Origin of adult male mediastinal germ-cell tumours

The origin of primary extragonadal germ-cell tumours, especially mediastinal and pineal germ-cell tumours in adult males remains uncertain, although the predominant view is that they originate in misplaced primordial germ cells retained in extra-gonadal sites, in contrast to gonadal germ-cell tumours which are considered to arise in premeiotic spermatocytes. We hypothesised that if mediastinal germ-cell tumours and gonadal germ-cell tumours were derived from precursor cells in different developmental states and in different cellular environments, non-random genetic changes in the two groups would be significantly different. To test this hypothesis, we compared non-random chromosomal abnormalities in mediastinal germ-cell tumours with those in gonadal germ-cell tumours. Our results show that although the two groups differed in the composition of histological subsets, their non-random chromosomal changes were essentially the same. These data suggest gonadal origin of all germ-cell tumours with occasional migration of precursors early in development to extragonadal sites to become established as primary extragonadal germ-cell tumours. Based on a review of cytogenetic data on carcinoma in situ, primary mediastinal and gonadal germ-cell tumours, embryonal migration of primordial germ-cells, and meiotic behaviour of spermatocytes, a model of origin of all germ-cell tumours in males is suggested.