- Author: Michael B Williams, MD, MS; Chief Editor: Bradley Fields Schwartz, DO, FACS more...
Testicular seminoma (see the image below) is a pathologic diagnosis in which only seminomatous elements are observed upon histopathologic review after a radical orchiectomy and in which serum alpha-fetoprotein (AFP) is within the reference range. Seminomas account for one third of testicular germ cell tumors (GCTs), which are the most common malignancy in men aged 15-35 years. The risk of testis cancer is 10-40 times higher in patients with a history of cryptorchidism; 10% of patients with GCTs have a history of cryptorchidism.
Signs and symptoms
The typical presentation in testicular seminoma is as follows:
- A male aged 15-35 years presents with a painless testicular lump that has been noticeable for several days to months
- Patients commonly have abnormal findings on semen analysis at presentation, and they may be subfertile
- Patients may present with a hydrocele, and scrotal ultrasonography may identify a nonpalpable testis tumor
Uncommon presentations include the following:
- Testicular pain, possibly with an acute onset; may be associated with a hydrocele
- A metastatic testis tumor may manifest as large retroperitoneal and/or chest lesions, while the primary tumor is nonpalpable
See Clinical Presentation for more detail.
Laboratory studies for testicular seminoma are as follows:
- An elevated AFP level rules out pure seminoma, despite possible contrary histopathologic orchiectomy findings
- Lactate dehydrogenase (LDH) is a less-specific marker for GCTs, but levels can correlate with overall tumor burden
- Beta–human chorionic gonadotropin (beta-hCG) levels are elevated inn 5-10% of patients with seminomas; elevation may correlate with metastatic disease but not with overall survival
- Placenta-like alkaline phosphatase levels can be elevated in patients with seminoma, especially as the tumor burden increases; however, it may also increase with smoking
- Consider this study in any male with a palpable testicular mass that is suspicious or questionable
- Other indications may include acute scrotal pain (especially when associated with a hydrocele), nonspecific scrotal pain, or swelling
- If an asymptomatic hydrocele obscures physical examination of the testicle, this study may be appropriate prior to surgical intervention
- This study may also be appropriate for males who are at the peak age range for testicular cancer (ie, 15-35 years)
- Scrotal ultrasonography commonly shows a homogeneous hypoechoic intratesticular mass
- Larger lesions may be more inhomogeneous
- Calcifications and cystic areas are less common in seminomas than in nonseminomatous tumors
Other imaging studies
- Abdominal and pelvic CT scanning: Can be used to identify metastatic disease to the retroperitoneal lymph nodes, but it results in understaging in approximately 15-20% of patients thought to be at stage I
- Chest CT scanning: Indicated only when abnormal findings are observed on a chest radiograph
- Fluoro-2-deoxy-D-glucose (FDG) PET scanning: May be useful in restaging assessments of residual masses following chemotherapy
Seminomas can have 3 histologic variants, as follows :
- Classic seminoma (the most common histologic type)
- Anaplastic seminoma (5-15% of patients)
- Spermatocytic seminoma (a rare variant that occurs in older adults)
See Workup for more detail.
In testicular seminoma, orchiectomy provides both diagnosis and therapy. Orchiectomy alone cures most stage I seminomas. To prevent relapse, the following are standard options in stage I disease :
- Single-agent carboplatin
Preferred treatments for more advanced stages are as follows:
- Stage IIA - Radiotherapy
- Stage IIB - Chemotherapy with etoposide and cisplatin (EP) or bleomycin, etoposide, and cisplatin (BEP)
- Stage IIC, III - Chemotherapy with EP or BEP
After treatment, patients require lifelong follow-up. Surveillance includes the following, with the frequency determined by disease stage and duration of follow-up:
- History and physical examination
- Serum tumor markers (beta-hCG, LDH, AFP)
- Chest radiography
- CT scan of the abdomen, with or without CT scan of the pelvis
The study of testicular germ cell tumors (GCTs) is a unique area of urologic oncology, as treatment algorithms have benefited from numerous randomized prospective clinical trials (unlike prostate cancer) and because metastatic disease is highly responsive to multimodal treatment (unlike renal cell carcinoma). Seminoma is a histologic subtype of GCTs, which are discussed separately as nonseminomas in Germ Cell Tumors.
The interest in GCTs is disproportional to its incidence because of its fascinating pathologic subtypes, success of multimodal therapy (even for metastatic disease), and almost universal incidence in otherwise healthy males aged 15-35 years. Testicular GCTs have various pathologic subtypes, including seminoma, embryonal, yolk sac, teratoma, and choriocarcinoma. The most important clinical distinction is between seminoma and nonseminoma, two broad categories with different treatment algorithms: (1) Seminoma as a classification refers to pure seminoma upon histopathologic review, and (2) the presence of any nonseminomatous elements (even if seminoma is prevalent) changes the classification to nonseminoma.
Testicular seminoma is a pathologic diagnosis in which only seminomatous elements are observed upon histopathologic review after a radical orchiectomy and in which serum alpha-fetoprotein (AFP) is within the reference range. Any elevation of AFP levels or nonseminomatous elements in the testis specimen mandates diagnosis of nonseminomatous GCT (NSGCT) and an appropriate treatment change.
GCTs have the following subtypes and frequencies: seminoma (40%), embryonal (25%), teratocarcinoma (25%), teratoma (5%), and choriocarcinoma (pure; 1%). Seminomas can be further subdivided into one of three categories based on histology: classic, anaplastic, and spermatocytic (see Histologic Findings).
Germ cell carcinoma in situ (CIS) is a premalignant condition with a natural history of progression to seminoma or embryonal cancer. Patients with infertility, intersex disorders, cryptorchidism, prior contralateral GCTs, or atrophic testes more commonly have CIS. Histologically, it demonstrates intratubular atypical germ cells within seminiferous tubules. Most patients with seminomas (except spermatocytic seminoma) and NSGCTs have CIS or severe atypia associated with the primary tumor. In patients with GCTs, 5% of those with contralateral testes harbor CIS.
Testicular microcalcifications observed on scrotal sonograms were long held to be implicated in the development of testicular carcinoma. However, an analysis of 83 patients with asymptomatic microcalcifications observed for 5 years demonstrated only one with testicular carcinoma development over the interim. This represented an odds ratio for the study population of 317 (95% CI, 36-2756), with over 98% of men with asymptomatic microcalcifications having a benign course. A recommendation of continued monthly self-examination without further intervention was given for management of this indolent finding.
Testicular GCTs are rare, representing only 1%-2% of all male malignancies and occurring in 1 of 250 men by age 65 years; however, GCT is the most common malignancy in men aged 15-35 years. Incidence rates are 3.7 and 0.9 cases per 100,000 persons per year for whites and blacks, respectively.
The incidence of testis cancer has increased from the early 1960s to the mid 1980s. Nonwhite populations have a lower incidence than white populations. The highest rates of testis cancer are in Denmark (11.5 cases per 100,000 persons per year), Norway (9 cases per 100,000 persons per year), and Switzerland (11 cases per 100,000 persons per year). Rates vary across Europe.
A review by Bray and colleagues (2006) of 41 cancer registries in 14 countries found the seminoma rates to be highest in Denmark and Switzerland (9 cases per 100,000 persons per year) and the lowest rates in Japan, Israel, and Finland (1-3 cases per 100,000 persons per year).
In a review of testicular GCT patients diagnosed in Norway from 1953-2012, Kvammen et al found that although relative survival has improved in recent decades, it generally continues to decline with increasing follow-up time, particularly beyond 15-30 years, regardless of disease extent at diagnosis. Relative survival was lower in patients diagnosed before 1980 or after age 40. These authors proposed that the likely main cause is treatment-induced late effects, with the continued use of adjuvant radiotherapy in seminomas until the year 2000 as the suspected culprit.
Race- and Age-related Demographics
Established data sets have consistently demonstrated a higher incidence of GCTs in whites than in African Americans—as high as a 5:1 ratio. McGlynn et al (2005) published an analysis of 9 registries of the Surveillance, Epidemiology, and End Results (SEER) database from 1973-2001. They found an increasing incidence among African Americans starting in the 1990s. The increased incidence was 100% for GCTs overall—124% for seminoma and 64% for nonseminoma. The reasons for this increase are unclear, and the author's review of the data suggests environmental or nonperinatal factors (occupation, physical activity, diet) rather than early screening as the predominant cause.
Testicular GCTs represent the most common malignancy in men aged 15-35 years. Seminoma accounts for one third of these diagnoses.
Miller FH, Whitney WS, Fitzgerald SW. Seminomas complicating undescended intraabdominal testes in patients with prior negative findings from surgical exploration. AJR Am J Roentgenol. 1999 Feb. 172(2):425-8. [Medline].
Panidis D, Rousso D, Stergiopoulos K. The effect of testicular seminoma in semen quality. Eur J Obstet Gynecol Reprod Biol. 1999 Apr. 83(2):219-22. [Medline].
Schwerk WB, Schwerk WN, Rodeck G. Testicular tumors: prospective analysis of real-time US patterns and abdominal staging. Radiology. 1987 Aug. 164(2):369-74. [Medline].
Looijenga LH, Oosterhuis JW. Pathogenesis of testicular germ cell tumours. Rev Reprod. 1999 May. 4(2):90-100. [Medline].
[Guideline] National Comprehensive Cancer Network. Testicular Cancer Version 2.2016. NCCN. Available at http://www.nccn.org/professionals/physician_gls/pdf/testicular.pdf. Accessed: March 2, 2016.
Klein FA, Melamed MR, Whitmore WF Jr. Intratubular malignant germ cells (carcinoma in situ) accompanying invasive testicular germ cell tumors. J Urol. 1985 Mar. 133(3):413-5. [Medline].
von der Maase H, Rorth M, Walbom-Jorgensen S. 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 Nov 29. 293(6559):1398-401. [Medline].
DeCastro BJ, Peterson AC, Costabile RA. A 5-year followup study of asymptomatic men with testicular microlithiasis. J Urol. 2008 Apr. 179(4):1420-3; discussion 1423. [Medline].
Swerdlow AJ. Epidemiology of Testicular Cancer. Raghavan D, Scher H, Leibel S, Lange P, eds. Principles and Practice of Genitourinary Oncology. Philadelphia, Pa: Lippincott-Raven; 1997.
Parkin DM, Muir CS. Cancer Incidence in Five Continents. Comparability and quality of data. IARC Sci Publ. 1992. (120):45-173. [Medline].
Bray F, Ferlay J, Devesa SS, McGlynn KA, Møller H. Interpreting the international trends in testicular seminoma and nonseminoma incidence. Nat Clin Pract Urol. 2006 Oct. 3(10):532-43. [Medline].
Kvammen O, Myklebust TA, Solberg A, Møller B, Klepp OH, Fossa SD, et al. Long-term Relative Survival after Diagnosis of Testicular Germ Cell Tumor. Cancer Epidemiol Biomarkers Prev. 2016 Feb 11. [Medline].
McGlynn KA, Devesa SS, Graubard BI, Castle PE. Increasing incidence of testicular germ cell tumors among black men in the United States. J Clin Oncol. 2005 Aug 20. 23(24):5757-61. [Medline].
Hemminki K, Li X. Familial risk in testicular cancer as a clue to a heritable and environmental aetiology. Br J Cancer. 2004 May 4. 90(9):1765-70. [Medline].
Richie JP. Neoplasms of the Testis. Walsh PC, Retik AB, Vaughan ED Jr, Wein AJ, eds. Campbell's Urology. 7th ed. Philadelphia, Pa: WB Saunders; 1998.
Coffey J, Linger R, Pugh J, Dudakia D, Sokal M, Easton DF, et al. Somatic KIT mutations occur predominantly in seminoma germ cell tumors and are not predictive of bilateral disease: report of 220 tumors and review of literature. Genes Chromosomes Cancer. 2008 Jan. 47(1):34-42. [Medline].
Horstman WG. Scrotal imaging. Urol Clin North Am. 1997 Aug. 24(3):653-71. [Medline].
Tsatalpas P, Beuthien-Baumann B, Kropp J, Manseck A, Tiepolt C, Hakenberg OW, et al. Diagnostic value of 18F-FDG positron emission tomography for detection and treatment control of malignant germ cell tumors. Urol Int. 2002. 68(3):157-63. [Medline].
Cremerius U, Wildberger JE, Borchers H, Zimny M, Jakse G, Günther RW. Does positron emission tomography using 18-fluoro-2-deoxyglucose improve clinical staging of testicular cancer?--Results of a study in 50 patients. Urology. 1999 Nov. 54(5):900-4. [Medline].
Spermon JR, De Geus-Oei LF, Kiemeney LA, Witjes JA, Oyen WJ. The role of (18)fluoro-2-deoxyglucose positron emission tomography in initial staging and re-staging after chemotherapy for testicular germ cell tumours. BJU Int. 2002 Apr. 89(6):549-56. [Medline].
Hinz S, Schrader M, Kempkensteffen C, Bares R, Brenner W, Krege S. The role of positron emission tomography in the evaluation of residual masses after chemotherapy for advanced stage seminoma. J Urol. 2008 Mar. 179(3):936-40; discussion 940. [Medline].
Fleming ID, Cooper JS, Henson DE, et al. AJCC Cancer Staging Manual. 5th ed. New York, NY: Lippincott-Raven; 1997.
Prow DM. Germ cell tumors: staging, prognosis, and outcome. Semin Urol Oncol. 1998 May. 16(2):82-93. [Medline].
Djaladat H, Burner E, Parikh PM, Beroukhim Kay D, Hays K. The Association Between Testis Cancer and Semen Abnormalities Before Orchiectomy: A Systematic Review. J Adolesc Young Adult Oncol. 2014 Dec 1. 3 (4):153-159. [Medline]. [Full Text].
Hallemeier CL, Choo R, Davis BJ, Leibovich BC, Costello BA, Pisansky TM. Excellent long-term disease control with modern radiotherapy techniques for stage I testicular seminoma--the Mayo Clinic experience. Urol Oncol. 2014 Jan. 32 (1):24.e1-6. [Medline].
Travis LB, Fosså SD, Schonfeld SJ, McMaster ML, Lynch CF, Storm H. Second cancers among 40,576 testicular cancer patients: focus on long-term survivors. J Natl Cancer Inst. 2005 Sep 21. 97(18):1354-65. [Medline].
Zagars GK, Ballo MT, Lee AK, Strom SS. Mortality after cure of testicular seminoma. J Clin Oncol. 2004 Feb 15. 22(4):640-7. [Medline].
Beard CJ, Travis LB, Chen MH, Arvold ND, Nguyen PL, Martin NE, et al. Outcomes in stage I testicular seminoma: a population-based study of 9193 patients. Cancer. 2013 Aug 1. 119 (15):2771-7. [Medline].
Oliver RT, Mason MD, Mead GM, von der Maase H, Rustin GJ, Joffe JK, et al. Radiotherapy versus single-dose carboplatin in adjuvant treatment of stage I seminoma: a randomised trial. Lancet. 2005 Jul 23-29. 366(9482):293-300. [Medline].
Dreicer R, Ritter MA. Management of stage III-IV (C) seminoma. Raghavan D, Scher H, Leibel S, Lange P, eds. Principles and Practice of Genitourinary Oncology. New York, NY: Lippincott-Raven; 1997.
Daugaard G, Giwercman A, Skakkebaek NE. Should the other testis be biopsied?. Semin Urol Oncol. 1996 Feb. 14(1):8-12. [Medline].
Herr HW, Sheinfeld J. Is biopsy of the contralateral testis necessary in patients with germ cell tumors?. J Urol. 1997 Oct. 158(4):1331-4. [Medline].
Kollmannsberger C, Tyldesley S, Moore C, Chi KN, Murray N, Daneshmand S, et al. Evolution in management of testicular seminoma: population-based outcomes with selective utilization of active therapies. Ann Oncol. 2011 Apr. 22(4):808-14. [Medline].
Warde P, Gospodarowicz MK, Banerjee D. Prognostic factors for relapse in stage I testicular seminoma treated with surveillance. J Urol. 1997 May. 157(5):1705-9; discussion 1709-10. [Medline].
Miki T, Saki S, Kotake T. [The role of salvage surgery following chemotherapy in advanced testicular cancer]. Hinyokika Kiyo. 1994 Oct. 40(10):951-5. [Medline].
Motzer R, Bosl G, Heelan R. Residual mass: an indication for further therapy in patients with advanced seminoma following systemic chemotherapy. J Clin Oncol. 1987 Jul. 5(7):1064-70. [Medline].
Duchesne GM, Stenning SP, Aass N. Radiotherapy after chemotherapy for metastatic seminoma--a diminishing role. MRC Testicular Tumour Working Party. Eur J Cancer. 1997 May. 33(6):829-35. [Medline].
De Santis M, Becherer A, Bokemeyer C, Stoiber F, Oechsle K, Sellner F, et al. 2-18fluoro-deoxy-D-glucose positron emission tomography is a reliable predictor for viable tumor in postchemotherapy seminoma: an update of the prospective multicentric SEMPET trial. J Clin Oncol. 2004 Mar 15. 22(6):1034-9. [Medline].
Bauman GS, Venkatesan VM, Ago CT. Postoperative radiotherapy for Stage I/II seminoma: results for 212 patients. Int J Radiat Oncol Biol Phys. 1998 Sep 1. 42(2):313-7. [Medline].
Beahrs O, Henson D, Hutter R. Handbook for staging of cancer. Manual of Staging of Cancer. 4th ed. Philadelphia, Pa: JB Lippincott; 1993. 195-7.
Bredael JJ, Vugrin D, Whitmore WF Jr. Autopsy findings in 154 patients with germ cell tumors of the testis. Cancer. 1982 Aug 1. 50(3):548-51. [Medline].
Coleman JM, Coleman RE, Turner AR, Radstone CR, Champion AE. The management and clinical course of testicular seminoma: 15 years' experience at a single institution. Clin Oncol (R Coll Radiol). 1998. 10(4):237-41. [Medline].
Kodama M, Murakami M, Kodama T. Chronological transition of the age-adjusted incidence rates (AAIRs) of 20 major neoplasias from early 1960s to mid-1980s. Anticancer Res. 1999 Jan-Feb. 19(1B):779-87. [Medline].
Mortensen MS, Gundgaard MG, Lauritsen J, et al. A nationwide cohort study of surveillance for stage I seminoma. J Clin Oncol. 2013; 31 (suppl; abstr 4502) [Epub ahead of print].
Nelson R. Surveillance Sufficient After Surgery in Early Seminoma. Available at http://www.medscape.com/viewarticle/804287. Accessed: May 19, 2013.
van Rooy EM, Sagerman RH. Long-term evaluation of postorchiectomy irradiation for stage I seminoma. Radiology. 1994 Jun. 191(3):857-61. [Medline].
|pTx||Primary tumor cannot be assessed|
|p0||No evidence of primary tumor|
|pTis||Intratubular germ cell neoplasia|
|pT1||Tumor limited to the testis and epididymis|
|No vascular/lymphatic invasion|
|May invade the tunica albuginea|
|No invasion of the tunica vaginalis|
|pT2||Tumor limited to the testis and epididymis|
|Vascular/lymphatic invasion or tumor extending through the tunica albuginea with involvement of the tunica vaginalis|
|Invades beyond the tunica albuginea or into the epididymis|
|pT3||Tumor invades the spermatic cord with or without vascular/lymphatic invasion|
|pT4||Tumor invades the scrotum with or without vascular/lymphatic invasion|
|Nx||Nodes not assessed|
|N0||No regional lymph node metastasis|
|N1||Lymph node mass or multiple lymph node masses ≤ 2 cm in greatest dimension|
|N2||Lymph node mass or multiple lymph node masses >2 cm but ≤ 5 cm in greatest dimension|
|N3||Lymph node mass >5 cm in greatest dimension|
|pN0||No evidence of tumor in lymph nodes|
|pN1||Lymph node mass ≤ 2 cm in greatest dimension|
|≤ 5 nodes positive|
|pN2||Lymph node mass >2 cm but < 5 cm in greatest dimension|
|>5 nodes positive|
|Evidence of extranodal extension of tumor|
|pN3||Lymph node mass >5 cm in greatest dimension|
|M0||No evidence of distant metastases|
|M1a||Nonregional nodal or pulmonary metastases|
|M2b||Nonpulmonary visceral metastases|
|S||LDH||hCG† (mIU/mL)||AFP (ng/mL)|
|Sx||Not assessed||Not assessed||Not assessed|
|S1||< 1.5 x N||and||< 5,000||and||< 1,000|
|S2||1.5-10 x N||or||5,000-50,000||or||1,000-10,000|
|S3||>10 x N||or||>50,000||or||>10,000|
|Stage IS||Any T||N0||M0||S1-S3|
|Stage II||Any T||Any N||M0||Sx|
|Stage IIA||Any T||N1||M0||S0-S1|
|Stage IIB||Any T||N2||M0||S0-S1|
|Stage IIC||Any T||N3||M0||S0-S1|
|Stage III||Any T||Any N||M1||Sx|
|Stage IIIA||Any T||Any N||M1a||S0-S1|
|Stage IIIB||Any T||Any N||M0-M1a||S2|
|Stage IIIC||Any T||Any N||M0-M1a||S3|
|…||Any T||Any N||M1b||Any S|