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INTRODUCTION

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Testicular germ cell tumors (GCTs) account for the majority of testicular cancers and are highly curable. This chapter primarily discusses 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, is described.

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OVERVIEW OF GERM CELL TUMORS

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Epidemiology

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The GCTs are the most common new cancer diagnosis in young men. Roughly an estimated 8,430 new cases were expected to be diagnosed in 2015 (1). Highlighting the high curability of this cancer, GCTs only claimed approximately 380 lives in 2015 (1) and carry a 5-year overall survival (OS) rate of approximately 95% (2,3). The 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 (5). 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 (6).

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Risk Factors

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Cryptorchidism is one of the few identifiable risk factors for the development of GCTs, although representing at most 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 support the theory that the etiology of GCTs lies 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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Tumor Biology

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The most common genetic abnormality found in GCTs is an isochromosome of the short arm of chromosome 12, which has been identified in approximately ...

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