Testicular cancer constitutes approximately 1% of cancer in males but it is the most common malignancy in young and middle age men (between 15 and 49 years of age). Its incidence has been rising in the past four decades. It is more common in Caucasian men and in Northern and Western Europe, especially in Nordic countries. The main risk factors for the development of testicular cancer are undescended testicles (cryptorchidism) and family history of testicular cancer. It is also more common in men with fertility problems. Men with a history of testicular cancer in one testis are more likely to develop cancer on other side.
Symptoms of testicular cancer may include a painless lump or swelling in the testis and scrotum, and pain or discomfort in the scrotum, lower abdomen, or lower back. Some cancers are associated with hormone production, which may cause enlargement of the breast (gynecomastia) and breast tenderness.
Tumors of germ cell origin account for approximately 95% of all testicular cancers. Germ cell tumors can be divided into two major categories: seminoma and non-seminomatous germ cell tumors. Non-seminomatous tumors may occur as pure (a single histological type) or mixed tumors. Tumors containing both seminomatous and non-seminomatous components are regarded as mixed non-seminomatous germ cell tumors.
Seminomas account for up to 50% of all germ cell tumors. They are characterized by evenly spaced and relatively large uniform tumor cells with distinct cell borders. Tumor cell nuclei are often centrally localized and show distinct nuclear membranes and one or two distinct nucleoli. The tumor stroma consists of a delicate fibrovascular network with thin collagenous septa containing variable amounts of small lymphocytes.
Of the non-seminomatous tumors, embryonal carcinoma accounts for 15-30% and represents the second most frequent pure type of testicular cancer. Embryonal carcinoma exhibits solid, acinar, tubular, or papillary growth patterns with areas of necrosis, hemorrhage, and fibrosis. Tumor cells are highly pleomorphic with large, irregular nuclei and indistinct cell borders. Embryonal carcinoma is a relatively undifferentiated germ cell tumor often associated with components of other tumors: yolk sac tumor, choriocarcinoma, tertoma (postupebrtal type), and even seminoma. Yolk sac tumor (endodermal sinus tumor) contains Schiller-Duval bodies, structures resembling glomerulus with mesodermal core and central blood vessel surrounded by layers of flattened tumor cells. Microcystic/reticular pattern is the most common growth pattern, and sometimes myxoid stroma and extracellular and intracellular hyaline globules can be found. Choriocarcinoma is composed of atypical syncitiotrophoblasts, cytotrophoblasts and intermediate trophoblasts. Teratomas can in turn be composed of both immature and mature components representing cell types and structures from all embryonic germ layers.
The distinction between different tumor types and components within a testicular tumor is based on microscopical examination and immunohistochemistry. Commonly used antibodies for the differential diagnostics of these tumors include D2-40, OCT 3/4, CD117, PLAP, SALL4, glypican 3, human chorionic gonadotropin (hCG), and alpha feto-protein (AFP) in addition to CD30 (TNFRSF8), and markers of intermediate filaments, e.g. cytokeratin (KRT) and vimentin (VIM).
Treatment and prognosis of testicular cancer depend on the histological type, stage of the disease, and patient age. Surgery and chemotherapy are the main treatment options. Seminoma is very radiosensitive tumor and a radiotherapy is an additional option. Patients with seminoma who are older than 40 years and with advanced stages (excluding the presence of metastasis in lungs) have a poor prognosis. Patients with non-seminomatous tumors have a poor prognosis if are older, have advanced disease (either at first presentation or later in clinical course), and if there are increased levels of tumor markers in the blood. Survival of patients with testicular cancer has improved greatly in past decades due to chemotherapy options. Nowadays it ranges from 99% in localized disease to 73% in distant disease.