Testicular Cancer

Testicular cancer is the most common cancer in young adult men and is highly curable with prompt treatment. Alpha-fetoprotein (AFP), beta human chorionic gonadotropin (beta-hCG), and lactate dehydrogenase (LDH) testing before testicular cancer treatment is mandatory. These laboratory tests are also used in monitoring.

Diagnosis

Indications for Testing

  • Testicular mass
  • Testicular pain
  • Nonresolving epididymitis/orchitis

Laboratory Testing

  • AFP, beta-hCG, and LDH serum concentrations – mandatory prior to testicular cancer treatment
  • Molecular testing – KIT (D816V) mutation in tissue (by polymerase chain reaction [PCR]) may be a marker of bilateral disease

Histology

  • 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

  • Transscrotal ultrasonography – imaging of mass, detecting contralateral disease
  • Staging
    • Chest x-ray
    • Computed tomography (CT) of abdomen and pelvis
    • Brain magnetic resonance imaging (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

Screening

U.S. Preventive Services Task Force (2011) and the American Academy of Family Physicians (Choosing Wisely, 2018) recommend against routine screening.

Monitoring

AFP, LDH, beta-hCG – markers of choice; refer to National Comprehensive Cancer Network (NCCN) Testicular Cancer guidelines (2016) for suggested monitoring schedule

  • Schedule varies based on tumor stage/type and treatment

Background

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
      • Nonseminomatous 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 that can be used as markers
    • 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
    • LDH
      • Nonhormonal and nonspecific 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

ARUP Lab Tests

Aid in evaluation of testicular masses; valuable aid in the management of nonseminomatous testicular cancer when used in conjunction with information available from clinical evaluation and other diagnostic procedures

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

Aid in evaluation of testicular masses

Aid in histologic diagnosis of testicular cancer

Stained and returned to client pathologist for interpretation; consultation available if needed

Related Tests

   

For information on body fluid reference ranges and/or interpretive guidance, visit http://aruplab.com/bodyfluids/

Medical Experts

Contributor

Genzen

Jonathan R. Genzen, MD, PhD
Associate Professor of Clinical Pathology, University of Utah
Chief Operations Officer, Medical Director of Automated Core Laboratory and Farmington Health Center Clinical Laboratory, ARUP Laboratories

References

Additional Resources
Resources from the ARUP Institute for Clinical and Experimental Pathology®