Testicular Cancer

Diagnosis

Indications for Testing

  • Testicular mass, testicular pain, initially diagnosed epididymitis that is unresolved

Laboratory Testing

  • In suspected testicular cancer, 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 – provides imaging of mass
  • Chest x-ray
  • CT of abdomen and pelvis – for staging purposes; performed after tissue diagnosis
  • Brain MRI and/or bone scan if indicated by symptoms and clinical findings

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 (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
    • Testicular torsion
  • Painless testicle
    • Hydrocele
    • Varicocele
    • Epididymal cyst
    • Spermatocele

Screening

  • U.S. Preventive Services Task Force recommends against screening

Monitoring

  • If serum markers are elevated prior to therapy, monitor weekly until normalized then follow the appropriate schedule below (see tables)
  • Post-orchiectomy elevation in markers suggestive of metastatic disease
  • Testicular cancer monitoring nonseminomatous and seminomatous
  • Testicular cancer – nonseminomatous

    Testicular Cancer – Nonseminomatous

    Surveillance for Stages 1A and 1B

    Year

    Months between serum
    markers and chest x-ray

    Months between
    abdominal/pelvic CT

    1

    1-2

    2-3

    2

    2

    3-4

    3

    3

    4

    4

    4

    6

    5

    6

    12

    6+

    12

    12

    Surveillance After Complete Response to Chemotherapy and/or Retroperitoneal Lymph Node Dissection

    Year

    Months between visits,
    markers, chest x-ray

    Months between
    abdominal/pelvic CT*

    1

    2-3

    6

    2

    2-3

    6-12

    3

    4

    12

    4

    4

    12

    5

    6

    12

    6+

    12

    If indicated

    *CT scans recommended for patients treated with chemotherapy alone. Baseline CT scan recommended for post-RPLND patients with additional scans as clinically indicated

    Testicular cancer – seminomatous

    Testicular Cancer – Seminomatous

    Monitoring After Primary Treatment

    Stage and

    Treatment Type

    Stages 1S and 1A-1B

    Stage 1A-1B

    Stage 2A-2B

    Stage 2C to Stage 3

    Radiation only

    Surveillance only
    or radiation or single-agent carboplatin

    Radiation or primary chemotherapy

    Chemotherapy

    Serum Markers
    (AFP, β-hCG, LD)

    • 3-4/yr during yr 1
    • 2/yr during yr 2
    • Annually thereafter
    • 3-4/yr during yrs 1-3
    • 2/yr during yrs 4-7
    • Annually thereafter
    • 3-4/yr during yrs 1-3
    • 2/yr during yr 4
    • Annually thereafter
    • 6/yr during yr 1
    • 4/yr during yr 2
    • 3/yr during yr 3
    • 2/yr during yr 4
    • Annually thereafter

    Chest x-ray

    • Each visit
    • Alternate visits (up to 10/yr)
    • Each visit

    Abdominal/pelvic CT

    • 1S – annual pelvic CT during yrs 1-3
    • 1A-1B – each visit
    • Each visit
    • Abdominal CT 4 months post treatment
    • 4 months post surgery then as indicated
    • PET scan as indicated

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
  • 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 used as markers – beta human chorionic gonadotrophin (β-hCG) and alpha fetoprotein (AFP)
  • Markers of testicular cancer
    • 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 – lymphatic
    • Cough – pulmonary

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 germ-cell tumors

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 germ-cell tumors

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 germ-cell tumors

   
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