Acta Neuropathologica Communications (Dec 2021)

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. Mardis,
  • Mohamed S. Abdelbaki,
  • Jonathan L. Finlay,
  • Daniel R. Boué,
  • Catherine E. Cottrell,
  • David R. Ghasemi,
  • Kristian W. Pajtler,
  • Diana S. Osorio

DOI
https://doi.org/10.1186/s40478-021-01296-2
Journal volume & issue
Vol. 9, no. 1
pp. 1 – 10

Abstract

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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.

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