Diffuse brainstem gliomas
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Diffuse brainstem gliomas, also known as diffuse intrinsic brainstem glioma (DIBG), is a term used to describe infiltrating astrocytomas, no longer recognized as a distinct entity in the 2016 update to the WHO classification of CNS tumors. It encompassed a variety of tumors, ranging from WHO grade II to WHO grade IV tumors. Using previous classifications, they accounted for 60-75% of all brainstem gliomas.
Recently, it has become apparent that a large proportion of these tumors (particularly diffuse intrinsic pontine gliomas) harbor K27M mutations in the histone H3 gene H3F3A, or less commonly in the related HIST1H3B genes. These mutations are shared by other midline pediatric tumors (e.g. thalamic and spinal cord).
As of the 2016 update to the WHO classification of CNS tumors, these have been given a distinct and separate diagnosis: diffuse midline glioma, H3 K27M–mutant.
NOTE: The remainder of this article is therefore largely of historical relevance only.
These tumors typically present in childhood (3 to 10 years of age) and make up 10-15% of all pediatric brain tumors and 20-30% of pediatric posterior fossa tumors.
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 tumor, and signs of raised intracranial pressure. Cerebellar signs may also be elicited including ataxia, dysarthria, nystagmus and sleep apnea.
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 tumors, 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:
- 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 tumor is exophytic, either outwards into the basal cisterns or centrally in the 4th ventricle.
Usually the tumor is homogeneous pre-treatment, however in a minority of patients areas of necrosis may be present.
Typically hypodense with little, if any, enhancement.
- T1: decreased intensity
- T2: heterogeneously increased
- T1 C+ (Gd): usually minimal (can enhance post radiotherapy)
- DWI: usually normal, occasionally mildly restricted
Treatment and prognosis
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.
Radiotherapy is the mainstay of treatment. Initial response may be 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:
- acute demyelinating encephalomyelitis (ADEM)
- neurofibromatosis type I (NF1)
- tuberous sclerosis (TS)
- osmotic demyelination
- Langerhans cell histiocytosis
They should also be distinguished from other tumors:
- 1. Barkovich AJ. Pediatric neuroimaging. Lippincott Williams & Wilkins. (2005) ISBN:0781757665. Read it at Google Books - Find it at Amazon
- 2. Koeller KK, Rushing EJ. From the archives of the AFIP: pilocytic astrocytoma: radiologic-pathologic correlation. Radiographics. 24 (6): 1693-708. doi:10.1148/rg.246045146 - Pubmed citation
- 3. Nelson MD, Soni D, Baram TZ. Necrosis in pontine gliomas: radiation induced or natural history? Radiology. 1994;191 (1): 279-82. Radiology (abstract) - Pubmed citation
- 4. Helton KJ, Phillips NS, Khan RB et-al. Diffusion tensor imaging of tract involvement in children with pontine tumors. AJNR Am J Neuroradiol. 2006;27 (4): 786-93. AJNR Am J Neuroradiol (full text) - Pubmed citation
- 5. Castel D, Philippe C, Calmon R et-al. Histone H3F3A and HIST1H3B K27M mutations define two subgroups of diffuse intrinsic pontine gliomas with different prognosis and phenotypes. Acta Neuropathol. 2015;130 (6): 815-27. doi:10.1007/s00401-015-1478-0 - Free text at pubmed - Pubmed citation
- 6. Louis DN, Perry A, Reifenberger G et-al. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol. 2016;131 (6): 803-20. doi:10.1007/s00401-016-1545-1 - Pubmed citation
- 7. Louis DN, Ohgaki H, Wiestler OD et-al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007;114 (2): 97-109. Acta Neuropathol. (full text) - doi:10.1007/s00401-007-0243-4 - Free text at pubmed - Pubmed citation