Testicular tumors

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.

• 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.

• 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]}

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%	-	-	Pure embryonal carcinomas are rare, but are a very common element of mixed germ cell tumors. Aggressive tumor with early metastases	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.	Consist of both cytotrophoblasts and syncytiotrophoblasts multinucleated giant cells
		Yolk sac tumor	∼ 5%	↑	-	Most common prepubertal testicular tumor	Yellow cut surface, glomeruloid structures (Schiller-Duval bodies)
		Mixed germ cell tumors	Most common overall	-/↑	-/↑	Even if seminoma is present, it is classified and treated as a nonseminoma.	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 corticosteroids → testosterone 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%	-	-	Derived from normal Sertoli cells, which facilitate spermatogenesis	Multiple Sertoli cells
	Secondary testicular tumors	Lymphoma	Most common testicular tumor in men > 60 years of age	-	-	Usually extranodal non-Hodgkin lymphoma	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]}

• 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]

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
• Symptoms :
  • Chest pain, dyspnea (on exertion), cough
  • Palpable abdominal mass, back pain, weight loss
  • Headache, nausea, vomiting, ataxia, change in vision
• 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
• 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]}

Suspicion of testicular tumor is usually established based on the clinical findings and ultrasound (to localize the tumor).

• Laboratory tests
  • Tumor markers : alpha fetoprotein (AFP), human chorionic gonadotropin (HCG) (see overview of testicular tumors) and lactate dehydrogenase (LDH)
  • Placental alkaline phosphatase (PLAP)
• Imaging
  • Ultrasound
    • Seminoma: hypoechoic, homogenous, sharp margins
    • Nonseminomas: variable echogenicity; , inhomogenous; , may be calcified or cystic
    • Microlithiasis: disseminated calcification as a possible precursor of carcinoma (starry sky appearance)
  • X-ray: to exclude metastasis
  • 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
• 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.

If testicular tumor is suspected, the testis is removed and sent to pathology without prior transscrotal biopsy!
References:^[2][20]

• 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 and Slightly elevated tumor markers	No distant metastases
Intermediate prognosis ∼ 70–80% 5-year survival rate	No distant metastases and Moderately elevated tumor markers	Distant metastases
Poor prognosis ∼ 50% 5-year survival rate	Distant metastases or Highly elevated tumor markers or Mediastinal primary tumor	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]