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Deferring gonadectomy in patients with Turner syndrome with a genetic Y component is not a safe practice

  • Sameer Mittal
    Affiliations
    Division of Urology, Children’s Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA 19104

    Division of Urology, Hospital of the University of Pennsylvania, Perelman Center for Advanced Care, 3400 Civic Center Blvd, 3rd Floor West Pavilion, Philadelphia, PA 19104
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  • John Weaver
    Affiliations
    Division of Urology, Children’s Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA 19104
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  • Aznive Aghababian
    Affiliations
    Division of Urology, Children’s Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA 19104

    Ross University School of Medicine, Bridgetown, Barbados
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  • Rebecca Edwins
    Affiliations
    Division of Urology, Children’s Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA 19104
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  • Karl Godlewski
    Affiliations
    Division of Urology, Children’s Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA 19104
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  • Katherine Fischer
    Affiliations
    Division of Urology, Children’s Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA 19104
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  • Sharmayne Siu
    Affiliations
    Division of Urology, Children’s Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA 19104
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  • Denise Gruccio
    Affiliations
    Division of Urology, Children’s Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA 19104

    Division of Urology, Hospital of the University of Pennsylvania, Perelman Center for Advanced Care, 3400 Civic Center Blvd, 3rd Floor West Pavilion, Philadelphia, PA 19104
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  • Jason Van Batavia
    Affiliations
    Division of Urology, Children’s Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA 19104

    Division of Urology, Hospital of the University of Pennsylvania, Perelman Center for Advanced Care, 3400 Civic Center Blvd, 3rd Floor West Pavilion, Philadelphia, PA 19104
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  • Arun Srinivasan
    Affiliations
    Division of Urology, Children’s Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA 19104

    Division of Urology, Hospital of the University of Pennsylvania, Perelman Center for Advanced Care, 3400 Civic Center Blvd, 3rd Floor West Pavilion, Philadelphia, PA 19104
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  • Christopher Long
    Affiliations
    Division of Urology, Children’s Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA 19104

    Division of Urology, Hospital of the University of Pennsylvania, Perelman Center for Advanced Care, 3400 Civic Center Blvd, 3rd Floor West Pavilion, Philadelphia, PA 19104
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  • Vaneeta Bamba
    Affiliations
    Division of Urology, Children’s Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA 19104

    Division of Urology, Hospital of the University of Pennsylvania, Perelman Center for Advanced Care, 3400 Civic Center Blvd, 3rd Floor West Pavilion, Philadelphia, PA 19104
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  • Vandana Batra
    Affiliations
    Division of Urology, Children’s Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA 19104

    Division of Urology, Hospital of the University of Pennsylvania, Perelman Center for Advanced Care, 3400 Civic Center Blvd, 3rd Floor West Pavilion, Philadelphia, PA 19104
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  • Tricia Bhatti
    Affiliations
    Division of Urology, Children’s Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA 19104

    Division of Urology, Hospital of the University of Pennsylvania, Perelman Center for Advanced Care, 3400 Civic Center Blvd, 3rd Floor West Pavilion, Philadelphia, PA 19104
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  • Thomas Kolon
    Correspondence
    Correspondence to: , Howard M. Snyder III MD Chair in Pediatric Urology, Fellowship Program Director, Associate Division Director, Children's Hospital of Philadelphia, Professor of Urology in Surgery, Perelman School of Medicine at University of Pennsylvania, Children’s Hospital of Philadelphia, Department of Surgery / Division of Urology, 3401 Civic Center Blvd, Wood 3rd Floor, Philadelphia, PA 19104. , Office: 215-590-4690, Fax: +215 590 3985.
    Affiliations
    Division of Urology, Children’s Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA 19104

    Division of Urology, Hospital of the University of Pennsylvania, Perelman Center for Advanced Care, 3400 Civic Center Blvd, 3rd Floor West Pavilion, Philadelphia, PA 19104
    Search for articles by this author
Published:January 10, 2023DOI:https://doi.org/10.1016/j.jpurol.2022.12.012

      Summary

      Introduction

      Patients with Turner syndrome who harbor Y chromosome material are known to be at increased risk of developing germ cell neoplasms. The optimal timing to perform gonadectomy to reduce the risk of cancer development in these patients is not well defined. We present outcomes of Turner with a Y component (TSY) patients who underwent gonadectomy at our institution.

      Hypothesis/objective

      We hypothesized that tumors could occur in a significant portion of TSY patients at any age and gonadectomy can be safely performed at diagnosis rather than deferred.

      Study design

      We performed an IRB-approved retrospective single center study in which we queried our institutions electronic health record to identify all patients with TSY who underwent gonadectomy at our institution from 2012 to 2021.

      Results

      In our series of 18 consecutive TSY patients, a tumor was identified in 6 patients (33.3%): 4 (22.2%) with dysgerminoma (DG) [Figure 1] and 2 (11.1%) with gonadoblastoma (GB).

      Discussion

      Our cohort of 18 consecutive TSY who underwent gonadectomy over a 9-year period is the largest published single site cohort to date. Additionally, our patient who was found to have GB at 40 days is to our knowledge the youngest TSY patient to be diagnosed with GB in the literature. This patient’s remarkably early incidence of tumor occurrence illustrates the urgency of protective gonadectomy. Given the high incidence of tumor formation in this population and the minimal morbidity associated with gonadectomy, we do not recommend delaying gonadectomy in this population for any reason. Our study is vulnerable to selection bias and confounding innate to any retrospective study. There was variation with respect to the frequency and timing of pre-operative imaging as a strict preoperative imaging protocol with sequential studies was not in place at our institution. Additionally, we do not have a comparison cohort of patients who are being followed without operative intervention as all TSY patients at our institution have undergone gonadectomy.

      Conclusion

      TSY patients cannot be safely observed for tumor formation based on clinical factors such as imaging or age. Gonadectomy is safe with a low complication rate and without tumor recurrence during three-year follow-up. We continue to recommend bilateral gonadectomy in this patient population at the time of diagnosis.

      Keywords

      Abbreviations:

      Turner with a Y component ((TSY)), Dysgerminoma ((DG)), Gonadoblastoma ((GB).), Differences of Sex Development ((DSD)
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      References

        • Ford C.E.
        • Jones K.W.
        • Polani P.E.
        • De Almeida J.C.
        • Briggs J.H.
        A sex-chromosome anomaly in a case of gonadal dysgenesis (Turner's syndrome).
        Lancet (London, England). 1959; 1 ([published Online First: Epub Date]|): 711-713https://doi.org/10.1016/s0140-6736(59)91893-8
        • Gravholt C.H.
        • Andersen N.H.
        • Conway G.S.
        • et al.
        Clinical practice guidelines for the care of girls and women with Turner syndrome: proceedings from the 2016 Cincinnati International Turner Syndrome Meeting.
        European journal of endocrinology. 2017; 177 ([published Online First: Epub Date]|): G1-g70https://doi.org/10.1530/eje-17-0430
        • Dabrowski E.
        • Johnson E.K.
        • Patel V.
        • et al.
        Turner Syndrome with Y Chromosome: Spontaneous Thelarche, Menarche, and Risk of Malignancy.
        Journal of pediatric and adolescent gynecology. 2020; 33 ([published Online First: Epub Date]|): 10-14https://doi.org/10.1016/j.jpag.2019.08.011
        • Saenger P.
        Clinical review 48: The current status of diagnosis and therapeutic intervention in Turner's syndrome.
        The Journal of clinical endocrinology and metabolism. 1993; 77 ([published Online First: Epub Date]|): 297-301https://doi.org/10.1210/jcem.77.2.8345029
        • Zelaya G.
        • López Marti J.M.
        • Marino R.
        • Garcia de Dávila M.T.
        • Gallego M.S.
        Gonadoblastoma in patients with Ullrich-Turner syndrome.
        Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society. 2015; 18 ([published Online First: Epub Date]|): 117-121https://doi.org/10.2350/14-08-1539-oa.1
        • Cools M.
        • Wolffenbuttel K.P.
        • Drop S.L.
        • Oosterhuis J.W.
        • Looijenga L.H.
        Gonadal development and tumor formation at the crossroads of male and female sex determination.
        Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation. 2011; 5 ([published Online First: Epub Date]|): 167-180https://doi.org/10.1159/000329477
        • Coyle D.
        • Kutasy B.
        • Han Suyin K.
        • et al.
        Gonadoblastoma in patients with 45,X/46,XY mosaicism: A 16-year experience.
        Journal of pediatric urology. 2016; 12 (283.e1-83.e7 doi:) ([published Online First: Epub Date]|)https://doi.org/10.1016/j.jpurol.2016.02.009
        • Brant W.O.
        • Rajimwale A.
        • Lovell M.A.
        • et al.
        Gonadoblastoma and Turner syndrome.
        The Journal of urology. 2006; 175 ([published Online First: Epub Date]|): 1858-1860https://doi.org/10.1016/s0022-5347(05)00932-8
        • Matsumoto F.
        • Shimada K.
        • Ida S.
        Tumors of bilateral streak gonads in patients with disorders of sex development containing y chromosome material.
        Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology. 2014; 23 ([published Online First: Epub Date]|): 93-97https://doi.org/10.1297/cpe.23.93
        • Shankar R.K.
        • Backeljauw P.F.
        Current best practice in the management of Turner syndrome.
        Therapeutic advances in endocrinology and metabolism. 2018; 9 ([published Online First: Epub Date]|): 33-40https://doi.org/10.1177/2042018817746291
        • Kwon A.
        • Hyun S.E.
        • Jung M.K.
        • et al.
        Risk of Gonadoblastoma Development in Patients with Turner Syndrome with Cryptic Y Chromosome.
        Material. Hormones & cancer. 2017; 8 ([published Online First: Epub Date]|): 166-173https://doi.org/10.1007/s12672-017-0291-8
      1. R S. Basic and Clinical Approach to Turner Syndrome: Proceeding of the 3rd Internation Symposium on Turner Syndrome. 3 ed, 1993.

        • Landin-Wilhelmsen K.
        • Bryman I.
        • Hanson C.
        • Hanson L.
        Spontaneous pregnancies in a Turner syndrome woman with Y-chromosome mosaicism.
        Journal of assisted reproduction and genetics. 2004; 21 ([published Online First: Epub Date]|): 229-230https://doi.org/10.1023/b:jarg.0000040239.40913.c3