Testicular Cancer

Diagnosis

Indications for Testing

  • Testicular mass, testicular pain, nonresolving epididymitis/orchitis

Laboratory Testing

  • For all suspected testicular cancers, determining concentrations of serum AFP, β-hCG and LD prior to treatment is mandatory
  • Genetic testing – KIT (D816V) mutation in tissue by PCR may be helpful

Histology

  • Immunohistochemistry
  • Comparison of different biochemical markers for testicular cancer

    Comparison of Different Biochemical Markers for Testicular Cancer

    Immunostain Class

    PP1

    OCT42

    CD1173

    AE1/AE34

    CAM 5.25

    CD306

    AFP7

    β-hCG8

    PLAP9

    HLA-G10

    Glypican 311

    ITGCN12
    Classical seminoma

    +

    +

    +

    -

    -

    -

    -

    +STC16

    +

    -

    -

    Spermatocytic
    seminoma

    -

    -

    -/+

    -

    -

    -

    0

    -

    -

    ?

    -

    YST13

    -

    -

    -

    +

    +

    -/+

    +

    -

    -/+

    -

    +

    CC14

    -

    -

    -

    +

    +

    -

    -

    +STC16

    +

    +

    +

    ED15

    -

    +

    -

    +

    +

    +

    -/+

    -

    +

    -

    -

    Podoplanin1, POU-family transcription factor2, cytokeratin stain3, cytokeratin stain4, cytokeratin stain5, cell membrane antigen6, alpha fetoprotein7, beta human chorionic gonadotropin8, placental-like alkaline phosphatase9, human antibody stain10, glycoprotein stain11, intratubular germ cell neoplasia12, yolk sac tumor13, choriocarcinomal4, embryonal carcinoma15, syncytiotrophoblastic cells16

  • 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
  • Staging
    • Chest x-ray
    • CT of abdomen and pelvis
    • Brain MRI and/or bone scan

Prognosis

  • For risk stratification, levels of AFP, β-hCG and LD must be measured in serum
  • High serum concentrations in nonseminoma associated with poor prognosis (in seminoma, not associated with poor prognosis)
    • AFP – >10,000 ng/mL
    • β-hCG – >50,000 IU/L
    • LD – >10 times the upper reference limit
      • LD activity is the best indicator of prognosis
  • Fertility usually affected by surgery and therapy; consider discussions of sperm banking

Differential Diagnosis

  • Painful testicle
    • Epididymitis/orchitis
    • Testicular torsion
  • Painless testicle
    • Hydrocele
    • Varicocele
    • Epididymal cyst
    • Spermatocele

Screening

  • U.S. Preventive Services Task Force (2011) recommends against screening

Monitoring

  • AFP, LD, β-hCG – markers of choice; see NCCN Testicular Cancer guidelines (2014) for suggested monitoring schedule
    • Schedule varies based on tumor stage/type and aggressiveness

Clinical Background

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)
  • Age – peak onset is 15-35 years
  • Sex – exclusively male
  • Ethnicity – rare in African Americans

Risk Factors

  • Personal history of testicular cancer
  • Cryptorchidism – three- to fourfold increased risk
  • Infertility/subfertility
  • Klinefelter syndrome
  • Family history of testicular cancer
    • Father with cancer history – fourfold increased risk
    • Brother with cancer history – eight- to tenfold increased risk

Pathophysiology

  • Cell types
    • Germ-cell tumors represent ~95% of testicular cancers and occasionally appear in extragonadal sites
      • Seminomatous
      • Non-seminomatous germ-cell tumors (NSGCT) – more clinically aggressive
        • Embryonal carcinomas
        • Choriocarcinoma
        • Yolk sac tumors
        • Teratoma – mature or immature
    • Lymphomas – uncommon
    • Leydig and Sertoli cell tumors – rare
  • Tumors may produce hormones which can be used as markers
    • AFP
      • Synthesized in fetal yolk sac, liver, intestine
      • Produced by nonseminomatous cells but may be found in both seminomatous and nonseminomatous tumors
      • Low levels may be present in normal males with benign disease
      • Elevated levels also occur in hepatocellular and gastrointestinal tumors and nephritis
    • β-hCG
    • Lactate dehydrogenase (LD)
      • Most useful in seminomatous testicular tumors
      • Direct relationship between serum LD activity and tumor burden
      • LD-1 isoenzyme is elevated in testicular cancer
    • Placental-like alkaline phosphatase (PLAP) 
      • Expressed 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

Indications for Laboratory Testing

  • 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
Test Name and Number Recommended Use Limitations Follow Up
Alpha Fetoprotein, Serum (Tumor Marker) 0080428
Method: Quantitative Chemiluminescent Immunoassay

Aid in evaluation of testicular masses

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

Result is not interpretable in pregnant females

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

Aid in evaluation of testicular masses

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

Result is not interpretable as a tumor marker in pregnant females

 
Lactate Dehydrogenase, Serum or Plasma 0020006
Method: Quantitative Enzymatic

Aid in evaluation of testicular masses

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

Aid in histologic diagnosis of testicular cancer

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

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

Aid in histologic diagnosis of testicular cancer

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

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

Aid in histologic diagnosis of testicular cancer

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

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

Aid in histologic diagnosis of testicular cancer

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

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

Aid in histologic diagnosis of testicular cancer

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

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

Aid in histologic diagnosis of testicular cancer

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

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

Aid in histologic diagnosis of testicular cancer

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

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

Aid in histologic diagnosis of testicular cancer

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

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

Aid in histologic diagnosis of testicular cancer

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

   
Additional Tests Available
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
Beta-hCG, Quantitative (Tumor Marker), CSF 0020730
Method: Quantitative Electrochemiluminescent Immunoassay

Useful in suspected CNS metastatic disease

Alpha Fetoprotein, CSF (Tumor Marker) 0020729
Method: Quantitative Chemiluminescent Immunoassay

Useful in suspected CNS metastatic disease

Lactate Dehydrogenase Total, Body Fluid 0020505
Method: Quantitative Enzymatic