Epidemiology, Biology, and Genetics of Adult Male Germ Cell Tumors

Abstract

While germ cell tumors (GCTs) comprise only about 1 % of cancers diagnosed each year in American men, they still constitute the most common malignancy to affect male adolescent and young adults (AYA) in the US and other developed countries. Most commonly, these tumors originate in the testis and comprise more than 95 % of all testicular malignancies. However, GCTs can also arise in extragonadal locations such as the mediastinum, pineal gland, and retroperitoneum. Despite having a nearly universal genetic marker, isochromosome 12p, GCTs are not a singular tumor type but rather a fascinating group of malignancies derived from the malignant transformation of developing germ cells. The pluripotential differentiating capacity of developing germ cells explains the intriguing biology and array of histologies found in GCTs. These histologies mimic the cell and tissue types seen during embryologic and extraembryologic fetal development. In this chapter, the authors review GCT epidemiology, highlighting well-known risk factors such as cryptorchidism as well as newly appreciated risk factors such as infertility and genetic polymorphisms, with plausible explanations of how these characteristics may be interrelated. An overview of the biology of GCT development and differentiation is also presented with an emphasis on recent insights and persistent controversies. The authors provide a detailed review of GCT genetics including potential candidate genes and regions within 12p and other frequent chromosomal aberrations. In the latter part of the chapter, the authors summarize the data supporting and refuting proposed explanations for the exquisite sensitivity of most GCTs to cisplatin, which underlies their unique curability even in the setting of widely metastatic disease. Finally, various mechanisms by which GCTs might acquire or have inherent cisplatin resistance are presented. As such, the reader of this chapter will be left with a solid understanding of the epidemiology, biology, and genetics of this fascinating malignancy.