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Anatomy and pathology of testicular tumors

Michelle S Hirsch, MD, PhD
Section Editor
Philip W Kantoff, MD
Deputy Editor
Michael E Ross, MD


Testicular neoplasms comprise the most common solid malignancy affecting males between the ages of 15 and 35, although they represent only approximately 1 percent of all solid tumors in men [1]. The two main categories of testicular tumors are germ cell tumors (GCTs), which account for 95 percent of cases, and sex cord-stromal tumors.

Testicular pathology is a nosologically complex subject because of the spectrum of histologic subtypes and variable clinical behavior, particularly among GCTs. Prediction of biologic behavior depends upon the type(s) of tumors present, as well as clinical features, including the age of the patient and primary site (ie, testicular versus retroperitoneal), since histologically identical tumors can behave differently depending upon these clinical parameters. Accurate histologic evaluation and staging will help determine if a patient should be treated surgically (orchiectomy, retroperitoneal lymph node dissection) and whether chemotherapy is indicated.

A second source of confusion is the nonuniform and often complex classification schemes for testicular tumors. Separation of a few of the major subtypes can be somewhat subjective (eg, there can be morphologic overlap between various subtypes of GCTs) [2,3]; however, in many cases these distinctions may not be pivotal in the choice of therapy and management. The classification scheme used herein is relatively simple, practical, widely accepted, and of proven clinical utility (table 1).

Pathologic evaluation is generally performed on the entire testis rather than on a biopsy sample. Examination of the entire testis allows identification of the histopathologic tumor type, as well as an assessment of the stage and extent of the disease, both of which have an important bearing on subsequent management and prognosis (table 2A-B). Histologic features help to determine higher stage include vascular or lymphatic invasion and spread beyond the tunica albuginea or into the spermatic cord [4].

The management of testicular tumors is discussed separately. (See "Overview of the treatment of testicular germ cell tumors".)

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Literature review current through: Sep 2017. | This topic last updated: Sep 27, 2017.
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  1. Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin 2017; 67:7.
  2. Ulbright TM. The most common, clinically significant misdiagnoses in testicular tumor pathology, and how to avoid them. Adv Anat Pathol 2008; 15:18.
  3. Ulbright TM. Germ cell tumors of the gonads: a selective review emphasizing problems in differential diagnosis, newly appreciated, and controversial issues. Mod Pathol 2005; 18 Suppl 2:S61.
  4. Testis. In: American Joint Committee on Cancer Staging Manual, 5th, Fleming ID, Cooper JS, Henson DE, et al (Eds), Lippincott-Raven Publishers, Philadelphia 1997. p.225.
  5. Setchell BP, Maddocks S, Brooks DE. Anatomy, vasculature, innervation, and fluids of the male reproductive tract. In: The Physiology of Reproduction, 2nd, Knobil E, Neill JD (Eds), Raven Press, New York 1994. p.1063.
  6. Weinstein MH. Lymphatic Drainage of the Testes. In: Atlas of the Urologic Clinics of North America: Testis Cancer, Rowland RG (Ed), W.B. Saunders Company, Philadelphia 1999. p.1.
  7. Howitt BE, Berney DM. Tumors of the Testis: Morphologic Features and Molecular Alterations. Surg Pathol Clin 2015; 8:687.
  8. Krag Jacobsen G, Barlebo H, Olsen J, et al. Testicular germ cell tumours in Denmark 1976-1980. Pathology of 1058 consecutive cases. Acta Radiol Oncol 1984; 23:239.
  9. Ulbright TM, Amin MB, Young RH. Tumors of the Testis, Adenexa, Spermatic Cord, and Scrotum. In: Atlas of Tumor Pathology, 3rd, Rosai J, Sobin LH (Eds), Armed Forces Institute of Pathology, Washington, DC 1999.
  10. Santagata S, Ligon KL, Hornick JL. Embryonic stem cell transcription factor signatures in the diagnosis of primary and metastatic germ cell tumors. Am J Surg Pathol 2007; 31:836.
  11. Cheng L, Sung MT, Cossu-Rocca P, et al. OCT4: biological functions and clinical applications as a marker of germ cell neoplasia. J Pathol 2007; 211:1.
  12. 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.
  13. Cao D, Humphrey PA, Allan RW. SALL4 is a novel sensitive and specific marker for metastatic germ cell tumors, with particular utility in detection of metastatic yolk sac tumors. Cancer 2009; 115:2640.
  14. Cao D, Li J, Guo CC, et al. SALL4 is a novel diagnostic marker for testicular germ cell tumors. Am J Surg Pathol 2009; 33:1065.
  15. Wang F, Liu A, Peng Y, et al. Diagnostic utility of SALL4 in extragonadal yolk sac tumors: an immunohistochemical study of 59 cases with comparison to placental-like alkaline phosphatase, alpha-fetoprotein, and glypican-3. Am J Surg Pathol 2009; 33:1529.
  16. Liu A, Cheng L, Du J, et al. Diagnostic utility of novel stem cell markers SALL4, OCT4, NANOG, SOX2, UTF1, and TCL1 in primary mediastinal germ cell tumors. Am J Surg Pathol 2010; 34:697.
  17. Ushiku T, Shinozaki A, Shibahara J, et al. SALL4 represents fetal gut differentiation of gastric cancer, and is diagnostically useful in distinguishing hepatoid gastric carcinoma from hepatocellular carcinoma. Am J Surg Pathol 2010; 34:533.
  18. Debacker C, Catala M, Labastie MC. Embryonic expression of the human GATA-3 gene. Mech Dev 1999; 85:183.
  19. Ralston A, Cox BJ, Nishioka N, et al. Gata3 regulates trophoblast development downstream of Tead4 and in parallel to Cdx2. Development 2010; 137:395.
  20. Van Esch H, Groenen P, Nesbit MA, et al. GATA3 haplo-insufficiency causes human HDR syndrome. Nature 2000; 406:419.
  21. Ordóñez NG. Value of GATA3 immunostaining in tumor diagnosis: a review. Adv Anat Pathol 2013; 20:352.
  22. Miettinen M, McCue PA, Sarlomo-Rikala M, et al. GATA3: a multispecific but potentially useful marker in surgical pathology: a systematic analysis of 2500 epithelial and nonepithelial tumors. Am J Surg Pathol 2014; 38:13.
  23. Reddy EK, Burke M, Giri S, et al. Testicular neoplasms: seminoma. J Natl Med Assoc 1990; 82:651.
  24. Stein M, Dale J, Kuten A, Moshkowitz B. Anaplastic seminoma and spermatocytic seminoma--a retrospective analysis. S Afr J Surg 1993; 31:144.
  25. Carrière P, Baade P, Fritschi L. Population based incidence and age distribution of spermatocytic seminoma. J Urol 2007; 178:125.
  26. Talerman A. Spermatocytic seminoma: clinicopathological study of 22 cases. Cancer 1980; 45:2169.
  27. Matoska J, Talerman A. Spermatocytic seminoma associated with rhabdomyosarcoma. Am J Clin Pathol 1990; 94:89.
  28. Cummings OW, Ulbright TM, Eble JN, Roth LM. Spermatocytic seminoma: an immunohistochemical study. Hum Pathol 1994; 25:54.
  29. Mostofi FK, Sesterhenn IA, Davis CJ Jr. Developments in histopathology of testicular germ cell tumors. Semin Urol 1988; 6:171.
  30. Talerman A, Haije WG, Baggerman L. Serum alphafetoprotein (AFP) in patients with germ cell tumors of the gonads and extragonadal sites: correlation between endodermal sinus (yolk sac) tumor and raised serum AFP. Cancer 1980; 46:380.
  31. Brown NJ. Yolk-sac tumor ("orchioblastoma") and other testicular tumours of childhood. In: Pathology of the Testis, Pugh RC (Ed), Blackwell Scientific, Oxford 1976. p.356.
  32. Pohl HG, Shukla AR, Metcalf PD, et al. Prepubertal testis tumors: actual prevalence rate of histological types. J Urol 2004; 172:2370.
  33. Magers MJ, Kao CS, Cole CD, et al. "Somatic-type" malignancies arising from testicular germ cell tumors: a clinicopathologic study of 124 cases with emphasis on glandular tumors supporting frequent yolk sac tumor origin. Am J Surg Pathol 2014; 38:1396.
  34. Howitt BE, Magers MJ, Rice KR, et al. Many postchemotherapy sarcomatous tumors in patients with testicular germ cell tumors are sarcomatoid yolk sac tumors: a study of 33 cases. Am J Surg Pathol 2015; 39:251.
  35. Mostofi FK, Price EB Jr. Tumors of the male genital system. In: Atlas of Tumor Pathology, 2nd, Firminger HI (Ed), Armed Forces Institute of Pathology, Washington, DC 1973. p.53.
  36. Brosman SA. Testicular tumors in prepubertal children. Urology 1979; 13:581.
  37. Jones TD, Wang M, Sung MT, et al. Clonal origin of metastatic testicular teratomas. Clin Cancer Res 2006; 12:5377.
  38. The male genital tract. In: Robbins Pathologic Basis of Disease, 6th, Cotran RS, Kumar V, Collins T (Eds), WB Saunders, Philadelphia 1999. p.1022.
  39. Cheng L, Zhang S, MacLennan GT, et al. Interphase fluorescence in situ hybridization analysis of chromosome 12p abnormalities is useful for distinguishing epidermoid cysts of the testis from pure mature teratoma. Clin Cancer Res 2006; 12:5668.
  40. Motzer RJ, Amsterdam A, Prieto V, et al. Teratoma with malignant transformation: diverse malignant histologies arising in men with germ cell tumors. J Urol 1998; 159:133.
  41. Comiter CV, Kibel AS, Richie JP, et al. Prognostic features of teratomas with malignant transformation: a clinicopathological study of 21 cases. J Urol 1998; 159:859.
  42. Ganjoo KN, Foster RS, Michael H, et al. Germ cell tumor associated primitive neuroectodermal tumors. J Urol 2001; 165:1514.
  43. Donadio AC, Motzer RJ, Bajorin DF, et al. Chemotherapy for teratoma with malignant transformation. J Clin Oncol 2003; 21:4285.
  44. Ehrlich Y, Beck SD, Ulbright TM, et al. Outcome analysis of patients with transformed teratoma to primitive neuroectodermal tumor. Ann Oncol 2010; 21:1846.
  45. Giannatempo P, Pond GR, Sonpavde G, et al. Treatment and Clinical Outcomes of Patients with Teratoma with Somatic-Type Malignant Transformation: An International Collaboration. J Urol 2016; 196:95.
  46. Göbel U, Schneider DT, Calaminus G, et al. Germ-cell tumors in childhood and adolescence. GPOH MAKEI and the MAHO study groups. Ann Oncol 2000; 11:263.
  47. Simmonds PD, Lee AH, Theaker JM, et al. Primary pure teratoma of the testis. J Urol 1996; 155:939.
  48. Ahmed T, Bosl GJ, Hajdu SI. Teratoma with malignant transformation in germ cell tumors in men. Cancer 1985; 56:860.
  49. Moch, H., Humphrey, et al. WHO Classification of Tumours of the Urinary System and Male Genital Organs, 4.
  50. Skakkebaek NE, Berthelsen JG, Müller J. Carcinoma-in-situ of the undescended testis. Urol Clin North Am 1982; 9:377.
  51. Gabrilove JL, Nicolis GL, Mitty HA, Sohval AR. Feminizing interstitial cell tumor of the testis: personal observations and a review of the literature. Cancer 1975; 35:1184.
  52. Muir CS, Nectoux J. Epidemiology of cancer of the testis and penis. Natl Cancer Inst Monogr 1979; :157.
  53. Atkin NB, Baker MC. Specific chromosome change, i(12p), in testicular tumours? Lancet 1982; 2:1349.
  54. 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.
  55. Bosl GJ, Ilson DH, Rodriguez E, et al. Clinical relevance of the i(12p) marker chromosome in germ cell tumors. J Natl Cancer Inst 1994; 86:349.
  56. Suijkerbuijk RF, Sinke RJ, Meloni AM, et al. Overrepresentation of chromosome 12p sequences and karyotypic evolution in i(12p)-negative testicular germ-cell tumors revealed by fluorescence in situ hybridization. Cancer Genet Cytogenet 1993; 70:85.
  57. Roelofs H, Mostert MC, Pompe K, et al. Restricted 12p amplification and RAS mutation in human germ cell tumors of the adult testis. Am J Pathol 2000; 157:1155.
  58. Rodriguez E, Houldsworth J, Reuter VE, et al. Molecular cytogenetic analysis of i(12p)-negative human male germ cell tumors. Genes Chromosomes Cancer 1993; 8:230.
  59. Ulbright TM, Amin MB, Young RH. Ulbright TM, Amin MB, Young RH. In: Atlas of Tumor Pathology, 3rd, Rosai J, Sobin LH (Eds), Armed Forces Institute of Pathology, Washington, DC 1999.
  60. Cheville JC, Sebo TJ, Lager DJ, et al. Leydig cell tumor of the testis: a clinicopathologic, DNA content, and MIB-1 comparison of nonmetastasizing and metastasizing tumors. Am J Surg Pathol 1998; 22:1361.
  61. Young RH. Sex cord-stromal tumors of the ovary and testis: their similarities and differences with consideration of selected problems. Mod Pathol 2005; 18 Suppl 2:S81.
  62. Lawrence WD, Young RH, Scully RE. Sex cord - stromal tumors. In: Pathology of the Testis and its Adenexa - Contemporary Issues in Surgical Pathology, Talerman A, Roth LM (Eds), Churchill Livingstone, New York 1986. Vol 7.
  63. Dilworth JP, Farrow GM, Oesterling JE. Non-germ cell tumors of testis. Urology 1991; 37:399.
  64. Freeman DA. Steroid hormone-producing tumors in man. Endocr Rev 1986; 7:204.
  65. Iczkowski KA, Bostwick DG, Roche PC, Cheville JC. Inhibin A is a sensitive and specific marker for testicular sex cord-stromal tumors. Mod Pathol 1998; 11:774.
  66. McCluggage WG, Shanks JH, Whiteside C, et al. Immunohistochemical study of testicular sex cord-stromal tumors, including staining with anti-inhibin antibody. Am J Surg Pathol 1998; 22:615.
  67. Ashley RA, McGee SM, Isotaolo PA, et al. Clinical and pathological features associated with the testicular tumor of the adrenogenital syndrome. J Urol 2007; 177:546.
  68. Giannarini G, Mogorovich A, Menchini Fabris F, et al. Long-term followup after elective testis sparing surgery for Leydig cell tumors: a single center experience. J Urol 2007; 178:872.
  69. Jimenez-Quintero LP, Ro JY, Zavala-Pompa A, et al. Granulosa cell tumor of the adult testis: a clinicopathologic study of seven cases and a review of the literature. Hum Pathol 1993; 24:1120.
  70. Garrett JE, Cartwright PC, Snow BW, Coffin CM. Cystic testicular lesions in the pediatric population. J Urol 2000; 163:928.
  71. Gibbons B, Tan SY, Yu CC, et al. Risk of gonadoblastoma in female patients with Y chromosome abnormalities and dysgenetic gonads. J Paediatr Child Health 1999; 35:210.
  72. Perez-Ordonez B, Srigley JR. Mesothelial lesions of the paratesticular region. Semin Diagn Pathol 2000; 17:294.
  73. McClure RF, Keeney GL, Sebo TJ, Cheville JC. Serous borderline tumor of the paratestis: a report of seven cases. Am J Surg Pathol 2001; 25:373.
  74. Henley JD, Ferry J, Ulbright TM. Miscellaneous rare paratesticular tumors. Semin Diagn Pathol 2000; 17:319.
  75. Dalle JH, Mechinaud F, Michon J, et al. Testicular disease in childhood B-cell non-Hodgkin's lymphoma: the French Society of Pediatric Oncology experience. J Clin Oncol 2001; 19:2397.
  76. Vega F, Medeiros LJ, Abruzzo LV. Primary paratesticular lymphoma: a report of 2 cases and review of literature. Arch Pathol Lab Med 2001; 125:428.
  77. Fonseca R, Habermann TM, Colgan JP, et al. Testicular lymphoma is associated with a high incidence of extranodal recurrence. Cancer 2000; 88:154.
  78. Tondini C, Ferreri AJ, Siracusano L, et al. Diffuse large-cell lymphoma of the testis. J Clin Oncol 1999; 17:2854.
  79. Shahab N, Doll DC. Testicular lymphoma. Semin Oncol 1999; 26:259.
  80. Seymour JF, Solomon B, Wolf MM, et al. Primary large-cell non-Hodgkin's lymphoma of the testis: a retrospective analysis of patterns of failure and prognostic factors. Clin Lymphoma 2001; 2:109.
  81. Vural F, Cagirgan S, Saydam G, et al. Primary testicular lymphoma. J Natl Med Assoc 2007; 99:1277.
  82. Gaynon PS, Qu RP, Chappell RJ, et al. Survival after relapse in childhood acute lymphoblastic leukemia: impact of site and time to first relapse--the Children's Cancer Group Experience. Cancer 1998; 82:1387.
  83. Gutjahr P, Humpl T. Testicular lymphoblastic leukemia/lymphoma. World J Urol 1995; 13:230.
  84. Forrest DL, Dalal BI, Naiman SC, et al. Testicular relapse of acute promyelocytic leukemia after allogeneic BMT. Bone Marrow Transplant 1997; 20:689.
  85. Ferry JA, Young RH, Scully RE. Testicular and epididymal plasmacytoma: a report of 7 cases, including three that were the initial manifestation of plasma cell myeloma. Am J Surg Pathol 1997; 21:590.
  86. Fischer C, Terpe HJ, Weidner W, Schulz A. Primary plasmacytoma of the testis. Case report and review of the literature. Urol Int 1996; 56:263.