Diffuse brainstem gliomas

Diffuse brainstem gliomas, also known as diffuse intrinsic brainstem glioma (DIBG), is a term used to describe infiltrating astrocytomas, no longer recognised as a distinct entity in the 2016 update to the WHO classification of CNS tumours. It encompassed a variety of tumours, ranging from WHO grade II to WHO grade IV tumours. Using previous classifications, they accounted for 60-75% of all brainstem gliomas

Recently, it has become apparent that a large proportion of these tumours (particularly diffuse intrinsic pontine gliomas) harbour K27M mutations in the histone H3 gene H3F3A, or less commonly in the related HIST1H3B genes. These mutations are shared by other midline paediatric tumours (e.g. thalamic and spinal cord).

As of the 2016 update to the WHO classification of CNS tumours, these have been given a distinct and separate diagnosis: diffuse midline glioma, H3 K27M–mutant

The rest (i.e. diffuse tumours of the brainstem gliomas without K27M mutations) now are classified as non-location-specific tumours based on IDH mutation and 1p19q co-deletion status. 

NOTE: The remainder of this article is therefore largely of historical relevance only. 

These tumours typically present in childhood (3 to 10 years of age) and make up 10-15% of all paediatric brain tumours and 20-30% of paediatric posterior fossa tumours.

There is an association with neurofibromatosis type I, which however carries a better prognosis with a more indolent course.

Typically patients present with multiple cranial nerve palsies, depending on the location of the tumour, and signs of raised intracranial pressure. Cerebellar signs may also be elicited including ataxia, dysarthria, nystagmus and sleep apnoea.

Recent genomic work has uncovered distinct mutations found in the majority of diffuse midline gliomas, particularly diffuse intrinsic pontine gliomas (DIPG). These mutations are in the histone H3F3A gene (K27M mutations) or less frequently HIST1H3B and HIST2H3C genes 5,6

As of the 2016 update to the WHO classification of CNS tumours, diffuse intrinsic brainstem glioma (DIBG) has been removed and diffuse midline glioma, H3 K27M–mutant has been added as a specific entity 6

Diffuse brainstem gliomas can be found throughout the brainstem:

  • mesencephalic
  • pontine: most common accounting for 60-75% of all cases
  • medullary: least common location

In diffuse intrinsic pontine gliomas (DIPG) the pons is enlarged, with the basilar artery displaced anteriorly against the clivus and potentially engulfed. The floor of the fourth ventricle is flattened ("flat floor of fourth ventricle sign") and obstructive hydrocephalus may be present. Occasionally the tumour is exophytic, either outwards into the basal cisterns or centrally in the 4th ventricle.

Usually the tumour is homogenous pre-treatment, however in a minority of patients areas of necrosis may be present.

CT

Typically hypodense with little, if any, enhancement.

MRI
  • T1: decreased intensity
  • T2: heterogeneously increased
  • T1 C+ (Gd): usually minimal (can enhance post radiotherapy)
  • DWI: usually normal, occasionally mildly restricted

Due to the high rate of severe complications with biopsy treatment has historically been commenced without histological confirmation, although due to recent identification of distinct mutations (see diffuse midline glioma H3 K27M–mutant) stereotactic biopsy is being performed in some centers, and may become routine when therapies specifically targeted to these mutations become available 5.

Treatment usually comprises of chemotherapy only. In children over 3 years of age (or preferably even older) then radiotherapy may be considered. Necrosis may result from radiotherapy, however, it may also be seen as part of the natural course of the tumour.

Initial response can be dramatic and falsely reassuring.

In the sporadic form, the prognosis is poor with 2-year survival being only 20% (median survival less than 1 year). This is dramatically different from focal brainstem gliomas (e.g pilocytic astrocytomas and tectal gliomas) which carry a good prognosis.

General imaging differential considerations include:

They should also be distinguished from other tumours:

Astrocytic tumour
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Article Information

rID: 6491
Section: Pathology
Synonyms or Alternate Spellings:
  • Diffuse pontine glioma
  • Diffuse brainstem glioma
  • Diffuse pontine gliomas
  • Diffuse intrinsic brainstem glioma (DIBG)
  • Diffuse brainstem glioma
  • Diffuse intrinsic pontine glioma (DIPG)

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Cases and Figures

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    Case 1: pontine
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    Case 2: pontine
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    Case 3: pontine
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    Case 6: pontine
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    Brainstem Glioma
    Case 4: medullary
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    Case 5: pontine
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