Thyroid carcinoma after Chernobyl latent period, morphology and aggressiveness.
The large numbers of papillary thyroid carcinomas that have occurred in those exposed to high levels of short-lived isotopes in fallout after Chernobyl provide a unique opportunity to correlate latency and tumour biology. We show that short latency is associated with tumours with a phenotype that is significantly less structurally differentiated, shows significantly less peritumour fibrosis, and significantly more invasive spread when compared to tumours with a longer latent period. In contrast, the type of differentiation (papillary or follicular architecture) is associated with age at exposure. These findings suggest that the initial mutation at the time of exposure played a major role in tumour latency and aggressiveness. We and others have shown that RET-PTC3 rearrangements are associated with the solid morphology seen in these short latency tumours, while classical papillary carcinomas more often show RET-PTC1 rearrangements. Studies in transgenic mice show similar findings, and in vitro studies show that RET-PTC3 induces more rapid growth than RET-PTC1. We therefore suggest that the solid morphology, high frequency of RET-PTC3 rearrangements and aggressive behaviour noted in early investigations of post-Chernobyl tumours were characteristic of short latency rather than the nature of the mutagen, and that successive overlapping waves of papillary carcinoma with differing latency, differing patterns of mutations and differing clinical behaviour are occurring in those exposed to Chernobyl fallout.