A. Symptoms
The most common symptom of testicular cancer is a painless enlargement of the testis. Enlargement is usually gradual, and a sensation of testicular heaviness is not unusual. The typical delay in treatment from initial recognition of the lesion by the patient to definitive therapy (orchiectomy) ranges from 3 to 6 months. The length of delay correlates with the incidence of metastases. The importance of patient awareness and self-examination is apparent. Acute testicular pain is seen in approximately 10% of cases and may be the result of intratesticular hemorrhage or infarction.

Approximately 10% of patients present with symptoms related to metastatic disease. Back pain (retroperitoneal metastases involving nerve roots) is the most common symptom. Other symptoms include cough or dyspnea (pulmonary metastases); anorexia, nausea, or vomiting (retroduodenal metastases); bone pain (skeletal metastases); and lower extremity swelling (venacaval obstruction).

Approximately 10% of patients are asymptomatic at presentation, and the tumor may be detected incidentally following trauma, or it may be detected by the patient’s sexual partner.

B. Signs
A testicular mass or diffuse enlargement is found in most cases. The mass is typically firm and nontender, and the epididymis should be easily separable from it. A hydrocele may accompany the testicular tumor and help to camouflage it. Transillumination of the scrotum can help to distinguish between these entities.

Palpation of the abdomen may reveal bulky retroperitoneal disease; assessment of supraclavicular, scalene, and inguinal nodes should be performed. Gynecomastia is present in 5% of all germ cell tumors but may be present in 30-50% of Sertoli and Leydig cell tumors. Its cause seems to be related to multiple complex hormonal interactions involving testosterone, estrone, estradiol, prolactin, and hCG. Hemoptysis may be seen in advanced pulmonary disease.

C. Laboratory Findings and Tumor Markers
Anemia may be detected in advanced disease. Liver function tests may be elevated in the presence of hepatic metastases. Renal function may be diminished (elevated serum creatinine) if ureteral obstruction secondary to bulky retroperitoneal disease is present. The assessment of renal function (creatinine clearance) is mandatory in patients with advanced disease who require chemotherapy.

Several biochemical markers are of importance in the diagnosis and management of testicular carcinoma, including AFP, hCG, and LDH. Alpha-fetoprotein is a glycoprotein with a molecular mass of 70,000 daltons and a half-life of 4-6 days. Although present in fetal serum in high levels, beyond the age of 1 year it is present only in trace amounts. While present to varying degrees in many NSGCTs (

Table 23-2), it is never found in seminomas.

Human chorionic gonadotropin is a glycoprotein with a molecular mass of 38,000 daltons and a half-life of 24 h. It is composed of 2 subunits: alpha and beta. The alpha subunit is similar to the alpha subunits of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and thyroid-stimulating hormone (TSH). The beta subunit conveys the activity to each of these hormones and allows for a highly sensitive and specific radioimmunoassay in the determination of hCG levels. A normal man should not have significant levels of beta-hCG. While more commonly elevated in NSGCTs, hCG levels may be elevated in up to 7% of seminomas.

Lactic acid dehydrogenase (LDH) is a cellular enzyme with a molecular mass of 134,000 daltons that has 5 isoenzymes; it is normally found in muscle (smooth, cardiac, skeletal), liver, kidney, and brain. Elevation of total serum LDH and in particular isoenzyme-I was shown to correlate with tumor burden in NSGCTs. LDH may also be elevated in seminoma.

Other markers have been described for testis cancer, including placental alkaline phosphatase (PLAP) and gamma-glutamyl transpeptidase (GGT). These markers, however, have not contributed as much to the management of patients as those mentioned previously.

D. Imaging
The primary testicular tumor can be rapidly and accurately assessed by scrotal ultrasonography. This technique can determine whether the mass is truly intratesticular, can be used to distinguish the tumor from epididymal pathology, and may also facilitate testicular examination in the presence of a hydrocele.

Once the diagnosis of testicular cancer has been established by inguinal orchiectomy, careful clinical staging of disease is mandatory. Chest radiographs (posteroanterior and lateral) and computed tomography (CT scan) of the abdomen and pelvis are used to assess the 2 most common sites of metastatic spread, namely, the lungs and retroperitoneum. The role of CT scanning of the chest remains controversial because of its decreased specificity. Of note is the fact that routine chest x-rays detect 85-90% of pulmonary metastases. Pedal lymphangiography (LAG) is rarely used owing to its invasiveness as well as low specificity, although it may be warranted in patients undergoing a surveillance protocol (see section on treatment).