Pathogenesis of testicular germ cell tumours

Human germ cell tumours comprise a heterogeneous group of neoplasms. In the testis, three entities are distinguished, the teratomas-yolk sac tumours o f the infantile testis, the seminomas and nonseminomas of adolescents and a dults, and the spermatocytic seminomas. Studies on epidemiology, histology, clinical behaviour, and chromosomal constitution of these tumours support the concept of distinct entities derived from germ cells but each with a di fferent pathogenesis. Either the teratomas of the infantile testis show no chromosomal aberrations, or display a pattern of over- and under-representa tion of (parts of) chromosomes as detected in the yolk sac tumours of the i nfantile testis. In contrast, the seminomas and nonseminomas reveal a consi stent pattern of losses and gains, that is, chromosomes 11, 13 and 18, and 7, 8 and X, respectively, that is different from that found in the infantil e testis teratomas and yolk sac tumours. The most consistent structural chr omosomal abnormality is an isochromosome 12p. Tumours lacking i(12p) have o ther structural abnormalities of 12p, among them amplification of 12p11.2-p 12.1. The pathogenetically relevant genes on 12p11.2-p12.1 are probably on a fragment of about 1.7 mb. Cain of 12p sequences may be related to invasiv e growth. Gain of chromosome 9 is the only consistent chromosomal anomaly o f spermatocytic seminomas. Infantile teratomas and spermatocytic seminomas are benign tumours. Infantile yolk sac tumour is a malignant germ cell tumo ur. Seminomas and nonseminomas are malignant, and the most common cancer in young Caucasian males. The cure rate of seminomas and nonseminomas with ra dio- and chemotherapy is over 90%, which is higher than that of any other s olid cancer in adults. Ln addition, the precursor lesions of these tumours can be treated readily, justifying efforts to develop means for early diagn osis. Finally, the pathogenetic relationship between seminomas and nonsemin omas, and the available animal models for the three groups of testicular ge rm cell tumours are discussed.