Testicular tumors

Testicular tumors are the most common solid malignancy in young men. Patients often present with a testicular mass and may report scrotal pain or discomfort. Diagnosis is based on scrotal ultrasound findings and initial serum tumor markers. Patients are referred to urology for a radical inguinal orchiectomy. Clinical staging is determined by tumor type and staging diagnostics (e.g., imaging, postorchiectomy serum tumor markers). Further management may include active surveillance, chemotherapy, radiation therapy, and/or retroperitoneal lymph node dissection. The overall prognosis of testicular tumors is excellent; cure is often possible even in advanced, metastatic stages.

• Most common solid malignant tumor in young men ^[1]
• Nonseminoma tumors are most common in men aged < 30 years, while seminomas are most common in men aged ≥ 30 years. ^[2]

Epidemiological data refers to the US, unless otherwise specified.

Risk factors for testicular tumors include the following: ^[3][4]

• Cryptorchidism
• Contralateral testicular cancer
• Germ cell neoplasia in situ (GCNIS)
• Family history of testicular cancer
• Klinefelter syndrome ^[5]
• Infertility
• Hypospadias

Testicular tumors are classified according to pathology.

hCG is always elevated in choriocarcinoma and sometimes elevated in seminoma. AFP is always elevated in yolk sac tumors. Both AFP and hCG may be elevated in mixed germ cell tumors.

Testicular tumors metastasize early into the retroperitoneum via the lymphatic system (drain to the para-aortic lymph nodes first), with the exception of early hematogenous metastasizing choriocarcinomas.

References:^{[9][10][11][11][12]}

Symptoms ^[4]

• General
  • Scrotal discomfort (ranging from painless to acute pain)
  • Scrotal heaviness and/or swelling
  • Dull lower abdominal pain
• Endocrine ^[13]
  • Androgen excess
    • Prominent external genitalia, pubic hair growth, accelerated skeletal and muscle development, and mature masculine voice
    • May cause precocious puberty in boys
  • Estrogen excess: gynecomastia, breast tenderness, and gonadal underdevelopment
  • hCG excess: gynecomastia, signs of hyperthyroidism ^[14]
• Metastatic disease
  • Bone metastases: lower back pain, bone pain
  • Pulmonary metastases: cough, shortness of breath, hemoptysis

Physical examination ^[4]

• Palpable testicular mass (e.g., hard, firm, or fixed areas)
• Negative transillumination test
• Inguinal and/or supraclavicular lymphadenopathy

Extragonadal germ cell tumors ^[15][16]

• Definition: primary germ cell tumors that arise outside of the gonads, anywhere along the body's midline from the pineal gland to the coccyx
• Epidemiology
  • 1–5% of all germ cell tumors
  • Nonseminomas are more common than seminomas
  • Mostly affects young men
• Location
  • Midline organs
  • Mediastinal > retroperitoneal > intracranial (pineal gland and suprasellar region)
  • Sacrococcygeal teratomas
    • Most common in infancy or early childhood ^[17]
    • Manifest as a mass near the caudal end, near the rectum
    • May cause obstruction, weakness, pain, and/or paralysis
• Clinical features: varies based on tumor location and size, e.g.,
  • Mediastinal: chest pain, dyspnea (on exertion), cough
  • Retroperitoneal: abdominal pain, back pain, weight loss
  • Intracranial: headache, nausea, vomiting, ataxia, change in vision
• Diagnosis
  • Varies based on presenting symptoms, e.g.,
    • Mediastinal: CT chest
    • Retroperitoneal: CT abdomen and pelvis
    • Intracranial: MRI brain
  • Scrotal ultrasound: to rule out primary gonadal tumor
  • Serum tumor markers: AFP, hCG, lactate dehydrogenase (LDH)
  • Tumor biopsy (confirmatory)
• Treatment: varies based on tumor location, size, and histopathology, options include,
  • Chemotherapy
  • Radiation therapy
  • Surgical resection
• Prognosis: The 5-year survival rate is ∼ 90% for seminomas and 45–60% for nonseminomas. ^[16]

Staging of testicular tumors is based on the American Joint Committee on Cancer (AJCC) groups, which combines TNM stage and postorchiectomy serum tumor marker levels.

• Suspect testicular cancer based on history, clinical features, and risk factors.
• Obtain a scrotal ultrasound to assess testicular mass and narrow the differential diagnosis.
• If malignancy is suspected on ultrasound, obtain baseline serum tumor markers.
• Consider sperm cyropreservation.
• Refer to urology for radical inguinal orchiectomy and histopathological confirmation.
• Obtain staging diagnostics, including postorchiectomy serum tumor markers.
• Classify clinical stage based on AJCC criteria (see “Staging”).
• Tailor postsurgical management of testicular cancer to clinical stage.
• Monitor for recurrence over 5 years.

Scrotal ultrasound ^[19][20]

• Indication: palpable scrotal abnormalities
• Techniques
  • Conventional ultrasound
  • Duplex ultrasound
  • Contrast-enhanced ultrasound
• Findings
  • Hypoechoic or inhomogeneous areas are suspicious for malignancy.
  • Ultrasound cannot definitively differentiate between benign and malignant lesions.

Serum tumor markers ^[4][20]

• Indications
  • Suspected testicular cancer
  • Postorchiectomy staging
  • Surveillance
• Laboratory studies: AFP, hCG, LDH
• Findings: vary by tumor type (See “Overview of testicular tumors.”)

Staging diagnostics ^[4][20]

Staging diagnostics are obtained following radical inguinal orchiectomy and histopathological confirmation of testicular cancer. See “Staging” for interpretation.

• Postorchiectomy serum tumor markers
• CT abdomen and pelvis with IV contrast
• CXR or CT chest
• Consider MRI brain and/or bone scan based on concern for metastases.

The regional lymph nodes for the testes are located in the retroperitoneum.

Testicular tumors may be painful; see also “Differential diagnoses of scrotal pain.”

The differential diagnoses listed here are not exhaustive.

Radical inguinal orchiectomy ^[4][20]

• Removal of the testicle and spermatic cord (up to the internal inguinal ring)
• Provides therapeutic removal of local tumor
• Allows histopathologic diagnosis of tumor

Testis-sparing surgery is not routinely recommended but may be considered in certain situations (e.g., equivocal ultrasound and negative serum tumor markers). ^[20]

If a testicular tumor is suspected, the testis should be removed and sent to pathology. Transscrotal biopsy should not be conducted because of the risk of tumor seeding!

Postsurgical management of testicular cancer

Postsurgical therapy is based on histopathology, clinical staging group (see “Staging”), and prognosis.

Seminoma ^[20][25][26]

• Stage I
  • Active surveillance ^[4]
  • Consider chemotherapy with carboplatin or radiation therapy in select patients (e.g., rete testis infiltration or tumor size ≥ 4 cm).
• Stage II
  • Radiation therapy
  • OR chemotherapy, e.g.:
    • Bleomycin, etoposide, and cisplatin (BEP)
    • Etoposide and cisplatin (EP)
  • OR retroperitoneal lymph node dissection (RPLND)
• Stage III
  • Chemotherapy: BEP or EP depending on prognosis
  • Evaluation of any residual disease that may require resection

Nonseminoma ^[20][25][26]

• Stage I
  • Active surveillance
  • OR RPLND
  • OR chemotherapy (e.g., BEP)
• Stage II: based on postorchiectomy tumor markers
  • Normal: RPLND and/or chemotherapy (e.g., BEP, EP)
  • Elevated: chemotherapy (e.g., BEP, EP)
• Stage III
  • Chemotherapy: BEP or EP depending on prognosis
  • Evaluation of any residual disease that may require resection

• The overall prognosis of testicular tumors is excellent, with a high cure rate and 5-year survival rates of > 95%. ^[4]
• Even in advanced, metastatic stages, testicular tumors are often curable.

The United States Preventive Services Taskforce and the National Cancer Institute do not recommend routine screening in asymptomatic adults due to the low incidence and high survival rates of testicular cancer. ^[27][28]