Familial Syndromes Associated with Testicular Tumors

  • Jesse K. McKenney
  • Claudio Lizarralde
  • Cristina Magi-Galluzzi
Chapter

Abstract

Extensive studies have shown that familial risk for testicular cancer is among the highest reported for any human cancer. There is strong evidence that genes play a role in familial testicular cancer; nevertheless, environmental and occupational exposures, behavior, and diet shared among members of a given family can be an important component difficult to separate. The existence of a true familial form of germ cell tumors is supported by segregation studies suggesting an autosomal recessive mode of inheritance. Linkage analyses have identified several genomic regions of modest interest on chromosomes 5, 6, and 12. Several rare tumor syndromes, such as Peutz–Jeghers syndrome, Carney complex, familial adenomatous polyposis syndrome, PTEN hamartoma tumor syndrome, Gorlin syndrome, Von Hipple-Lindau disease, hereditary hemochromatosis, Li-Fraumeni syndrome, neurofibromatosis type 1, and adrenogenital syndrome, include specific testicular tumors.

Keywords

Testicular cancer Familial germ cell tumors Tumor syndromes Peutz–Jeghers Carney complex Familial adenomatous polyposis PTEN Gorlin Von Hipple-Lindau Hereditary hemochromatosis Li-Fraumeni Neurofibromatosis Adrenogenital 

References

  1. 1.
    Gallagher DJ, Feifer A, Coleman JA. Genitourinary cancer predisposition syndromes. Hematol Oncol Clin North Am. 2010;24(5):861–83.CrossRefPubMedGoogle Scholar
  2. 2.
    Nordsborg RB, Meliker JR, Wohlfahrt J, Melbye M, Raaschou-Nielsen O. Cancer in first-degree relatives and risk of testicular cancer in Denmark. Int J Cancer. 2011;129(10):2485–91.CrossRefPubMedCentralPubMedGoogle Scholar
  3. 3.
    LutkeHolzik MF, Rapley EA, Hoekstra HJ, Sleijfer DT, Nolte IM, Sijmons RH. Genetic predisposition to testicular germ-cell tumours. Lancet Oncol. 2004;5(6):363–71.CrossRefGoogle Scholar
  4. 4.
    Greene MH, Kratz CP, Mai PL, Mueller C, Peters JA, Bratslavsky G, et al. Familial testicular germ cell tumors in adults: 2010 summary of genetic risk factors and clinical phenotype. Endocr Relat Cancer. 2010;17(2):R109–21.CrossRefPubMedCentralPubMedGoogle Scholar
  5. 5.
    Kratz CP, Mai PL, Greene MH. Familial testicular germ cell tumours. Best Prac Res Clin Endocrinol Metab. 2010;24(3):503–13.CrossRefGoogle Scholar
  6. 6.
    Kanetsky PA, Mitra N, Vardhanabhuti S, Li M, Vaughn DJ, Letrero R, et al. Common variation in KITLG and at 5q31.3 predisposes to testicular germ cell cancer. Nat Genet. 2009;41(7):811–5.CrossRefPubMedCentralPubMedGoogle Scholar
  7. 7.
    Rapley EA, Turnbull C, Al Olama AA, Dermitzakis ET, Linger R, Huddart RA, et al. A genome-wide association study of testicular germ cell tumor. Nat Genet. 2009;41(7):807–10.CrossRefPubMedCentralPubMedGoogle Scholar
  8. 8.
    Sasaki A, Taketomi T, Kato R, Saeki K, Nonami A, Sasaki M, et al. Mammalian Sprouty4 suppresses Ras-independent ERK activation by binding to Raf1. Nat Cell Biol. 2003;5(5):427–32.CrossRefPubMedGoogle Scholar
  9. 9.
    Frolov A, Chahwan S, Ochs M, Arnoletti JP, Pan ZZ, Favorova O, et al. Response markers and the molecular mechanisms of action of Gleevec in gastrointestinal stromal tumors. Mol Cancer Ther. 2003;2(8):699–709.PubMedGoogle Scholar
  10. 10.
    Ulbright TM, Amin MB, Young RH. Intratubular large cell hyalinizingsertoli cell neoplasia of the testis: a report of 8 cases of a distinctive lesion of the Peutz-Jeghers syndrome. Am J Surg Pathol. 2007;31(6):827–35.CrossRefPubMedGoogle Scholar
  11. 11.
    Kaluzny A, Matuszewski M, Wojtylak S, Krajka K, Cichy W, Plawski A, et al. Organ-sparing surgery of the bilateral testicular large cell calcifying sertoli cell tumor in patient with atypical Peutz-Jeghers syndrome. Int Urol Nephrol. 2012;44(4):1045–8.CrossRefPubMedCentralPubMedGoogle Scholar
  12. 12.
    Libe R, Horvath A, Vezzosi D, Fratticci A, Coste J, Perlemoine K, et al. Frequent phosphodiesterase 11A gene (PDE11A) defects in patients with Carney complex (CNC) caused by PRKAR1A mutations: PDE11A may contribute to adrenal and testicular tumors in CNC as a modifier of the phenotype. J Clin Endocrinol Metab. 2011;96(1):E208–14.CrossRefPubMedCentralPubMedGoogle Scholar
  13. 13.
    Stratakis CA, Kirschner LS, Carney JA. Clinical and molecular features of the Carney complex: diagnostic criteria and recommendations for patient evaluation. J Clin Endocrinol Metab. 2001;86(9):4041–6.CrossRefPubMedGoogle Scholar
  14. 14.
    Washecka R, Dresner MI, Honda SA. Testicular tumors in Carney’s complex. J Urol. 2002;167(3):1299–302.CrossRefPubMedGoogle Scholar
  15. 15.
    Gourgari E, Saloustros E, Stratakis CA. Large-cell calcifying Sertoli cell tumors of the testes in pediatrics. Curr Opin Pediatr. 2012;24(4):518–22.CrossRefPubMedCentralPubMedGoogle Scholar
  16. 16.
    Wieacker P, Stratakis CA, Horvath A, Klose S, Nickel I, Buhtz P, et al. Male infertility as a component of Carney complex. Andrologia. 2007;39(5):196–7.CrossRefPubMedGoogle Scholar
  17. 17.
    Losada Grande EJ, Al Kassam Martinez D, Gonzalez Boillos M. Carney complex. Endocrinol Nutr. 2011;58(6):308–14.CrossRefPubMedGoogle Scholar
  18. 18.
    Boikos SA, Stratakis CA. Carney complex: the first 20 years. Curr Opin Oncol. 2007;19(1):24–9.CrossRefPubMedGoogle Scholar
  19. 19.
    Claes K, Dahan K, Tejpar S, De Paepe A, Bonduelle M, Abramowicz M, et al. The genetics of familial adenomatous polyposis (FAP) and MutYH-associated polyposis (MAP). Acta Gastroenterol Belg. 2011;74(3):421–6.PubMedGoogle Scholar
  20. 20.
    Tanwar PS, Zhang L, Teixeira JM. Adenomatous polyposis coli (APC) is essential for maintaining the integrity of the seminiferous epithelium. Mol Endocrinol. 2011;25(10):1725–39.CrossRefPubMedCentralPubMedGoogle Scholar
  21. 21.
    Kato N, Shibuya H, Fukase M, Tamura G, Motoyama T. Involvement of adenomatous polyposis coli (APC) gene in testicular yolk sac tumor of infants. Hum Pathol. 2006;37(1):48–53.CrossRefPubMedGoogle Scholar
  22. 22.
    Castillejo A, Sanchez-Heras AB, Jover R, Castillejo MI, Guarinos C, Oltra S, et al. Recurrent testicular germ cell tumors in a family with MYH-associated polyposis. J Clin Oncol. 2012;30(23):e216–7.CrossRefPubMedGoogle Scholar
  23. 23.
    Calva D, Howe JR. Hamartomatous polyposis syndromes. Surg Clin North Am. 2008;88(4):779–817, vii.CrossRefPubMedCentralPubMedGoogle Scholar
  24. 24.
    Lindsay C, Boardman L, Farrell M. Testicular hamartomas in cowden disease. J Clin Ultrasound. 2003;31(9):481–3.CrossRefPubMedGoogle Scholar
  25. 25.
    Rasalkar DD, Paunipagar BK. Testicular hamartomas and epididymal tumor in a cowden disease: a case report. Case Rep Med. 2010;2010:135029.Google Scholar
  26. 26.
    Woodhouse JB, Delahunt B, English SF, Fraser HH, Ferguson MM. Testicular lipomatosis in Cowden’s syndrome. Mod Pathol. 2005;18(9):1151–6.CrossRefPubMedGoogle Scholar
  27. 27.
    Mazereeuw-Hautier J, Assouere MN, Moreau-Cabarrot A, Longy M, Bonafe JL. Cowden’s syndrome: possible association with testicular seminoma. Br J Dermatol. 2004;150(2):378–9.CrossRefPubMedGoogle Scholar
  28. 28.
    Devi M, Leonard N, Silverman S, Al-Qahtani M, Girgis R. Testicular mixed germ cell tumor in an adolescent with cowden disease. Oncology. 2007;72(3–4):194–6.CrossRefPubMedGoogle Scholar
  29. 29.
    Hendriks YM, Verhallen JT, van derSmagt JJ, Kant SG, Hilhorst Y, Hoefsloot L, et al. Bannayan-Riley-Ruvalcaba syndrome: further delineation of the phenotype and management of PTEN mutation-positive cases. Fam Cancer. 2003;2(2):79–85.CrossRefPubMedGoogle Scholar
  30. 30.
    Walker RN, Murphy TJ, Wilkerson ML. Testicular hamartomas in a patient with Bannayan-Riley-Ruvalcaba syndrome. J Ultrasound Med. 2008;27(8):1245–8.PubMedGoogle Scholar
  31. 31.
    Ueda M, Kanematsu A, Nishiyama H, Yoshimura K, Watanabe K, Yorifuji T, et al. Testicular thecoma in an 11-year-old boy with nevoid basal-cell carcinoma syndrome (Gorlin syndrome). J Pediatr Surg. 2010;45(3):E1–3.CrossRefPubMedGoogle Scholar
  32. 32.
    Glasker S, Tran MG, Shively SB, Ikejiri B, Lonser RR, Maxwell PH, et al. Epididymalcystadenomas and epithelial tumourlets: effects of VHL deficiency on the human epididymis. J Pathol. 2006;210(1):32–41.CrossRefPubMedGoogle Scholar
  33. 33.
    Onitilo AA, Engel JM, Sajjad SM. The possible role of hemochromatosis in testicular cancer. Med Hypotheses. 2011;77(2):179–81.CrossRefPubMedGoogle Scholar
  34. 34.
    Stecher CW, Gronbaek K, Hasle H. A novel splice mutation in the TP53 gene associated with Leydig cell tumor and primitive neuroectodermal tumor. Pediatr Blood Cancer. 2008;50(3):701–3.CrossRefPubMedGoogle Scholar
  35. 35.
    Hartley AL, Birch JM, Kelsey AM, Marsden HB, Harris M, Teare MD. Are germ cell tumors part of the Li-Fraumeni cancer family syndrome? Cancer Genet Cytogenet. 1989;42(2):221–6.CrossRefPubMedGoogle Scholar
  36. 36.
    Scott RJ, Krummenacher F, Mary JL, Weber W, Spycher M, Muller H. Hereditary p53 mutation in a patient with multiple tumors: significance for genetic counseling. Schweiz Med Wochenschr. 1993;123(25):1287–92. Vererbbare p53-Mutation bei einem Patienten mit Mehrfachtumoren: Bedeutung fur die genetische Beratung. ger.PubMedGoogle Scholar
  37. 37.
    Kume H, Tachikawa T, Teramoto S, Isurugi K, Kitamura T. Bilateral testicular tumour in neurofibromatosis type 1. Lancet. 2001;357(9253):395–6.CrossRefPubMedGoogle Scholar
  38. 38.
    Gessl A, Lemmens-Gruber R, Kautzky-Willer A. Adrenal disorders. Handb Exp Pharmacol. 2012;214:341–59.CrossRefPubMedGoogle Scholar
  39. 39.
    Speiser PW, White PC. Congenital adrenal hyperplasia. N Engl J Med. 2003;349(8):776–88.CrossRefPubMedGoogle Scholar
  40. 40.
    White PC. Congenital adrenal hyperplasias. Best Pract Res Clin Endocrinol Metab. 2001;15(1):17–41.CrossRefPubMedGoogle Scholar
  41. 41.
    Rich MA, Keating MA. Leydig cell tumors and tumors associated with congenital adrenal hyperplasia. Urol Clin North Am. 2000;27(3):519–28, x.CrossRefPubMedGoogle Scholar
  42. 42.
    Claahsen-vander Grinten HL, Otten BJ, Stikkelbroeck MM, Sweep FC, Hermus AR. Testicular adrenal rest tumours in congenital adrenal hyperplasia. Best Pract Res Clin Endocrinol Metab. 2009;23(2):209–20.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Jesse K. McKenney
    • 1
  • Claudio Lizarralde
    • 1
  • Cristina Magi-Galluzzi
    • 1
  1. 1.Department of PathologyCleveland Clinic, Robert J. Tomsich Pathology and Laboratory Medicine InstituteClevelandUSA

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