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

Acta Neuropathologica Communications

Diana L. Thomas¹  Daniel R. Boué¹  Christopher R. Pierson²  Jonathan L. Finlay³  Kristian W. Pajtler⁴  David R. Ghasemi⁵  Jeremy Jones⁶  Diana P. Rodriguez⁶  Mohamed S. Abdelbaki⁷  Margaret Shatara⁷  Diana S. Osorio⁸  Darren Klawinski⁸  Eric A. Sribnick⁹  James Fitch^1,10  Kristen Leraas^1,10  Elizabeth Hamelberg^1,10  Stephanie LaHaye^1,10  Carol Deeg^1,10  Benjamin Kelly^1,10  Kathleen M. Schieffer^1,11  Catherine E. Cottrell^1,12  Ruthann Pfau^1,12  Vincent Magrini^1,13  Katherine E. Miller^1,13  Peter White^1,13  Richard K. Wilson^1,13  Elaine R. Mardis^1,13 

[1] Department of Pathology and Laboratory Medicine, Nationwide Children’s Hospital, Columbus, OH, USA;The Department of Pathology, The Ohio State University, Columbus, OH, USA;Department of Pathology and Laboratory Medicine, Nationwide Children’s Hospital, Columbus, OH, USA;The Department of Pathology, The Ohio State University, Columbus, OH, USA;Division of Anatomy, Department of Biomedical Education, The Ohio State University, Columbus, OH, USA;Emeritus Professor of Pediatrics and Radiation Oncology, The Ohio State University, Columbus, OH, USA;Hopp Children’s Cancer Center Heidelberg (KiTZ), 69120, Heidelberg, Germany;Department of Pediatric Oncology, Hematology, and Immunology, University Hospital Heidelberg, Heidelberg, Germany;Hopp Children’s Cancer Center Heidelberg (KiTZ), 69120, Heidelberg, Germany;Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), 69120, Heidelberg, Germany;The Department of Radiology, Nationwide Children’s Hospital, Columbus, OH, USA;The Division of Hematology and Oncology, St. Louis Children’s Hospital, School of Medicine in St. Louis, Washington University, St. Louis, MO, USA;The Division of Hematology, Oncology, Blood and Marrow Transplant, Nationwide Children’s Hospital and The Ohio State University, Columbus, OH, USA;The Division of Pediatric Neurosurgery, Nationwide Children’s Hospital and The Ohio State University, Columbus, OH, USA;The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children’s Hospital, 575 Children’s Crossroad, 43215, Columbus, OH, USA;The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children’s Hospital, 575 Children’s Crossroad, 43215, Columbus, OH, USA;The Department of Pathology, The Ohio State University, Columbus, OH, USA;The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children’s Hospital, 575 Children’s Crossroad, 43215, Columbus, OH, USA;The Department of Pathology, The Ohio State University, Columbus, OH, USA;The Department of Pediatrics, The Ohio State University, Columbus, OH, USA;The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children’s Hospital, 575 Children’s Crossroad, 43215, Columbus, OH, USA;The Department of Pediatrics, The Ohio State University, Columbus, OH, USA;

关键词: Ependymoma;    MYC;    MYCN;    Spinal;    Amplification;    FISH;    DNA methylation array;    Pediatric;   

DOI  :  10.1186/s40478-021-01296-2

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY