Update on the integrated histopathological and genetic classification of medulloblastoma - a practical diagnostic guideline

Clin Neuropathol. Nov/Dec 2016;35(6):344-352. doi: 10.5414/NP300999.

Abstract

The revised WHO classification of tumors of the CNS 2016 has introduced the concept of the integrated diagnosis. The definition of medulloblastoma entities now requires a combination of the traditional histological information with additional molecular/genetic features. For definition of the histopathological component of the medulloblastoma diagnosis, the tumors should be assigned to one of the four entities classic, desmoplastic/nodular (DNMB), extensive nodular (MBEN), or large cell/anaplastic (LC/A) medulloblastoma. The genetically defined component comprises the four entities WNT-activated, SHH-activated and TP53 wildtype, SHH-activated and TP53 mutant, or non-WNT/non-SHH medulloblastoma. Robust and validated methods are available to allow a precise diagnosis of these medulloblastoma entities according to the updated WHO classification, and for differential diagnostic purposes. A combination of immunohistochemical markers including β-catenin, Yap1, p75-NGFR, Otx2, and p53, in combination with targeted sequencing and copy number assessment such as FISH analysis for MYC genes allows a precise assignment of patients for risk-adapted stratification. It also allows comparison to results of study cohorts in the past and provides a robust basis for further treatment refinement. .

MeSH terms

  • Biomarkers, Tumor / genetics
  • Cerebellar Neoplasms / classification
  • Cerebellar Neoplasms / diagnosis
  • Cerebellar Neoplasms / genetics*
  • Cerebellar Neoplasms / pathology*
  • Humans
  • Medulloblastoma / classification
  • Medulloblastoma / diagnosis
  • Medulloblastoma / genetics*
  • Medulloblastoma / pathology*
  • Practice Guidelines as Topic*
  • World Health Organization

Substances

  • Biomarkers, Tumor