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Testicular cancer is by far the most common neoplasm among young males between the ages of 20 and 40 years and with an increasing incidence rate worldwide. Congenital malformations of the male genitals, such as cryptorchidism or inguinal hernia are established risk factors. Men with a family history of testicular cancer are also associated with an increased risk of the disease. In the testes more than 90 % of tumors develop from germ cells (progenitor cells) and represent a histologically heterogeneous group. Germ cell tumors in extragonadal localizations are rare. Isochromosome i(12p), the typical marker chromosome in testicular germ cell tumors, occurs as an early event in tumorigenesis. Spermatocytic seminoma is a rare variant of germ cell tumors and according to the current classification is a distinct entity with different morphological, clinical and also cytogenetical features compared with other germ cell tumors.

Carcinoma in situ (CIS), also known as intratubular germ cell neoplasia unclassified, is the common obligate precursor lesion of malignant testicular seminomatous and non-seminomatous germ cell tumors (GCT), which show a steadily increasing incidence in Europe. Although GCT is a potentially curable cancer with excellent prognosis even in patients with organ metastasis, many patients suffer from chemotherapy-associated effects and some develop a secondary (non-germ cell) malignancy. Recently, genome-wide association studies revealed genetic predispositions linked to six genes (KITL, SPRY4, BAK1, TERT, ATF7IP, DMRT1). Exposure to environmental factors was also linked to increased prevalence of testicular dysgenesis and CIS/GCT by the action of hormone disruptors on embryonal gonadal tissue during pregnancy. By unknown mechanisms these genetic and environmental factors might create a disturbed microenvironment in the fetal testis leading to survival of embryonic germ cells and subsequent malignant transformation might result in CIS. Molecular pathways involved in this process include activated cKIT pathway and LIN28 associated deregulation of miRNA targets. The challenge for the future is to identify high risk patients prior to invasive GCT, to develop non-invasive tests for detection of CIS on seminal material and elucidate the precise role of the microenvironment in CIS initiation.