Medulloblastoma - Revision history

Jensflorian: /* Genetically defined */

2019-11-20T15:20:48Z

Genetically defined

← Older revision		Revision as of 15:20, 20 November 2019
Line 150:		Line 150:
	**Infantile, p53 wildtype: Usu. desmoplastic/nodular, 10q loss.		**Infantile, p53 wildtype: Usu. desmoplastic/nodular, 10q loss.
	**SHH-p53 mutant: Usu. large cell/anaplastic, 17q loss.		**SHH-p53 mutant: Usu. large cell/anaplastic, 17q loss.
	*Group 3 (approx. 20%).		*Non WNT/Non SHH:
	**Classic and large cell/anaplastic, MYC amplification, isochromosome 17q.		**Group 3 (approx. 20%).
	*Group 4 (approx. 40%).		***Classic and large cell/anaplastic, MYC amplification, isochromosome 17q.
	**Classic phenotype, MYCN amplification, isodicentric 17q.		**Group 4 (approx. 40%).
	** Group 3+4 ~~are often designated together~~ as ~~Non~~-~~Wnt/Non-SHH tumours~~.		***Classic phenotype, MYCN amplification, isodicentric 17q.
			Note: Within Group 3+4 two or more of chromosome 7 gain, chromosome 8 loss, and chromosome 11 loss separates standard risk medulloblastoma samples into favorable and classifies the remaining i17q diploid cases as high-risk.

	==Prognosis==		==Prognosis==

Jensflorian: + infobox

2018-06-29T11:56:19Z

+ infobox

← Older revision		Revision as of 11:56, 29 June 2018
Line 1:		Line 1:
			{{ Infobox diagnosis
			\| Name = {{PAGENAME}}
			\| Image = Medulloblastoma with rosettes.jpg
			\| Width =
			\| Caption = Classic medulloblastoma [[H&E stain]].
			\| Synonyms =
			\| Micro =
			\| Subtypes =
			\| LMDDx = small cell round blue tumous.
			\| Stains = Reticulin +ve (in desmoplastic MB)
			\| IHC = MAP2+ve
			\| EM =
			\| Molecular =
			\| IF =
			\| Gross = cerebellar.
			\| Grossing =
			\| Site = brain - usu. [[cerebellum]]
			\| Assdx =
			\| Syndromes =
			\| Clinicalhx =
			\| Signs =
			\| Symptoms =
			\| Prevalence = common - esp. in children
			\| Bloodwork =
			\| Rads =
			\| Endoscopy =
			\| Prognosis = subtype-dependent (WHO Grade IV)
			\| Other =
			\| ClinDDx =
			\| Tx =
			}}

	'''Medulloblastoma''' is a [[malignant]] [[small round cell tumour]] that is found in the [[cerebellum]] or dorsal brainstem. It is the most common malignant CNS tumour in children.		'''Medulloblastoma''' is a [[malignant]] [[small round cell tumour]] that is found in the [[cerebellum]] or dorsal brainstem. It is the most common malignant CNS tumour in children.

Jensflorian: /* Histologically defined */

2018-06-29T11:52:08Z

Histologically defined

← Older revision		Revision as of 11:52, 29 June 2018
Line 85:		Line 85:
	*#Desmoplastic/nodular medulloblastoma (DNMB).		*#Desmoplastic/nodular medulloblastoma (DNMB).
	*#Medulloblastoma with extensive nodularity (MBEN).		*#Medulloblastoma with extensive nodularity (MBEN).

			====Classic variant====
			*Densely packed embryonal cells.
			*Mitosis / apoptosis present.
			*Nodules of neurocytic differentiation without internodular reticulin.
			*Rarely spongioblastic pattern (ribboning).

	====Anaplastic variant====		====Anaplastic variant====

Jensflorian: update

2018-06-29T11:48:17Z

update

← Older revision		Revision as of 11:48, 29 June 2018
Line 1:		Line 1:
	'''Medulloblastoma''' is a [[malignant]] [[small round cell tumour]] that is found in the [[cerebellum]].		'''Medulloblastoma''' is a [[malignant]] [[small round cell tumour]] that is found in the [[cerebellum]] or dorsal brainstem. It is the most common malignant CNS tumour in children.


	~~Morphologically identical supratentorial tumours are called ''[[primitive neuroectodermal tumour]]'' (PNET).~~

	==General==		==General==
	*Mostly paediatric population (mean age: 9 years).		*Mostly paediatric population (mean age: 9 years).
			*Tumors consists of histologically and molecular distinct subgroups.
			*All subgroups correspond to WHO grade IV.
	*May be seen as a component of [[nevoid basal cell carcinoma syndrome]] (NBCCS) AKA Gorlin syndrome, [[Li-Fraumeni syndrome]], Turcot syndrome, Rubinstain-Taybi syndrome and Nijmegen breakage syndrome.		*May be seen as a component of [[nevoid basal cell carcinoma syndrome]] (NBCCS) AKA Gorlin syndrome, [[Li-Fraumeni syndrome]], Turcot syndrome, Rubinstain-Taybi syndrome and Nijmegen breakage syndrome.
	**Show molecularly spatially homogeneous transcriptomes, allowing for accurate subgrouping of tumors from a single biopsy.<ref>{{Cite journal \| last1 = Morrissy \| first1 = AS. \| last2 = Cavalli \| first2 = FMG. \| last3 = Remke \| first3 = M. \| last4 = Ramaswamy \| first4 = V. \| last5 = Shih \| first5 = DJH. \| last6 = Holgado \| first6 = BL. \| last7 = Farooq \| first7 = H. \| last8 = Donovan \| first8 = LK. \| last9 = Garzia \| first9 = L. \| title = Spatial heterogeneity in medulloblastoma. \| journal = Nat Genet \| volume = 49 \| issue = 5 \| pages = 780-788 \| month = May \| year = 2017 \| doi = 10.1038/ng.3838 \| PMID = 28394352 }}</ref>		**Show molecularly spatially homogeneous transcriptomes, allowing for accurate subgrouping of tumors from a single biopsy.<ref>{{Cite journal \| last1 = Morrissy \| first1 = AS. \| last2 = Cavalli \| first2 = FMG. \| last3 = Remke \| first3 = M. \| last4 = Ramaswamy \| first4 = V. \| last5 = Shih \| first5 = DJH. \| last6 = Holgado \| first6 = BL. \| last7 = Farooq \| first7 = H. \| last8 = Donovan \| first8 = LK. \| last9 = Garzia \| first9 = L. \| title = Spatial heterogeneity in medulloblastoma. \| journal = Nat Genet \| volume = 49 \| issue = 5 \| pages = 780-788 \| month = May \| year = 2017 \| doi = 10.1038/ng.3838 \| PMID = 28394352 }}</ref>
	*Commonly spread via cerebrospinal fluid (CSF).<ref>{{Ref APBR\|424 Q34}}</ref>		*Commonly spread via cerebrospinal fluid (CSF).<ref>{{Ref APBR\|424 Q34}}</ref>
	**May be detected in [[CSF cytopathology]] specimens.		**May be detected in [[CSF cytopathology]] specimens.
	*All subgroups correspond to WHO grade IV.

	==Gross==		==Gross==
	*Location: cerebellum - '''key feature''' or dorsal brainstem (lower rhombic lip).		*Location: cerebellum - '''key feature''' or dorsal brainstem (lower rhombic lip).
	**~~Morphologically~~ identical supratentorial tumours ~~are called ''[[primitive neuroectodermal tumour]]'' (PNET)~~.		**For morphologically identical supratentorial tumours see possible DDx.
	**Supratentorial and spinal metastases from initial ~~tumor~~ possible.		**Supratentorial and spinal metastases from initial medulloblastoma possible.

	==Microscopic==		==Microscopic==
	Features:<ref>URL: [http://moon.ouhsc.edu/kfung/jty1/neurotest/Q93-Ans.htm http://moon.ouhsc.edu/kfung/jty1/neurotest/Q93-Ans.htm]. Accessed on: 26 October 2010.</ref>		Features:<ref>URL: [http://moon.ouhsc.edu/kfung/jty1/neurotest/Q93-Ans.htm http://moon.ouhsc.edu/kfung/jty1/neurotest/Q93-Ans.htm]. Accessed on: 26 October 2010.</ref>
	*[[Small round cell tumour]].		*[[Small round cell tumour]].
			*Mild to moderate nuclear pleomorphism.
			*High mitotic count.
	*Homer-Wright [[rosette]]s:		*Homer-Wright [[rosette]]s:
	**Rosette with a meshwork of fibers (neuropil) at the centre.<ref>{{cite journal \|author=Wippold FJ, Perry A \|title=Neuropathology for the neuroradiologist: rosettes and pseudorosettes \|journal=AJNR Am J Neuroradiol \|volume=27 \|issue=3 \|pages=488–92 \|year=2006 \|month=March \|pmid=16551982 \|doi= \|url=}}</ref>		**Rosette with a meshwork of fibers (neuropil) at the centre.<ref>{{cite journal \|author=Wippold FJ, Perry A \|title=Neuropathology for the neuroradiologist: rosettes and pseudorosettes \|journal=AJNR Am J Neuroradiol \|volume=27 \|issue=3 \|pages=488–92 \|year=2006 \|month=March \|pmid=16551982 \|doi= \|url=}}</ref>
Line 39:		Line 43:
	DDx:		DDx:
	*[[Small round cell tumours]].		*[[Small round cell tumours]].
	** [[AT/RT]] (INI1 loss)		** [[AT/RT]]. (INI1 loss)
	** CNS-embryonal tumour (aka CNS-[[PNET]])		** CNS-embryonal tumour (aka CNS-[[PNET]]).
	** ETMR (LIN28)-positive		** ETMR (LIN28)-positive.
	** Ewing Sarcoma family members		** Ewing Sarcoma family members.
	** Small cell glioblastoma (Olig2 +ve) - esp. after RT and longer latency. <ref>{{Cite journal \| last1 = Phi \| first1 = JH. \| last2 = Park \| first2 = AK. \| last3 = Lee \| first3 = S. \| last4 = Choi \| first4 = SA. \| last5 = Baek \| first5 = IP. \| last6 = Kim \| first6 = P. \| last7 = Kim \| first7 = EH. \| last8 = Park \| first8 = HC. \| last9 = Kim \| first9 = BC. \| title = Genomic analysis reveals secondary glioblastoma after radiotherapy in a subset of recurrent medulloblastomas. \| journal = Acta Neuropathol \| volume = \| issue = \| pages = \| month = Apr \| year = 2018 \| doi = 10.1007/s00401-018-1845-8 \| PMID = 29644394 }}</ref>		** Small cell glioblastoma (Olig2 +ve) - esp. after RT and longer latency. <ref>{{Cite journal \| last1 = Phi \| first1 = JH. \| last2 = Park \| first2 = AK. \| last3 = Lee \| first3 = S. \| last4 = Choi \| first4 = SA. \| last5 = Baek \| first5 = IP. \| last6 = Kim \| first6 = P. \| last7 = Kim \| first7 = EH. \| last8 = Park \| first8 = HC. \| last9 = Kim \| first9 = BC. \| title = Genomic analysis reveals secondary glioblastoma after radiotherapy in a subset of recurrent medulloblastomas. \| journal = Acta Neuropathol \| volume = \| issue = \| pages = \| month = Apr \| year = 2018 \| doi = 10.1007/s00401-018-1845-8 \| PMID = 29644394 }}</ref>
			** Anaplastic ependymoma.

	==Images==		==Images==
Line 97:		Line 102:
	===Genetically defined===		===Genetically defined===
	*WNT (brainstem-related, usu. CTNNB1 mutations, less common: CSNK2B, AXIN2, APC, approx. 10%).<ref>{{Cite journal \| last1 = Wefers \| first1 = AK. \| last2 = Warmuth-Metz \| first2 = M. \| last3 = Pöschl \| first3 = J. \| last4 = von Bueren \| first4 = AO. \| last5 = Monoranu \| first5 = CM. \| last6 = Seelos \| first6 = K. \| last7 = Peraud \| first7 = A. \| last8 = Tonn \| first8 = JC. \| last9 = Koch \| first9 = A. \| title = Subgroup-specific localization of human medulloblastoma based on pre-operative MRI. \| journal = Acta Neuropathol \| volume = 127 \| issue = 6 \| pages = 931-3 \| month = \| year = 2014 \| doi = 10.1007/s00401-014-1271-5 \| PMID = 24699697 }}</ref>		*WNT (brainstem-related, usu. CTNNB1 mutations, less common: CSNK2B, AXIN2, APC, approx. 10%).<ref>{{Cite journal \| last1 = Wefers \| first1 = AK. \| last2 = Warmuth-Metz \| first2 = M. \| last3 = Pöschl \| first3 = J. \| last4 = von Bueren \| first4 = AO. \| last5 = Monoranu \| first5 = CM. \| last6 = Seelos \| first6 = K. \| last7 = Peraud \| first7 = A. \| last8 = Tonn \| first8 = JC. \| last9 = Koch \| first9 = A. \| title = Subgroup-specific localization of human medulloblastoma based on pre-operative MRI. \| journal = Acta Neuropathol \| volume = 127 \| issue = 6 \| pages = 931-3 \| month = \| year = 2014 \| doi = 10.1007/s00401-014-1271-5 \| PMID = 24699697 }}</ref>
	**Caution: Some WNT-activated MB may show additional subclonal SHH-mutations.<ref>{{Cite journal \| last1 = Iorgulescu \| first1 = JB. \| last2 = Van Ziffle \| first2 = J. \| last3 = Stevers \| first3 = M. \| last4 = Grenert \| first4 = JP. \| last5 = Bastian \| first5 = BC. \| last6 = Chavez \| first6 = L. \| last7 = Stichel \| first7 = D. \| last8 = Buchhalter \| first8 = I. \| last9 = Samuel \| first9 = D. \| title = Deep sequencing of WNT-activated medulloblastomas reveals secondary SHH pathway activation. \| journal = Acta Neuropathol \| volume = 135 \| issue = 4 \| pages = 635-638 \| month = Apr \| year = 2018 \| doi = 10.1007/s00401-018-1819-x \| PMID = 29435664 }}</ref>		** Usu. classic MB in histology.
			** Caution: Some WNT-activated MB may show additional subclonal SHH-mutations.<ref>{{Cite journal \| last1 = Iorgulescu \| first1 = JB. \| last2 = Van Ziffle \| first2 = J. \| last3 = Stevers \| first3 = M. \| last4 = Grenert \| first4 = JP. \| last5 = Bastian \| first5 = BC. \| last6 = Chavez \| first6 = L. \| last7 = Stichel \| first7 = D. \| last8 = Buchhalter \| first8 = I. \| last9 = Samuel \| first9 = D. \| title = Deep sequencing of WNT-activated medulloblastomas reveals secondary SHH pathway activation. \| journal = Acta Neuropathol \| volume = 135 \| issue = 4 \| pages = 635-638 \| month = Apr \| year = 2018 \| doi = 10.1007/s00401-018-1819-x \| PMID = 29435664 }}</ref>
			** Peak incidence: 7-14 years (15% adults).
			** Beta-catenin nuclear +ve.
			** Excellent prognosis.
	*SHH (PTCH1 & SUFU in infant, PTCH1, SMO, Gli2, MYCN in non-infant, approx 30%).<ref>{{Cite journal \| last1 = Neumann \| first1 = JE. \| last2 = Swartling \| first2 = FJ. \| last3 = Schüller \| first3 = U. \| title = Medulloblastoma: experimental models and reality. \| journal = Acta Neuropathol \| volume = \| issue = \| pages = \| month = Jul \| year = 2017 \| doi = 10.1007/s00401-017-1753-3 \| PMID = 28725965 }}</ref>		*SHH (PTCH1 & SUFU in infant, PTCH1, SMO, Gli2, MYCN in non-infant, approx 30%).<ref>{{Cite journal \| last1 = Neumann \| first1 = JE. \| last2 = Swartling \| first2 = FJ. \| last3 = Schüller \| first3 = U. \| title = Medulloblastoma: experimental models and reality. \| journal = Acta Neuropathol \| volume = \| issue = \| pages = \| month = Jul \| year = 2017 \| doi = 10.1007/s00401-017-1753-3 \| PMID = 28725965 }}</ref>
	**~~infantile~~ and adult cases are biologically different, esp p53 mutant tumors are associated with poor outcome.<ref>{{Cite journal \| last1 = Kool \| first1 = M. \| last2 = Jones \| first2 = DT. \| last3 = Jäger \| first3 = N. \| last4 = Northcott \| first4 = PA. \| last5 = Pugh \| first5 = TJ. \| last6 = Hovestadt \| first6 = V. \| last7 = Piro \| first7 = RM. \| last8 = Esparza \| first8 = LA. \| last9 = Markant \| first9 = SL. \| title = Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition. \| journal = Cancer Cell \| volume = 25 \| issue = 3 \| pages = 393-405 \| month = Mar \| year = 2014 \| doi = 10.1016/j.ccr.2014.02.004 \| PMID = 24651015 }}</ref>		**Origin in the cerebellar granule neuron cell precursors.
			**Infantile and adult cases are biologically different, esp p53 mutant tumors are associated with poor outcome.<ref>{{Cite journal \| last1 = Kool \| first1 = M. \| last2 = Jones \| first2 = DT. \| last3 = Jäger \| first3 = N. \| last4 = Northcott \| first4 = PA. \| last5 = Pugh \| first5 = TJ. \| last6 = Hovestadt \| first6 = V. \| last7 = Piro \| first7 = RM. \| last8 = Esparza \| first8 = LA. \| last9 = Markant \| first9 = SL. \| title = Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition. \| journal = Cancer Cell \| volume = 25 \| issue = 3 \| pages = 393-405 \| month = Mar \| year = 2014 \| doi = 10.1016/j.ccr.2014.02.004 \| PMID = 24651015 }}</ref>
			**Infantile, p53 wildtype: Usu. desmoplastic/nodular, 10q loss.
			**SHH-p53 mutant: Usu. large cell/anaplastic, 17q loss.
	*Group 3 (approx. 20%).		*Group 3 (approx. 20%).
			**Classic and large cell/anaplastic, MYC amplification, isochromosome 17q.
	*Group 4 (approx. 40%).		*Group 4 (approx. 40%).
			**Classic phenotype, MYCN amplification, isodicentric 17q.
	** Group 3+4 are often designated together as Non-Wnt/Non-SHH tumours.		** Group 3+4 are often designated together as Non-Wnt/Non-SHH tumours.

Jensflorian: /* IHC */ Subgrouping

2018-05-02T12:10:27Z

IHC: Subgrouping

← Older revision		Revision as of 12:10, 2 May 2018
Line 32:		Line 32:
	* Nestin +ve		* Nestin +ve
	* [[INI1]] retained (no loss)		* [[INI1]] retained (no loss)
			Genetic grouping with IHC:<ref>{{Cite journal \| last1 = Pietsch \| first1 = T. \| last2 = Haberler \| first2 = C. \| title = Update on the integrated histopathological and genetic classification of medulloblastoma - a practical diagnostic guideline. \| journal = Clin Neuropathol \| volume = 35 \| issue = 6 \| pages = 344-352 \| month = \| year = \| doi = 10.5414/NP300999 \| PMID = 27781424 }}</ref>
			* WNT: beta-catein: nuclear +ve, YAP1+ve, OTX2+ve.
			* SHH: YAP1+ve, OTX2-ve, p75+ve.
			* Non-WNT/Non-SHH: * SHH: YAP1-ve, OTX2+ve, p75+ve.

	DDx:		DDx:
	*[[Small round cell tumours]].		*[[Small round cell tumours]].
	** [[AT/RT]] (INI1 loss)		** [[AT/RT]] (INI1 loss)
	** CNS-[[PNET]]		** CNS-embryonal tumour (aka CNS-[[PNET]])
	** ETMR (LIN28)-positive		** ETMR (LIN28)-positive
	** Ewing Sarcoma family members		** Ewing Sarcoma family members

Jensflorian: /* IHC */ DDx

2018-05-02T12:04:21Z

IHC: DDx

← Older revision		Revision as of 12:04, 2 May 2018
Line 39:		Line 39:
	** ETMR (LIN28)-positive		** ETMR (LIN28)-positive
	** Ewing Sarcoma family members		** Ewing Sarcoma family members
	** Small cell glioblastoma		** Small cell glioblastoma (Olig2 +ve) - esp. after RT and longer latency. <ref>{{Cite journal \| last1 = Phi \| first1 = JH. \| last2 = Park \| first2 = AK. \| last3 = Lee \| first3 = S. \| last4 = Choi \| first4 = SA. \| last5 = Baek \| first5 = IP. \| last6 = Kim \| first6 = P. \| last7 = Kim \| first7 = EH. \| last8 = Park \| first8 = HC. \| last9 = Kim \| first9 = BC. \| title = Genomic analysis reveals secondary glioblastoma after radiotherapy in a subset of recurrent medulloblastomas. \| journal = Acta Neuropathol \| volume = \| issue = \| pages = \| month = Apr \| year = 2018 \| doi = 10.1007/s00401-018-1845-8 \| PMID = 29644394 }}</ref>

	==Images==		==Images==

Jensflorian: /* Genetically defined */ Dual phenotype-MB

2018-04-10T13:18:39Z

Genetically defined: Dual phenotype-MB

← Older revision		Revision as of 13:18, 10 April 2018
Line 93:		Line 93:
	===Genetically defined===		===Genetically defined===
	*WNT (brainstem-related, usu. CTNNB1 mutations, less common: CSNK2B, AXIN2, APC, approx. 10%).<ref>{{Cite journal \| last1 = Wefers \| first1 = AK. \| last2 = Warmuth-Metz \| first2 = M. \| last3 = Pöschl \| first3 = J. \| last4 = von Bueren \| first4 = AO. \| last5 = Monoranu \| first5 = CM. \| last6 = Seelos \| first6 = K. \| last7 = Peraud \| first7 = A. \| last8 = Tonn \| first8 = JC. \| last9 = Koch \| first9 = A. \| title = Subgroup-specific localization of human medulloblastoma based on pre-operative MRI. \| journal = Acta Neuropathol \| volume = 127 \| issue = 6 \| pages = 931-3 \| month = \| year = 2014 \| doi = 10.1007/s00401-014-1271-5 \| PMID = 24699697 }}</ref>		*WNT (brainstem-related, usu. CTNNB1 mutations, less common: CSNK2B, AXIN2, APC, approx. 10%).<ref>{{Cite journal \| last1 = Wefers \| first1 = AK. \| last2 = Warmuth-Metz \| first2 = M. \| last3 = Pöschl \| first3 = J. \| last4 = von Bueren \| first4 = AO. \| last5 = Monoranu \| first5 = CM. \| last6 = Seelos \| first6 = K. \| last7 = Peraud \| first7 = A. \| last8 = Tonn \| first8 = JC. \| last9 = Koch \| first9 = A. \| title = Subgroup-specific localization of human medulloblastoma based on pre-operative MRI. \| journal = Acta Neuropathol \| volume = 127 \| issue = 6 \| pages = 931-3 \| month = \| year = 2014 \| doi = 10.1007/s00401-014-1271-5 \| PMID = 24699697 }}</ref>
			**Caution: Some WNT-activated MB may show additional subclonal SHH-mutations.<ref>{{Cite journal \| last1 = Iorgulescu \| first1 = JB. \| last2 = Van Ziffle \| first2 = J. \| last3 = Stevers \| first3 = M. \| last4 = Grenert \| first4 = JP. \| last5 = Bastian \| first5 = BC. \| last6 = Chavez \| first6 = L. \| last7 = Stichel \| first7 = D. \| last8 = Buchhalter \| first8 = I. \| last9 = Samuel \| first9 = D. \| title = Deep sequencing of WNT-activated medulloblastomas reveals secondary SHH pathway activation. \| journal = Acta Neuropathol \| volume = 135 \| issue = 4 \| pages = 635-638 \| month = Apr \| year = 2018 \| doi = 10.1007/s00401-018-1819-x \| PMID = 29435664 }}</ref>
	*SHH (PTCH1 & SUFU in infant, PTCH1, SMO, Gli2, MYCN in non-infant, approx 30%).<ref>{{Cite journal \| last1 = Neumann \| first1 = JE. \| last2 = Swartling \| first2 = FJ. \| last3 = Schüller \| first3 = U. \| title = Medulloblastoma: experimental models and reality. \| journal = Acta Neuropathol \| volume = \| issue = \| pages = \| month = Jul \| year = 2017 \| doi = 10.1007/s00401-017-1753-3 \| PMID = 28725965 }}</ref>		*SHH (PTCH1 & SUFU in infant, PTCH1, SMO, Gli2, MYCN in non-infant, approx 30%).<ref>{{Cite journal \| last1 = Neumann \| first1 = JE. \| last2 = Swartling \| first2 = FJ. \| last3 = Schüller \| first3 = U. \| title = Medulloblastoma: experimental models and reality. \| journal = Acta Neuropathol \| volume = \| issue = \| pages = \| month = Jul \| year = 2017 \| doi = 10.1007/s00401-017-1753-3 \| PMID = 28725965 }}</ref>
	**infantile and adult cases are biologically different, esp p53 mutant tumors are associated with poor outcome.<ref>{{Cite journal \| last1 = Kool \| first1 = M. \| last2 = Jones \| first2 = DT. \| last3 = Jäger \| first3 = N. \| last4 = Northcott \| first4 = PA. \| last5 = Pugh \| first5 = TJ. \| last6 = Hovestadt \| first6 = V. \| last7 = Piro \| first7 = RM. \| last8 = Esparza \| first8 = LA. \| last9 = Markant \| first9 = SL. \| title = Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition. \| journal = Cancer Cell \| volume = 25 \| issue = 3 \| pages = 393-405 \| month = Mar \| year = 2014 \| doi = 10.1016/j.ccr.2014.02.004 \| PMID = 24651015 }}</ref>		**infantile and adult cases are biologically different, esp p53 mutant tumors are associated with poor outcome.<ref>{{Cite journal \| last1 = Kool \| first1 = M. \| last2 = Jones \| first2 = DT. \| last3 = Jäger \| first3 = N. \| last4 = Northcott \| first4 = PA. \| last5 = Pugh \| first5 = TJ. \| last6 = Hovestadt \| first6 = V. \| last7 = Piro \| first7 = RM. \| last8 = Esparza \| first8 = LA. \| last9 = Markant \| first9 = SL. \| title = Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition. \| journal = Cancer Cell \| volume = 25 \| issue = 3 \| pages = 393-405 \| month = Mar \| year = 2014 \| doi = 10.1016/j.ccr.2014.02.004 \| PMID = 24651015 }}</ref>

Jensflorian: /* Histologically defined */ desmoplastic

2017-09-21T15:26:28Z

Histologically defined: desmoplastic

← Older revision		Revision as of 15:26, 21 September 2017
Line 82:		Line 82:
	*Severe anaplasia.		*Severe anaplasia.
	*Polygonal cells.		*Polygonal cells.

			====Desmoplastic/nodular variant====
			Features:
			*Nodular, reticulin-free zones (pale islands).
			**Mitotic activity is reduced.
			*Densely packed internodal, reticulin-positive tumor areas.
			*Absence of neuroblastic rosettes.
			*Neuronal markers (NeuN, Synaptophysin) can be +ve.

	===Genetically defined===		===Genetically defined===

Jensflorian: /* General */ inherited diseases

2017-09-21T15:11:13Z

General: inherited diseases

← Older revision		Revision as of 15:11, 21 September 2017
Line 4:		Line 4:

	==General==		==General==
	*Mostly paediatric population.		*Mostly paediatric population (mean age: 9 years).
	*May be seen as a component of [[nevoid basal cell carcinoma syndrome]] (NBCCS).		*May be seen as a component of [[nevoid basal cell carcinoma syndrome]] (NBCCS) AKA Gorlin syndrome, [[Li-Fraumeni syndrome]], Turcot syndrome, Rubinstain-Taybi syndrome and Nijmegen breakage syndrome.
	**Show molecularly spatially homogeneous transcriptomes, allowing for accurate subgrouping of tumors from a single biopsy.<ref>{{Cite journal \| last1 = Morrissy \| first1 = AS. \| last2 = Cavalli \| first2 = FMG. \| last3 = Remke \| first3 = M. \| last4 = Ramaswamy \| first4 = V. \| last5 = Shih \| first5 = DJH. \| last6 = Holgado \| first6 = BL. \| last7 = Farooq \| first7 = H. \| last8 = Donovan \| first8 = LK. \| last9 = Garzia \| first9 = L. \| title = Spatial heterogeneity in medulloblastoma. \| journal = Nat Genet \| volume = 49 \| issue = 5 \| pages = 780-788 \| month = May \| year = 2017 \| doi = 10.1038/ng.3838 \| PMID = 28394352 }}</ref>		**Show molecularly spatially homogeneous transcriptomes, allowing for accurate subgrouping of tumors from a single biopsy.<ref>{{Cite journal \| last1 = Morrissy \| first1 = AS. \| last2 = Cavalli \| first2 = FMG. \| last3 = Remke \| first3 = M. \| last4 = Ramaswamy \| first4 = V. \| last5 = Shih \| first5 = DJH. \| last6 = Holgado \| first6 = BL. \| last7 = Farooq \| first7 = H. \| last8 = Donovan \| first8 = LK. \| last9 = Garzia \| first9 = L. \| title = Spatial heterogeneity in medulloblastoma. \| journal = Nat Genet \| volume = 49 \| issue = 5 \| pages = 780-788 \| month = May \| year = 2017 \| doi = 10.1038/ng.3838 \| PMID = 28394352 }}</ref>
	*Commonly spread via cerebrospinal fluid (CSF).<ref>{{Ref APBR\|424 Q34}}</ref>		*Commonly spread via cerebrospinal fluid (CSF).<ref>{{Ref APBR\|424 Q34}}</ref>
	**May be detected in [[CSF cytopathology]] specimens.		**May be detected in [[CSF cytopathology]] specimens.
			*All subgroups correspond to WHO grade IV.

	==Gross==		==Gross==

Jensflorian: /* Gross */ update

2017-09-21T15:07:17Z

Gross: update

← Older revision		Revision as of 15:07, 21 September 2017
Line 11:		Line 11:

	==Gross==		==Gross==
	*Location: cerebellum - '''key feature'''.		*Location: cerebellum - '''key feature''' or dorsal brainstem (lower rhombic lip).
	**Morphologically identical supratentorial tumours are called ''[[primitive neuroectodermal tumour]]'' (PNET).		**Morphologically identical supratentorial tumours are called ''[[primitive neuroectodermal tumour]]'' (PNET).
	**Supratentorial and spinal metastases from initial tumor possible.		**Supratentorial and spinal metastases from initial tumor possible.

← Older revision		Revision as of 13:18, 10 April 2018
Line 93:		Line 93:
	===Genetically defined===		===Genetically defined===
	*WNT (brainstem-related, usu. CTNNB1 mutations, less common: CSNK2B, AXIN2, APC, approx. 10%).<ref>{{Cite journal \| last1 = Wefers \| first1 = AK. \| last2 = Warmuth-Metz \| first2 = M. \| last3 = Pöschl \| first3 = J. \| last4 = von Bueren \| first4 = AO. \| last5 = Monoranu \| first5 = CM. \| last6 = Seelos \| first6 = K. \| last7 = Peraud \| first7 = A. \| last8 = Tonn \| first8 = JC. \| last9 = Koch \| first9 = A. \| title = Subgroup-specific localization of human medulloblastoma based on pre-operative MRI. \| journal = Acta Neuropathol \| volume = 127 \| issue = 6 \| pages = 931-3 \| month = \| year = 2014 \| doi = 10.1007/s00401-014-1271-5 \| PMID = 24699697 }}</ref>		*WNT (brainstem-related, usu. CTNNB1 mutations, less common: CSNK2B, AXIN2, APC, approx. 10%).<ref>{{Cite journal \| last1 = Wefers \| first1 = AK. \| last2 = Warmuth-Metz \| first2 = M. \| last3 = Pöschl \| first3 = J. \| last4 = von Bueren \| first4 = AO. \| last5 = Monoranu \| first5 = CM. \| last6 = Seelos \| first6 = K. \| last7 = Peraud \| first7 = A. \| last8 = Tonn \| first8 = JC. \| last9 = Koch \| first9 = A. \| title = Subgroup-specific localization of human medulloblastoma based on pre-operative MRI. \| journal = Acta Neuropathol \| volume = 127 \| issue = 6 \| pages = 931-3 \| month = \| year = 2014 \| doi = 10.1007/s00401-014-1271-5 \| PMID = 24699697 }}</ref>
			**Caution: Some WNT-activated MB may show additional subclonal SHH-mutations.<ref>{{Cite journal \| last1 = Iorgulescu \| first1 = JB. \| last2 = Van Ziffle \| first2 = J. \| last3 = Stevers \| first3 = M. \| last4 = Grenert \| first4 = JP. \| last5 = Bastian \| first5 = BC. \| last6 = Chavez \| first6 = L. \| last7 = Stichel \| first7 = D. \| last8 = Buchhalter \| first8 = I. \| last9 = Samuel \| first9 = D. \| title = Deep sequencing of WNT-activated medulloblastomas reveals secondary SHH pathway activation. \| journal = Acta Neuropathol \| volume = 135 \| issue = 4 \| pages = 635-638 \| month = Apr \| year = 2018 \| doi = 10.1007/s00401-018-1819-x \| PMID = 29435664 }}</ref>
	*SHH (PTCH1 & SUFU in infant, PTCH1, SMO, Gli2, MYCN in non-infant, approx 30%).<ref>{{Cite journal \| last1 = Neumann \| first1 = JE. \| last2 = Swartling \| first2 = FJ. \| last3 = Schüller \| first3 = U. \| title = Medulloblastoma: experimental models and reality. \| journal = Acta Neuropathol \| volume = \| issue = \| pages = \| month = Jul \| year = 2017 \| doi = 10.1007/s00401-017-1753-3 \| PMID = 28725965 }}</ref>		*SHH (PTCH1 & SUFU in infant, PTCH1, SMO, Gli2, MYCN in non-infant, approx 30%).<ref>{{Cite journal \| last1 = Neumann \| first1 = JE. \| last2 = Swartling \| first2 = FJ. \| last3 = Schüller \| first3 = U. \| title = Medulloblastoma: experimental models and reality. \| journal = Acta Neuropathol \| volume = \| issue = \| pages = \| month = Jul \| year = 2017 \| doi = 10.1007/s00401-017-1753-3 \| PMID = 28725965 }}</ref>
	**infantile and adult cases are biologically different, esp p53 mutant tumors are associated with poor outcome.<ref>{{Cite journal \| last1 = Kool \| first1 = M. \| last2 = Jones \| first2 = DT. \| last3 = Jäger \| first3 = N. \| last4 = Northcott \| first4 = PA. \| last5 = Pugh \| first5 = TJ. \| last6 = Hovestadt \| first6 = V. \| last7 = Piro \| first7 = RM. \| last8 = Esparza \| first8 = LA. \| last9 = Markant \| first9 = SL. \| title = Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition. \| journal = Cancer Cell \| volume = 25 \| issue = 3 \| pages = 393-405 \| month = Mar \| year = 2014 \| doi = 10.1016/j.ccr.2014.02.004 \| PMID = 24651015 }}</ref>		**infantile and adult cases are biologically different, esp p53 mutant tumors are associated with poor outcome.<ref>{{Cite journal \| last1 = Kool \| first1 = M. \| last2 = Jones \| first2 = DT. \| last3 = Jäger \| first3 = N. \| last4 = Northcott \| first4 = PA. \| last5 = Pugh \| first5 = TJ. \| last6 = Hovestadt \| first6 = V. \| last7 = Piro \| first7 = RM. \| last8 = Esparza \| first8 = LA. \| last9 = Markant \| first9 = SL. \| title = Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition. \| journal = Cancer Cell \| volume = 25 \| issue = 3 \| pages = 393-405 \| month = Mar \| year = 2014 \| doi = 10.1016/j.ccr.2014.02.004 \| PMID = 24651015 }}</ref>