Thyroid Growth and Cancer

Abstract

It is proposed that most papillary thyroid cancers originate in infancy and childhood, based on the early rise in sporadic thyroid carcinoma incidence, the pattern of radiation-induced risk (highest in those exposed as infants), and the high prevalence of sporadic papillary thyroid cancers in children and adolescents (ultrasound screening after the Fukushima accident). The early origin can be linked to the growth pattern of follicular cells, with a high mitotic rate in infancy falling to very low replacement levels in adult life. The cell of origin of thyroid cancers, the differentiated follicular cell, has a limited growth potential. Unlike cancers originating in stem cells, loss of the usually tight link between differentiation and replicative senescence is required for immortalisation. It is suggested that this loss distinguishes larger clinically significant papillary thyroid cancers from micro-papillary thyroid cancers of little clinical significance. Papillary carcinogenesis can then be divided into 3 stages: (1) initiation, the first mutation in the carcinogenic cascade, for radiation-induced papillary thyroid cancers usually a RET rearrangement, (2) progression, acquisition of the additional mutations needed for low-grade malignancy, and (3) escape, further mutations giving immortality and a higher net growth rate. Most papillary thyroid cancers will not have achieved full immortality by adulthood, and remain as so-called micro-carcinomas with a very low growth rate. The use of the term ‘cancer' to describe micro-papillary thyroid cancers in older patients encourages overtreatment and alarms patients. Invasive papillary thyroid tumours show a spectrum of malignancy, which at its lowest poses no threat to life. The treatment protocols and nomenclature for small papillary carcinomas need to be reconsidered in the light of the new evidence available, the continuing discovery of smaller lesions, and the model of thyroid carcinogenesis proposed.

Natural history of thyroid cancer [Review]

“…1B) [18]. The origin of thyroid cancer is the thyrocyte, as also proposed in the late-onset multi-step carcinogenesis model.…”

Development of the thyroid gland

“…The scattered distribution of these cells is suggestive of a putative stem cell niche. However, although the adult thyroid contains a population of cells with stem properties that appears to be activated upon tissue regeneration after partial thyroidectomy (Hoshi et al, 2007;Okamoto et al, 2013), a stem cell concept for the thyroid gland is controversial given the very slow replacement of individual follicular cells; indeed, the expected turnover of adult thyrocytes is more than 8 years (Coclet et al, 1989), in contrast to the high mitotic rate of thyroid cells in fetal life and infancy (Williams, 2015).…”

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

“…Introduction of ultrasound and fine needle aspiration (FNA), coupled with superficial location of the thyroid gland, resulted in detection of large numbers of thyroid nodules, while "radiation phobia" [5], suboptimal quality of specimens and insufficient experience with pediatric material [6] contributed to occasional overdiagnosis of malignancy. Availability of children at schools and kindergartens for the mass screening explains for the TC incidence increase predominantly in this age group and also for differences compared to the Fukushima accident in Japan [2], where screening intensity has probably been less dependent on the age. The Fukushima Prefecture program was set up to screen everyone under the age of 19 at the time of the accident.…”

“…After CA the risk was greatest in those who were infants at the time of the accident, falling rapidly with increasing age. None of the Fukushima TC cases had been infants at the time of the accident, the majority being adolescents [2].…”

“…Early reports of a TC increase after the CA were doubted as radioiodine was thought to have low or absent carcinogenicity in humans [2]. High incidence and the short latent period were deemed unusual; the number of TC in children and adolescents exposed to radiation has been higher than expected on the basis of previous knowledge [1,3].…”