In 2016, medulloblastoma classification was restructured to allow for incorporation of updated data about medulloblastoma biology, genomics, and clinical behavior. For the first time, medulloblastomas were classified according to molecular characteristics (“genetically defined” categories) as well as histologic characteristics (“histologically defined” categories). Current genetically-defined categories include WNT-activated, SHH-activated TP53 wildtype, SHH-activated TP53-mutant, and non-WNT/non-SHH. In this article, we review the most recent update to the classification of medulloblastomas, provide a practical approach to immunohistochemical and molecular testing for these tumors, and demonstrate how to use key molecular genetic findings to develop an integrated diagnosis.
LouisDNOhgakiHWiestlerODCaveneeWK.WHO Classification of Tumours of the Central Nervous System. Lyon, France: International Agency for Research on Cancer; 2016.
2.
LouisDNWesselingPBrandnerS, et al. Data sets for the reporting of tumors of the central nervous system: recommendations from the international collaboration on cancer reporting.Arch Pathol Lab Med. 2019;144(2):196–206.
3.
LouisDNPerryAReifenbergerG, et al. The 2016 World Health Organization classification of tumors of the central nervous system: a summary. Acta Neuropathol. 2016;131(6):803–820.
4.
GibsonPTongYRobinsonG, et al. Subtypes of medulloblastoma have distinct developmental origins.Nature. 2010;468(7327):1095–1099.
5.
RamaswamyVRemkeMBouffetE, et al. Risk stratification of childhood medulloblastoma in the molecular era: the current consensus. Acta Neuropathol (Berl). 2016;131(6):821–831.
6.
SurunAVarletPBrugièresL, et al. Medulloblastomas associated with an APC germline pathogenic variant share the good prognosis of CTNNB1-mutated medulloblastomas.Neuro-Oncol. 2020;22(1):128–138.
7.
DasARamaswamyV.Less treatment for wing less medulloblastoma: germline data re-emphasize this.Neuro-Oncol. 2020;22(1):7–9.
8.
EllisonDWDaltonJKocakM, et al. Medulloblastoma: clinicopathological correlates of SHH, WNT, and non-SHH/WNT molecular subgroups.Acta Neuropathol (Berl). 2011;121(3):381–396.
9.
ZhukovaNRamaswamyVRemkeM, et al. Subgroup-specific prognostic implications of TP53 mutation in medulloblastoma. J Clin Oncol Off J Am Soc Clin Oncol. 2013;31(23):2927–2935.
10.
CavalliFMGRemkeMRampasekL, et al. Intertumoral heterogeneity within medulloblastoma subgroups.Cancer Cell. 2017;31(6):737–754.e6.
11.
Fruehwald-PallamarJPuchnerSBRossiA, et al. Magnetic resonance imaging spectrum of medulloblastoma.Neuroradiology. 2011;53(6):387–396.
12.
WaszakSMNorthcottPABuchhalterI, et al. Spectrum and prevalence of genetic predisposition in medulloblastoma: a retrospective genetic study and prospective validation in a clinical trial cohort. Lancet Oncol. 2018;19(6):785–798.
13.
BegemannMWaszakSMRobinsonGW, et al. Germline GPR161 mutations predispose to pediatric medulloblastoma.J Clin Oncol. 2019;38(1):43–50.
14.
WaszakSMRobinsonGWGudenasBL, et al. Germline elongator mutations in sonic hedgehog medulloblastoma.Nature. 2020;580(7803):396–401.
15.
KoolMJonesDTWJägerN, et al. Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition.Cancer Cell. 2014;25(3):393–405.
16.
RamaswamyVNörCTaylorMD. p53 and meduloblastoma.Cold Spring Harb Perspect Med. 2016;6(2):a026278.
17.
SharmaTSchwalbeECWilliamsonD, et al. Second-generation molecular subgrouping of medulloblastoma: an international meta-analysis of group 3 and group 4 subtypes.Acta Neuropathol (Berl). 2019;138(2):309–326.
18.
ShihDJHNorthcottPARemkeM, et al. Cytogenetic prognostication within medulloblastoma subgroups.J Clin Oncol. 2014;32(9):886–896.
19.
EberhartCGKepnerJLGoldthwaitePT, et al. Histopathologic grading of medulloblastomas. Cancer. 2002;94(2):552–560.
20.
GoschzikTSchwalbeECHicksD, et al. Prognostic effect of whole chromosomal aberration signatures in standard-risk, non-WNT/non-SHH medulloblastoma: a retrospective, molecular analysis of the HIT-SIOP PNET 4 trial. Lancet Oncol. 2018;19(12):1602–1616.
21.
KoolMKorshunovARemkeM, et al. Molecular subgroups of medulloblastoma: an international meta-analysis of transcriptome, genetic aberrations, and clinical data of WNT, SHH, Group 3, and Group 4 medulloblastomas.Acta Neuropathol (Berl). 2012;123(4):473–484.
22.
TaylorMDNorthcottPAKorshunovA, et al. Molecular subgroups of medulloblastoma: the current consensus.Acta Neuropathol (Berl). 2012;123(4):465–472.
23.
JuraschkaKTaylorMD.Medulloblastoma in the age of molecular subgroups: a review: JNSPG 75th anniversary invited review article. J Neurosurg Pediatr. 2019;24(4):353–363.
