Medulloblastoma pathophysiology: Difference between revisions

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Latest revision as of 22:31, 12 September 2019

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

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	Brain tissue invasion 4 or more mitosis/10 HPF Necrosis Increased cell count High nucleus:cytoplasm ratio Increased nucleoli size Presence of sheeting
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 demonstrating Homer-Wright rosettes^[2]
Medulloblastoma demonstrating cerebellar infiltrative growth^[2]
Medulloblastoma demonstrating demsomplastic nodular growth^[2]
Anaplastic large cell medulloblastoma^[2]
Medulloblastoma^[2]
Desmoplastic medulloblastoma on reticulin stain demonstrating pale islands structure^[2]
Desmoplastic medulloblastoma on MIB-1 immunostaining^[2]
Medulloblastoma demonstrating areas of geographic necrosis^[2]
Medulloblastoma demonstrating epitheloid ribboning and nuclear moulding of tumor cells^[2]
Medulloblastoma demonstrating partial MAP2 immunoreactivity^[2]

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.

Template:WikiDoc Sources

[wiki-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

[patho-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

[pmid8515724-3] 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.

[pmid7777574-4] 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.

[pmid8542595-5] 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.

[pmid3139544-6] 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.

[pmid22832581-7] 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.

[pmid22189395-8] 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

[pmid7754860-9] 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.

[radio-10] 10.0 ^10.1 Medulloblastoma. Radiopaedia(2015) http://radiopaedia.org/articles/medulloblastoma Accessed on September, 28 2015

[pmid1931625-11] 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.

[pmid10064395-12] 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.

[pmid17618441-13] 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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@@ Line 1: / Line 1: @@
 __NOTOC__
 {{Medulloblastoma}}
-{{CMG}} {{AE}}{{HL}}
+{{CMG}} {{AE}}{{HL}} {{AE}}{{sali}}
+==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>
-==Overview==
 ==Pathogenesis==
-Medulloblastomas usually form in the fourth ventricle, between the brainstem and the cerebellum.  Tumors with similar appearance and characteristics originate in other parts of the brain, but they are not identical to medulloblastoma. <ref>Roger Packer M.D, [http://virtualtrials.com/medullo.cfm Medulloblastoma] Clinical Trials and Noteworthy Treatments for Brain Tumors 2002.</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 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.
-Although it is thought that medulloblastomas originate from immature or embryonal cells at their earliest stage of development, the exact cell of origin, or "medulloblast" has yet to be identified.
-It is currently thought that medulloblastoma arises from cerebellar "stem cells" that have been prevented from dividing and differentiating into their normal cell types. This accounts from the varying histologic variants seen on biopsy. '''Rosette''' formation is highly characteristic of medulloblastoma and is seen in up to half of the cases.
 ==Genetics==
-Molecular genetics reveal a loss of genetic information on the distal part of chromosome 17, distal to the ''[[p53]]'' gene, possibly accounting for the neoplastic transformation of the undifferentiated cerebellar cells. Medulloblastomas are also seen in [[Gorlin syndrome]] as well as [[Turcot syndrome]]. Another research has strongly implicated the [[JC virus]], the virus that causes [[progressive multifocal leukoencephalopathy|multifocal leukoencephalopathy]].
+* 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>
+* [[Gene]]s 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:<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:'''
+::* 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:<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>
+:* [[Turcot syndrome]]
+:* [[Coffin-Siris syndrome]]
+:* [[Cowden syndrome]]
+:* [[Gardner syndrome]]
+:* [[Li-Fraumeni syndrome]]
+:* [[Rubinstein-Taybi syndrome]]
 ==Gross Pathology==
-Histologically, the tumor is solid, pink-gray in color, and is well circumscribed.
+* 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:
+==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>
+* 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''.<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>
+{| style="border: 0px; font-size: 90%; margin: 3px; width: 800px"
+| 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:
+<gallery>
+Image:
+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:
+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:
+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:
+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:
+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:
+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:
+AFIP405820M-MEDULLOBLASTOMA.jpg|Medulloblastoma<ref name="patho">Medulloblastoma.Librepathology(2015) http://librepathology.org/wiki/index.php/Medulloblastoma Accessed on September, 28th 2015</ref>
+Image:
+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:
+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:
+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:
+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:
+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>
-==Mircoscopic Pathology==
- The tumor is very cellular, many mitoses, little cytoplasm, and has the tendency to form clusters and rosettes.
 ==References==
 {{Reflist|2}}
@@ Line 27: / Line 142: @@
 [[Category:Neurosurgery]]
 [[Category:Types of cancer]]
+ [[Category:Up-To-Date]]
+[[Category:Oncology]]
+[[Category:Medicine]]
+[[Category:Neurology]]
+[[Category:Neurosurgery]]