DICER1-sarcomas of GYN tract: Expanding on an emerging entity

Hum Pathol. 2024 Oct:152:105636. doi: 10.1016/j.humpath.2024.105636. Epub 2024 Aug 8.

Abstract

Tumors with pathogenic DICER1 mutation are rare and encompass sporadic or hereditary benign, intermediate and malignant tumors. DICER1-associated sarcomas are heterogeneous; however, the prototypical ones in the GYN-tract include embryonal rhabdomyosarcoma, adenosarcoma and moderately to poorly differentiated Sertoli-Leydig tumor. In this report, we present three unique uterine sarcomas with DICER1 mutation and remarkable diffuse round/spindle cell morphology. The tumors occurred in cervix (n = 1), and uterine corpus (n = 2). The patient ages were 30, 37 and 59 years with tumor size of 8.8, 10 and 8.6 cm, respectively. Morphologically all three tumors were characterized by distinct spindle/round cell morphology and various amounts of neuroectodermal differentiation (yolk sac-like tubules, blastomatous areas and rosette formation). Other morphologic features of DICER1-sarcoma reported in the literature including cambium layer, focal or diffuse anaplasia, solid and cystic architecture, and chondroid/osteoid areas were absent. All three sarcomas were positive for SALL4 and had variable neuroendocrine marker expression. Whole genome methylation analysis was performed on one of the uterine sarcomas, which clustered the tumor with embryonal tumor with multilayered rosettes. Follow up information was available on all three cases. Two patients were alive with no evidence of disease 13 and 14 months post operation, while one patient had imaging evidence of local recurrence 4 months post operation. In summary, we describe three unique DICER1-sarcomas and expand the phenotypic spectrum of this emerging entity, particularly with GYN-tract origin.

Keywords: DICER1; ERMS; ETMR; Embryonal rhabdomyosarcoma; Embryonal tumor with multilayered rosettes; GYN tract; Neuroectodermal; PNET; SALL4; Sarcoma.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics
  • DEAD-box RNA Helicases* / genetics
  • DNA Methylation
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Middle Aged
  • Mutation*
  • Phenotype
  • Ribonuclease III* / genetics
  • Sarcoma / genetics
  • Sarcoma / pathology
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / pathology
  • Uterine Neoplasms* / genetics
  • Uterine Neoplasms* / pathology

Substances

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