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

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.

Refinement of diagnostic criteria for pediatric-type diffuse high-grade glioma, IDH- and H3-wildtype, MYCN-subtype including histopathology, TP53, MYCN and ID2 status

“…Moreover, the current series described for the first time a pHGG-MYCN without amplifications of MYCN and ID2 but harboring a MYC amplification. This example may illustrate the phenomenon previously described where a spinal ependymoma classified as “MYCN amplified” by DNA-methylation profiling but harbored a MYC amplification [ 3 ]. DNA-methylation analysis is still only limited to a small number of centres worldwide or may not be contributive (8/29 cases from this cohort presented a low calibrated score for a methylation class), so alternative methods for routine practice need to be validated.…”

Childhood cancer data initiative: Status report

“…The Nationwide Children's Hospital Steve and Cindy Rasmussen Institute for Genomic Medicine (IGM) performs molecular testing (tumor/normal exome, 20 Archer FusionPlex, methylation arrays 21 ) using CLIA-and New York State Department of Health-certified assays with corresponding analytical pipelines (Table 1). Their objective is to return results of the assays to clinicians 14 days after receiving samples.…”

Recent Molecular and Genetic Findings in Intramedullary Spinal Cord Tumors

“…“Spinal ependymoma, MYCN -amplified” is a new category in the 2021 WHO classification [ 4 ]. Although MYCN -amplified ependymomas are very rare, they are associated with aggressive behavior and unfavorable outcomes [ 60 , 61 ]1 ( Table 1 ). Ghasemi et al [ 62 ] investigated 13 MYCN -amplified ependymomas, of which 10 were WHO grade 3 and 3 were WHO grade 2 on histopathological examination.…”