Comparative Histopathologic Analysis of "Radiogenic" and "Sporadic" Papillary Thyroid Carcinoma: Patients Born Before and After the Chernobyl Accident.

BACKGROUND: The issue of whether radiation-induced thyroid cancer is pathologically different from sporadic remains not fully answered. This study compared structural characteristics and invasive features of papillary thyroid carcinoma (PTC) in two age-matched groups: patients who were children (≤4 years old) at the time of the Chernobyl accident and who lived in three regions of Ukraine most contaminated by radioactive iodine 131I ("radiogenic" cancer), and those who lived in the same regions but who were born after 1987 and were not exposed to 131I ("sporadic" cancer). Further, the histopathologic features of PTC were analyzed in relation to age and individual 131I thyroid dose. METHODS: The study included 301 radiogenic and 194 sporadic PTCs. According to age at surgery, patients were subdivided into children (≤14 years old), adolescents (15-18 years old), and adults (19-28 years old). Statistical analyses included univariate tests and multivariable logistic regression within and across the age subgroups. Analyses of morphological features related to 131I doses were conducted among exposed patients on categorical and continuous scales controlling for sex and age. RESULTS: Among children, radiogenic PTC displayed a significantly higher frequency of tumors with a dominant solid growth pattern, intrathyroidal spread, extrathyroidal extension, lymphatic/vascular invasion, and distant metastases. Exposed adolescents more frequently displayed extrathyroidal extension, lymphatic/vascular invasion, and distant metastases. Exposed adults more frequently had intrathyroidal spread and extrathyroidal extension. The frequency of PTC with dominant papillary pattern and oxyphilic cell metaplasia was significantly lower in radiogenic compared to sporadic tumors for all age groups. Manifestations of tumor aggressiveness were most frequent in children compared to adolescents and adults regardless of etiology. CONCLUSIONS: Radiogenic PTC is less likely to demonstrate a dominant papillary growth pattern and more likely to display more aggressive tumor behavior than sporadic PTC. Histopathologic tumor aggressiveness declines with patient age in both radiogenic and sporadic cases.

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

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.