Well-differentiated Sertoli-Leydig Cell Tumors (SLCTs) Are Not Associated With DICER1 Pathogenic Variants and Represent a Different Tumor Type to Moderately and Poorly Differentiated SLCTs

Am J Surg Pathol. 2023 Apr 1;47(4):490-496. doi: 10.1097/PAS.0000000000002010. Epub 2022 Dec 30.


Sertoli-Leydig cell tumors (SLCTs) are uncommon ovarian sex cord-stromal neoplasms which are currently classified into well, moderately, and poorly differentiated and retiform types. Well-differentiated SLCT is the least common and typically occurs in pure form, whereas moderately and poorly differentiated and retiform types often comprise a morphologic spectrum with an admixture of all 3. DICER1 pathogenic variants are very common in SLCTs but, as far as we are aware, have not been reported in well-differentiated neoplasms, although the number of cases studied is small due to the rarity of this neoplasm. We undertook DICER1 molecular testing in a cohort of 18 well-differentiated SLCTs and show all these to be DICER1 wild-type. None of the cases harbored the p. FOXL2 C134W hotspot mutation. Based upon the DICER1 molecular results, together with morphologic observations, we propose that well-differentiated SLCT is an unrelated neoplasm to the more common moderately/poorly differentiated and retiform SLCTs and is a fundamentally distinct and unrelated tumor type within the ovarian sex cord-stromal tumor family. The implications for tumor nomenclature and recommendations for future tumor classification are discussed within the context of tumors collectively known as SLCTs.

MeSH terms

  • DEAD-box RNA Helicases / genetics
  • Female
  • Humans
  • Male
  • Molecular Diagnostic Techniques
  • Mutation
  • Ovarian Neoplasms* / genetics
  • Ovarian Neoplasms* / pathology
  • Ribonuclease III / genetics
  • Sertoli-Leydig Cell Tumor* / genetics
  • Sertoli-Leydig Cell Tumor* / pathology
  • Sex Cord-Gonadal Stromal Tumors* / genetics
  • Sex Cord-Gonadal Stromal Tumors* / pathology


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