Application of Genome-Wide DNA Methylation Analysis to Differentiate a Case of Radiation-Induced Glioblastoma From Late-Relapsed Medulloblastoma

J Neuropathol Exp Neurol. 2021 Jun 4;80(6):552-557. doi: 10.1093/jnen/nlab043.

Abstract

Recurrent medulloblastoma can be difficult to diagnose with conventional diagnostic methods because other lesions mimic tumor relapse, particularly at later stages. We report 2 cases of medulloblastoma, both of which seemed to develop late recurrences. Case 1 was a 6-year-old girl who had a medulloblastoma with focal desmoplasia. She was in complete remission for 9 years after treatment but developed an intradural lesion in her thoracic spine, which was pathologically confirmed as tumor recurrence by biopsy. Case 2 was a 10-year-old girl who had a nonmetastatic medulloblastoma. She developed a left cerebellar mass 5 years after the initial diagnosis; the pathological diagnosis was tumor relapse. We performed t-distributed stochastic neighbor embedding of the methylation data from these cases and reference data. In contrast to the consistency of methylation profiling and copy number abnormalities between primary and recurrent tumors of Case 1, the analysis of the recurrent tumor in Case 2 was distinct from medulloblastomas and clustered with "IDH-wild type glioblastomas," suggesting that the recurrent tumor was a radiation-induced glioblastoma. This report highlights the clinical utility of molecular genetic/epigenetic analysis combined with a standard diagnostic approach to confirm the diagnosis of brain tumor recurrence.

Keywords: Medulloblastoma; Methylation analysis; Recurrence.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain Neoplasms / diagnosis
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / pathology
  • Cerebellar Neoplasms / diagnosis
  • Cerebellar Neoplasms / genetics
  • Cerebellar Neoplasms / pathology
  • Child
  • Chronic Disease
  • DNA Methylation / physiology*
  • Female
  • Glioblastoma / diagnosis
  • Glioblastoma / genetics*
  • Glioblastoma / pathology
  • Humans
  • Medulloblastoma / diagnosis
  • Medulloblastoma / genetics*
  • Medulloblastoma / pathology
  • Neoplasm Recurrence, Local / diagnosis
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / pathology