What is gonadal cancer?

Gonadal Cancer: Types, Diagnosis, and Management

Gonadal cancer refers to malignant tumors that develop in the gonads (testes or ovaries), primarily arising from germ cells, sex cord-stromal cells, or other gonadal tissues, with distinct histological subtypes and clinical presentations depending on the site of origin.

Types of Gonadal Cancer

Germ Cell Tumors (GCTs)

• Testicular GCTs:

  • Account for 95% of testicular cancers 1
  • Approximately 55-60% are pure seminomas and 40-45% are non-seminomas 1
  • Most common solid neoplasm in young adult males aged 15-44 years 1
  • Incidence rate of 30.9 per million per year in Europe 1

• Ovarian GCTs:

  • Account for approximately 5% of all ovarian cancers 1
  • Rare with incidence rate of 0.7 per million per year in Europe 1
  • Most common in young women and children 1

• Extragonadal GCTs:

  • Account for 5% of all GCTs, occurring outside the gonads 1
  • Usually found in the body's midline (retroperitoneum, mediastinum, cerebrum) 1
  • Incidence rate of 0.7 per million per year in Europe 1

Sex Cord-Stromal Tumors (SCSTs)

• Account for 3-5% of ovarian malignancies 1
• Include granulosa cell tumors, Sertoli-Leydig cell tumors, and others 1
• Often produce hormones causing endocrine manifestations 1
• Yearly-adjusted incidence rate is 2.1/1,000 women 1

Small Cell Carcinoma of the Ovary (SCCO)

• Very rare, accounting for less than 1% of ovarian cancers 1
• Usually affects young women and children 1

Histological Classification

Germ Cell Tumors

• Seminoma/Dysgerminoma: Most common pure GCT in both sexes 1
• Non-seminomatous tumors:
  • Embryonal carcinoma
  • Yolk sac tumor
  • Choriocarcinoma
  • Teratoma (mature/immature)
  • Mixed germ cell tumors 1, 2

Sex Cord-Stromal Tumors

• Granulosa cell tumors (adult and juvenile forms)
• Fibromas, thecomas and fibrothecomas
• Sertoli cell, Leydig cell and Sertoli-Leydig cell tumors
• Gynandroblastomas
• Steroid cell tumors
• Sex cord tumors with annular tubules 1

Diagnosis

Clinical Presentation

• Testicular GCTs:

  • Unilateral testicular mass (palpable or incidental)
  • Scrotal pain (27%)
  • Back or flank pain (11%)
  • Gynaecomastia (1%) 1

• Ovarian GCTs and SCSTs:

  • Pelvic pain or pressure
  • Pelvic mass
  • Menstrual irregularities 1
  • Endocrine manifestations (virilization, precocious puberty, postmenopausal bleeding) 1

Diagnostic Workup

• Imaging:

  • Testicular ultrasound (high-frequency >10 MHz probe) for testicular masses 1
  • Pelvic ultrasound for ovarian masses 1
  • Abdomino-pelvic CT scan 1
  • Chest X-ray 1
  • PET scan in selected cases 1

• Laboratory Tests:

  • Serum tumor markers:
    • α-fetoprotein (AFP)
    • β-human chorionic gonadotropin (β-hCG)
    • Lactate dehydrogenase (LDH) 1
  • Specific markers for SCSTs:
    • Estradiol and inhibins (granulosa cell tumors)
    • Testosterone (Sertoli-Leydig cell tumors) 1

• Definitive Diagnosis:

  • Radical orchiectomy for testicular masses 1
  • Surgical exploration and histopathological examination for ovarian masses 1
  • Immunohistochemistry markers:
    • OCT3/4, SALL4, SOX2 for primitive GCTs 1
    • α-inhibin, calretinin, CD99, melan A for SCSTs 1

Management

Testicular Cancer

• Stage I Seminoma:

  • Radical inguinal orchiectomy as initial treatment 1, 3
  • Post-orchiectomy options:
    • Surveillance
    • Adjuvant carboplatin
    • Adjuvant radiotherapy 3

• Advanced Seminoma:

  • Chemotherapy with BEP (bleomycin, etoposide, cisplatin) regimen 1, 3

• Non-seminoma:

  • Radical inguinal orchiectomy followed by risk-adapted treatment 1
  • Options include surveillance, retroperitoneal lymph node dissection, or chemotherapy 1

Ovarian Germ Cell Tumors

• Stage I:

  • Fertility-sparing surgery (unilateral salpingo-oophorectomy) 1
  • Comprehensive surgical staging in selected cases 1

• Advanced Stage:

  • Debulking surgery followed by platinum-based chemotherapy 1

Sex Cord-Stromal Tumors

• Localized disease:

  • Fertility-sparing surgery in young patients 1
  • Complete staging not always necessary 1

• Advanced disease:

  • Debulking surgery followed by platinum-based chemotherapy 1

Prognosis and Follow-up

• Testicular GCTs:

  • Cure rates approach 100% in stage I disease 1

  • 80% cure rate in metastatic disease 1

  • Regular follow-up with tumor markers and imaging 1, 3

• Ovarian GCTs:

  • Excellent prognosis with modern treatment approaches 1
  • Regular follow-up similar to epithelial ovarian cancers 1

• SCSTs:

  • Generally good prognosis, especially in early-stage disease 1
  • Long-term follow-up needed due to risk of late recurrence 1

Special Considerations

• Fertility Preservation:

  • Sperm banking before treatment in males 3, 4
  • Fertility-sparing surgery when possible in females 1

• Genetic Predisposition:

  • Increased risk in individuals with family history 1
  • Higher risk of contralateral testicular cancer (5% of men with GCT) 1

• Disorders of Sex Development (DSD):

  • Increased risk of gonadal GCTs in certain DSD conditions 5
  • Gonadal biopsy with immunohistochemical markers may help assess risk 5

Common Pitfalls to Avoid

• Misdiagnosing testicular masses as epididymitis 3
• Attributing back pain from metastatic disease to musculoskeletal issues 3
• Overlooking small intertubular growth of seminomas 2
• Confusing yolk sac tumors with clear cell or endometrioid carcinomas 2
• Mistaking syncytiotrophoblast cells alone for choriocarcinoma 2