Difference between revisions of "Medulloblastoma"

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===Genetically defined===
===Genetically defined===
*WNT
*WNT (brainstem-related, usu. CTNNB1 mutations, less common: CSNK2B, AXIN2, APC).<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  
*SHH (PTCH1 & SUFU in infant, PTCH1, SMO, Gli2, MYCN in non-infant).<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>
*Group 3
*Group 3

Revision as of 14:44, 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

Gross

  • Location: cerebellum - key feature.
    • 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.

Genetically defined

  • WNT (brainstem-related, usu. CTNNB1 mutations, less common: CSNK2B, AXIN2, APC).[5]
  • SHH (PTCH1 & SUFU in infant, PTCH1, SMO, Gli2, MYCN in non-infant).[6]
    • infantile and adult cases are biologically different, esp p53 mutant tumors are associated with poor outcome.[7]
  • Group 3
  • Group 4

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. Online 'Mendelian Inheritance in Man' (OMIM) 601309
  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.