Medulloblastoma pathophysiology: Difference between revisions
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==Overview== | ==Overview== | ||
Medulloblastoma arises from the cerebellar [[stem cell]]s, which are normally involved in the anatomical development of the [[cerebellum]] and posterior cranial fossa structures. Medulloblastoma is an invasive and rapidly growing [[brain]] [[tumor]] which may metastasize to different organs of the body. [[Genes]] involved in the pathogenesis of medulloblastoma include ''CTNNB1'' [[gene]], ''PTCH1'' gene, ''MLL2'' gene, ''SMARCA4'' gene, ''DDX3X'' gene, ''CTDNEP1'' gene, ''KDM6A'' gene, and ''TBR1'' gene. Medullobastomas are associated with a number of syndromes that include [[Gorlin syndrome]] and [[Turcot syndrome]].<ref name="wiki"> Medulloblastoma. Wikipedia(2015) https://en.wikipedia.org/wiki/Medulloblastoma Accessed on September, 28 2015</ref> On gross pathology, a pink, solid, and well circumscribed mass is a characteristic finding of medulloblastoma. On microscopic histopathological analysis, round tumor cells, elevated [[mitotic]] rate, increased [[nucleus]]:[[cytoplasmic]] ratio, and Homer-Wright rosettes are characteristic findings of medulloblastoma.<ref name="patho">Medulloblastoma. Libre Pathology (2015) http://librepathology.org/wiki/index.php/Medulloblastoma Accessed on September, 28 2015</ref> | Medulloblastoma arises from the cerebellar [[stem cell]]s, which are normally involved in the anatomical development of the [[cerebellum]] and posterior cranial fossa structures. Medulloblastoma is an invasive and rapidly growing [[brain]] [[tumor]] which may metastasize to different organs of the body. [[Genes]] involved in the pathogenesis of medulloblastoma include ''CTNNB1'' [[gene]], ''PTCH1'' gene, ''MLL2'' gene, ''SMARCA4'' gene, ''DDX3X'' gene, ''CTDNEP1'' gene, ''KDM6A'' gene, and ''TBR1'' gene. Medullobastomas are associated with a number of syndromes that include [[Gorlin syndrome]] and [[Turcot syndrome]].<ref name="wiki">Medulloblastoma. Wikipedia(2015) https://en.wikipedia.org/wiki/Medulloblastoma Accessed on September, 28 2015</ref> On gross pathology, a pink, solid, and well circumscribed mass is a characteristic finding of medulloblastoma. On microscopic histopathological analysis, round tumor cells, elevated [[mitotic]] rate, increased [[nucleus]]:[[cytoplasmic]] ratio, and Homer-Wright rosettes are characteristic findings of medulloblastoma.<ref name="patho">Medulloblastoma. Libre Pathology (2015) http://librepathology.org/wiki/index.php/Medulloblastoma Accessed on September, 28 2015</ref> | ||
==Pathogenesis== | ==Pathogenesis== | ||
* Medulloblastoma arises from the cerebellar [[stem cell]]s, which are normally involved in the anatomical development of the [[cerebellum]] and [[posterior cranial fossa]] structures.<ref name="wiki"> Medulloblastoma. Wikipedia(2015) https://en.wikipedia.org/wiki/Medulloblastoma Accessed on September 2015</ref><ref name="pmid8515724">{{cite journal |vauthors=Evans G, Burnell L, Campbell R, Gattamaneni HR, Birch J |title=Congenital anomalies and genetic syndromes in 173 cases of medulloblastoma |journal=Med. Pediatr. Oncol. |volume=21 |issue=6 |pages=433–4 |date=1993 |pmid=8515724 |doi= |url=}}</ref> | * Medulloblastoma arises from the cerebellar [[stem cell]]s, which are normally involved in the anatomical development of the [[cerebellum]] and [[posterior cranial fossa]] structures.<ref name="wiki">Medulloblastoma. Wikipedia(2015) https://en.wikipedia.org/wiki/Medulloblastoma Accessed on September 2015</ref><ref name="pmid8515724">{{cite journal |vauthors=Evans G, Burnell L, Campbell R, Gattamaneni HR, Birch J |title=Congenital anomalies and genetic syndromes in 173 cases of medulloblastoma |journal=Med. Pediatr. Oncol. |volume=21 |issue=6 |pages=433–4 |date=1993 |pmid=8515724 |doi= |url=}}</ref> | ||
* Medulloblastoma is usually located at the [[infratentorial]] region, where it forms a mass between the [[brain stem]] and the cerebellum in the vicinity of the [[fourth ventricle]]. | * Medulloblastoma is usually located at the [[infratentorial]] region, where it forms a mass between the [[brain stem]] and the cerebellum in the vicinity of the [[fourth ventricle]]. | ||
* Medulloblastoma is an invasive and rapidly growing [[brain]] [[tumor]]. | * Medulloblastoma is an invasive and rapidly growing [[brain]] [[tumor]]. | ||
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==Associated Conditions== | ==Associated Conditions== | ||
*Medulloblastoma is associated with a number of syndromes that include:<ref name="wiki"> Medulloblastoma. Wikipedia(2015) https://en.wikipedia.org/wiki/Medulloblastoma Accessed on September, 28 2015</ref><ref name="radio">Medulloblastoma. Radiopaedia(2015) http://radiopaedia.org/articles/medulloblastoma Accessed on September, 28 2015</ref> | *Medulloblastoma is associated with a number of syndromes that include:<ref name="wiki">Medulloblastoma. Wikipedia(2015) https://en.wikipedia.org/wiki/Medulloblastoma Accessed on September, 28 2015</ref><ref name="radio">Medulloblastoma. Radiopaedia(2015) http://radiopaedia.org/articles/medulloblastoma Accessed on September, 28 2015</ref> | ||
:* [[Gorlin syndrome]]<ref name="pmid1931625">{{cite journal |vauthors=Evans DG, Farndon PA, Burnell LD, Gattamaneni HR, Birch JM |title=The incidence of Gorlin syndrome in 173 consecutive cases of medulloblastoma |journal=Br. J. Cancer |volume=64 |issue=5 |pages=959–61 |date=November 1991 |pmid=1931625 |pmc=1977448 |doi= |url=}}</ref> | :* [[Gorlin syndrome]]<ref name="pmid1931625">{{cite journal |vauthors=Evans DG, Farndon PA, Burnell LD, Gattamaneni HR, Birch JM |title=The incidence of Gorlin syndrome in 173 consecutive cases of medulloblastoma |journal=Br. J. Cancer |volume=64 |issue=5 |pages=959–61 |date=November 1991 |pmid=1931625 |pmc=1977448 |doi= |url=}}</ref> | ||
:* [[Turcot syndrome]] | :* [[Turcot syndrome]] | ||
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* On gross pathology, a pink, solid, and well circumscribed mass is a characteristic finding of medulloblastoma.<ref name="wiki">Medulloblastoma. Wikipedia(2015) https://en.wikipedia.org/wiki/Medulloblastoma Accessed on September, 29th 2015</ref> | * On gross pathology, a pink, solid, and well circumscribed mass is a characteristic finding of medulloblastoma.<ref name="wiki">Medulloblastoma. Wikipedia(2015) https://en.wikipedia.org/wiki/Medulloblastoma Accessed on September, 29th 2015</ref> | ||
* The following image demonstrates the gross pathology observed in medulloblastoma: | * The following image demonstrates the gross pathology observed in medulloblastoma: | ||
==Microscopic Pathology== | ==Microscopic Pathology== | ||
* On microscopic histopathological analysis, round [[tumor]] cells, elevated [[mitotic]] rate, increased [[nucleus]]:[[cytoplasm]] ratio, and Homer-Wright rosettes are characteristic findings of medulloblastoma.<ref name="patho">Medulloblastoma. Librepathology(2015) http://librepathology.org/wiki/index.php/Medulloblastoma Accessed on September, 28th 2015</ref><ref name="pmid10064395">{{cite journal |vauthors=McLendon RE, Friedman HS, Fuchs HE, Kun LE, Bigner SH |title=Diagnostic markers in paediatric medulloblastoma: a Paediatric Oncology Group Study |journal=Histopathology |volume=34 |issue=2 |pages=154–62 |date=February 1999 |pmid=10064395 |doi= |url=}}</ref> | * On microscopic histopathological analysis, round [[tumor]] cells, elevated [[mitotic]] rate, increased [[nucleus]]:[[cytoplasm]] ratio, and Homer-Wright rosettes are characteristic findings of medulloblastoma.<ref name="patho">Medulloblastoma. Librepathology(2015) http://librepathology.org/wiki/index.php/Medulloblastoma Accessed on September, 28th 2015</ref><ref name="pmid10064395">{{cite journal |vauthors=McLendon RE, Friedman HS, Fuchs HE, Kun LE, Bigner SH |title=Diagnostic markers in paediatric medulloblastoma: a Paediatric Oncology Group Study |journal=Histopathology |volume=34 |issue=2 |pages=154–62 |date=February 1999 |pmid=10064395 |doi= |url=}}</ref> | ||
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Revision as of 14:07, 26 May 2019
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Medulloblastoma Microchapters |
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Medulloblastoma pathophysiology On the Web |
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American Roentgen Ray Society Images of Medulloblastoma pathophysiology |
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Risk calculators and risk factors for Medulloblastoma pathophysiology |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Haytham Allaham, M.D. [2] Associate Editor(s)-in-Chief: Syed Musadiq Ali M.B.B.S.[3]
Overview
Medulloblastoma arises from the cerebellar stem cells, which are normally involved in the anatomical development of the cerebellum and posterior cranial fossa structures. Medulloblastoma is an invasive and rapidly growing brain tumor which may metastasize to different organs of the body. Genes involved in the pathogenesis of medulloblastoma include CTNNB1 gene, PTCH1 gene, MLL2 gene, SMARCA4 gene, DDX3X gene, CTDNEP1 gene, KDM6A gene, and TBR1 gene. Medullobastomas are associated with a number of syndromes that include Gorlin syndrome and Turcot syndrome.[1] On gross pathology, a pink, solid, and well circumscribed mass is a characteristic finding of medulloblastoma. On microscopic histopathological analysis, round tumor cells, elevated mitotic rate, increased nucleus:cytoplasmic ratio, and Homer-Wright rosettes are characteristic findings of medulloblastoma.[2]
Pathogenesis
- Medulloblastoma arises from the cerebellar stem cells, which are normally involved in the anatomical development of the cerebellum and posterior cranial fossa structures.[1][3]
- Medulloblastoma is usually located at the infratentorial region, where it forms a mass between the brain stem and the cerebellum in the vicinity of the fourth ventricle.
- Medulloblastoma is an invasive and rapidly growing brain tumor.
- Unlike most brain tumors, medulloblastoma may spread through the cerebrospinal fluid and metastasize to different organs of the body.
Genetics
- Development of medulloblastoma is the result of multiple genetic mutations.[1][4][5][6]
- Genes involved in the pathogenesis of medulloblastoma include:
- CTNNB1 gene on chromosome 3
- PTCH1 gene located on chromosome 9
- MLL2 gene located on chromosome 12
- SMARCA4 gene located on chromosome 19
- DDX3X gene located on X chromosome
- CTDNEP1 gene located on chromosome 17
- KDM6A gene located on X chromosome
- TBR1 gene located on chromosome 2
- Medulloblastoma may be classified into at least four major subtypes based on a molecular classification system which includes:[7][8][9]
- WNT subgroup:
- Present among 10% of medulloblastoma patients
- Cytogenetic markers include classic monosomy 6
- Molecular markers include beta-catenin
- SHH subgroup:
- Present among 25% of medulloblastoma patients
- Cytogenetic markers include chromosome 9q deletion
- Molecular markers include SFRP1 or GAB1
- Group 3:
- Present among 30% of medulloblastoma patients
- Cytogenetic markers include isochromosome 17q
- Molecular markers include MYC activation
- Group 4:
- Present among 35% of medulloblastoma patients
- Cytogenetic markers include isochromosome 17q
- Molecular markers are still under investigation
Associated Conditions
Gross Pathology
- On gross pathology, a pink, solid, and well circumscribed mass is a characteristic finding of medulloblastoma.[1]
- The following image demonstrates the gross pathology observed in medulloblastoma:
Microscopic Pathology
- On microscopic histopathological analysis, round tumor cells, elevated mitotic rate, increased nucleus:cytoplasm ratio, and Homer-Wright rosettes are characteristic findings of medulloblastoma.[2][12]
- Medulloblastoma may be classified into two subtypes based on WHO histological classification system which include classic medulloblastoma and variant medulloblastoma.
- Variant medulloblastoma may be further classified into desmoplastic medulloblastoma, large cell medulloblastoma, anaplastic medulloblastoma, and medulloblastoma with extensive nodularity.[2][10]
- The table below differentiates between the five main groups of medulloblastoma according to the WHO histological classification system:[13]
| Grade | Histologic features |
|---|---|
|
Classic medulloblastoma |
|
|
Desmoplastic medulloblastoma variant |
|
|
Medulloblastoma with extensive nodularity variant |
|
|
Large cell / anaplastic medulloblastoma variant |
|
- Shown below is a series of microscopic images observed in medulloblastoma:
-
![Medulloblastoma [2]](/images/b/b9/Cerebellar_medulloblastoma_%281%29_in_adult.JPG)
Medulloblastoma [2] -
![Medulloblastoma[2]](/images/a/a8/Cerebellar_medulloblastoma_%282%29_in_adult.JPG)
Medulloblastoma[2] -
![Medulloblastoma demonstrating Homer-Wright rosettes[2]](/images/b/bc/Medulloblastoma_with_rosettes.jpg)
Medulloblastoma demonstrating Homer-Wright rosettes[2] -
![Medulloblastoma demonstrating cerebellar infiltrative growth[2]](/images/8/8c/Medulloblastoma_stratum_moleculare_x40_%281%29.jpg)
Medulloblastoma demonstrating cerebellar infiltrative growth[2] -
![Medulloblastoma demonstrating demsomplastic nodular growth[2]](/images/6/6e/Desmoplastic_nodular_medulloblastoma.jpg)
-
![Anaplastic large cell medulloblastoma[2]](/images/c/ce/Anaplastic_medulloblastoma_x200.jpg)
Anaplastic large cell medulloblastoma[2] -
![Medulloblastoma[2]](/images/e/ef/AFIP405820M-MEDULLOBLASTOMA.jpg)
Medulloblastoma[2] -
![Desmoplastic medulloblastoma on reticulin stain demonstrating pale islands structure[2]](/images/0/02/Desmoplastic_medulloblastoma_reticulin_stain_pale_island.jpg)
-
![Desmoplastic medulloblastoma on MIB-1 immunostaining[2]](/images/6/68/Desmoplastic_medulloblastom_MIB1_proliferation.jpg)
Desmoplastic medulloblastoma on MIB-1 immunostaining[2] -
![Medulloblastoma demonstrating areas of geographic necrosis[2]](/images/d/dd/Medulloblastoma_Areas_of_geographic_necrosis.jpg)
-
![Medulloblastoma demonstrating epitheloid ribboning and nuclear moulding of tumor cells[2]](/images/5/5e/Medulloblastoma_nuclear_moulding_HE_stain.jpg)
-
![Medulloblastoma demonstrating partial MAP2 immunoreactivity[2]](/images/d/db/Medulloblastoma_MAP2_IHC.jpg)
Medulloblastoma demonstrating partial MAP2 immunoreactivity[2]
![Medulloblastoma [2]](/index.php/File:Cerebellar_medulloblastoma_(1)_in_adult.JPG)
![Medulloblastoma[2]](/index.php/File:Cerebellar_medulloblastoma_(2)_in_adult.JPG)
![Medulloblastoma demonstrating Homer-Wright rosettes[2]](/index.php/File:Medulloblastoma_with_rosettes.jpg)
![Medulloblastoma demonstrating cerebellar infiltrative growth[2]](/index.php/File:Medulloblastoma_stratum_moleculare_x40_(1).jpg)
![Medulloblastoma demonstrating demsomplastic nodular growth[2]](/index.php/File:Desmoplastic_nodular_medulloblastoma.jpg)
![Anaplastic large cell medulloblastoma[2]](/index.php/File:Anaplastic_medulloblastoma_x200.jpg)
![Medulloblastoma[2]](/index.php/File:AFIP405820M-MEDULLOBLASTOMA.jpg)
![Desmoplastic medulloblastoma on reticulin stain demonstrating pale islands structure[2]](/index.php/File:Desmoplastic_medulloblastoma_reticulin_stain_pale_island.jpg)
![Desmoplastic medulloblastoma on MIB-1 immunostaining[2]](/index.php/File:Desmoplastic_medulloblastom_MIB1_proliferation.jpg)
![Medulloblastoma demonstrating areas of geographic necrosis[2]](/index.php/File:Medulloblastoma_Areas_of_geographic_necrosis.jpg)
![Medulloblastoma demonstrating epitheloid ribboning and nuclear moulding of tumor cells[2]](/index.php/File:Medulloblastoma_nuclear_moulding_HE_stain.jpg)
![Medulloblastoma demonstrating partial MAP2 immunoreactivity[2]](/index.php/File:Medulloblastoma_MAP2_IHC.jpg)
References
- ↑ 1.0 1.1 1.2 1.3 1.4 Medulloblastoma. Wikipedia(2015) https://en.wikipedia.org/wiki/Medulloblastoma Accessed on September, 28 2015
- ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.14 Medulloblastoma. Libre Pathology (2015) http://librepathology.org/wiki/index.php/Medulloblastoma Accessed on September, 28 2015
- ↑ Evans G, Burnell L, Campbell R, Gattamaneni HR, Birch J (1993). "Congenital anomalies and genetic syndromes in 173 cases of medulloblastoma". Med. Pediatr. Oncol. 21 (6): 433–4. PMID 8515724.
- ↑ Kozmik Z, Sure U, Rüedi D, Busslinger M, Aguzzi A (June 1995). "Deregulated expression of PAX5 in medulloblastoma". Proc. Natl. Acad. Sci. U.S.A. 92 (12): 5709–13. doi:10.1073/pnas.92.12.5709. PMC 41766. PMID 7777574.
- ↑ Yokota N, Aruga J, Takai S, Yamada K, Hamazaki M, Iwase T, Sugimura H, Mikoshiba K (January 1996). "Predominant expression of human zic in cerebellar granule cell lineage and medulloblastoma". Cancer Res. 56 (2): 377–83. PMID 8542595.
- ↑ Katsetos CD, Liu HM, Zacks SI (October 1988). "Immunohistochemical and ultrastructural observations on Homer Wright (neuroblastic) rosettes and the "pale islands" of human cerebellar medulloblastomas". Hum. Pathol. 19 (10): 1219–27. PMID 3139544.
- ↑ Northcott PA, Shih DJ, Peacock J, Garzia L, Morrissy AS, Zichner T; et al. (2012). "Subgroup-specific structural variation across 1,000 medulloblastoma genomes". Nature. 488 (7409): 49–56. doi:10.1038/nature11327. PMC 3683624. PMID 22832581.
- ↑ Leary SE, Olson JM (2012) The molecular classification of medulloblastoma: driving the next generation clinical trials. Curr Opin Pediatr 24 (1):33-9. DOI:10.1097/MOP.0b013e32834ec106 PMID: 22189395
- ↑ Sure U, Berghorn WJ, Bertalanffy H, Wakabayashi T, Yoshida J, Sugita K, Seeger W (1995). "Staging, scoring and grading of medulloblastoma. A postoperative prognosis predicting system based on the cases of a single institute". Acta Neurochir (Wien). 132 (1–3): 59–65. PMID 7754860.
- ↑ 10.0 10.1 Medulloblastoma. Radiopaedia(2015) http://radiopaedia.org/articles/medulloblastoma Accessed on September, 28 2015
- ↑ Evans DG, Farndon PA, Burnell LD, Gattamaneni HR, Birch JM (November 1991). "The incidence of Gorlin syndrome in 173 consecutive cases of medulloblastoma". Br. J. Cancer. 64 (5): 959–61. PMC 1977448. PMID 1931625.
- ↑ McLendon RE, Friedman HS, Fuchs HE, Kun LE, Bigner SH (February 1999). "Diagnostic markers in paediatric medulloblastoma: a Paediatric Oncology Group Study". Histopathology. 34 (2): 154–62. PMID 10064395.
- ↑ Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A; et al. (2007). "The 2007 WHO classification of tumours of the central nervous system". Acta Neuropathol. 114 (2): 97–109. doi:10.1007/s00401-007-0243-4. PMC 1929165. PMID 17618441.