Brain Stem Gliomas pathophysiology: Difference between revisions
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{{Brain Stem Gliomas}} | {{Brain Stem Gliomas}} | ||
{{CMG}}{{AE}}{{SR}} | {{CMG}}{{AE}}{{SR}}{{HK}} | ||
==Overview== | ==Overview== | ||
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== | ||
===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> | |||
*'''''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.<ref name="pmid286639932">{{cite journal |vauthors=Uekawa K, Nakamura H, Shinojima N, Takezaki T, Yano S, Kuratsu JI |title=Adult Diffuse Astrocytoma in the Medulla Oblongata: Molecular Biological Analyses Including H3F3A Mutation of Histone H3.3 |journal=NMC Case Rep J |volume=3 |issue=2 |pages=29–33 |date=April 2016 |pmid=28663993 |pmc=5386147 |doi=10.2176/nmccrj.cr.2015-0012 |url=}}</ref> | |||
*'''''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=== | ===Gross pathology=== | ||
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'''<ref name="pmid23293772">{{cite journal |vauthors=Warren KE |title=Diffuse intrinsic pontine glioma: poised for progress |journal=Front Oncol |volume=2 |issue= |pages=205 |date=2012 |pmid=23293772 |pmc=3531714 |doi=10.3389/fonc.2012.00205 |url=}}</ref> | ||
:*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'''<ref name="pmid1822688">{{cite journal |vauthors=Boydston WR, Sanford RA, Muhlbauer MS, Kun LE, Kirk E, Dohan FC, Schweitzer JB |title=Gliomas of the tectum and periaqueductal region of the mesencephalon |journal=Pediatr Neurosurg |volume=17 |issue=5 |pages=234–8 |date=1991 |pmid=1822688 |doi=10.1159/000120603 |url=}}</ref> | ||
**Includes diffuse, focal, exophytic and tectal variants. | **Includes diffuse, focal, exophytic and tectal variants. | ||
**Focal brainstem gliomas are more common here than elsewhere in the brainstem | **Focal brainstem gliomas are more common here than elsewhere in the brainstem | ||
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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=== | |||
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> | |||
=== | |||
The brain stem gliomas are classified into 4 subtypes, and each has its distinct | |||
*'''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'''<ref name="pmid28663993">{{cite journal |vauthors=Uekawa K, Nakamura H, Shinojima N, Takezaki T, Yano S, Kuratsu JI |title=Adult Diffuse Astrocytoma in the Medulla Oblongata: Molecular Biological Analyses Including H3F3A Mutation of Histone H3.3 |journal=NMC Case Rep J |volume=3 |issue=2 |pages=29–33 |date=April 2016 |pmid=28663993 |pmc=5386147 |doi=10.2176/nmccrj.cr.2015-0012 |url=}}</ref> | ||
**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== | ||
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{{WH}} | {{WH}} | ||
{{WS}} | {{WS}} | ||
[[Category:Up-To-Date]] | |||
[[Category:Oncology]] | |||
[[Category:Medicine]] | |||
[[Category:Neurology]] | |||
[[Category:Neurosurgery]] | |||
Latest revision as of 01:38, 21 October 2019
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Brain Stem Gliomas pathophysiology On the Web |
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Risk calculators and risk factors for Brain Stem Gliomas pathophysiology |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Sujit Routray, M.D. [2]Syed Hassan A. Kazmi BSc, MD [3]
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.[2]
- 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[3]
- 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[4]
- 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:[5]
- 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[6]
- 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
- ↑ Uekawa K, Nakamura H, Shinojima N, Takezaki T, Yano S, Kuratsu JI (April 2016). "Adult Diffuse Astrocytoma in the Medulla Oblongata: Molecular Biological Analyses Including H3F3A Mutation of Histone H3.3". NMC Case Rep J. 3 (2): 29–33. doi:10.2176/nmccrj.cr.2015-0012. PMC 5386147. PMID 28663993.
- ↑ Warren KE (2012). "Diffuse intrinsic pontine glioma: poised for progress". Front Oncol. 2: 205. doi:10.3389/fonc.2012.00205. PMC 3531714. PMID 23293772.
- ↑ Boydston WR, Sanford RA, Muhlbauer MS, Kun LE, Kirk E, Dohan FC, Schweitzer JB (1991). "Gliomas of the tectum and periaqueductal region of the mesencephalon". Pediatr Neurosurg. 17 (5): 234–8. doi:10.1159/000120603. PMID 1822688.
- ↑ Pathophysiology of Brainstem gliomas. Dr Yuranga Weerakkody and Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/brainstem-glioma
- ↑ Uekawa K, Nakamura H, Shinojima N, Takezaki T, Yano S, Kuratsu JI (April 2016). "Adult Diffuse Astrocytoma in the Medulla Oblongata: Molecular Biological Analyses Including H3F3A Mutation of Histone H3.3". NMC Case Rep J. 3 (2): 29–33. doi:10.2176/nmccrj.cr.2015-0012. PMC 5386147. PMID 28663993.