Testicular cancer is the most common malignancy in men in the 20–40-year age group. The germ-cell tumors (GCTs) are the most prevalent type of testicular cancer. Their incidence has risen over the past two decades, as has the most prevalent risk factor for GCT, an undescended testis (cryptorchidism), suggesting that numbers of men afflicted with testicular cancer will continue to rise for the foreseeable future.
Unlike ovarian tumors, which are likely to arise from the epithelium covering the gland, 90% of primary testicular tumors arise from intratubular germ cells. Histologically, there are six distinct types of GCT. Five of these occur in young men and one is seen exclusively in older men (Fig. 40.1). The five subtypes seen in young men include seminoma, choriocarcinoma, endodermal sinus tumor (yolk sac carcinoma), embryonal carcinoma and teratomas, both benign and malignant. Spermatocytic seminomas are typically seen in men over 50 and are quite rare. The germ cells of origin in GCT affecting young and old men are distinct and appear to be at different stages of maturation. The associated tumors therefore have distinct neoplastic behaviors.
All GCTs of young men arise from spermatogonial cells. The five tumors that develop from this single precursor cell type are quite heterogeneous and several exhibit embryonal-like differentiation. Prognosis and treatment depends upon whether GCTs are pure seminomas (SGCTs) or mixed cell tumors (nonseminomas, NSGCTs). Seminomas have a homogeneous germ-cell morphology. Nonseminomas have features of embryonal cells and can mimic the histogenesis of the very early embryo. Embryonal carcinoma is the most primitive, or pluripotent, of the NSGCTs. It can progress along extraembryonic lines as choriocarcinoma or yolk sac carcinoma, or along embryonic lines as a teratoma. Individual tumors can contain a mixture of any of the histologic subtypes.
About 80% of GCTs secrete tumor markers that can be detected in the serum. Tumors with yolk sac components typically secrete alpha fetoprotein (AFP), an embryonic protein normally produced by the yolk sac during development. Other NSGCTs can also secrete AFP but seminomas do not. Human chorionic gonadotropin (hCG) is typically secreted by choriocarcinomas; however, small amounts of hCG production have been found in SGCTs as well as NSGCTs. The distribution of these two markers by specific cell types suggests the associated tumors arise from precursors at different levels of differentiation. AFP is a very primitive marker of embryonal differentiation whereas hCG represents trophoblastic differentiation. A third marker, placental-like alkaline phosphatase (PLAP), is found in carcinoma in situ (CIS) and about 50% of seminomas. Clinical paradigms using serum levels of AFP and hCG have been developed to assist in the diagnosis and staging of GCT.
Most GCTs are diagnosed at an early tumor stage when the tumor is confined to the testis. Serum screening, physical exam and testicular ultrasounds are useful in identifying early tumors in patients at high risk for GCT, such as formerly cryptorchid men and intersex individuals who keep their gonads. Men who present with solid testicular masses are usually treated by radical orchidectomy (removal of the testis). When GCT metastasizes, it typically spreads unilaterally to the para-aortic nodes. Distant metastases are generally found only in tumors with trophoblastic components.
Like gestational trophoblast disease in women (Chapter 45), GCT has a very high cure rate. Virtually all patients with early stage disease can expect to be cured. Initial treatment of stage I disease involves removal of the affected testes, followed by either retroperitoneal lymph node dissection, a short course of adjuvant chemotherapy or close surveillance. Even metastatic disease responds to chemotherapy with cure rates in excess of 90%.
Leydig cell tumors are a very rare form of testicular cancer (1–3%) and are associated with isosexual precocious puberty (Chapter 28). Gonadal stromal tumors (sex cord-stromal tumors) include both Sertoli–Leydig cell and granulosa-theca cell tumors. They are extraordinarily rare in boys and men and are associated with phenotypic feminization.
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