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Testicular dysgenesis syndrome and carcinoma in situ of the testes

Nature Clinical Practice Urology volume 4, pages 402–403 (2007)Cite this article

The term testicular dysgenesis syndrome (TDS) was first coined in 2001,1 when it was hypothesized that abnormal spermatogenesis, testicular cancer, undescended testes and hypospadias have a common etiology in some cases. According to this hypothesis, all these clinical problems may result from a developmental disorder that originates in early fetal life.

It has been textbook knowledge for decades that disorders of sex development caused by rare congenital abnormalities, including defects of the Y chromosome, might cause gonadal dysgenesis and are associated with a high risk of testicular germ cell cancer. These rare disorders are often linked to undescended testes and complete or incomplete failure of normal penile development, sometimes resulting in severe hypospadias;2 however, we became aware that similar testicular developmental abnormalities (e.g. undifferentiated seminiferous tubules and microliths) can also be found in testicular biopsies from normally developed men presenting with infertility and/or testicular cancer.3,4 In addition, the association between decreased male fertility and testicular neoplasia is now firmly established.5,6 The vast majority of testicular neoplasms are germ cell tumors preceded by a common precursor, carcinoma in situ (CIS). Histologically, the various types of testicular dysgenesis (including CIS) are found in close vicinity to testicular tumors, or in the contralateral gonad of patients with testicular cancer. This is in line with our thinking that all testicular germ cell cancers have a prenatal origin in a dysgenetic testis.

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References

  1. Skakkebæk NE et al. (2001) Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects. Hum Reprod 16: 972–978

    Article  Google Scholar 

  2. Manuel M et al. (1976) The age of occurence of gonadal tumors in intersex patients with a Y chromosome. Am J Obstet Gynecol 124: 293–300

    Article  CAS  Google Scholar 

  3. Kang JL et al. (1994) The association of testicular carcinoma in situ with intratubular microcalcifications. J Urol Pathol 2: 235–242

    Google Scholar 

  4. Høi-Hansen CE et al. (2003) Histological evidence of testicular dysgenesis in contralateral biopsies from 218 patients with testicular germ cell cancer. J Pathol 200: 370–374

    Article  Google Scholar 

  5. Berthelsen JG (1987) Testicular cancer and fertility. Int J Androl 10: 371–380

    Article  CAS  Google Scholar 

  6. Møller H and Skakkebæk NE (1999) Risk of testicular cancer in subfertile men: case–control study. Br Med J 318: 559–562

    Article  Google Scholar 

  7. Rajpert-De Meyts E (2006) Developmental model for the pathogenesis of testicular carcinoma in situ: genetic and environmental aspects. Hum Reprod Update 12: 303–323

    Article  CAS  Google Scholar 

  8. Boisen KA et al. (2004) Difference in prevalence of congenital cryptorchidism in infants between two Nordic countries. Lancet 363: 1264–1269

    Article  CAS  Google Scholar 

  9. Jørgensen N et al. (2002) East-West gradient in semen quality in the Nordic-Baltic area: a study of men from the general population in Denmark, Norway, Estonia and Finland. Hum Reprod 17: 2199–2208

    Article  Google Scholar 

  10. Sharpe RM (2006) Pathways of endocrine disruption during male sexual differentiation and masculinization. Best Pract Res Clin Endocrinol Metab 20: 91–110

    Article  CAS  Google Scholar 

  11. Skakkebæk NE et al. (2003) Association between testicular dysgenesis syndrome (TDS) and testicular neoplasia: evidence from 20 adult patients with signs of maldevelopment of the testis. APMIS 111: 1–9

    Article  Google Scholar 

  12. Rørth, M. et al. (2000) Carcinoma in situ in the testis. Scand J Urol Nephrol Suppl 205: 166–186

    Article  Google Scholar 

  13. Petersen PM et al. (1999) Impaired testicular function in patients with carcinoma in situ of the testis. J Clin Oncol 17: 173–179

    Article  CAS  Google Scholar 

  14. Hemminki K and Chen B (2006) Familial risks in testicular cancer as aetiological clues. Int J Androl 29: 205–210

    Article  Google Scholar 

Download references

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Authors and Affiliations

  1. and N Skaekkebæk is a Professor in the Department of Growth and Reproduction, UN Joensen is a researcher, N Jørgensen is a consultant, Rigshospitalet, Copenhagen, Denmark.,

    Ulla N Joensen, Niels Jørgensen & Niels E Skakkebæk

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  1. Ulla N Joensen
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  2. Niels Jørgensen
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  3. Niels E Skakkebæk
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Correspondence to Niels E Skakkebæk.

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Joensen, U., Jørgensen, N. & Skakkebæk, N. Testicular dysgenesis syndrome and carcinoma in situ of the testes. Nat Rev Urol 4, 402–403 (2007). https://doi.org/10.1038/ncpuro0859

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