Testicular Cancer

  • Diagnosis
  • Screening
  • Monitoring
  • Background
  • Lab Tests
  • References
  • Related Topics

Indications for Testing

  • Testicular mass
  • Testicular pain
  • Nonresolving epididymitis/orchitis

Laboratory Testing

  • AFP, beta-hCG and LD serum concentrations prior to testicular cancer treatment is mandatory
  • Molecular testing
    • KIT (D816V) mutation in tissue (by PCR) may be a marker of bilateral disease

Histology

  • Immunohistochemistry
  • Testicular removal provides tissue for diagnosis
    • Do not perform fine-needle aspiration (FNA) or trans-scrotal biopsy due to risk of tumor seeding along needle track
  • Imaging Studies

    • Trans-scrotal ultrasonography – imaging of mass, detecting contralateral disease
    • Staging
      • Chest x-ray
      • CT of abdomen and pelvis
      • Brain MRI and/or bone scan

    Prognosis

    • Serum AFP, beta-hCG and LD must be measured for risk stratification
      • High serum concentrations in nonseminoma associated with poor prognosis (in seminoma, not associated with poor prognosis)
        • AFP – >10,000 ng/mL
        • Beta-hCG – >50,000 IU/L
        • LD – >10 times the upper reference limit
          • LD activity is the best indicator of prognosis

    Differential Diagnosis

    • Painful testicle
      • Epididymitis/orchitis
      • Testicular torsion
    • Painless testicle
      • Hydrocele
      • Varicocele
      • Epididymal cyst
      • Spermatocele
    • U.S. Preventive Services Task Force (2011) recommends against routine screening
    • AFP, LD, beta-hCG – markers of choice; see NCCN Testicular Cancer guidelines (2015) for suggested monitoring schedule
      • Schedule varies based on tumor stage/type and aggressiveness

    Testicular cancer is the most common cancer in young adult men and is highly curable with prompt treatment.

    Epidemiology

    • Incidence – 5-6/100,000 (SEER, 2015)
    • Age – peak onset is ~15-35 years
    • Sex – exclusively male
    • Ethnicity – rare in African Americans, highest incidence in Caucasians

    Risk Factors

    • Personal history of testicular cancer
    • Family history of testicular cancer – biggest risk if sibling had testicular cancer
    • Cryptorchidism
    • Infertility/subfertility
    • Klinefelter syndrome

    Pathophysiology

    • Intratubular germ cell neoplasia in utero appears to be precursor
    • Cell types
      • Germ-cell tumors represent most testicular cancers; occasionally detected in extragonadal sites
        • Seminomatous
        • Non-seminomatous germ-cell tumors (NSGCT) – clinically more aggressive
          • Embryonal carcinomas
          • Choriocarcinoma
          • Yolk sac tumors
          • Teratoma – mature or immature
      • Sex cord/gonadal stromal tumors
        • Leydig cell tumor
        • Sertoli cell tumor
        • Granulosa cell tumor
        • The coma/fibroma group of tumors
        • Other sex cord/gonadal stromal tumors
        • Mixed germ cell and sex cord/gonadal stromal tumors
      • Lymphomas – uncommon
    • ​Tumors may produce hormones which can be used as markers
      • AFP
        • Synthesized in fetal yolk sac, liver, intestine
        • Most useful in nonseminomatous tumors but may be found in both seminomatous and nonseminomatous tumors
        • Elevated levels also occur in hepatocellular and gastrointestinal tumors and nephritis
      • Beta-hCG
      • Lactate dehydrogenase (LD)
        • Most useful in seminomatous tumors
        • Direct relationship between serum LD activity and tumor burden
        • LD-1 isoenzyme is elevated
      • Placental-like alkaline phosphatase (PLAP)
        • Detected in many testicular tumors
        • Most useful in identifying seminomatous testicular tumors by immunohistochemistry

    Clinical Presentation

    • Testicular mass/nodule
      • Painless or painful
      • May be mistaken as epididymitis; however, does not respond to antibiotic therapy
    • Metastatic disease
      • Systemic – anorexia, malaise, weight loss
      • Gynecomastia
      • Thromboembolic events
      • Adenopathy
      • Cough, dyspnea

    Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

    Alpha Fetoprotein, Serum (Tumor Marker) 0080428
    Method: Quantitative Chemiluminescent Immunoassay

    Limitations

    Cannot be interpreted as absolute evidence of the presence or absence of malignant disease

    Beta-hCG, Quantitative (Tumor Marker) 0070029
    Method: Quantitative Electrochemiluminescent Immunoassay

    Limitations

    Cannot be interpreted as absolute evidence of the presence or absence of malignant disease

    Results obtained with different test methods or kits cannot be used interchangeably

    Lactate Dehydrogenase, Serum or Plasma 0020006
    Method: Quantitative Enzymatic

    Octamer Transcription Factor-3 and -4 (Oct 3/4) by Immunohistochemistry 2004058
    Method: Immunohistochemistry

    CD117 (c-Kit) by Immunohistochemistry 2003806
    Method: Immunohistochemistry

    Pan Cytokeratin (AE1,3) by Immunohistochemistry 2003433
    Method: Immunohistochemistry

    Cytokeratin 8,18 Low Molecular Weight (CAM 5.2) by Immunohistochemistry 2003493
    Method: Immunohistochemistry

    CD30 (Ki-1) by Immunohistochemistry 2003547
    Method: Immunohistochemistry

    Alpha-1-Fetoprotein (AFP) by Immunohistochemistry 2003436
    Method: Immunohistochemistry

    Human Chorionic Gonadotropin (Beta-hCG) by Immunohistochemistry 2003920
    Method: Immunohistochemistry

    Placental Alkaline Phosphatase (PLAP) by Immunohistochemistry 2004097
    Method: Immunohistochemistry

    Sal-like 4 (SALL4) by Immunohistochemistry 2005432
    Method: Immunohistochemistry

    Related Tests

    Guidelines

    Albers P, Albrecht W, Algaba F, Bokemeyer C, Cohn-Cedermark G, Fizazi K, Horwich A, Laguna MPilar, Nicolai N, Oldenburg J. Guidelines on Testicular Cancer: 2015 Update. Eur Urol. 2015; 68(6): 1054-68. PubMed

    Gilligan TD, Hayes DF, Seidenfeld J, Temin S. ASCO Clinical Practice Guideline on Uses of Serum Tumor Markers in Adult Males With Germ Cell Tumors. J Oncol Pract. 2010; 6(4): 199-202. PubMed

    NCCN Clinical Practice Guidelines in Oncology, Testicular Cancer. National Comprehensive Cancer Network. Fort Washington, PA [Accessed: Aug 2015]

    Oldenburg J, Fosså SD, Nuver J, Heidenreich A, Schmoll H, Bokemeyer C, Horwich A, Beyer J, Kataja V, ESMO Guidelines Working Group. Testicular seminoma and non-seminoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013; 24 Suppl 6: vi125-32. PubMed

    Protocol for the Examination of Specimens from Patients with Malignant Germ Cell and Sex Cord-Stromal Tumors of the Testis. Based on AJCC/UICC TNM, 7th ed. Protocol web posting date: October 2009. College of American Pathologists (CAP). Northfield, IL [Accessed: Aug 2015]

    USPSTF Recommendations for STI Screening. U.S. Preventive Services Task Force. Rockville, MD [Accessed: Aug 2015]

    General References

    Bahrami A, Ro JY, Ayala AG. An overview of testicular germ cell tumors. Arch Pathol Lab Med. 2007; 131(8): 1267-80. PubMed

    Barlow LJ, Badalato GM, McKiernan JM. Serum tumor markers in the evaluation of male germ cell tumors. Nat Rev Urol. 2010; 7(11): 610-7. PubMed

    Favilla V, Cimino S, Madonia M, Morgia G. New advances in clinical biomarkers in testis cancer. Front Biosci (Elite Ed). 2010; 2: 456-77. PubMed

    Hanna NH, Einhorn LH. Testicular cancer--discoveries and updates. N Engl J Med. 2014; 371(21): 2005-16. PubMed

    Ilic D, Misso ML. Screening for testicular cancer. Cochrane Database Syst Rev. 2011; CD007853. PubMed

    Khan O, Protheroe A. Testis cancer. Postgrad Med J. 2007; 83(984): 624-32. PubMed

    Mannuel HD, Hussain A. Update on testicular germ cell tumors. Curr Opin Oncol. 2010; 22(3): 236-41. PubMed

    Salem M, Gilligan T. Serum tumor markers and their utilization in the management of germ-cell tumors in adult males. Expert Rev Anticancer Ther. 2011; 11(1): 1-4. PubMed

    References from the ARUP Institute for Clinical and Experimental Pathology®

    Lones MA, Raphael M, McCarthy K, Wotherspoon A, Terrier-Lacombe M, Ramsay AD, Maclennan K, Cairo MS, Gerrard M, Michon J, Patte C, Pinkerton R, Sender L, Auperin A, Sposto R, Weston C, Heerema NA, Sanger WG, von Allmen D, Perkins SL. Primary follicular lymphoma of the testis in children and adolescents. J Pediatr Hematol Oncol. 2012; 34(1): 68-71. PubMed

    Willmore-Payne C, Holden JA, Chadwick BE, Layfield LJ. Detection of c-kit exons 11- and 17-activating mutations in testicular seminomas by high-resolution melting amplicon analysis. Mod Pathol. 2006; 19(9): 1164-9. PubMed

    Medical Reviewers

    Last Update: April 2016