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Child's Nervous System

, Volume 34, Issue 5, pp 809–815 | Cite as

Medulloblastoma, WNT-activated/SHH-activated: clinical impact of molecular analysis and histogenetic evaluation

  • Eduardo Cambruzzi
Review Paper

Abstract

Purpose

Medulloblastoma (MDB) is a small cell poorly differentiated embryonal tumor of the cerebellum, which more frequently compromises children. Overall prognosis is favorable, but dependent of stage, histopathological pattern and molecular group. Approximately 30% of the affected patients will die from the disease. WHO 2016 Classification of Tumors of the Central Nervous System (CNS) has been classified MDB into four principal groups: WNT-activated MDB, SHH-activated MDB, group 3 MDB, and group 4 MDB. WNT-activated MDB is associated to monosomy 6, CTNNB1, DDX3X and TP53 mutations, beta-catenin nuclear immunoexpression, and a better prognosis than SHH-activated MDB.

Discussion

WNT-activated tumors account approximately for 10% of cases of MDBs, and are thought to arise from cells in the dorsal brain stem/lower rhombic lip progenitor cells. SHH-activated MDB more frequently arises in the lateral hemispheres of the cerebellum, and clinical outcome in this group is variable. TP53-mutant SHHactivated MDB usually shows the large cell/anaplastic pattern, and can be related to MYCN amplification, GLI2 amplification and 17p loss. TP53-wildtype SHH-activated MDB is more commonly of desmoplastic/nodular morphology, and can be related to PTCH1 deletion and 10q loss. Gene expression and methylation profiling is the gold standard for defining molecular groups of MDB. In immunohistochemistry assays, anti-GAB1 antibody expression is positive in tumors showing SHH pathway activation or PTCH mutation, while positive immunoexpression for YAP1 antibody can be only found in WNT-activated and SHH-activated MDB.

Keywords

Medulloblastoma WNT-activated SHH-activated Embryonal neuroepithelial tumor Central nervous system tumors Prognosis 

Notes

Compliance with ethical standards

Conflict of interest

The author declares that there is no conflict of interests.

Ethical approval

This article does not contain any studies with human participants or animals performed by the author.

Informed consent

Not applicable.

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© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Universidade Federal do Rio Grande do SulPorto AlegreBrazil
  2. 2.Department of Pathology, Santa Rita HospitalComplexo Hospitalar Santa CasaPorto AlegreBrazil
  3. 3.Hospital N. Sra. da ConceiçãoPorto AlegreBrazil
  4. 4.Universidade Luterana do BrasilCanoasBrazil
  5. 5.Instituto de CardiologiaFundação Universitária de CardiologiaPorto AlegreBrazil

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