Testicular Cancer

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

Indications for Testing

  • Testicular mass
  • Testicular pain
  • Nonresolving epididymitis/orchitis

Laboratory Testing

  • Alpha-fetoprotein (AFP), beta-hCG and lactate dehydrogenase (LDH) 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 LDH 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
      • LDH – >10 times the upper reference limit
        • LDH 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
  • Alpha-fetoprotein (AFP), lactate dehydrogenase (LDH), beta-hCG – markers of choice; refer to NCCN Testicular Cancer guidelines (2016) for suggested monitoring schedule
    • Schedule varies based on tumor stage/type and treatment

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 – highest 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
      • Coma/fibroma group of tumors
      • Other sex cord/gonadal stromal tumors
      • Mixed germ cell and sex cord/gonadal stromal tumors
    • Lymphomas – uncommon
  • ​Tumor markers – tumors may produce hormones which can be used as markers
    • Alpha-fetoprotein (AFP)​
      • Required for staging
      • 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
      • Required for staging
      • Synthesized in placental trophoblastic cells
      • Most useful in germ cell tumors (seminomatous, choriocarcinoma)
      • Increased serum hCG concentrations also observed in melanoma, carcinomas of the breast, gastrointestinal tract and lung, and in benign conditions, including cirrhosis, duodenal ulcer, and inflammatory bowel disease
    • Lactate dehydrogenase (LDH)
      • Non-hormonal and non-specific tumor marker
      • Required for staging
      • Most useful in seminomatous tumors
      • Direct relationship between serum LDH 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

Guidelines

Albers P, Albrecht W, Algaba F, Bokemeyer C, Cohn-Cedermark G, Fizazi K, Horwich A, Laguna MP, 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: Dec 2016]

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: Oct 2013. College of American Pathologists (CAP). Northfield, IL [Revised Oct 2013; Accessed: Dec 2016]

USPSTF Testicular Cancer: Screening. U.S. Preventive Services Task Force. Rockville, MD [Accessed: Dec 2016]

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®

Greene DN, Petrie MS, Pyle AL, Kamer SM, Grenache DG. Performance characteristics of the Beckman Coulter total βhCG (5th IS) assay Clin Chim Acta. 2015; 439: 61-7. PubMed

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: December 2016