Clinically aggressive pediatric spinal ependymoma with novel MYC amplification demonstrates molecular and histopathologic similarity to newly described MYCN-amplified spinal ependymomas

Margaret Shatara, Kathleen M. Schieffer, Darren Klawinski, Diana L. Thomas, Christopher R. Pierson, Eric A. Sribnick, Jeremy Jones, Diana P. Rodriguez, Carol Deeg, Elizabeth Hamelberg, Stephanie LaHaye, Katherine E. Miller, James Fitch, Benjamin Kelly, Kristen Leraas, Ruthann Pfau, Peter White, Vincent Magrini, Richard K. Wilson, Elaine R. MardisMohamed S. Abdelbaki, Jonathan L. Finlay, Daniel R. Boué, Catherine E. Cottrell, David R. Ghasemi, Kristian W. Pajtler, Diana S. Osorio

Research output: Contribution to journalArticlepeer-review

Abstract

Primary spinal cord tumors contribute to ≤ 10% of central nervous system tumors in individuals of pediatric or adolescent age. Among intramedullary tumors, spinal ependymomas make up ~ 30% of this rare tumor population. A twelve-year-old male presented with an intradural, extramedullary mass occupying the dorsal spinal canal from C6 through T2. Gross total resection and histopathology revealed a World Health Organization (WHO) grade 2 ependymoma. He recurred eleven months later with extension from C2 through T1-T2. Subtotal resection was achieved followed by focal proton beam irradiation and chemotherapy. Histopathology was consistent with WHO grade 3 ependymoma. Molecular profiling of the primary and recurrent tumors revealed a novel amplification of the MYC (8q24) gene, which was confirmed by fluorescence in situ hybridization studies. Although MYC amplification in spinal ependymoma is exceedingly rare, a newly described classification of spinal ependymoma harboring MYCN (2p24) amplification (SP-MYCN) has been defined by DNA methylation-array based profiling. These individuals typically present with a malignant progression and dismal outcomes, contrary to the universally excellent survival outcomes seen in other spinal ependymomas. DNA methylation array-based classification confidently classified this tumor as SP-MYCN ependymoma. Notably, among the cohort of 52 tumors comprising the SP-MYCN methylation class, none harbor MYC amplification, highlighting the rarity of this genomic amplification in spinal ependymoma. A literature review comparing our individual to reported SP-MYCN tumors (n = 26) revealed similarities in clinical, histopathologic, and molecular features. Thus, we provide evidence from a single case to support the inclusion of MYC amplified spinal ependymoma within the molecular subgroup of SP-MYCN.

Original languageEnglish
Article number192
JournalActa Neuropathologica Communications
Volume9
Issue number1
DOIs
StatePublished - Dec 2021

Keywords

  • Amplification
  • DNA methylation array
  • Ependymoma
  • FISH
  • MYC
  • MYCN
  • Pediatric
  • Spinal

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