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__NOTOC__
__NOTOC__
{{Medulloblastoma}}
{{Medulloblastoma}}
{{CMG}} {{AE}}{{HL}}
{{CMG}} {{AE}}{{HL}} {{AE}}{{sali}}
 
==Overview==
==Overview==
Medulloblastoma arises from the cerebellar [[stem cell]]s, which are normally involved in the anatomical development of the [[cerebellum]] and other posterior fossa structures. Medulloblastoma is an invasive and rapidly growing [[tumor]] which frequently 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 is 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 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:cytoplasm ratio, and presence of 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>
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 other posterior fossa structures.<ref name="wiki"> Medulloblastoma. Wikipedia(2015) https://en.wikipedia.org/wiki/Medulloblastoma Accessed on September 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.<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]].<ref name="wiki"> Medulloblastoma. Wikipedia(2015) https://en.wikipedia.org/wiki/Medulloblastoma Accessed on September 2015</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 an invasive and rapidly growing [[tumor]].<ref name="wiki"> Medulloblastoma. Wikipedia(2015) https://en.wikipedia.org/wiki/Medulloblastoma Accessed on September 2015</ref>
* 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.<ref name="wiki"> Medulloblastoma. Wikipedia(2015) https://en.wikipedia.org/wiki/Medulloblastoma Accessed on September 2015</ref>
* Unlike most brain tumors, medulloblastoma may spread through the [[cerebrospinal fluid]] and metastasize to different organs of the body.


==Genetics==
==Genetics==
* Development of medulloblastoma is the result of multiple [[genetic mutation]]s.<ref name="wiki">Medulloblastoma. Wikipedia(2015) https://en.wikipedia.org/wiki/Medulloblastoma Accessed on September, 29th 2015</ref>
* Development of medulloblastoma is the result of multiple [[genetic mutation]]s.<ref name="wiki">Medulloblastoma. Wikipedia(2015) https://en.wikipedia.org/wiki/Medulloblastoma Accessed on September, 29 2015</ref><ref name="pmid7777574">{{cite journal |vauthors=Kozmik Z, Sure U, Rüedi D, Busslinger M, Aguzzi A |title=Deregulated expression of PAX5 in medulloblastoma |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=92 |issue=12 |pages=5709–13 |date=June 1995 |pmid=7777574 |pmc=41766 |doi=10.1073/pnas.92.12.5709 |url=}}</ref><ref name="pmid8542595">{{cite journal |vauthors=Yokota N, Aruga J, Takai S, Yamada K, Hamazaki M, Iwase T, Sugimura H, Mikoshiba K |title=Predominant expression of human zic in cerebellar granule cell lineage and medulloblastoma |journal=Cancer Res. |volume=56 |issue=2 |pages=377–83 |date=January 1996 |pmid=8542595 |doi= |url=}}</ref><ref name="pmid3139544">{{cite journal |vauthors=Katsetos CD, Liu HM, Zacks SI |title=Immunohistochemical and ultrastructural observations on Homer Wright (neuroblastic) rosettes and the "pale islands" of human cerebellar medulloblastomas |journal=Hum. Pathol. |volume=19 |issue=10 |pages=1219–27 |date=October 1988 |pmid=3139544 |doi= |url=}}</ref>
* [[Genes]] involved in the pathogenesis of medulloblastoma include:<ref name="wiki">Medulloblastoma. Wikipedia(2015) https://en.wikipedia.org/wiki/Medulloblastoma Accessed on September, 29th 2015</ref>
* [[Gene]]s involved in the pathogenesis of medulloblastoma include:
:* ''CTNNB1'' gene on [[chromosome 3]]
:* ''CTNNB1'' gene on [[chromosome 3]]
:* ''PTCH1'' gene located on [[chromosome 9]]
:* ''PTCH1'' gene located on [[chromosome 9]]
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:* ''DDX3X'' gene located on [[X chromosome]]
:* ''DDX3X'' gene located on [[X chromosome]]
:* ''CTDNEP1'' gene located on [[chromosome 17]]
:* ''CTDNEP1'' gene located on [[chromosome 17]]
:* ''KDM6A'' gene located on X chromosome
:* ''KDM6A'' gene located on [[X chromosome]]
:* ''TBR1'' gene located on [[chromosome 2]]
:* ''TBR1'' gene located on [[chromosome 2]]
* Molecular subtypes of medulloblastoma include:<ref name="pmid22189395">Leary SE, Olson JM (2012) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=22189395 The molecular classification of medulloblastoma: driving the next generation clinical trials.] ''Curr Opin Pediatr'' 24 (1):33-9. [http://dx.doi.org/10.1097/MOP.0b013e32834ec106 DOI:10.1097/MOP.0b013e32834ec106] PMID: [http://pubmed.gov/22189395 22189395]</ref>
* Medulloblastoma may be classified into at least four major subtypes based on a molecular classification system which includes:<ref name="pmid22832581">{{cite journal| author=Northcott PA, Shih DJ, Peacock J, Garzia L, Morrissy AS, Zichner T et al.| title=Subgroup-specific structural variation across 1,000 medulloblastoma genomes. | journal=Nature | year= 2012 | volume= 488 | issue= 7409 | pages= 49-56 | pmid=22832581 | doi=10.1038/nature11327 | pmc=PMC3683624 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22832581  }} </ref><ref name="pmid22189395">Leary SE, Olson JM (2012) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=22189395 The molecular classification of medulloblastoma: driving the next generation clinical trials.] ''Curr Opin Pediatr'' 24 (1):33-9. [http://dx.doi.org/10.1097/MOP.0b013e32834ec106 DOI:10.1097/MOP.0b013e32834ec106] PMID: [http://pubmed.gov/22189395 22189395]</ref><ref name="pmid7754860">{{cite journal |vauthors=Sure U, Berghorn WJ, Bertalanffy H, Wakabayashi T, Yoshida J, Sugita K, Seeger W |title=Staging, scoring and grading of medulloblastoma. A postoperative prognosis predicting system based on the cases of a single institute |journal=Acta Neurochir (Wien) |volume=132 |issue=1-3 |pages=59–65 |date=1995 |pmid=7754860 |doi= |url=}}</ref>
:* WNT subgroup:
:* '''WNT subgroup:'''
::* Present among 10% of medulloblastoma patients
::* Present among 10% of medulloblastoma patients
::* Present among older children
::* Cytogenetic markers include classic [[monosomy]] 6
::* Cytogenetic markers include classic [[monosomy]] 6
::* Molecular markers include [[Beta-catenin]]
::* Molecular markers include [[beta-catenin]]
:* SHH subgroup:
:* '''SHH subgroup:'''
::* Present among 25% of medulloblastoma patients
::* Present among 25% of medulloblastoma patients
::* Present among infants and adults
::* Cytogenetic markers include [[chromosome]] 9q deletion
::* Cytogenetic markers include [[chromosome]] 9q loss
::* Molecular markers include ''SFRP1'' or ''GAB1''
::* Molecular markers include ''SFRP1'' or ''GAB1''
:* Group 3 medulloblastoma:
:* '''Group 3''':
::* Present among 30% of medulloblastoma patients
::* Present among 30% of medulloblastoma patients
::* Present among younger younger children
::* [[Cytogenetic]] markers include isochromosome 17q
::* [[Cytogenetic]] markers include isochromosome 17q
::* Molecular markers include ''MYC'' activation in 50% of this subtype
::* Molecular markers include ''MYC'' activation
:* Group 4 medulloblastoma:
:* '''Group 4''':
::* Present among 35% of medulloblastoma patients
::* Present among 35% of medulloblastoma patients
::* Present among younger younger children
::* Cytogenetic markers include [[isochromosome]] 17q
::* Cytogenetic markers include [[isochromosome]] 17q
::* [[Molecular]] markers are still under investigation
::* [[Molecular]] markers are still under investigation


==Associated Conditions==
==Associated Conditions==
*Medullobastomas is associated with a number of syndromes that include:<ref name="wiki"> Medulloblastoma. Wikipedia(2015) https://en.wikipedia.org/wiki/Medulloblastoma Accessed on September 2015</ref><ref name="radio">Medulloblastoma. Radiopaedia(2015) http://radiopaedia.org/articles/medulloblastoma Accessed on September, 28th 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]]
 
:*[[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]]
:* [[Coffin-Siris syndrome]]
:* [[Coffin-Siris 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:
<gallery>
==Microscopic Pathology==
Image:
* 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>
Medulloblastoma gross pathology Dr Frank Gaillard.jpg|Image courtesy of  Dr Frank Gaillard [http://www.radiopaedia.org Radiopaedia](original file [http://radiopaedia.org/images/6319216 "here"]). [http://radiopaedia.org/licence Creative Commons BY-SA-NC]
* Medulloblastoma may be classified into two subtypes based on WHO histological classification system which include classic medulloblastoma and variant medulloblastoma.
</gallery>
* Variant medulloblastoma may be further classified into ''desmoplastic medulloblastoma'', ''large cell medulloblastoma'', ''anaplastic​ medulloblastoma'', and ''medulloblastoma with extensive nodularity''.<ref name="patho">Medulloblastoma. Libre Pathology(2015) http://librepathology.org/wiki/index.php/Medulloblastoma Accessed on September, 28th 2015</ref><ref name="radio">Medulloblastoma. radiopaedia(2015) http://radiopaedia.org/articles/medulloblastoma Accessed on September, 28th 2015</ref><br>
* The table below differentiates between the five main groups of medulloblastoma according to the WHO histological classification system:<ref name="pmid17618441">{{cite journal| author=Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A et al.| title=The 2007 WHO classification of tumours of the central nervous system. | journal=Acta Neuropathol | year= 2007 | volume= 114 | issue= 2 | pages= 97-109 | pmid=17618441 | doi=10.1007/s00401-007-0243-4 | pmc=PMC1929165 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17618441  }} </ref>


==Mircoscopic Pathology==
{| style="border: 0px; font-size: 90%; margin: 3px; width: 800px"
* On microscopic histopathological analysis, round tumor cells, elevated mitotic rate, increased nucleus:cytoplasm ratio, and presence of 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>
| valign="top" |
|+
! style="background: #4479BA; width: 200px;" | {{fontcolor|#FFF|Grade  }}
! style="background: #4479BA; width: 400px;" | {{fontcolor|#FFF|Histologic features}}
|-
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |
'''Classic medulloblastoma'''
| style="padding: 5px 5px; background: #F5F5F5;" |
*Dense sheet like growth of cells
*Hyperchromatic round-to-oval nucleus
*Increased mitotic activity
*Conspicuous [[apoptosis]]
*Homer-Wright rosettes
*Necrosis is less common     
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |
'''Desmoplastic medulloblastoma variant'''
| style="padding: 5px 5px; background: #F5F5F5;" |
* [[Brain]] tissue invasion
* 4 or more [[mitosis]]/10 HPF
* [[Necrosis]]
* Increased cell count
* High [[nucleus]]:[[cytoplasm]] ratio
* Increased [[nucleoli]] size
* Presence of sheeting
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |
'''Medulloblastoma with extensive nodularity variant'''
| style="padding: 5px 5px; background: #F5F5F5;" |
* Cellular uniformity
* Fine fibrillary matrix
* Occasional presence of mature [[ganglion cell]]s
|-
| style="padding: 5px 5px; background: #DCDCDC;font-weight: bold" |
'''Large cell / anaplastic medulloblastoma variant'''
| style="padding: 5px 5px; background: #F5F5F5;" |
* Demonstrate high mitotic activity
* [[Pleomorphism]]
* Large round nucleus with variable eosinophilic cytoplasm
* [[Hemorrhage]]
* Necrosis is common
|}
<br>
* Shown below is a series of microscopic images observed in medulloblastoma:
* Shown below is a series of microscopic images observed in medulloblastoma:
<gallery>
<gallery>
Image:
Image:
Medulloblsatoma.JPG|Medulloblastoma smear<ref name="patho">Medulloblastoma. Librepathology(2015) http://librepathology.org/wiki/index.php/Medulloblastoma Accessed on September, 28th 2015</ref>
Cerebellar medulloblastoma (1) in adult.JPG|Medulloblastoma <ref name="patho">Medulloblastoma. Librepathology(2015) http://librepathology.org/wiki/index.php/Medulloblastoma Accessed on September, 28th 2015</ref>
Image:
Image:
Medulloblsatoma 2.JPG|Medulloblastoma smear <ref name="patho">Medulloblastoma. Librepathology(2015) http://librepathology.org/wiki/index.php/Medulloblastoma Accessed on September, 28th 2015</ref>
Cerebellar medulloblastoma (2) in adult.JPG|Medulloblastoma<ref name="patho">Medulloblastoma. Librepathology(2015) http://librepathology.org/wiki/index.php/Medulloblastoma Accessed on September, 28th 2015</ref>
Image:
Image:
Medulloblastoma 3.jpg|Medulloblastoma smear demonstrating Homer-Wright rosettes<ref name="patho">Medulloblastoma. Librepathology(2015) http://librepathology.org/wiki/index.php/Medulloblastoma Accessed on September, 28th 2015</ref>
Medulloblastoma with rosettes.jpg|Medulloblastoma demonstrating Homer-Wright rosettes<ref name="patho">Medulloblastoma. Librepathology(2015) http://librepathology.org/wiki/index.php/Medulloblastoma Accessed on September, 28th 2015</ref>
Image:
Image:
Medulloblastoma 4.jpg|Medulloblastoma smear demonstrating [[cerebellar]] infiltrative growth<ref name="patho">Medulloblastoma. Librepathology(2015) http://librepathology.org/wiki/index.php/Medulloblastoma Accessed on September, 28th 2015</ref>
Medulloblastoma stratum moleculare x40 (1).jpg|Medulloblastoma demonstrating [[cerebellar]] infiltrative growth<ref name="patho">Medulloblastoma. Librepathology(2015) http://librepathology.org/wiki/index.php/Medulloblastoma Accessed on September, 28th 2015</ref>
Image:
Image:
Medulloblastoma 5.jpg|Medullloblastoma smear demonstrating demsomplastic [[nodular]] growth<ref name="patho">Medulloblastoma. Librepathology(2015) http://librepathology.org/wiki/index.php/Medulloblastoma Accessed on September, 28th 2015</ref>  
Desmoplastic nodular medulloblastoma.jpg|Medulloblastoma demonstrating demsomplastic [[nodular]] growth<ref name="patho">Medulloblastoma. Librepathology(2015) http://librepathology.org/wiki/index.php/Medulloblastoma Accessed on September, 28th 2015</ref>  
Image:
Image:
Medulloblastoma 6.jpg|[[Anaplastic]] large cell medulloblastoma smear<ref name="patho">Medulloblastoma. Librepathology(2015) http://librepathology.org/wiki/index.php/Medulloblastoma Accessed on September, 28th 2015</ref>  
Anaplastic medulloblastoma x200.jpg|[[Anaplastic]] large cell medulloblastoma<ref name="patho">Medulloblastoma. Librepathology(2015) http://librepathology.org/wiki/index.php/Medulloblastoma Accessed on September, 28th 2015</ref>  
Image:
Image:
Medulloblastoma 7.jpg|Medulloblastoma smear<ref name="patho">Medulloblastoma. Librepathology(2015) http://librepathology.org/wiki/index.php/Medulloblastoma Accessed on September, 28th 2015</ref>  
AFIP405820M-MEDULLOBLASTOMA.jpg|Medulloblastoma<ref name="patho">Medulloblastoma.Librepathology(2015) http://librepathology.org/wiki/index.php/Medulloblastoma Accessed on September, 28th 2015</ref>  
Image:
Image:
Medulloblastoma 8.jpg|Desmoplastic medulloblastoma smear on [[reticulin]] stain demonstrating "pale islands"<ref name="patho">Medulloblastoma. Librepathology(2015) http://librepathology.org/wiki/index.php/Medulloblastoma Accessed on September, 28th 2015</ref>  
Desmoplastic medulloblastoma reticulin stain pale island.jpg|Desmoplastic medulloblastoma on [[reticulin]] stain demonstrating pale islands structure<ref name="patho">Medulloblastoma. Librepathology(2015) http://librepathology.org/wiki/index.php/Medulloblastoma Accessed on September, 28th 2015</ref>  
Image:
Image:
Medulloblastoma 9.jpg|[[Desmoplastic]] medulloblastoma on MIB-1 immunostaining<ref name="patho">Medulloblastoma. Librepathology(2015) http://librepathology.org/wiki/index.php/Medulloblastoma Accessed on September, 28th 2015</ref>
Desmoplastic medulloblastom MIB1 proliferation.jpg|[[Desmoplastic]] medulloblastoma on MIB-1 immunostaining<ref name="patho">Medulloblastoma. Librepathology(2015) http://librepathology.org/wiki/index.php/Medulloblastoma Accessed on September, 28th 2015</ref>
Image:
Image:
Medulloblastoma Areas of geographic necrosis..jpg| Medulloblastoma smear demonstrating areas of geographic [[necrosis]]<ref name="patho">Medulloblastoma. Librepathology(2015) http://librepathology.org/wiki/index.php/Medulloblastoma Accessed on September, 28th 2015</ref>
Medulloblastoma Areas of geographic necrosis.jpg| Medulloblastoma demonstrating areas of geographic [[necrosis]]<ref name="patho">Medulloblastoma. Librepathology(2015) http://librepathology.org/wiki/index.php/Medulloblastoma Accessed on September, 28th 2015</ref>
Image:
Image:
Medulloblastoma Epitheloid ribboning and nuclear moulding of tumor cells..jpg|Medulloblastoma smear demonstrating epitheloid ribboning and [[nuclear]] moulding of [[tumor]] cells<ref name="patho">Medulloblastoma. Librepathology(2015) http://librepathology.org/wiki/index.php/Medulloblastoma Accessed on September, 28th 2015</ref>
Medulloblastoma nuclear moulding HE stain.jpg|Medulloblastoma demonstrating epitheloid ribboning and [[nuclear]] moulding of [[tumor]] cells<ref name="patho">Medulloblastoma. Librepathology(2015) http://librepathology.org/wiki/index.php/Medulloblastoma Accessed on September, 28th 2015</ref>
Image:
Image:
Medulloblastoma Partial MAP2 immunoreactivity..jpg|Medulloblastoma smear demonstrating partial MAP2 immunoreactivity<ref name="patho">Medulloblastoma. Librepathology(2015) http://librepathology.org/wiki/index.php/Medulloblastoma Accessed on September, 28th 2015</ref>
Medulloblastoma MAP2 IHC.jpg|Medulloblastoma demonstrating partial MAP2 immunoreactivity<ref name="patho">Medulloblastoma. Librepathology(2015) http://Libre Pathology.org/wiki/index.php/Medulloblastoma Accessed on September, 28th 2015</ref>
</gallery>
</gallery>


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[[Category:Neurosurgery]]
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[[Category:Types of cancer]]
[[Category:Types of cancer]]
[[Category:Up-To-Date]]
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Latest revision as of 22:31, 12 September 2019

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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

Genetics

  • 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

  • Medulloblastoma is associated with a number of syndromes that include:[1][10]

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

  • Dense sheet like growth of cells
  • Hyperchromatic round-to-oval nucleus
  • Increased mitotic activity
  • Conspicuous apoptosis
  • Homer-Wright rosettes
  • Necrosis is less common

Desmoplastic medulloblastoma variant

Medulloblastoma with extensive nodularity variant

  • Cellular uniformity
  • Fine fibrillary matrix
  • Occasional presence of mature ganglion cells

Large cell / anaplastic medulloblastoma variant

  • Demonstrate high mitotic activity
  • Pleomorphism
  • Large round nucleus with variable eosinophilic cytoplasm
  • Hemorrhage
  • Necrosis is common


  • Shown below is a series of microscopic images observed in medulloblastoma:
  • Medulloblastoma [2]

    Medulloblastoma [2]

  • Medulloblastoma[2]

    Medulloblastoma[2]

  • Medulloblastoma demonstrating Homer-Wright rosettes[2]

    Medulloblastoma demonstrating Homer-Wright rosettes[2]

  • Medulloblastoma demonstrating cerebellar infiltrative growth[2]

    Medulloblastoma demonstrating cerebellar infiltrative growth[2]

  • Medulloblastoma demonstrating demsomplastic nodular growth[2]

    Medulloblastoma demonstrating demsomplastic nodular growth[2]

  • Anaplastic large cell medulloblastoma[2]

    Anaplastic large cell medulloblastoma[2]

  • Medulloblastoma[2]

    Medulloblastoma[2]

  • Desmoplastic medulloblastoma on reticulin stain demonstrating pale islands structure[2]

    Desmoplastic medulloblastoma on reticulin stain demonstrating pale islands structure[2]

  • Desmoplastic medulloblastoma on MIB-1 immunostaining[2]

    Desmoplastic medulloblastoma on MIB-1 immunostaining[2]

  • Medulloblastoma demonstrating areas of geographic necrosis[2]

    Medulloblastoma demonstrating areas of geographic necrosis[2]

  • Medulloblastoma demonstrating epitheloid ribboning and nuclear moulding of tumor cells[2]

    Medulloblastoma demonstrating epitheloid ribboning and nuclear moulding of tumor cells[2]

  • Medulloblastoma demonstrating partial MAP2 immunoreactivity[2]

    Medulloblastoma demonstrating partial MAP2 immunoreactivity[2]

References

  1. ↑ 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. ↑ 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
  3. ↑ 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.
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ 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
  9. ↑ 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. ↑ 10.0 10.1 Medulloblastoma. Radiopaedia(2015) http://radiopaedia.org/articles/medulloblastoma Accessed on September, 28 2015
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ 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.


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