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Diagnosis in short

Classic medulloblastoma H&E stain.
LM DDx small cell round blue tumous.
Stains Reticulin +ve (in desmoplastic MB)
Gross cerebellar.
Site brain - usu. cerebellum

Prevalence common - esp. in children
Prognosis subtype-dependent (WHO Grade IV)

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.


  • 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.
    • Show molecularly spatially homogeneous transcriptomes, allowing for accurate subgrouping of tumors from a single biopsy.[1]
  • Commonly spread via cerebrospinal fluid (CSF).[2]


  • Location: cerebellum - key feature or dorsal brainstem (lower rhombic lip).
    • For morphologically identical supratentorial tumours see possible DDx.
    • Supratentorial and spinal metastases from initial medulloblastoma possible.




  • 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)

Genetic grouping with IHC:[5]

  • 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.


  • Small round cell tumours.
    • AT/RT. (INI1 loss)
    • CNS-embryonal tumour (aka CNS-PNET).
    • ETMR (LIN28)-positive.
    • Ewing Sarcoma family members.
    • Small cell glioblastoma (Olig2 +ve) - esp. after RT and longer latency. [6]
    • Anaplastic ependymoma.





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).

Classic variant

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

Anaplastic variant


  • Larger cells.
  • Severe anaplasia.
  • Polygonal cells.

Desmoplastic/nodular variant


  • 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%).[7]
    • Usu. classic MB in histology.
    • Caution: Some WNT-activated MB may show additional subclonal SHH-mutations.[8]
    • 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%).[9]
    • Origin in the cerebellar granule neuron cell precursors.
    • Infantile and adult cases are biologically different, esp p53 mutant tumors are associated with poor outcome.[10]
    • Infantile, p53 wildtype: Usu. desmoplastic/nodular, 10q loss.
    • SHH-p53 mutant: Usu. large cell/anaplastic, 17q loss.
  • Group 3 (approx. 20%).
    • Classic and large cell/anaplastic, MYC amplification, isochromosome 17q.
  • Group 4 (approx. 40%).
    • Classic phenotype, MYCN amplification, isodicentric 17q.
    • Group 3+4 are often designated together as Non-Wnt/Non-SHH tumours.


  • Prognosis based on histology:[11][12][13] DNMB & MBEN > classic > anaplastic & large cell variant.
  • Prognosis based on genetics:[14] WNT > SHH (without Tp53 mut) > Group 4 > Group 3 > SHH (with Tp53 mut).

See also


  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: 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. Pietsch, T.; Haberler, C.. "Update on the integrated histopathological and genetic classification of medulloblastoma - a practical diagnostic guideline.". Clin Neuropathol 35 (6): 344-352. doi:10.5414/NP300999. PMID 27781424.
  6. Phi, JH.; Park, AK.; Lee, S.; Choi, SA.; Baek, IP.; Kim, P.; Kim, EH.; Park, HC. et al. (Apr 2018). "Genomic analysis reveals secondary glioblastoma after radiotherapy in a subset of recurrent medulloblastomas.". Acta Neuropathol. doi:10.1007/s00401-018-1845-8. PMID 29644394.
  7. 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.
  8. Iorgulescu, JB.; Van Ziffle, J.; Stevers, M.; Grenert, JP.; Bastian, BC.; Chavez, L.; Stichel, D.; Buchhalter, I. et al. (Apr 2018). "Deep sequencing of WNT-activated medulloblastomas reveals secondary SHH pathway activation.". Acta Neuropathol 135 (4): 635-638. doi:10.1007/s00401-018-1819-x. PMID 29435664.
  9. Neumann, JE.; Swartling, FJ.; Schüller, U. (Jul 2017). "Medulloblastoma: experimental models and reality.". Acta Neuropathol. doi:10.1007/s00401-017-1753-3. PMID 28725965.
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. 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.