Embryogenesis and Metastatic Testicular Germ Cell Tumors of Adolescents

Abstract

This issue of Klinische Padiatrie contains two highly interesting contributions to the field of clinical management of human germ cell tumors of adolescents and young adults [1] [4]. Although both cases in fact relate to metastatic disease, they also show the benefit and relevance of early diagnosis of this particular type of cancer. Testicular germ cell tumors of adolescents and young adults are the seminomas and nonseminomas, also referred to type II TGCTs [17] [20]. Histologically, the nonseminomas are divided into the stem cell component, known as embryonal carcinoma, the yolk sac tumor and choriocarcinoma [extra-embryonal elements], and teratoma [somatic differentiation]. In other words, these tumors show similarities to early embryogenesis, and are in fact really totipotent. They have unique epidemiological characteristics [11] [13]. In fact, they are one of the few solid cancers in adolescents and young adults [2], and represent the most frequent solid tumor in the age group of 15–45 years in the Caucasian population. The cells of origin is the malignant counterpart of an embryonic germ cell, either a primordial germ cell or gonocyte, known as carcinoma in situ(CIS) [18], intratubular germ cell neoplasia unclassified [20], or testicular intratubular neoplasia (TIN) [7]. Specific risk factors for this type of cancer are identified, amongst others cryptorchidism, sub- and infertility, familial predisposition and certain variants of disorders of sex development [6], all related to a delayed maturation of primordial germ cells/gonocytes into pre-spermatogonia. This has been suggested to be part of the so-called testicular dysgenesis syndrome [19]. Invasive TGCTs are characterized on the chromosomal level by gain of the short arm of chromosome 12, mainly due to isochromosome 12p formation [17], which interestingly can also be identified in human embryonic stem cells, grown in vitro [8]. TGCTs are exceptional because of the fact that they can be effectively treated, using a combinatory strategy of surgery, irradiation and/or chemotherapy in most cases [12]. In fact, overall, they are highly sensitive to DNA damaging agents, which can be related to their embryonic origin. However, this specific sensitivity is lost in the mature teratomas, which indeed have no embryonic characteristics anymore, and are in that context similar to normal adult tissue [14] [15], and therefore need surgical intervention for sure. In spite of this sensitivity, it has become obvious that late effects of chemotherapy exposure at young age occur [10]. This has initiated further studies on limiting exposure thereby reducing these side effects. Another clinical obstacle is development of refractory disease, which is often the cause of death of patients with this disease, because of highly limited treatment options [3] [9] [16].