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Diffuse Midline Glioma

Summary

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  • Aggressive, infiltrative brain tumour typically affecting children and young adults
  • Characterised by a specific histone H3 mutation (H3K27M)
  • Poor prognosis with median survival of 9-12 months despite treatment1

Pathophysiology

  • Arises from glial cells in midline structures of the brain
  • H3K27M mutation leads to epigenetic dysregulation and altered gene expression
  • Infiltrative growth pattern with diffuse spread along white matter tracts
  • Often associated with oedema and mass effect

Demographics

  • Peak incidence in children and young adults (median age 5-11 years)
  • Slight male predominance (male:female ratio 1.14:1)
  • Accounts for 10-20% of all paediatric brain tumours
  • Rare in adults, but can occur

Diagnosis

  • Clinical presentation:
    • Depends on tumour location (e.g., brainstem, thalamus, spinal cord)
    • Common symptoms: cranial nerve palsies, ataxia, hemiparesis, headache
  • Histopathology:
    • WHO grade 4 glioma
    • Immunohistochemistry positive for H3K27M mutation
  • Molecular testing:
    • Confirmation of H3K27M mutation in H3F3A or HIST1H3B/C genes

Imaging

  • MRI is the imaging modality of choice
  • T1-weighted imaging:
    • Hypointense to isointense mass
    • Variable enhancement pattern (often minimal or heterogeneous)
  • T2-weighted and FLAIR imaging:
    • Hyperintense mass with infiltrative appearance
    • Surrounding oedema and mass effect
  • Diffusion-weighted imaging:
    • Variable restricted diffusion
  • MR spectroscopy:
    • Elevated choline, reduced N-acetylaspartate
    • Presence of lactate and lipid peaks

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  • 20-year-old patient presented with headaches, blurred vision, nausea and vomiting.
  • MRI showed a diffuse T2-hyperintense lesion centred in a mildly expanded cerebellar peduncle.
  • Lower ADC values, potentially representing areas of higher cellularity, corresponded to a region of mildly increased rCBV (1.4 relative to the contralateral side).

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  • 20-year-old patient presented with acute onset headache.
  • MRI showed a acute obstructive hydrocephalus secondary to a solid-cystic lesion centred on the left thalamus.
  • Low ADC values within the solid and enhancing component of the tumour indicated hypercellularity.
  • Biopsy revealed a H3 K27M-mutant diffuse midline glioma.

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  • A 55-year-old patient presented with headache, nausea and vomiting.
  • MRI showed an enhancing lesion in the right side of the pons with slightly reduced ADC values.
  • Given an extensive travel history the imaging differential included both neoplasia and infection/inflammation.
  • Biopsy revealed an H3 K27M-mutant diffuse midline glioma.

Treatment

  • Radiotherapy is the mainstay (temporary benefit); surgery is usually limited to biopsy. Prognosis remains poor

Differential diagnosis

Differential Diagnosis Differentiating Feature
Pilocytic Astrocytoma Typically well-circumscribed, cystic appearance on MRI
Medulloblastoma Usually located in the cerebellum, enhances more homogeneously
Ependymoma Often has calcifications, may have cystic components
Brainstem Encephalitis Patchy T2 signal without diffuse expansion of the pons; may enhance; often involves multiple brainstem levels
Pontine Tegmental Cap Dysplasia Characteristic "molar tooth" appearance on axial MRI; congenital; associated with curved superior cerebellar peduncles
Demyelinating Disease Multiple lesions including supratentorial; ovoid periventricular plaques; no diffuse brainstem expansion
Metastatic Tumour Ring or nodular enhancement; multiple lesions; no diffuse T2 brainstem expansion
Lymphoma Typically enhances more homogeneously, often multiple lesions
Primitive Neuroectodermal Tumour (PNET) Usually more heterogeneous, may have cystic/necrotic areas
Ganglioglioma Often has calcifications, less invasive appearance

  1. Miguel Llordes et al. Epidemiology, Diagnostic Strategies, and Therapeutic Advances in Diffuse Midline Glioma. 2023. Journal of clinical medicine - Open in new tab. ↩