- Clinical science
Testicular tumors
Summary
Testicular tumors most commonly occur in men between 20 and 35 years of age, and are the most common solid malignancy in this group. Most often, patients present with a painless nodule or swelling of the testis. Diagnosis is made primarily based on palpation and findings on testicular ultrasound. Diagnostic staging further includes an abdominopelvic and chest CT, determination of serologic tumor markers (AFP, HCG, LDH), and radical inguinal orchiectomy of the affected side to confirm the diagnosis and to evaluate the histopathology (seminoma vs. nonseminoma). The necessity and choice of adjuvant treatment depends on tumor pathology, staging, and prognosis. Treatment options include active surveillance, retroperitoneal radiotherapy, retroperitoneal lymph node dissection, and platinum-based chemotherapy. The overall prognosis of testicular tumors is excellent; patients can often be cured even in advanced, metastatic stages.
Epidemiology
- Most common solid malignant tumor in young men in the US
- Peak incidence: 20–35 years; (nonseminomas peak in the third decade, seminomas in the fourth decade of life)
- Ethnicity: ∼ 4 times more common in white populations and ∼ 3 times more common in Hispanics compared to Asian and black populations in the US
References:[1][2][3]
Epidemiological data refers to the US, unless otherwise specified.
Etiology
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Risk factors
- Cryptorchidism (increased risk for germ cell tumors) [4]
- Contralateral testicular cancer
- Germ cell neoplasia in situ (GCNIS)
- Family history of testicular cancer
- Klinefelter syndrome, Down syndrome (increased risk for germ cell tumors) [3]
- Subfertility/infertility, hypospadia
References:[5][1][3][4][6][7]
Classification
Testicular tumors are classified according to pathology.
Overview of testicular tumors | |||||||
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Frequency | AFP | HCG | Characteristics | Pathology | |||
Germ cell tumors (95%) | Seminoma tumor | ∼ 40% | - | -/↑ |
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Nonseminoma tumors | Embryonal carcinoma | ∼ 25% | - | - |
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Teratoma | ∼ 25% | - | - |
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Testicular choriocarcinoma | ∼ 5% | - | ↑↑ |
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Yolk sac tumor | ∼ 5% | ↑ | - |
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Mixed germ cell tumors | Most common overall | -/↑ | -/↑ |
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Non germ cell tumors (5%) | Leydig cell tumors | ∼ 2% | - | - |
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Sertoli cell tumors | < 1% | - | - |
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Secondary testicular tumors | Lymphoma | Most common testicular tumor in men > 60 years of age | - | - |
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HCG is always elevated in cases of choriocarcinoma and sometimes in seminoma. AFP is always elevated in yolk sac tumors. In mixed germ cell tumors, both AFP and HCG may be elevated.
Testicular tumors metastasize early via the lymphatic system into the retroperitoneum (drain to the para-aortic lymph nodes first), with the exception of early hematogenously metastasizing choriocarcinomas.
References:[8][9][3][10][11][11][12][13][14]
Clinical features
- Painless testicular nodule or swelling
- Negative transillumination test
- Dull lower abdominal or scrotal discomfort is more common than acute scrotal pain (30–40% of cases).
- In metastatic disease (10% of cases)
- Cough, shortness of breath, chest pain
- Lower back or bone pain
- Gynecomastia
- Paraneoplastic hyperthyroidism
Until proven otherwise, a firm nodule on the testis should be considered cancer!
References:[2][3][15]
Subtypes and variants
Extragonadal germ cell tumors
- 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: 5–10% of all germ cell tumors; mostly affects young males
- Location: midline organs; mediastinal > retroperitoneal > intracranial
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Symptoms :
- Chest pain, dyspnea (on exertion), cough
- Palpable abdominal mass, back pain, weight loss
- Headache, nausea, vomiting, ataxia, change in vision
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Diagnosis
- Testicular ultrasound: to rule out gonadal primary tumor
- Tumor markers: alpha fetoprotein (AFP) and human chorionic gonadotropin (HCG)
- Tumor biopsy (confirmatory) :Nonseminomas are more common than seminomas
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Therapy
- Determined by the location, size, and histology of the tumor
- Chemotherapy , radiation therapy , and/or surgical resection
- Prognosis: The 5-year survival is ∼ 95% for seminomas and 45–60% for nonseminomas.
References:[16][17][18][19]
Stages
Staging of testicular tumors is based on the American Joint Committee on Cancer (AJCC) groups, which combines TNM stage and serum tumor marker levels.
Simplified AJCC classification | |
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Stage I | Limited to the testicles without lymph node involvement |
Stage II | Retroperitoneal (beneath the diaphragm) lymph node involvement
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Stage III | Distant metastases or nonregional lymph node involvement, or retroperitoneal lymph node involvement with moderately to highly elevated tumor markers |
References:[3]
Diagnostics
Suspicion of testicular tumor is usually established based on the clinical findings and ultrasound (to localize the tumor).
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Laboratory tests
- Tumor markers : alpha fetoprotein (AFP), human chorionic gonadotropin (HCG) (see overview of testicular tumors) and lactate dehydrogenase (LDH)
- Placental alkaline phosphatase (PLAP)
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Imaging
- Ultrasound
- X-ray: to exclude metastasis
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CT: Because of the descended testis, the regional lymph nodes are located retroperitoneally (e.g., para-aortocaval) beneath the diaphragm.
- High-resolution abdominopelvic and chest CT
- Cranial CT or MRI if distant metastasis to the brain is suspected
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Histopathological confirmation: following radical inguinal orchiectomy
- See overview of testicular tumors.
- Rarely, intraoperative frozen section to confirm diagnosis if clinical findings are ambiguous
- If performed, a specimen from radical lymphadenectomy or metastasis surgery may be histopathologically analyzed.
- See overview of testicular tumors.
If testicular tumor is suspected, the testis is removed and sent to pathology without prior transscrotal biopsy!
References:[2][20]
Differential diagnoses
Differential diagnosis of painless testicular swelling | ||
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Clinical features | Ultrasound | |
Testicular tumor |
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Hydrocele testis |
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Varicocele testis |
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Spermatocele testis |
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Scrotal hernia |
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References:[21]
The differential diagnoses listed here are not exhaustive.
Treatment
Surgery
- Prior to surgery: sperm cryopreservation
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Radical inguinal orchiectomy
- In acute, life-threatening disease, orchiectomy may be delayed until after polychemotherapy.
- Contralateral transscrotal biopsy: controversial; currently not recommended in the US
Adjuvant radiotherapy and chemotherapy
- Adjuvant therapy is based on the clinical staging group, histology (seminoma vs. nonseminoma), and the prognosis.
Staging according to the classification | Seminoma | Nonseminoma |
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Stage I |
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Stage II |
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Stage III |
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1BEP = chemotherapy with cisplatin, etoposide, and bleomycin, 2EP = chemotherapy with etoposide, cisplatin, 3RPLND= retroperitoneal lymph node dissection |
- Treatment options for recurrent disease
- Salvage chemotherapy: cisplatin-based (BEP or EP) , VIP , VeIP or TIP
- Surgical resection: salvage RPLND or resection of metastases
- In cases of brain metastasis, additional whole-brain radiation with 40 Gy may be considered.
- Regular follow-up via chest x-ray, abdominopelvic CT, and assessment of tumor markers
- Close surveillance of unaffected testis to look for germ cell neoplasia in situ, especially in patients with risk factors
References:[22][23][24][3][10]
Prognosis
- The overall prognosis of testicular tumors is excellent, with a high cure rate and 5-year survival rates of > 95%.
- Even in advanced, metastatic stages, testicular tumors are often curable.
IGCCCG classification | Nonseminoma | Seminoma |
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Good prognosis ∼ 90% 5-year survival rate |
| No distant metastases |
Intermediate prognosis ∼ 70–80% 5-year survival rate |
| Distant metastases |
Poor prognosis ∼ 50% 5-year survival rate |
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Testicular tumors, particularly seminomas, are one of the few cancers that can be cured even in very advanced stages with adequate treatment. Patients with nonseminomas have a significantly poorer prognosis but still an excellent overall survival rate!
References:[25]