse hyperintensity involving a large portion of one cerebral hemisphere
    • T1: Hypointense signal in the affected areas
    • T1 post-contrast: Variable enhancement patterns, often minimal or absent
    • DWI: May show areas of restricted diffusion
    • MR spectroscopy: Elevated choline and reduced N-acetylaspartate peaks
  • CT:
    • May show subtle hypodensity and mass effect
    • Calcifications are uncommon

panels-1

  • A 20-year-old patient presented with rapidly progressive spasticity and ataxia.
  • MRI showed diffuse bihemispheric ill-defined T2-weighted hyperintensity without diffusion restriction or enhancement.
  • Biopsy revealed a H3 G34-mutant diffuse hemispheric glioma.

Treatment

  • Maximal safe resection and radiotherapy ± chemotherapy; prognosis remains poor

Differential diagnosis

Differential Diagnosis Differentiating Feature
Acute disseminated encephalomyelitis (ADEM) Diffuse bilateral white matter and basal ganglia involvement; no progressive mass effect; no H3K27M imaging correlate
Multiple sclerosis Periventricular ovoid lesions; "Dawson's fingers" on sagittal FLAIR; no hemispheric mass effect
Lymphoma Homogeneous enhancement; periventricular; restricted diffusion; hyperdense on non-contrast CT
Metastatic disease Multiple lesions at grey-white junction; ring or nodular enhancement; surrounding vasogenic oedema
Vasculitis Multifocal cortical and subcortical infarcts in multiple territories; vessel wall enhancement on high-resolution MRI
Progressive multifocal leukoencephalopathy (PML) Subcortical U-fibre involvement; no enhancement; restricted diffusion at active edge; no mass effect
Leukodystrophy Symmetric white matter involvement; specific patterns (anterior, posterior, or central) depending on type
Encephalitis Cortical and limbic T2 signal; often bilateral temporal involvement; may show restricted DWI in active areas
Posterior reversible encephalopathy syndrome (PRES) Posterior-predominant vasogenic oedema; elevated ADC; no hemispheric mass
Glioblastoma Prominent central necrosis with irregular ring enhancement; more established mass effect

  1. Crowell et al. A review of diffuse hemispheric glioma, H3 G34-mutant disease development, DNA repair, microenvironment, and treatments on the horizon. 2025. NPJ precision oncology - Open in new tab. ↩