Differential Diagnosis of Tumors in the Adrenogenital Syndrome

  • Manuel Nistal
  • Pilar González-Peramato
  • Álvaro Serrano
Chapter
First Online:

Abstract

The differential diagnosis of testicular tumors of the adrenogenital syndrome (TTAGS) with Leydig cell tumors (LCT) is not always easy. In childhood, both tumors show a pattern of hyperandrogenism, and the symptoms can be similar. The macroscopic clues in favor of TTAGS are the bilateral nature of the tumors and its location in the mediastinum testis. Among the histological data, the good delineation of the tumor nodules is outstanding: sheets of large polygonal cells with an eosinophilic cytoplasm intersected by broad fibrous bands, abundant lipofuscins, the absence of mitosis, and the presence of fat and lymphoid tissue. The peritumoral parenchyma does not show spermatogenesis. Adults often consult by infertility secondary to obstruction of the tubuli recti that are compressed by the tumor nodules. TTAGS and Leydig cell tumors share the same immunohistochemical phenotype (calretinin, inhibin, synaptophysin, and CD56) although there are differences in the intensity of positivity and the distribution of the expression – focal versus diffuse in some cases. The absence of androgen receptors and expression of INSL3 constitute the most relevant histological differential fact.

Keywords

Congenital Adrenal Hyperplasia Rete Testis Testicular Tumor Leydig Cell Tumor CYP11B1 Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.

References

  1. 1.
    Forest MG. Recent advances in the diagnosis and management of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Hum Reprod Update. 2004;10:469–85.CrossRefPubMedGoogle Scholar
  2. 2.
    Bercovici JP, Fiet J, Gibault L, Volant A, Abalain JH, Floch HH, Sonnet E, Fournier G. Testicular adrenal rest tumours in salt wasting congenital adrenal hyperplasia (in vivo and in vitro studies). J Steroid Biochem Mol Biol. 2005;93:67–72.CrossRefPubMedGoogle Scholar
  3. 3.
    Ulbright TM, Young RH. Tumors of the testis and adjacent structures, AFIP atlas of tumor pathology series 4, fascicle, 18th ed. Silver Spring, Maryland: American Registry of Pathology; 2013.Google Scholar
  4. 4.
    Val P, Jeays-Ward K, Swain A. Identification of a novel population of adrenal-like cells in the mammalian testis. Dev Biol. 2006;299:250–6.CrossRefPubMedGoogle Scholar
  5. 5.
    Paner GP, Kristiansen G, McKenney JK, Amin MB. Rete testis-associated nodular steroid cell nests: description of putative pluripotential testicular hilus steroid cells. Am J Surg Pathol. 2011;35:505–11.CrossRefPubMedGoogle Scholar
  6. 6.
    Murphy H, George C, De Kretser D, Judd S. Successful treatment with ICSI of infertility caused by azoospermia associated with adrenal rest in the testes: case report. Hum Reprod. 2001;16:263–7.CrossRefPubMedGoogle Scholar
  7. 7.
    Stikkelbroeck NM, Otten BJ, Pasic A, Jager GJ, Sweep CG, Noordam K, Hermus AR. High prevalence of testicular adrenal rest tumors, impaired spermatogenesis, and Leydig cell failure in adolescent and adult males with congenital adrenal hyperplasia. J Clin Endocrinol Metab. 2001;86:5721–8.CrossRefPubMedGoogle Scholar
  8. 8.
    Hicks MJ, Cipriani N, Pytel P, Shimada H. The pineal, pituitary, parathyroid, thyroid and adrenal glands. In: Husain AN, Stocker JT, Dehmer LP, editors. 4rd ed. Stocker and Dehner’s pediatric pathology. Wolters Kluger: Philadelphia; 2016.Google Scholar
  9. 9.
    Lack E, Paal E. Neoplasm of the testis. In: Bostwick DG, Cheng L, editors. Urologic surgical pathology. 3rd ed. Philadelphia: Elsevier Health Sciences; 2014.Google Scholar
  10. 10.
    Sabine N, Malone M, Ashworth M, et al. Diagnostic pediatric surgical pathology. Edinburgh: Elsevier; 2010.Google Scholar
  11. 11.
    Al-Ahmadie H. “Testicular tumors,” in pediatric pathology. Alphen aan den Rijn: Wolters Kluwer; 2011.Google Scholar
  12. 12.
    Ulbright TM, Young RH. Testicular and paratesticular tumors and tumor-like lesions in the first 2 decades. Semin Diagn Pathol. 2014;31:323–81.CrossRefPubMedGoogle Scholar
  13. 13.
    Wilkins L, Fleischmann W, Howard JE. Macrogenitosomiaprecox associated with hyperplasia of the androgenic tissue of the adrenal and death from cortico adrenal insufficiency. Case report. Endocrinology. 1940;26:385–3.CrossRefGoogle Scholar
  14. 14.
    Stikkelbroeck NM, Suliman HM, Otten BJ, Hermus AR, Blickman JG, Jager GJ. Testicular adrenal rest tumours in postpubertal males with congenital adrenal hyperplasia: sonographic and MR features. Eur Radiol. 2003;13:1597–603.CrossRefPubMedGoogle Scholar
  15. 15.
    Rutgers JL, Young RH, Scully RE. The testicular “tumor” of the adrenogenital syndrome. A report of six cases and review of the literature on testicular masses in patients with adrenocortical disorders. Am J Surg Pathol. 1988;12:503–13.CrossRefPubMedGoogle Scholar
  16. 16.
    Claahsen-van der Grinten HL, Otten BJ, Hermus AR, Sweep FC, Hulsbergen-van de Kaa CA. Testicular adrenal rest tumors in patients with congenital adrenal hyperplasia can cause severe testicular damage. Fertil Steril. 2008;89:597–601.CrossRefPubMedGoogle Scholar
  17. 17.
    Claahsen-van der Grinten HL, Sweep FC, Blickman JG, Hermus AR, Otten BJ. Prevalence of testicular adrenal rest tumours in male children with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Eur J Endocrinol. 2007;157:339–44.CrossRefPubMedGoogle Scholar
  18. 18.
    Al-Agha OM, Axiotis CA. An in-depth look at Leydig cell tumor of the testis. Arch Pathol Lab Med. 2007;131:311–7.PubMedGoogle Scholar
  19. 19.
    Souverijns G, Peene P, Keuleers H, Vanbockrijck M. Ectopic localization of adrenal cortex. Eur Radiol. 2000;10:1165–8.CrossRefPubMedGoogle Scholar
  20. 20.
    Charfi N, Kamoun M, Feki Mnif M, Mseddi N, Mnif F, Kallel N, Ben Naceur B, Rekik N, Fourati H, Daoud E, Mnif Z, Hadj Sliman M, Sellami-Boudawara T, Abid M. Leydig cell tumor associated with testicular adrenal rest tumors in a patient with congenital adrenal hyperplasia due to 11β-hydroxylase deficiency. Case Rep Urol. 2012;2012:648643.PubMedPubMedCentralGoogle Scholar
  21. 21.
    Rich MA, Keating MA. Leydig cell tumors and tumors associated with congenital adrenal hyperplasia. Urol Clin North Am. 2000;27:519–28.CrossRefPubMedGoogle Scholar
  22. 22.
    Teixeira SR, Elias PC, Andrade MT, Melo AF, Elias Junior J. The role of imaging in congenital adrenal hyperplasia. Arq Bras Endocrinol Metabol. 2014;58:701–8.CrossRefPubMedGoogle Scholar
  23. 23.
    Avila NA, Premkumar A, Shawker TH, Jones JV, Laue L, Cutler Jr GB. Testicular adrenal rest tissue in congenital adrenal hyperplasia: findings at Gray-scale and color Doppler US. Radiology. 1996;198:99–104.CrossRefPubMedGoogle Scholar
  24. 24.
    Fitoz S, Atasoy C, Adiyaman P, Berberoglu M, Erden I, Ocal G. Testicular adrenal rests in a patient with congenital adrenal hyperplasia: US and MRI features. Comput Med Imaging Graph. 2006;30:465–8.CrossRefPubMedGoogle Scholar
  25. 25.
    Young RH. Testicular tumors–some new and a few perennial problems. Arch Pathol Lab Med. 2008;132:548–64.PubMedGoogle Scholar
  26. 26.
    Ashley RA, McGee SM, Isotaolo PA, Kramer SA, Cheville JC. Clinical and pathological features associated with the testicular tumor of the adrenogenital syndrome. J Urol. 2007;177:546–9.CrossRefPubMedGoogle Scholar
  27. 27.
    Santonja C, Varona C, Burgos FJ, Nistal M. Leydig cell tumor of testis with adipose metaplasia. Appl Pathol. 1989;7:201–4.PubMedGoogle Scholar
  28. 28.
    Ulbright TM, Srigley JR, Hatzianastassiou DK, Young RH. Leydig cell tumors of the testis with unusual features: adipose differentiation, calcification with ossification, and spindle-shaped tumor cells. Am J Surg Pathol. 2002;26:1424–33.CrossRefPubMedGoogle Scholar
  29. 29.
    Leschek EW, Chan WY, Diamond DA, Kaefer M, Jones J, Barnes KM, Cutler Jr GB. Nodular Leydig cell hyperplasia in a boy with familial male-limited precocious puberty. J Pediatr. 2001;138:949–51.CrossRefPubMedGoogle Scholar
  30. 30.
    Wang Z, Yang S, Shi H, Du H, Xue L, Wang L, Dong Y, Han A. Histopathological and immunophenotypic features of testicular tumour of the adrenogenital syndrome. Histopathology. 2011;58:1013–8.CrossRefPubMedGoogle Scholar
  31. 31.
    Vukina J, Chism DD, Sharpless JL, Raynor MC, Milowsky MI, Funkhouser WK. Metachronous bilateral testicular leydig-like tumors leading to the diagnosis of congenital adrenal hyperplasia (adrenogenital syndrome). Case Rep Pathol. 2015;2015:459318.PubMedPubMedCentralGoogle Scholar
  32. 32.
    Lottrup G, Nielsen JE, Skakkebæk NE, Juul A, Rajpert-De Meyts E. Abundance of DLK1, differential expression of CYP11B1, CYP21A2 and MC2R, and lack of INSL3 distinguish testicular adrenal rest tumours from Leydig cell tumours. Eur J Endocrinol. 2015;172:491–9.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Manuel Nistal
    • 1
  • Pilar González-Peramato
    • 2
  • Álvaro Serrano
    • 3
  1. 1.Universidad Autónoma de Madrid (UAM)Department of Anatomy, Histology and Neuroscience, School of MedicineMadridSpain
  2. 2.School of Medicine, Universidad Autónoma de Madrid (UAM), University Hospital La Paz, Department of PathologyMadridSpain
  3. 3.University Hospital Clinico San Carlos, Department of UrologyMadridSpain

Personalised recommendations