Brain Stem Gliomas pathophysiology: Difference between revisions
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==Overview== | ==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 | Brainstem gliomas may arise from [[glial cells]] of the [[brainstem]], a majority of these [[tumors]] are found in the [[pons]]. Other areas include [[Midbrain tectum|tectal area]] and [[medulla]]. Genetic mutations in [[Histone gene|histone genes]], activin A receptor gene, [[Tyrosine kinase|tyrosine kinase mutations]] and [[TP53|TP53 mutations]] have been implicated in the development of brain stem gliomas. 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 [[Histopathology|microscopic pathology]]. | ||
==Pathophysiology== | ==Pathophysiology== | ||
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===Cytogenetic Characteristics of Diffuse Intrinsic Pontine Gliomas (DIPGs)=== | ===Cytogenetic Characteristics of Diffuse Intrinsic Pontine Gliomas (DIPGs)=== | ||
Diffuse brainstem gliomas also known as diffuse intrinsic pontine gliomas (DIPGs) as the name suggests are predominantly present in the pons. DIPGs exhibit [[Genotype|genotypic]] modifications that differ from other high grade gliomas, both adult and pediatric. The gene expression profile of DIPG also varies from that of non–brain stem pediatric high-grade gliomas, further supporting a distinctive biology for this subset of pediatric gliomas. DIPG patirents may have the following genomic abnormalities:<ref>Pathophysiology of brainstem gliomas. NIH National cancer institute. http://www.cancer.gov/types/brain/hp/child-glioma-treatment-pdq#section/_35</ref> | Diffuse brainstem gliomas also known as diffuse intrinsic pontine gliomas (DIPGs) as the name suggests are predominantly present in the pons. DIPGs exhibit [[Genotype|genotypic]] modifications that differ from other high grade gliomas, both adult and pediatric. The gene expression profile of DIPG also varies from that of non–brain stem pediatric high-grade gliomas, further supporting a distinctive biology for this subset of pediatric gliomas. DIPG patirents may have the following genomic abnormalities:<ref>Pathophysiology of brainstem gliomas. NIH National cancer institute. http://www.cancer.gov/types/brain/hp/child-glioma-treatment-pdq#section/_35</ref> | ||
*'''''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. | *'''''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. | *'''''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''). | *'''''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''). | ||
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===Gross pathology=== | ===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. | Brain stem gliomas may occur in the ''[[pons]]'', ''[[midbrain]]'', ''[[Midbrain tectum|tectum]]'', ''[[Dorsum (biology)|dorsum]] of the [[medulla]] at the [[Cervicomedullary glioma|cervicomedullary junction]]'', or in multiple regions of the brain stem. As a general rule, [[Mesencephalic duct|mesencephalic]] tumors tend to be of a ''lower grade'' than those in the [[pons]] and [[medulla]]. | ||
*'''Pontine''' | *'''Pontine''' | ||
:*Most common location | :*Most common location | ||
:*Classic location for the childhood 'brainstem glioma' which tends to refer to a diffuse pontine glioma | :*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 | :*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 | :*Overall survival of pontine gliomas is 10% at 5 years | ||
*'''Mesencephalic''' | *'''Mesencephalic''' | ||
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**Least common location | **Least common location | ||
**Includes focal dorsally exophytic, focal, diffuse and cervicomedullary junction variants | **Includes focal dorsally exophytic, focal, diffuse and cervicomedullary junction variants | ||
**Cervicomedullary junction tumours usually represent upper cervical tumours extending superiorly | **[[Cervicomedullary glioma|Cervicomedullary]] junction tumours usually represent upper cervical tumours extending superiorly | ||
**Most common location for '''NF1-associated tumors''' | **Most common location for '''NF1-associated tumors''' | ||
===Microscopic pathology=== | ===Microscopic pathology=== | ||
The brain stem gliomas are classified into 4 subtypes, and each has its distinct | The brain stem gliomas are classified into 4 subtypes, and each has its distinct [[histological]] features:<ref>Pathophysiology of Brainstem gliomas. Dr Yuranga Weerakkody and Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/brainstem-glioma</ref> | ||
*'''Diffuse brainstem gliomas''' | *'''Diffuse brainstem gliomas''' | ||
**Also called as diffuse intrinsic pontine gliomas (DIPGs) | **Also called as diffuse intrinsic pontine gliomas (DIPGs) | ||
**Usually fibrillary astrocytomas | **Usually [[fibrillary astrocytomas]] | ||
**''WHO grades II-IV'' | **''WHO grades II-IV'' | ||
**Grade does '''not''' impact on prognosis, and thus biopsy is usually not necessary | **Grade does '''not''' impact on [[prognosis]], and thus biopsy is usually not necessary | ||
**75% of brain stem gliomas | **75% of brain stem gliomas | ||
*'''Focal glioma''' | *'''Focal glioma''' | ||
**Fibrillary astrocytoma (grade II): ''most common histology'' | **[[Fibrillary astrocytomas|Fibrillary astrocytoma]] (grade II): ''most common histology'' | ||
**Pilocytic astrocytoma | **[[Pilocytic astrocytoma]] | ||
**Ganglioglioma | **[[Ganglioglioma]] | ||
*'''(Dorsally) exophytic glioma''' | *'''(Dorsally) exophytic glioma''' | ||
**Low grade astrocytoma | **[[Low grade astrocytoma]] | ||
**Ganglioglioma | **[[Ganglioglioma]] | ||
*'''NF1-associated brainstem glioma''' | *'''NF1-associated brainstem glioma''' | ||
**Seen in up to 9% of | **Seen in up to 9% of [[Neurofibromatosis type I|neurofibromatosis-1]] (NF-1) patients | ||
**Most frequently seen in the medulla | **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 | **Appears similar to a sporadic focal brainstem glioma but has an even better [[prognosis]], with little if any progression | ||
==References== | ==References== | ||
Revision as of 01:33, 21 October 2019
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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
Brainstem gliomas may arise from glial cells of the brainstem, a majority of these tumors are found in the pons. Other areas include tectal area and medulla. Genetic mutations in histone genes, activin A receptor gene, tyrosine kinase mutations and TP53 mutations have been implicated in the development of brain stem gliomas. 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.
Pathophysiology
Cytogenetic Characteristics of Diffuse Intrinsic Pontine Gliomas (DIPGs)
Diffuse brainstem gliomas also known as diffuse intrinsic pontine gliomas (DIPGs) as the name suggests are predominantly present in the pons. DIPGs exhibit genotypic modifications that differ from other high grade gliomas, both adult and pediatric. The gene expression profile of DIPG also varies from that of non–brain stem pediatric high-grade gliomas, further supporting a distinctive biology for this subset of pediatric gliomas. DIPG patirents may have the following genomic abnormalities:[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
- NF1-associated brainstem glioma
- Seen in up to 9% of neurofibromatosis-1 (NF-1) 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