Extragonadal germ cell tumors

Abstract

Germ cell tumors (GCTs) are relatively uncommon in childhood, accounting for about 2% to 3% of all neoplasms in patients younger than 15 years. With an annual incidence of approximately 4 per million in this age group, there are about 250 new cases in the United States each year. Germ cell tumors can arise in the gonads or in extragonadal sites, doing so with nearly equal frequency overall. However, extragonadal and testicular tumors predominate in children younger than 3 years, and gonadal tumors predominate in older children. Approximately 30% to 40% of all GCTs are malignant, though the percentage is somewhat higher when considering only extragonadal tumors. Overall, GCTs are more likely to develop in girls than in boys. Germ cell tumors arise from primordial germ cells derived from the embryonic yolk sac endoderm. These primordial germ cells are first recognized in the caudal portion of the yolk sac, near the allantoic stalk, at about the 24th day (2–3 mm embryos). During the 5th and 6th weeks of embryogenesis, these cells migrate along the mesentery of the hindgut toward the genital ridge, which is forming from mesenchyme and mesodermal epithelium. The path of the migrating cells appears to be directed by the interaction of the c-kit ligand, stem cell factor (expressed with an increasing gradient from the yolk sac to the genital ridges), and the c-kit receptor (expressed on the primordial germ cells).