Thyroid carcinoma after Chernobyl latent period, morphology and aggressiveness

Abstract

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.

RET rearrangements in post-Chernobyl papillary thyroid carcinomas with a short latency analysed by interphase FISH

“…These findings on post-Chernobyl PTCs developed with short and long latency after irradiation suggest that multiple clones develop from follicular cells to form papillary cancer. This interpretation is supported by other studies on papillary cancers (Sugg et al, 1998;Tallini et al, 1998;Fusco et al, 2002) and the recent demonstration that the histology of post-Chernobyl PTCs is inhomogeneous and is changing with time after the accident (Williams et al, 2004). This is borne out in this study, as the proportion of tumours of a solidfollicular morphology is increased in those of longer latency, and those of a purely solid morphology is decreased (Figure 3).…”

“…These papillary carcinomas were then further subdivided according to their dominant architectureeither papillary, follicular or solid. This categorisation has been used in other papers detailing the morphological subtypes of papillary carcinoma post-Chernobyl (Williams et al, 2004). Where two components were present in equal proportions, both features are given (e.g.…”

A Radiation-Induced Gene Signature Distinguishes Post-Chernobyl from Sporadic Papillary Thyroid Cancers

“…(5)] in the incidence of childhood thyroid carcinoma has been observed in Belarus and Ukraine and to a lesser extent in the Russian Federation starting in 1990 (6). A comparison of these tumors with carcinomas in patients in the same age group in Italy and France revealed that the post-Chernobyl thyroid carcinomas were less influenced by gender and were nearly always papillary (7). A solid papillary histological type was found in 93% of children in the Ukraine (8), and an increased prevalence of ultrasonographic thyroid abnormalities (nodules, cysts) was found (9,10).…”

Pseudoangiomatous stromal hyperplasia of the breast

“…For example, the "marked solid component and more aggressive behavior [which] characterize tumors with shorter latency" (22) were, obviously, the features of older and more advanced cancers. Then it becomes clear why "short latency is associated with tumors with a phenotype that is significantly less structurally differentiated, shows significantly less peritumor fibrosis, and significantly more invasive spread when compared to tumors with a longer latent period" (36). The concluding point is that information on molecular-genetic and immunological characteristics of supposedly radiogenic post-Chernobyl tumors, accumulated as a result of international research, requires re-evaluation and new interpretation.…”