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Clinicians Practicing Obstetrics and Gynecology Are Uniquely Situated to Recognize DICER1 Syndrome

  • Katherine G. Hayes
    Correspondence
    Address correspondence to: Katherine G Hayes, MD, University of Utah, 50 N Medical Drive, Salt Lake City, UT 84132. Phone: (801) 662-1712.
    Affiliations
    Department of Obstetrics & Gynecology, University of Utah, Salt Lake City, Utah

    Division of Pediatric Gynecology, Intermountain Primary Children's Hospital, Salt Lake City, Utah
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  • Amanda V. French
    Affiliations
    Division of Pediatric Gynecology, Department of Obstetrics and Gynecology, Tufts Children's Hospital and Tufts Medical Center, Boston, Massachusetts
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      ABSTRACT

      Pediatric gynecologic malignancies are rare, present with diverse pathologic findings, and can be associated with genetic syndromes such as Peutz-Jeghers, Lynch, and Li-Fraumeni. DICER1 mutation is an emerging entity that has been demonstrated to cause a hereditary tumor predisposition syndrome. Previously, gynecologic manifestations of DICER1 syndrome have been described in single or small case reports with an array of pathologic findings. Here, we discuss pediatric and adolescent patients with gynecologic DICER1-associated tumors, outline the significance of DICER1, and suggest points of care where the syndrome may be diagnosed in the context of routine obstetric and gynecology practice. Patients presenting with a personal or family history suspicious for DICER1 syndrome should undergo both germline and somatic testing, as the presence of DICER1 mutations will have an impact on both treatment and surveillance strategies.

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      References

        • Doros L
        • Schultz KA
        • Stewart DR
        • et al.
        DICER1-related disorders.
        University of Washington, Seattle1993 (Available at:) (Accessed January 9, 2021)
        • Foulkes WD
        • Priest JR
        • Duchaine TF
        DICER1: mutations, microRNAs and mechanisms.
        Nat Rev Cancer. 2014; 14: 662-672
        • Kurzynska-Kokorniak A
        • Koralewska N
        • Pokornowska M
        • et al.
        The many faces of Dicer: the complexity of the mechanisms regulating Dicer gene expression and enzyme activities.
        Nucleic Acids Res. 2015; 43: 4365
        • Hill DA
        • Ivanovich J
        • Priest JR
        • et al.
        DICER1 mutations in familial pleuropulmonary blastoma.
        Science. 2009; 325: 965
        • Manivel JC
        • Priest JR
        • Watterson J
        • et al.
        Pleuropulmonary blastoma. The so-called pulmonary blastoma of childhood.
        Cancer. 1988; 62: 1516
        • Slade I
        • Bacchelli C
        • Davies H
        • et al.
        DICER1 syndrome: clarifying the diagnosis, clinical features and management implications of a pleiotropic tumour predisposition syndrome.
        J Med Genet. 2011; 48: 273
        • Conlon N
        • Schultheis AM
        • Piscuoglio S
        • et al.
        A survey of DICER1 hotspot mutations in ovarian and testicular sex cord-stromal tumors.
        Mod Pathol. 2015; 28: 1603
        • Oost EE
        • Charles A
        • Choong CS
        • et al.
        Ovarian sex cord-stromal tumors in patients with probable or confirmed germline DICER1 mutations.
        Int J Gynecol Pathol. 2015; 34: 266
        • Schultz KAP
        • Harris AK
        • Finch M
        • et al.
        DICER1-related Sertoli-Leydig cell tumor and gynandroblastoma: clinical and genetic findings from the International Ovarian and Testicular Stromal Tumor Registry.
        Gynecol Oncol. 2017; 147: 521
        • Priest JR
        • Williams GM
        • Mize WA
        • et al.
        Nasal chondromesenchymal hamartoma in children with pleuropulmonary blastoma-a report from the International Pleuropulmonary Blastoma Registry registry.
        Int J Pediatr Otorhinolaryngol. 2010; 74: 1240-1244https://doi.org/10.1016/j.ijporl.2010.07.022
        • Erler P
        • Keutgen XM
        • Crowley MJ
        • et al.
        Dicer expression and microRNA dysregulation associate with aggressive features in thyroid cancer.
        Surg (United States). 2014; 156: 1342-1350https://doi.org/10.1016/j.surg.2014.08.007
        • McCluggage WG
        • Apellaniz-Ruiz M
        • Chong AL
        • et al.
        Embryonal rhabdomyosarcoma of the ovary and fallopian tube: rare neoplasms associated with germline and somatic DICER1 mutations.
        Am J Surg Pathol. 2020; 44: 738-747https://doi.org/10.1097/PAS.0000000000001442
        • Sahakitrungruang T
        • Srichomthong C
        • Pornkunwilai S
        • et al.
        Germline and somatic DICER1 mutations in a pituitary blastoma causing infantile-onset Cushing’s disease.
        J Clin Endocrinol Metab. 2014; 99: 1487-1492https://doi.org/10.1210/jc.2014-1016
        • de Kock L
        • Priest JR
        • Foulkes WD
        • et al.
        An update on the central nervous system manifestations of DICER1 syndrome.
        Acta Neuropathol. 2020; 139: 689-701https://doi.org/10.1007/s00401-019-01997-y
        • Apellaniz-Ruiz M
        • Segni M
        • Kettwig M
        • et al.
        Mesenchymal hamartoma of the liver and DICER1 syndrome.
        N Engl J Med. 2019; 380: 1834-1842https://doi.org/10.1056/nejmoa1812169
        • Apellaniz-Ruiz M
        • De Kock L
        • Sabbaghian N
        • et al.
        Familial multinodular goiter and Sertoli-Leydig cell tumors associated with a large intragenic in-frame DICER1 deletion.
        Eur J Endocrinol. 2018; 178: K11
        • Yoon J-Y
        • Apellaniz-Ruiz M
        • Chong A-L
        • et al.
        The value of DICER1 mutation analysis in “subtle” diagnostically challenging embryonal rhabdomyosarcomas of the uterine cervix.
        Int J Gynecol Pathol. 2020; 40: 435-440https://doi.org/10.1097/pgp.0000000000000718
        • Schultz KAP
        • Williams GM
        • Kamihara J
        • et al.
        Dicer1 and associated conditions: identification of at-risk individuals and recommended surveillance strategies.
        Clin Cancer Res. 2018; 24 (doi:10.1002/cncr.27633.Percutaneous): 2251-2261
      1. American College of Obstetricians and Gynecologists: The initial reproductive health visit. Available at: https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2020/10/the-initial-reproductive-health-visit. Accessed December 20, 2020.

        • De Kock L
        • Druker H
        • Weber E
        • et al.
        Ovarian embryonal rhabdomyosarcoma is a rare manifestation of the DICER1 syndrome.
        Hum Pathol. 2015; 46: 917
        • De Kock L
        • Terzic T
        • McCluggage WG
        • et al.
        DICER1 mutations are consistently present in moderately and poorly differentiated Sertoli-Leydig cell tumors.
        Am J Surg Pathol. 2017; 41: 1178
        • Luke AM
        • Moroney JW
        • Snitchler A
        • et al.
        Ovarian Sertoli-Leydig cell tumor with elevated Inhibin B as a cause of secondary amenorrhea in an adolescent with germ line DICER1 mutation.
        J Pediatr Adolesc Gynecol. 2017; 30: 598
        • Wu MK
        • De Kock L
        • Conwell LS
        • et al.
        Functional characterization of multiple DICER1 mutations in an adolescent.
        Endocr Relat Cancer. 2016; 23: L1
        • Ring KL
        • Garcia C
        • Thomas MH
        • et al.
        Current and future role of genetic screening in gynecologic malignancies.
        Am J Obstet Gynecol. 2017; 217: 512
        • Karnezis AN
        • Wang Y
        • Keul J
        • et al.
        DICER1 and FOXL2 mutation status correlates with clinicopathologic features in ovarian Sertoli-Leydig cell tumors.
        Am J Surg Pathol. 2019; 43: 628
        • Schultz KAP
        • Harris AK
        • Finch M
        • et al.
        DICER1-related Sertoli-Leydig cell tumor and gynandroblastoma: clinical and genetic findings from the International Ovarian and Testicular Stromal Tumor Registry.
        Gynecol Oncol. 2017; 147: 521
        • Salani R
        • Backes FJ
        • Fung Kee Fung M
        • et al.
        Posttreatment surveillance and diagnosis of recurrence in women with gynecologic malignancies: Society of Gynecologic Oncologists recommendations.
        Am J Obstet Gynecol. 2011; 204: 466-478https://doi.org/10.1016/j.ajog.2011.03.008