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INTRODUCTION

Testicular germ cell tumors (GCTs) represent 95% of all testicular neoplasms. Non-germ cell tumors of the testis are much less common. Approximately 5% of GCTs arise in extragonadal locations including the mediastinum, retroperitoneum, and pineal gland. Treatment for testicular GCTs is determined by pathology and stage. The development of effective chemotherapy for this disease represents a landmark achievement in oncology. About 95% of newly diagnosed patients with testicular GCTs will be cured. For this reason, testicular cancer has been called “a model for a curable neoplasm.”

INCIDENCE

In 2016, ∼8700 cases of testicular GCTs will be diagnosed in the United States, with <400 deaths. These tumors are diagnosed most commonly in men between 20 and 40 years. It has recently been reported that the incidence of GCTs is increasing in men 50 years and older.

GLOBAL CONSIDERATIONS

Image not available. The incidence of testicular GCTs appears to be increasing worldwide. The disease has the highest incidence in Scandinavia, Western Europe, and Australia/New Zealand. Africa and Asia have the lowest incidence. The incidence in the United States and the United Kingdom is intermediate. While there does not appear to be a distinct biology related to geography, several countries have reported a migration to earlier stage disease in part related to public awareness and earlier diagnosis.

EPIDEMIOLOGY

GCTs are predominantly seen in young Caucasian men. The disease is much less commonly seen in African Americans. Although most patients with GCTs do not have a family history of this disease, there are rare familial cases. Interestingly, the risk of GCT is higher in male siblings and cousins than in offspring of the patient. Although epidemiological studies have been performed attempting to identify a relationship with environmental exposures, no conclusive causal links have been established.

Risk Factors

The strongest risk factors for testicular GCT include a prior history of the disease, cryptorchidism, and a history of testicular intratubular germ cell neoplasia (ITGCN). Patients with a prior history of testicular GCT have a 2% risk of developing a contralateral GCT. These are more commonly metachronous than synchronous. Men with cryptorchidism have approximately a four- to sixfold increased risk of developing testicular GCT. Orchidopexy before puberty decreases but does not eliminate this risk. Interestingly, the contralateral descended testis is also at risk for this disease. Men undergoing infertility evaluation in which a testicular biopsy demonstrates ITGCN have a 50% risk of developing GCT. Although scrotal ultrasound of patients with testicular GCT may demonstrate testicular microcalcifications that may be related to ITGCN, the significance of testicular microcalcifications in the general population is unclear.

BIOLOGY

The primordial germ cell is the cell of origin for GCTs. All malignant GCTs arise from ITGCN. The molecular events that result in the development of ITGCN and subsequent malignant GCT have not been fully determined. However, genetic analysis of GCTs have demonstrated an excess copy number of isochromosome 12p (i[12p]) in most cases. Several genome-wide association studies have identified independent loci associated with testicular GCT ...

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