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  • Germ cell tumors (GCTs) are the most common new cancer diagnosis in young men and are divided into two types, seminoma and nonseminoma germ cell tumors (NSGCTs).

  • In a young man without obvious testicular primary or unknown primary tumor, serum tumor markers, specifically human chorionic gonadotropinβ-, α-fetoprotein (AFP), and cytogenetic study, namely i(12p), have unique diagnostic and prognostic significance in GCTs.

  • GCTs follow a distinct pattern of spread and metastasis—the right testicle drains to the interaortocaval lymph nodes, and the left testicle drains to the left paraaortic lymph nodes.

  • Approximately half of testicular GCTs show histologic elements other than seminoma or produce serum elevation of AFP indicating nonseminoma. These cancers are collectively known as mixed NSGCTs, and they form a group of histologically and clinically diverse cancers.

  • Optimal management of patients with high-risk or mixed NSGCTs requires a multidisciplinary approach, integrating chemotherapy and surgery, to achieve the highest cure rates.

  • Patients who pose a unique diagnostic or therapeutic challenge should be considered for early referral to a large tertiary care center.


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). In addition, the rare entity of extragonadal GCTs, which can arise in the mediastinum, retroperitoneum, or pineal body, is described.



The GCTs are the most common new cancer diagnosis in young men. Approximately 9600 new cases were expected to be diagnosed in 2020.1 Highlighting the high curability of this cancer, GCTs only claimed approximately 440 lives in 2020 and carry a 5-year overall survival (OS) rate of approximately 95%.1–3 The GCTs have a bimodal age distribution, with most men diagnosed between ages 15 and 25 years. There is a second peak of diagnosis around age 60 years, 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

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 White 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

Risk Factors

Cryptorchidism is one of the few identifiable risk factors for the development of GCTs, representing at most about 10% of cases. When present, cryptorchidism imparts a ...

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