Send to

Choose Destination
Gynecol Oncol. 2020 Mar;156(3):647-653. doi: 10.1016/j.ygyno.2019.12.037. Epub 2020 Jan 15.

Gynecologic and reproductive health in patients with pathogenic germline variants in DICER1.

Author information

National Human Genome Research Institute, National Institutes of Health, Dpt. Health & Human Services, Bethesda, MD 20892, USA. Electronic address:
Westat, Rockville, MD 20850, USA.
Department of Obstetrics and Gynecology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Department of Obstetrics and Gynaecology, Royal Surrey County Hospital, Guildford GU2 7XX, United Kingdom.
Department of Pathology, Center for Cancer and Immunology Research, Children's National Medical Center, Washington, D.C. 20010, USA; International Pleuropulmonary Blastoma/DICER1 Registry, Children's Minnesota, Minneapolis, MN 55404, USA; International Ovarian and Testicular Stromal Tumor Registry, Children's Minnesota, Minneapolis, MN 55404, USA.
Division of Anatomic and Molecular Pathology, Lauren V. Ackerman Laboratory of Surgical Pathology, Barnes-Jewish and St. Louis Children's Hospitals, Washington University Medical Center, St. Louis, MO 63110, USA.
International Pleuropulmonary Blastoma/DICER1 Registry, Children's Minnesota, Minneapolis, MN 55404, USA; International Ovarian and Testicular Stromal Tumor Registry, Children's Minnesota, Minneapolis, MN 55404, USA; Cancer and Blood Disorders Program, Children's Minnesota, Minneapolis, MN 55404, USA.
Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20850, USA.
Office of the Clinical Director, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, 20892, USA.



Germline pathogenic variation in DICER1 underlies a tumor-predisposition disorder with increased risk for cervical embryonal rhabdomyosarcoma and ovarian sex-cord stromal tumors, particularly Sertoli-Leydig cell tumors. The gynecologic and reproductive health of these females has not yet been described.


All female subjects recruited from November 2011 to July 2018 participating in an epidemiologic study of families with pathogenic DICER1 germline variation were included in this cross-sectional analysis. Participant evaluation included obstetric-gynecologic history, physical examination, hormone testing, pelvic ultrasound and record review.


Of 64 females aged 2-72 years, fifteen underwent treatment for pleuropulmonary blastoma as children and three were treated for cervical embryonal rhabdomyosarcoma. Of nine patients reporting a history of ovarian tumors, all presented with virilization or amenorrhea; eight occurred in adolescence. Post-pubertal females with no history of ovarian tumors experienced normal pubertal development, reported regular menstrual cycles, were fertile and underwent natural menopause at median age of 52 years. Thirty-two of 33 women who tried to conceive successfully delivered liveborn children. Of these 32, 10 experienced pregnancy-related thyroid enlargement resulting in thyroidectomy within one year of pregnancy; nine others had undergone pre-pregnancy thyroidectomy.


In these DICER1-carrier females, DICER1-related gynecological tumors occurred during childhood or adolescence in some after which women generally experienced healthy reproductive lives. Individual education and screening for these tumors is warranted. The high rate of DICER1-related multinodular goiter resulting in pre- and post-pregnancy thyroidectomy underscores the importance of thyroid monitoring during pregnancy to ensure maternal and fetal wellbeing.


Cervical embryonal rhabdomyosarcoma; DICER1-related multinodular goiter; Ovarian sex-cord stromal tumors; Pleuropulmonary blastoma; Sertoli-Leydig cell tumors of the ovary

Conflict of interest statement

Declaration of competing interest Dr. Hill is owner of ResourcePath LLC, a private company with a mission to develop liquid biopsy diagnostics for rare cancers which includes DICER1-related cancers described in this work. None of the diagnostics under development are discussed in this work. Dr. Stewart provides contract telegenetics services to Genome Medical, Inc.

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center