Williams Dillwyn
Department of Public Health, University of Cambridge, Cambridge, UK.
Eur Thyroid J. 2015 Sep;4(3):164-73. doi: 10.1159/000437263. Epub 2015 Aug 26.
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.
基于散发性甲状腺癌发病率的早期上升、辐射诱发风险模式（婴儿期受辐射者风险最高）以及儿童和青少年中散发性甲状腺癌的高患病率（福岛事故后的超声筛查），有人提出大多数甲状腺乳头状癌起源于婴儿期和儿童期。早期起源可能与滤泡细胞的生长模式有关，婴儿期有丝分裂率高，成年后降至极低的更替水平。甲状腺癌的起源细胞，即分化的滤泡细胞，其生长潜力有限。与起源于干细胞的癌症不同，要实现永生化需要打破通常存在于分化与复制性衰老之间的紧密联系。有人认为，这种打破将具有临床意义的较大甲状腺乳头状癌与临床意义不大的微小甲状腺乳头状癌区分开来。甲状腺乳头状癌的发生可分为三个阶段：（1）起始阶段，致癌级联反应中的首次突变，对于辐射诱发的甲状腺乳头状癌通常是RET重排；（2）进展阶段，获得低度恶性所需的额外突变；（3）逃逸阶段，进一步的突变赋予细胞永生化和更高的净生长率。大多数甲状腺乳头状癌在成年时不会完全实现永生化，仍为所谓的微癌，生长速度非常低。在老年患者中使用“癌症”一词来描述微小甲状腺乳头状癌会导致过度治疗并使患者感到恐慌。侵袭性甲状腺乳头状肿瘤显示出一系列恶性程度，其最低程度对生命不构成威胁。鉴于现有新证据、不断发现更小的病变以及所提出的甲状腺癌发生模型，需要重新考虑小甲状腺乳头状癌的治疗方案和命名。
