Histopathological features of papillary thyroid carcinomas detected during four screening examinations of a Ukrainian-American cohort

Abstract

Background:There are limited data on the histopathology of papillary thyroid carcinomas (PTCs) diagnosed in irradiated populations. We evaluated the associations between iodine-131 dose and the histopathological characteristics of post-Chernobyl PTCs, the changes in these characteristics over time, and their associations with selected somatic mutations.Methods:This study included 115 PTCs diagnosed in a Ukrainian-American cohort (n=13 243) during prescreening and four successive thyroid screenings. Of these PTCs, 65 were subjected to somatic mutation profiling. All individuals were <18 years at the time of the Chernobyl accident and had direct thyroid radioactivity measurements. Statistical analyses included multivariate linear and logistic regression.Results:We identified a borderline significant linear-quadratic association (P=0.063) between iodine-131 dose and overall tumour invasiveness (presence of extrathyroidal extension, lymphatic/vascular invasion, and regional or distant metastases). Irrespective of dose, tumours with chromosomal rearrangements were more likely to have lymphatic/vascular invasion than tumours without chromosomal rearrangements (P=0.020) or tumours with BRAF or RAS point mutations (P=0.008). Controlling for age, there were significant time trends in decreasing tumour size (P<0.001), the extent of lymphatic/vascular invasion (P=0.005), and overall invasiveness (P=0.026).Conclusions:We determined that the invasive properties of PTCs that develop in iodine-131-exposed children may be associated with radiation dose. In addition, based on a subset of cases, tumours with chromosomal rearrangements appear to have a more invasive phenotype. The increase in small, less invasive PTCs over time is a consequence of repeated screening examinations.

Comparative histopathological analysis of sporadic pediatric papillary thyroid carcinoma from Japan and Ukraine

“…It is interesting to note that the absence of difference in tumor architecture in childhood patients (see Table 2) and the higher frequency of the dominant papillary growth pattern in adolescents of Japan vs. Ukraine (see Table 3) might be partly explained by the presence of BRAF V600E mutation in corresponding tumors, which is known to associate with the papillary tumor structure [14]. Reviewing two relatively recent molecular genetic analyses of Ukrainian [15] and Japanese [16] PTC, we found no statistically significant difference in the prevalence of this mutation between Ukrainian and Japanese sporadic childhood PTC (2/8, 25.0% vs. 3/9 33.3%, respectively; p=1.000).…”

Meeting report: the 5th International expert symposium in Fukushima on radiation and health

“…Prospective cohort studies in Ukraine, Belarus and Russia concur that the risk remains elevated even until today, i.e., 30 years after the accident. However, as the UkrAm study shows, excess relative risk per dose unit is declining with time in each consequent round of ultrasound screening [6], and is accompanied by time-dependent pathomorphological evolution of tumor characteristics to the less aggressive phenotype with corresponding molecular genetic changes [7]. In the individuals exposed at young age in Ukraine and Russia who then developed thyroid cancer, mean radiation doses to the thyroid ranged 0.4–3.4 Gy or exceeded 0.2 Gy, respectively [6, 8], which is an important fact in view of low thyroid doses in Fukushima [9–11].…”

Malignancies after Chernobyl Accident: What Is True and What Is Untrue

“…Morphologically, TC in patients from contaminated territories were more aggressive than usual [11][12][13][14]. Correlations between radiation doses to the thyroid, tumor invasiveness and "aggressive solid-follicular" pattern were reported [9,10]. However, the time factor was not discussed in Bogdanova et al [9]: the cases with higher doses were probably diagnosed averagely earlier, when the pool of neglected cancers was still untapped.…”

“…Accordingly, there was a pool of undiagnosed TC prior to the accident. The percentage of more advanced cancers was negatively associated with the time between the accident and surgery [8][9][10] probably due to the gradual exhaustion by the screening of the pool of advanced cancers. Morphologically, TC in patients from contaminated territories were more aggressive than usual [11][12][13][14].…”

“…Correlations between radiation doses to the thyroid, tumor invasiveness and "aggressive solid-follicular" pattern were reported [9,10]. However, the time factor was not discussed in Bogdanova et al [9]: the cases with higher doses were probably diagnosed averagely earlier, when the pool of neglected cancers was still untapped. Accordingly, a weak negative correlation (Spearman's r = -0.12, P=0.15) between the "latency" (time from exposure to surgery) and thyroid dose was found in Zablotska et al [10].…”