Testicular cancer: Germ-cell tumors (GCTs)
Introduction At first impression, human GCT are a heterogeneous group of neoplasms. They can occur in the gonads (testes, ovaries, and dysgenetic gonads) and in extra-gonadal localizations, i.e. particularly along the midline of the body. This is likely explained by the migration route of primordial germ cells (PGC) from the yolk sac to the gonadal blastema during early embryogenesis (1). In a comprehensive classification encompassing all anatomical localizations, and taking into account clinical presentation, cytogenetic findings, and imprinting status, GCT can be classified into five types, related to the maturation stages of the germ cell of origin. This has been recognized by the World Health Organization (WHO; 2), as well as specialized pathologists in this particular field (3,4). In the testis, three of these types occur: Type I, teratomas/yolk-sac tumors of neonates and infants; Type II, seminomatous and non-seminomatous tumors in young adults; and Type III, spermatocytic seminomas in elderly men (see 5 for a review). In the adult testis Type II GCT are the most frequent cancers in the age group 15 to 45 years, comprising 1% of all cancers in Caucasian males. They are, however, although usually successfully treated, still the top cause of cancer death in this age range. Types I and III GCT are more rare than Type II GCT, and virtually always benign. Apart from GCT there are testicular stromal tumors (Leydig-cell tumors and Sertoli-cell tumors) which are most often benign, and the primary malignant lymphomas of the testis, usually of the diffuse large B-cell lymphoma type. Finally, there are very rare cancers, like cancer of the rete testis, and cancers derived from tissues that are not specific for the testis, such as sarcomas and cancers that have metastasized to the testis. This chapter will only deal with Type II GCT of the testis. Pathology Seminomas comprise about 50% of Type II GCTs, non-seminomas about 30%, and the remaining combine a seminoma and a non-seminoma component, so-called combined tumors, according to the British classification system (6). The median age of presentation for these tumors is, respectively, 35, 25, and 30 years.