• Clinical science

Testicular tumors

Abstract

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

References:[5][1][3][4][6][7]

Classification

Testicular tumors are classified according to pathology.

Overview of testicular tumors
Frequency AFP HCG Characteristics Pathology

Germ cell tumors (95%)
Seminoma tumor

∼ 40%

- -/↑
  • Good radiosensitivity; slow growth, late metastases, and better overall prognosis compared to nonseminomas
  • Uniform white cut section
Nonseminoma tumors Embryonal carcinoma ∼ 25%

-

-

  • Grey-white regressive changes with hemorrhage, necrosis, and cysts
Teratoma ∼ 25% - -
  • Rare in adults, but common in children
  • Typically benign but may be malignant in adults (teratocarcinoma)
  • Composed of tissue from different germinal layers.
  • May be immature or may contain fully differentiated elements muscle, cartilage, bone, teeth) in mature teratomas
Testicular choriocarcinoma ∼ 5% - ↑↑
  • Highly malignant and most aggressive
  • Early hematogenous metastasis to the lungs or brain is common.
Yolk sac tumor ∼ 5% -
  • Most common prepubertal testicular tumor
  • Yellow cut surface, glomeruloid structures (Schiller-Duval bodies)
Mixed germ cell tumors Most common overall -/↑ -/↑
  • Heterogeneous cut surface with solid areas, hemorrhage, and necrosis
Non germ cell tumors (5%) Leydig cell tumors ∼ 2% - -
  • Definition: rare tumors which arise from the hormone producing stromal cells of the testes.
  • Epidemiology: usually develop after the age of 4
  • Pathophysiology: produces ↑↑ amounts of testosterone and a small amount of estrogen, progesterone, and corticosteroidstestosterone excess causes precocious puberty in males (and masculinization in females)
  • Clinical features
    • Androgen excess features, like prominent external genitalia, pubic hair growth, accelerated skeletal and muscle development, and mature masculine voice
    • Occassionally, estrogen excess features, like gynecomastia, breast tenderness, and gonadogenital underdevelopment.
    • Malignant transformation is very rare.
  • Reinke crystals (eosinophilic cytoplasmic inclusions)
Sertoli cell tumors < 1% - -
Secondary testicular tumors Lymphoma Most common testicular tumor in men > 60 years of age - -
  • Usually diffuse large B-cell lymphomas

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

Until proven otherwise, a firm nodule on the testis should be considered cancer!
References:[2][3][15]

Subtypes and variants

Extragonadal germ cell tumors

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
Stage I Limited to the testicles without lymph node involvement
Stage II

Retroperitoneal (beneath the diaphragm) lymph node involvement

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).

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
Clinical features Ultrasound
Testicular tumor
  • Usually painless mass (however, may feel dull ache or "heavy" sensation in the testicle)
  • Palpation of solid mass
  • Negative transillumination test
  • Solid mass with variable echogenicity
Hydrocele testis
  • Fluctuant swelling of the scrotum
  • Palpation of an elastic soft swelling
  • Positive transillumination test
  • Hypoechoic mass around the testis
Varicocele testis
  • Usually painless ; swelling may be reduced when supine
  • Visible or palpable strands and “bag of worms” sensation
  • Negative transillumination test
  • Dilated hypoechoic pampiniform vessels
Spermatocele testis
  • Fluctuant swelling of the upper testicular pole
  • Positive transillumination test
  • Hypoechoic dilation of epididymal duct
Scrotal hernia
  • Visible groin protrusion
  • Bowel sounds on auscultation over scrotum
  • Herniated bowels

References:[21]

The differential diagnoses listed here are not exhaustive.

Treatment

Surgery

  • Prior to surgery: sperm cryopreservation
  • 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
Stage I

Stage II

  • Radiation therapy or
  • Chemotherapy: 3 cycles of BEP1 or 4 cycles of EP2
  • Stage II C: 3–4 cycles BEP1or 4 cycles of EP2
Stage III
  • Chemotherapy (depending on prognosis): 3–4 cycles BEP1 or 4 cycles of EP2 followed by evaluation of any residual disease that may require resection
1BEP = chemotherapy with cisplatin, etoposide, and bleomycin, 2EP = chemotherapy with etoposide, cisplatin, 3RPLND= retroperitoneal lymph node dissection
  • Treatment options for recurrent disease
  • 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

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

  • N/A

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]