Expanding the spectrum of dicer1-associated sarcomas

Mod Pathol. 2020 Jan;33(1):164-174. doi: 10.1038/s41379-019-0366-x. Epub 2019 Sep 19.

Abstract

DICER1 syndrome is a hereditary cancer predisposition syndrome caused by deleterious germline DICER1 mutations. Characteristic "hotspot" somatic mutations of DICER1 have been identified in DICER1-associated tumors. With the exception of genitourinary embryonal rhabdomyosarcoma and anaplastic sarcoma of the kidney, sarcomas are rarely reported in DICER1 syndrome. Herein, we report the clinical, histopathologic, and molecular findings of a germline DICER1-associated ovarian sarcoma in a 5-year-old female, a somatic DICER1-associated metastatic peritoneal sarcoma in a 16-year-old female, and a somatic DICER1-associated primary intracranial sarcoma in a 4-year-old male. A comprehensive review of the literature, including 83 DICER1-associated sarcomas, illustrates an unequivocal histologic pattern mimicking pleuropulmonary blastoma, regardless of the site of origin. The features include undifferentiated small round blue cells, poorly differentiated spindle cells, and large bizarre pleomorphic cells (anaplasia), often with rhabdomyoblastic and/or chondroid differentiation, and rare bone/osteoid formation. This unique heterogeneous histologic pattern should raise suspicion for pathogenic DICER1 mutation(s) warranting a detailed review of the family history and DICER1 mutation analysis. In addition to expanding the phenotypic spectrum of DICER1-associated conditions, identification of pathogenic DICER1 variants facilitates optimized genetic counseling, caregiver education and judicious imaging-based surveillance.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Brain Neoplasms / genetics*
  • Child, Preschool
  • DEAD-box RNA Helicases / genetics*
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Male
  • Mutation
  • Ovarian Neoplasms / genetics*
  • Peritoneal Neoplasms / genetics*
  • Ribonuclease III / genetics*
  • Sarcoma / genetics*

Substances

  • DICER1 protein, human
  • Ribonuclease III
  • DEAD-box RNA Helicases