DICER1-associated embryonal rhabdomyosarcoma and adenosarcoma of the gynecologic tract: Pathology, molecular genetics, and indications for molecular testing

Genes Chromosomes Cancer. 2021 Mar;60(3):217-233. doi: 10.1002/gcc.22913. Epub 2020 Nov 19.


Gynecologic sarcomas are uncommon neoplasms, the majority occurring in the uterus. Due to the diverse nature of these, the description of "new" morphological types and the rarity of some of them, pathological diagnosis and treatment is often challenging. Finding genetic alterations specific to, and frequently occurring, in a certain type can aid in the diagnosis. DICER1 is a highly conserved ribonuclease crucial in the biogenesis of microRNAs and mutations in DICER1 (either somatic or germline) have been detected in a wide range of sarcomas including genitourinary embryonal rhabdomyosarcomas (ERMS) and adenosarcomas. Importantly, DICER1-associated sarcomas share morphological features irrespective of the site of origin such that the pathologist can strongly suspect a DICER1 association. A review of the literature shows that almost all gynecologic ERMS reported (outside of the vagina) harbor DICER1 alterations, while approximately 20% of adenosarcomas also do so. These two tumor types exhibit significant morphological overlap and DICER1 tumor testing may be helpful in distinguishing between them, because a negative result makes ERMS unlikely. Given that germline pathogenic DICER1 variants are frequent in uterine (corpus and cervix) ERMS and pathogenic germline variants in this gene cause a hereditary cancer predisposition syndrome (DICER1 syndrome), patients diagnosed with these neoplasms should be referred to medical genetic services. Cooperation between pathologists and geneticists is crucial and will help in improving the diagnosis and management of these uncommon sarcomas.

Keywords: DICER1 syndrome; adenosarcoma; embryonal rhabdomyosarcoma; genetic screening; gynecologic tract; hotspot mutations.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenosarcoma / genetics
  • Adenosarcoma / pathology
  • DEAD-box RNA Helicases / genetics*
  • DEAD-box RNA Helicases / metabolism
  • Female
  • Genital Neoplasms, Female / genetics*
  • Genital Neoplasms, Female / metabolism
  • Germ-Line Mutation
  • Humans
  • MicroRNAs / genetics
  • Molecular Diagnostic Techniques / methods
  • Mutation
  • Rhabdomyosarcoma, Embryonal / diagnosis
  • Rhabdomyosarcoma, Embryonal / genetics*
  • Rhabdomyosarcoma, Embryonal / pathology
  • Ribonuclease III / genetics*
  • Ribonuclease III / metabolism


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

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