DICER1-associated metastatic abdominopelvic primitive neuroectodermal tumor with an EWSR1 rearrangement in a 16-yr-old female

Cold Spring Harb Mol Case Stud. 2020 Oct 7;6(5):a005603. doi: 10.1101/mcs.a005603. Print 2020 Oct.

Abstract

We report a case of a DICER1-associated EWSR1-rearranged malignant primitive neuroectodermal tumor (PNET) arising in a patient with DICER1 tumor predisposition syndrome. A 16-yr-old female with a history of multinodular goiter presented with a widely metastatic abdominal small round blue cell tumor with neuroectodermal differentiation. EWSR1 gene rearrangement was identified in the tumor by fluorescence in situ hybridization (FISH). Genetic analysis revealed biallelic pathogenic DICER1 variation. The patient was treated with an aggressive course of chemotherapy, surgery, and radiation with complete pathologic response. We believe this case to represent a new expression of the DICER1 tumor predisposition syndrome, an entity caused by deleterious germline mutations in the DICER1 gene, encoding a ribonuclease active in the processing of miRNA. Patients with germline mutations in DICER1 develop a diverse group of benign and malignant tumors. Some of these tumors have been noted to have immature neuroepithelium as a component, including the ciliary body medulloepithelioma and the recently described DICER1-associated presacral malignant teratoid neoplasm. To our knowledge, abdominal sarcomas that resemble PNET histology with an EWSR1 rearrangement have not previously been described as a classical expression of the DICER1 syndrome phenotype.

Keywords: Ewing's sarcoma; multinodular goiter; neoplasm of the genitourinary tract.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • DEAD-box RNA Helicases / metabolism
  • Female
  • Gene Rearrangement / genetics
  • Germ-Line Mutation
  • Humans
  • In Situ Hybridization, Fluorescence
  • Neoplasm Metastasis / genetics
  • Neuroectodermal Tumors / genetics*
  • Neuroectodermal Tumors / metabolism
  • RNA-Binding Protein EWS / genetics*
  • RNA-Binding Protein EWS / metabolism
  • Ribonuclease III / metabolism
  • Sarcoma, Ewing / genetics
  • Sarcoma, Ewing / metabolism

Substances

  • EWSR1 protein, human
  • RNA-Binding Protein EWS
  • DICER1 protein, human
  • Ribonuclease III
  • DEAD-box RNA Helicases