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Testicular germ cell neoplasia in situ (formerly called intratubular germ cell neoplasia of unclassified type)

Ximing J Yang, MD, PhD
Jerome P Richie, MD, FACS
Section Editor
William K Oh, MD
Deputy Editor
Michael E Ross, MD


Testicular germ cell neoplasia in situ (GCNIS; formerly called intratubular germ cell neoplasia of the unclassified type [1]) is generally considered a precursor of all testicular germ cell tumors (GCTs), except for spermatocytic seminomas in older adult men and yolk sac tumors and mature teratomas in infants. However, this is not an epithelial lesion, and thus the latter terms are not preferred. GCNIS is noninvasive because the neoplastic cells are confined within the seminiferous tubules.

GCNIS is discussed here. Related topics include:

(See "Epidemiology of and risk factors for testicular germ cell tumors".)

(See "Clinical manifestations, diagnosis, and staging of testicular germ cell tumors".)

(See "Overview of the treatment of testicular germ cell tumors".)

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Literature review current through: Nov 2017. | This topic last updated: Oct 19, 2016.
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  1. Moch, H., Humphrey, et al. WHO Classification of Tumours of the Urinary System and Male Genital Organs, 4.
  2. Jacobsen GK, Henriksen OB, von der Maase H. Carcinoma in situ of testicular tissue adjacent to malignant germ-cell tumors: a study of 105 cases. Cancer 1981; 47:2660.
  3. Huyghe E, Soulie M, Escourrou G, et al. Conservative management of small testicular tumors relative to carcinoma in situ prevalence. J Urol 2005; 173:820.
  4. Dieckmann KP, Skakkebaek NE. Carcinoma in situ of the testis: review of biological and clinical features. Int J Cancer 1999; 83:815.
  5. Skakkebaek NE, Berthelsen JG, Müller J. Carcinoma-in-situ of the undescended testis. Urol Clin North Am 1982; 9:377.
  6. Batata MA, Chu FC, Hilaris BS, et al. Testicular cancer in cryptorchids. Cancer 1982; 49:1023.
  7. von der Maase H, Rørth M, Walbom-Jørgensen S, et al. Carcinoma in situ of contralateral testis in patients with testicular germ cell cancer: study of 27 cases in 500 patients. Br Med J (Clin Res Ed) 1986; 293:1398.
  8. Dieckmann KP, Loy V. Prevalence of contralateral testicular intraepithelial neoplasia in patients with testicular germ cell neoplasms. J Clin Oncol 1996; 14:3126.
  9. Dieckmann KP, Loy V, Büttner P. Prevalence of bilateral testicular germ cell tumours and early detection based on contralateral testicular intra-epithelial neoplasia. Br J Urol 1993; 71:340.
  10. Müller J, Skakkebaek NE. Testicular carcinoma in situ in children with the androgen insensitivity (testicular feminisation) syndrome. Br Med J (Clin Res Ed) 1984; 288:1419.
  11. Manivel JC, Simonton S, Wold LE, Dehner LP. Absence of intratubular germ cell neoplasia in testicular yolk sac tumors in children. A histochemical and immunohistochemical study. Arch Pathol Lab Med 1988; 112:641.
  12. Manivel JC, Reinberg Y, Niehans GA, Fraley EE. Intratubular germ cell neoplasia in testicular teratomas and epidermoid cysts. Correlation with prognosis and possible biologic significance. Cancer 1989; 64:715.
  13. Linke J, Loy V, Dieckmann KP. Prevalence of testicular intraepithelial neoplasia in healthy males. J Urol 2005; 173:1577.
  14. Hoei-Hansen CE, Rajpert-De Meyts E, Daugaard G, Skakkebaek NE. Carcinoma in situ testis, the progenitor of testicular germ cell tumours: a clinical review. Ann Oncol 2005; 16:863.
  15. Petersen PM, Giwercman A, Skakkebaek NE, Rørth M. Gonadal function in men with testicular cancer. Semin Oncol 1998; 25:224.
  16. Skakkebaek NE, Berthelsen JG, Giwercman A, Müller J. Carcinoma-in-situ of the testis: possible origin from gonocytes and precursor of all types of germ cell tumours except spermatocytoma. Int J Androl 1987; 10:19.
  17. Almstrup K, Hoei-Hansen CE, Wirkner U, et al. Embryonic stem cell-like features of testicular carcinoma in situ revealed by genome-wide gene expression profiling. Cancer Res 2004; 64:4736.
  18. De Meytes ER, Giwercman A, Skakkebaek NE. Carcinoma in situ of the testis- a precursor of testicular germ cell cancer: biological and clinical aspects. In: Comprehensive Textbook of Genitourinary Oncology, Vogelzang NJ, Scardino PT, Shipley WU, Coffey DS (Eds), Lippincott, Williams and Wilkins, Philadelphia 2000. p.900.
  19. Rajpert-De Meyts E, Skakkebaek NE. Expression of the c-kit protein product in carcinoma-in-situ and invasive testicular germ cell tumours. Int J Androl 1994; 17:85.
  20. Jacobsen GK, Nørgaard-Pedersen B. Placental alkaline phosphatase in testicular germ cell tumours and in carcinoma-in-situ of the testis. An immunohistochemical study. Acta Pathol Microbiol Immunol Scand A 1984; 92:323.
  21. Jørgensen N, Rajpert-De Meyts E, Graem N, et al. Expression of immunohistochemical markers for testicular carcinoma in situ by normal human fetal germ cells. Lab Invest 1995; 72:223.
  22. Rajpert-De Meyts E, Jørgensen N, Müller J, Skakkebaek NE. Prolonged expression of the c-kit receptor in germ cells of intersex fetal testes. J Pathol 1996; 178:166.
  23. Rajpert-De Meyts E, Kvist M, Skakkebaek NE. Heterogeneity of expression of immunohistochemical tumour markers in testicular carcinoma in situ: pathogenetic relevance. Virchows Arch 1996; 428:133.
  24. Miyai K, Yamamoto S, Iwaya K, et al. Allelotyping analysis suggesting a consecutive progression from intratubular germ cell neoplasia to seminoma and then to embryonal carcinoma of the adult testis. Hum Pathol 2013; 44:2312.
  25. Almstrup K, Hoei-Hansen CE, Nielsen JE, et al. Genome-wide gene expression profiling of testicular carcinoma in situ progression into overt tumours. Br J Cancer 2005; 92:1934.
  26. Berney DM, Lee A, Shamash J, Oliver RT. The association between intratubular seminoma and invasive germ cell tumors. Hum Pathol 2006; 37:458.
  27. Cancer incidence in Denmark, 1985, Dane Cancer Registry, Copenhagen, Danish Cancer Society, 1988.
  28. Sharma P, Dhillon J, Sexton WJ. Intratubular Germ Cell Neoplasia of the Testis, Bilateral Testicular Cancer, and Aberrant Histologies. Urol Clin North Am 2015; 42:277.
  29. Giwercman A, Müller J, Skakkebaek NE. Prevalence of carcinoma in situ and other histopathological abnormalities in testes from 399 men who died suddenly and unexpectedly. J Urol 1991; 145:77.
  30. Fosså SD, Chen J, Schonfeld SJ, et al. Risk of contralateral testicular cancer: a population-based study of 29,515 U.S. men. J Natl Cancer Inst 2005; 97:1056.
  31. Engeler DS, Hösli PO, John H, et al. Early orchiopexy: prepubertal intratubular germ cell neoplasia and fertility outcome. Urology 2000; 56:144.
  32. Petersen PM, Giwercman A, Hansen SW, et al. Impaired testicular function in patients with carcinoma-in-situ of the testis. J Clin Oncol 1999; 17:173.
  33. Jacobsen R, Bostofte E, Engholm G, et al. Risk of testicular cancer in men with abnormal semen characteristics: cohort study. BMJ 2000; 321:789.
  34. Richiardi L, Akre O, Montgomery SM, et al. Fecundity and twinning rates as measures of fertility before diagnosis of germ-cell testicular cancer. J Natl Cancer Inst 2004; 96:145.
  35. Bettocchi C, Coker CB, Deacon J, et al. A review of testicular intratubular germ cell neoplasia in infertile men. J Androl 1994; 15 Suppl:14S.
  36. Pryor JP, Cameron KM, Chilton CP, et al. Carcinoma in situ in testicular biopsies from men presenting with infertility. Br J Urol 1983; 55:780.
  37. Giwercman A, Thomsen JK, Hertz J, et al. Prevalence of carcinoma in situ of the testis in 207 oligozoospermic men from infertile couples: prospective study of testicular biopsies. BMJ 1997; 315:989.
  38. Daugaard G, Rørth M, von der Maase H, Skakkebaek NE. Management of extragonadal germ-cell tumors and the significance of bilateral testicular biopsies. Ann Oncol 1992; 3:283.
  39. Levin HS. Tumors of the testis in intersex syndromes. Urol Clin North Am 2000; 27:543.
  40. Müller J. Abnormal infantile germ cells and development of carcinoma-in-situ in maldeveloped testes: a stereological and densitometric study. Int J Androl 1987; 10:543.
  41. Müller J, Ritzén EM, Ivarsson SA, et al. Management of males with 45,X/46,XY gonadal dysgenesis. Horm Res 1999; 52:11.
  42. Gourlay WA, Johnson HW, Pantzar JT, et al. Gonadal tumors in disorders of sexual differentiation. Urology 1994; 43:537.
  43. Müller J, Skakkebaek NE, Ritzén M, et al. Carcinoma in situ of the testis in children with 45,X/46,XY gonadal dysgenesis. J Pediatr 1985; 106:431.
  44. Ramani P, Yeung CK, Habeebu SS. Testicular intratubular germ cell neoplasia in children and adolescents with intersex. Am J Surg Pathol 1993; 17:1124.
  45. Dieckmann KP, Kulejewski M, Heinemann V, Loy V. Testicular biopsy for early cancer detection--objectives, technique and controversies. Int J Androl 2011; 34:e7.
  46. von der Maase H. Is a contralateral testicular biopsy in patients with unilateral germ cell testicular cancer indicated as a routine procedure? Acta Oncol 2005; 44:523.
  47. Giwercman A, Berthelsen JG, Müller J, et al. Screening for carcinoma-in-situ of the testis. Int J Androl 1987; 10:173.
  48. Dieckmann KP, Souchon R, Hahn E, Loy V. False-negative biopsies for testicular intraepithelial neoplasia. J Urol 1999; 162:364.
  49. Dieckmann KP, Kulejewski M, Pichlmeier U, Loy V. Diagnosis of contralateral testicular intraepithelial neoplasia (TIN) in patients with testicular germ cell cancer: systematic two-site biopsies are more sensitive than a single random biopsy. Eur Urol 2007; 51:175.
  50. Nagler HM, Kaufman DG, O'Toole KM, Sawczuk IS. Carcinoma in situ of the testes: diagnosis by aspiration flow cytometry. J Urol 1990; 143:359.
  51. de Jong J, Stoop H, Dohle GR, et al. Diagnostic value of OCT3/4 for pre-invasive and invasive testicular germ cell tumours. J Pathol 2005; 206:242.
  52. Jones TD, Ulbright TM, Eble JN, et al. OCT4 staining in testicular tumors: a sensitive and specific marker for seminoma and embryonal carcinoma. Am J Surg Pathol 2004; 28:935.
  53. Giwercman A, Marks A, Bailey D, et al. A monoclonal antibody as a marker for carcinoma in situ germ cells of the human adult testis. APMIS 1988; 96:667.
  54. Giwercman A, Lindenberg S, Kimber SJ, et al. Monoclonal antibody 43-9F as a sensitive immunohistochemical marker of carcinoma in situ of human testis. Cancer 1990; 65:1135.
  55. Giwercman A, Andrews PW, Jørgensen N, et al. Immunohistochemical expression of embryonal marker TRA-1-60 in carcinoma in situ and germ cell tumors of the testis. Cancer 1993; 72:1308.
  56. van Echten J, Oosterhuis JW, Looijenga LH, et al. No recurrent structural abnormalities apart from i(12p) in primary germ cell tumors of the adult testis. Genes Chromosomes Cancer 1995; 14:133.
  57. Lenz S, Giwercman A, Skakkebaek NE, et al. Ultrasound in detection of early neoplasia of the testis. Int J Androl 1987; 10:187.
  58. Giwercman A, Lenz S, Skakkebaek NE. Carcinoma in situ in atrophic testis: biopsy based on abnormal ultrasound pattern. Br J Urol 1993; 72:118.
  59. Lenz S, Skakkebaek NE, Hertel NT. Abnormal ultrasonic pattern in contralateral testes in patients with unilateral testicular cancer. World J Urol 1996; 14 Suppl 1:S55.
  60. Giwercman A, Hopman AH, Ramaekers FC, Skakkebaek NE. Carcinoma in situ of the testis. Detection of malignant germ cells in seminal fluid by means of in situ hybridization. Am J Pathol 1990; 136:497.
  61. Brackenbury ET, Hargreave TB, Howard GC, McIntyre MA. Seminal fluid analysis and fine-needle aspiration cytology in the diagnosis of carcinoma in situ of the testis. Eur Urol 1993; 23:123.
  62. Meng FJ, Zhou Y, Giwercman A, et al. Fluorescence in situ hybridization analysis of chromosome 12 anomalies in semen cells from patients with carcinoma in situ of the testis. J Pathol 1998; 186:235.
  63. Schmoll HJ, Souchon R, Krege S, et al. European consensus on diagnosis and treatment of germ cell cancer: a report of the European Germ Cell Cancer Consensus Group (EGCCCG). Ann Oncol 2004; 15:1377.
  64. von der Maase H, Giwercman A, Skakkebaek NE. Radiation treatment of carcinoma-in-situ of testis. Lancet 1986; 1:624.
  65. Giwercman A, von der Maase H, Berthelsen JG, et al. Localized irradiation of testes with carcinoma in situ: effects on Leydig cell function and eradication of malignant germ cells in 20 patients. J Clin Endocrinol Metab 1991; 73:596.
  66. Daugaard G, Giwercman A, Skakkeback NE. Editorial Comments. J Urol 1997; 158:1334.
  67. Sedlmayer F, Höltl W, Kozak W, et al. Radiotherapy of testicular intraepithelial neoplasia (TIN): a novel treatment regimen for a rare disease. Int J Radiat Oncol Biol Phys 2001; 50:909.
  68. Petersen PM, Giwercman A, Daugaard G, et al. Effect of graded testicular doses of radiotherapy in patients treated for carcinoma-in-situ in the testis. J Clin Oncol 2002; 20:1537.
  69. Classen J, Dieckmann K, Bamberg M, et al. Radiotherapy with 16 Gy may fail to eradicate testicular intraepithelial neoplasia: preliminary communication of a dose-reduction trial of the German Testicular Cancer Study Group. Br J Cancer 2003; 88:828.
  70. Daugaard G, Giwercman A, Skakkebaek NE. Should the other testis be biopsied? Semin Urol Oncol 1996; 14:8.
  71. Christensen TB, Daugaard G, Geertsen PF, von der Maase H. Effect of chemotherapy on carcinoma in situ of the testis. Ann Oncol 1998; 9:657.
  72. von der Maase H, Meinecke B, Skakkebaek NE. Residual carcinoma-in-situ of contralateral testis after chemotherapy. Lancet 1988; 1:477.
  73. Fosså SD, Aass N. Cisplatin-based chemotherapy does not eliminate the risk of a second testicular cancer. Br J Urol 1989; 63:531.