DICER1-Associated Gynecologic Neoplasms: An Update and Review

DICER1 plays a crucial role in the biogenesis and maturation of microRNAs. Germline mutations in the DICER1 gene are associated with an increased risk of developing a wide range of benign and malignant neoplasms. The same tumors may also arise sporadically due to somatic DICER1 mutations. In syndromic patients, a germline loss-of-function DICER1 mutation is usually followed by a somatic hotspot mutation in the tumor as a second hit. In the gynecologic tract, DICER1 -associated neoplasms include most commonly embryonal rhabdomyosarcoma and moderately to poorly differentiated Sertoli-Leydig cell tumor, and less frequently pleuropulmonary blastoma-like peritoneal sarcoma, adenosarcoma, gynandroblastoma, juvenile granulosa cell tumor, and Sertoli cell tumor. Irrespective of the primary site of origin, DICER1 -associated neoplasms frequently share characteristic morphology, including primitive mesenchyme, fetal-type epithelium, fetal-type cartilage, rhabdomyoblastic and/or neuroectodermal differentiation, osteoid formation, and anaplasia. Recognition of these distinctive features in gynecologic tumors should prompt consideration of a DICER1 -associated neoplasm followed by genetic testing, thereby facilitating surveillance for patients and their families. As illustrated in this review, the morphologic spectrum of most DICER1 -mutant gynecologic neoplasms (eg, DICER1 -related Wilms-like uterine tumor) appears to be wider than that of any known type of sarcoma. Therefore, we propose that the term “ DICER1 -related primitive polyphenotypic neoplasm” may be more inclusive of the diverse histologic features and thus more appropriate for these unique neoplasms.