Difference between revisions of "Medulloblastoma"

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==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.
**Gene: ''patched'' (abbreviated ''PTCH1'').<ref name=omim601309>{{OMIM|601309}}</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'''.
*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.
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==Subtypes==
==Subtypes==
===Histologically defined===
*Classic medulloblastoma (~85% of all medulloblastomas).
*Classic medulloblastoma (~85% of all medulloblastomas).
*Variants of medulloblastoma (~15% of all medulloblastomas together):
*Variants of medulloblastoma (~15% of all medulloblastomas together):
*#Anaplastic variant.
*#Anaplastic / Large cell variant.
*#Large cell variant.
*#Desmoplastic/nodular medulloblastoma (DNMB).
*#Desmoplastic/nodular medulloblastoma (DNMB).
*#Medulloblastoma with extensive nodularity (MBEN).
*#Medulloblastoma with extensive nodularity (MBEN).
Notes:
*Prognosis:<ref name=pmid18841049>{{cite journal |author=Gulino A, Arcella A, Giangaspero F |title=Pathological and molecular heterogeneity of medulloblastoma |journal=Curr Opin Oncol |volume=20 |issue=6 |pages=668–75 |year=2008 |month=November |pmid=18841049 |doi=10.1097/CCO.0b013e32831369f4 |url=}}</ref><ref name=pmid20940197>{{cite journal |author=Rutkowski S, von Hoff K, Emser A, ''et al.'' |title=Survival and Prognostic Factors of Early Childhood Medulloblastoma: An International Meta-Analysis |journal=J Clin Oncol |volume=28 |issue=33 |pages=4961–4968 |year=2010 |month=November |pmid=20940197 |doi=10.1200/JCO.2010.30.2299 |url=}}</ref> DNMB & MBEN > classic > anaplastic variant, large cell variant.


====Anaplastic variant====
====Anaplastic variant====
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*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===
*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>
*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>
*Group 3 (approx. 20%).
*Group 4 (approx. 40%).
** Group 3+4 are often designated together as Non-Wnt/Non-SHH tumours.
==Prognosis==
*Prognosis based on histology:<ref name=pmid18841049>{{cite journal |author=Gulino A, Arcella A, Giangaspero F |title=Pathological and molecular heterogeneity of medulloblastoma |journal=Curr Opin Oncol |volume=20 |issue=6 |pages=668–75 |year=2008 |month=November |pmid=18841049 |doi=10.1097/CCO.0b013e32831369f4 |url=}}</ref><ref name=pmid20940197>{{cite journal |author=Rutkowski S, von Hoff K, Emser A, ''et al.'' |title=Survival and Prognostic Factors of Early Childhood Medulloblastoma: An International Meta-Analysis |journal=J Clin Oncol |volume=28 |issue=33 |pages=4961–4968 |year=2010 |month=November |pmid=20940197 |doi=10.1200/JCO.2010.30.2299 |url=}}</ref><ref>{{Cite journal  | last1 = Rutkowski | first1 = S. | last2 = Bode | first2 = U. | last3 = Deinlein | first3 = F. | last4 = Ottensmeier | first4 = H. | last5 = Warmuth-Metz | first5 = M. | last6 = Soerensen | first6 = N. | last7 = Graf | first7 = N. | last8 = Emser | first8 = A. | last9 = Pietsch | first9 = T. | title = Treatment of early childhood medulloblastoma by postoperative chemotherapy alone. | journal = N Engl J Med | volume = 352 | issue = 10 | pages = 978-86 | month = Mar | year = 2005 | doi = 10.1056/NEJMoa042176 | PMID = 15758008 }}
</ref> DNMB & MBEN > classic > anaplastic & large cell variant.
*Prognosis based on genetics:<ref>{{Cite journal  | last1 = Ramaswamy | first1 = V. | last2 = Remke | first2 = M. | last3 = Bouffet | first3 = E. | last4 = Bailey | first4 = S. | last5 = Clifford | first5 = SC. | last6 = Doz | first6 = F. | last7 = Kool | first7 = M. | last8 = Dufour | first8 = C. | last9 = Vassal | first9 = G. | title = Risk stratification of childhood medulloblastoma in the molecular era: the current consensus. | journal = Acta Neuropathol | volume = 131 | issue = 6 | pages = 821-31 | month = Jun | year = 2016 | doi = 10.1007/s00401-016-1569-6 | PMID = 27040285 }}</ref> WNT > SHH (without Tp53 mut) > Group 4 > Group 3 > SHH (with Tp53 mut).


==See also==
==See also==

Revision as of 15:26, 21 September 2017

Medulloblastoma is a malignant small round cell tumour that is found in the cerebellum.

Morphologically identical supratentorial tumours are called primitive neuroectodermal tumour (PNET).

General

  • Mostly paediatric population (mean age: 9 years).
  • 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.[1]
  • Commonly spread via cerebrospinal fluid (CSF).[2]
  • All subgroups correspond to WHO grade IV.

Gross

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

Microscopic

Features:[3]

IHC

  • MAP2 usu. +ve
  • Synaptophysin +ve (weak to strong)
  • NSE +ve/-ve
  • NF +ve/-ve
  • Chromogranin +ve/-ve
  • GFAP +ve/-ve (mostly along blood vessels)
  • Vimentin +ve
  • Nestin +ve
  • INI1 retained (no loss)

DDx:

Images

Case:

www:

Subtypes

Histologically defined

  • Classic medulloblastoma (~85% of all medulloblastomas).
  • Variants of medulloblastoma (~15% of all medulloblastomas together):
    1. Anaplastic / Large cell variant.
    2. Desmoplastic/nodular medulloblastoma (DNMB).
    3. Medulloblastoma with extensive nodularity (MBEN).

Anaplastic variant

Features:

  • Larger cells.
  • Severe anaplasia.
  • 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

  • WNT (brainstem-related, usu. CTNNB1 mutations, less common: CSNK2B, AXIN2, APC, approx. 10%).[5]
  • SHH (PTCH1 & SUFU in infant, PTCH1, SMO, Gli2, MYCN in non-infant, approx 30%).[6]
    • infantile and adult cases are biologically different, esp p53 mutant tumors are associated with poor outcome.[7]
  • Group 3 (approx. 20%).
  • Group 4 (approx. 40%).
    • Group 3+4 are often designated together as Non-Wnt/Non-SHH tumours.

Prognosis

  • Prognosis based on histology:[8][9][10] DNMB & MBEN > classic > anaplastic & large cell variant.
  • Prognosis based on genetics:[11] WNT > SHH (without Tp53 mut) > Group 4 > Group 3 > SHH (with Tp53 mut).

See also

References

  1. Morrissy, AS.; Cavalli, FMG.; Remke, M.; Ramaswamy, V.; Shih, DJH.; Holgado, BL.; Farooq, H.; Donovan, LK. et al. (May 2017). "Spatial heterogeneity in medulloblastoma.". Nat Genet 49 (5): 780-788. doi:10.1038/ng.3838. PMID 28394352.
  2. Lefkowitch, Jay H. (2006). Anatomic Pathology Board Review (1st ed.). Saunders. pp. 424 Q34. ISBN 978-1416025887.
  3. URL: http://moon.ouhsc.edu/kfung/jty1/neurotest/Q93-Ans.htm. Accessed on: 26 October 2010.
  4. Wippold FJ, Perry A (March 2006). "Neuropathology for the neuroradiologist: rosettes and pseudorosettes". AJNR Am J Neuroradiol 27 (3): 488–92. PMID 16551982.
  5. Wefers, AK.; Warmuth-Metz, M.; Pöschl, J.; von Bueren, AO.; Monoranu, CM.; Seelos, K.; Peraud, A.; Tonn, JC. et al. (2014). "Subgroup-specific localization of human medulloblastoma based on pre-operative MRI.". Acta Neuropathol 127 (6): 931-3. doi:10.1007/s00401-014-1271-5. PMID 24699697.
  6. Neumann, JE.; Swartling, FJ.; Schüller, U. (Jul 2017). "Medulloblastoma: experimental models and reality.". Acta Neuropathol. doi:10.1007/s00401-017-1753-3. PMID 28725965.
  7. Kool, M.; Jones, DT.; Jäger, N.; Northcott, PA.; Pugh, TJ.; Hovestadt, V.; Piro, RM.; Esparza, LA. et al. (Mar 2014). "Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition.". Cancer Cell 25 (3): 393-405. doi:10.1016/j.ccr.2014.02.004. PMID 24651015.
  8. Gulino A, Arcella A, Giangaspero F (November 2008). "Pathological and molecular heterogeneity of medulloblastoma". Curr Opin Oncol 20 (6): 668–75. doi:10.1097/CCO.0b013e32831369f4. PMID 18841049.
  9. Rutkowski S, von Hoff K, Emser A, et al. (November 2010). "Survival and Prognostic Factors of Early Childhood Medulloblastoma: An International Meta-Analysis". J Clin Oncol 28 (33): 4961–4968. doi:10.1200/JCO.2010.30.2299. PMID 20940197.
  10. Rutkowski, S.; Bode, U.; Deinlein, F.; Ottensmeier, H.; Warmuth-Metz, M.; Soerensen, N.; Graf, N.; Emser, A. et al. (Mar 2005). "Treatment of early childhood medulloblastoma by postoperative chemotherapy alone.". N Engl J Med 352 (10): 978-86. doi:10.1056/NEJMoa042176. PMID 15758008.
  11. Ramaswamy, V.; Remke, M.; Bouffet, E.; Bailey, S.; Clifford, SC.; Doz, F.; Kool, M.; Dufour, C. et al. (Jun 2016). "Risk stratification of childhood medulloblastoma in the molecular era: the current consensus.". Acta Neuropathol 131 (6): 821-31. doi:10.1007/s00401-016-1569-6. PMID 27040285.