Primary CNS Alveolar Rhabdomyosarcoma: Importance of Epigenetic and Transcriptomic Assays for Accurate Diagnosis

J Neuropathol Exp Neurol. 2019 Nov 1;78(11):1073-1075. doi: 10.1093/jnen/nlz083.

Abstract

We present the case of a 22-year-old woman who developed increasing headaches, nausea, and vomiting. Imaging identified a 3 × 3 cm heterogeneously enhancing cystic mass in the posterior III ventricular/pineal region. Pathology review of the initial lesion revealed a highly malignant spindle cell neoplasm composed of round to mostly oval elongated cells with relatively small amounts of cytoplasm arranged in sheets and fascicles with focal storiform pattern. Whole genome methylation analysis through unsupervised clustering with data generated from other primary intracranial tumors and peripheral sarcomas was performed at the German Cancer Research Center (DKFZ) and classified the tumor with the group of alveolar rhabdomyosarcomas (ARMS). Further RNA sequencing revealed an in frame PAX3 (EX 7)-NCOA2 (EX12) fusion confirming the diagnosis. This is the first evidence of occurrence of PAX3-NCOA2 in primary CNS ARMS.

Keywords: Alveolar rhabdomyosarcoma; Central nervous system; RNA fusion.

Publication types

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

MeSH terms

  • Adult
  • Brain / metabolism
  • Brain / pathology
  • Central Nervous System Neoplasms / diagnosis*
  • Central Nervous System Neoplasms / genetics
  • Central Nervous System Neoplasms / metabolism
  • Central Nervous System Neoplasms / pathology
  • DNA Methylation
  • Epigenesis, Genetic
  • Epigenomics*
  • Female
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Nuclear Receptor Coactivator 2 / genetics
  • PAX3 Transcription Factor / genetics
  • Rhabdomyosarcoma, Alveolar / diagnosis*
  • Rhabdomyosarcoma, Alveolar / genetics*
  • Rhabdomyosarcoma, Alveolar / metabolism
  • Rhabdomyosarcoma, Alveolar / pathology
  • Transcriptome
  • Young Adult

Substances

  • NCOA2 protein, human
  • Nuclear Receptor Coactivator 2
  • PAX3 Transcription Factor
  • PAX3 protein, human