Brain Stem Gliomas pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Sujit Routray, M.D. [2]
Overview
On gross pathology, brainstem gliomas can be classified into four subtypes: diffuse, focal, dorsal exophytic and cervicomedullary. Each of the four subtypes has its distinct microscopic pathology. Genes involved in the pathogenesis of diffuse intrinsic pontine gliomas include histone h3, acvr1, pdgfra, and tp53.
Pathophysiology
Cytogenetic Characteristics of Diffuse Intrinsic Pontine Gliomas (DIPGs)
The genomic characteristics of DIPGs appear to differ from those of most other pediatric high-grade gliomas and from those of adult high-grade gliomas. The gene expression profile of DIPG differs from that of non–brain stem pediatric high-grade gliomas, further supporting a distinctive biology for this subset of pediatric gliomas. A number of chromosomal and genomic abnormalities have been reported for DIPG, including the following:[1]
- Histone H3 genes: Approximately 80% of DIPG tumors have a mutation in a specific amino acid in the histone H3.1 (H3F3A) or H3.3 (HIST1H3B) genes. These same mutations are observed in pediatric high-grade gliomas at other midline locations but are uncommon in cortical pediatric high-grade gliomas and in adult high-grade gliomas.
- Activin A receptor, type I (ACVR1) gene: Approximately 20% of DIPG cases have activating mutations in the ACVR1 gene, with most occurring concurrently with H3.3 mutations. Germline mutations in ACVR1 cause the autosomal dominant syndrome fibrodysplasia ossificans progressiva (FOP), although there is no cancer predisposition in FOP.
- Receptor tyrosine kinase amplification: PDGFRA amplification occurs in approximately 30% of cases, with lower rates of amplification observed for some other receptor tyrosine kinases (e.g., MET and IGF1R).
- TP53 deletion: DIPG tumors commonly show deletion of the TP53 gene on chromosome 17p. Additionally, TP53 is commonly mutated in DIPG tumors, particularly those with histone H3 gene mutations. Aneuploidy is commonly observed in cases with TP53 mutations.
Gross pathology
Brain stem gliomas may occur in the pons, midbrain, tectum, dorsum of the medulla at the cervicomedullary junction, or in multiple regions of the brain stem. As a general rule, mesencephalic tumors tend to be of a lower grade than those in the pons and medulla.
- Pontine
- Most common location
- Classic location for the childhood 'brainstem glioma' which tends to refer to a diffuse pontine glioma
- Focal dorsally exophytic brainstem glioma is an uncommon variant accounting for only 10% of pontine tumours, and has a much better prognosis, as it usually represents a pilocytic astrocytoma
- Overall survival of pontine gliomas is 10% at 5 years
- Mesencephalic
- Includes diffuse, focal, exophytic and tectal variants.
- Focal brainstem gliomas are more common here than elsewhere in the brainstem
- Tectal plate gliomas are typically indolent
- Medullary
- Least common location
- Includes focal dorsally exophytic, focal, diffuse and cervicomedullary junction variants
- Cervicomedullary junction tumours usually represent upper cervical tumours extending superiorly
- Most common location for NF1-associated tumors
Microscopic pathology
The brain stem gliomas are classified into 4 subtypes, and each has its distinct histological features:[2]
- Diffuse brainstem gliomas
- Also called as diffuse intrinsic pontine gliomas (DIPGs)
- Usually fibrillary astrocytomas
- WHO grades II-IV
- Grade does not impact on prognosis, and thus biopsy is usually not necessary
- 75% of brain stem gliomas
- Focal glioma
- Fibrillary astrocytoma (grade II): most common histology
- Pilocytic astrocytoma
- Ganglioglioma
- (Dorsally) exophytic glioma
- Low grade astrocytoma
- Ganglioglioma
- NF1-associated brainstem glioma
- Seen in up to 9% of NF1 patients
- Most frequently seen in the medulla
- Appears similar to a sporadic focal brainstem glioma but has an even better prognosis, with little if any progression
References
- ↑ Pathophysiology of brainstem gliomas. NIH National cancer institute. http://www.cancer.gov/types/brain/hp/child-glioma-treatment-pdq#section/_35
- ↑ Pathophysiology of Brainstem gliomas. Dr Yuranga Weerakkody and Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/brainstem-glioma