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.

Keywords: Chernobyl; Fukushima; Papillary microcarcinoma; Thyroid cancer pathogenesis; Thyroid growth.

Fig. 1

The large increase in incidence of thyroid cancer over the last few decades is illustrated by cancer registry data from Japan and the USA. The reasons for the differing patterns of age-related incidence are not known but might be related to stable dietary iodide differences. a Japan from 1975 to 2010 (data from the National Cancer Center Japan [14]). b USA (SEER) from 1991 to 2009.

Fig. 2

Thyroid cancer frequency (percentage distribution) by age at exposure to fallout from Chernobyl and in the first 3 years after Fukushima. The Chernobyl distribution shows the high risk related to a young age at exposure to radiation with a steep fall with increasing age. The Fukushima distribution lacks any increased risk in the youngest, and the increasing incidence with age is similar to the normal increase, suggesting there has been no radiation-related increase in the first 3 years after the accident. The slight rise in those aged over 10 after Chernobyl probably also represents the normal incidence.