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Germ cell tumors (GCTs), the majority arising from the testicle, are a highly curable group of cancers primarily seen in young men. This group of patients should present a special consideration for oncologists, as appropriate management in the frontline setting can lead to many years of life recovered, making GCT the paradigm of the curable solid tumors. This chapter will primarily discuss GCTs arising in the testicle, dividing this category into seminoma versus nonseminoma germ cell tumors (NSGCTs). Then, the rare entity of extragonadal GCTs, which can arise in the mediastinum, retroperitoneum, or pineal body, will be described.

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Epidemiology

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GCTs are the most common cancer in young men. Roughly 8400 new cases were being diagnosed in the United States in 2009, representing only a fraction of new genitourinary cancers which are estimated to be over 280,000 (1). Highlighting the high curability of this cancer, GCTs only claimed approximately 380 lives in 2009 (1) and carry a 5-year overall survival (OS) rate of greater than 90% (2,3). GCTs have a bimodal age distribution, with most men diagnosed between ages 15 and 25. There is a second peak of diagnosis around age 60, which largely represents seminoma histology and a lower mortality risk. Lifetime risk for the development of GCTs is approximately 0.5% or 1 in 200 (4).

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Worldwide, GCTs are six times more common in developed countries, with the largest incidence reported in Denmark and Switzerland and the lowest in Japan, Finland, and Israel (4). In the United States, the overall incidence of GCTs appears to be gradually increasing. The incidence has specifically increased among African Americans, with the greatest increase in seminoma histology. This does not appear to be related to screening or earlier diagnosis. Caucasian men, although still representing the group most likely to be diagnosed, are more likely to be identified at an earlier stage than in the past (5,6).

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Risk Factors

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Cryptorchidism is one of the major identifiable risk factors for the development of GCTs, although representing only about 10% of cases. When present, cryptorchidism imparts a relative risk between 2.5 and 17.1 (7,8). This increased risk includes the contralateral testicle, even if descended normally or via orchiopexy. It is unclear if orchiopexy reduces the lifetime risk of GCTs, although data showing increased incidence even in the contralateral testicle supports the theory that the etiology of GCTs lie in abnormal gonadal development rather than anatomic malposition (9,10). Men with a prior history of GCTs also have an increased risk of GCTs in the contralateral testicle, suggesting a genetic predisposition, although men with a family history of GCTs account for only 1.5% of patients with new diagnosis (11). A personal history of GCT carries an increased lifetime risk of secondary cancers, irrespective of histologic type (12).

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