APILLARY and follicular (differentiated) thyroid carcinomas are among the most curable cancers. However, some patients are at high risk for recurrent disease or even death. Most of these patients can be identified at the time of diagnosis by using well-established prognostic indicators. The extent of the initial treatment and follow-up care should therefore be tailored to the level of risk. Although treatment guidelines have been published, 1,2 clinical procedures vary considerably among clinicians. 3
EPIDEMIOLOGY
Although thyroid nodules are common, differentiated thyroid carcinomas are relatively rare. Clinically detectable thyroid carcinomas constitute less than 1 percent of all human cancers. The annual incidence rate in various parts of the world ranges from 0.5 to 10 cases per 100,000 population. 4 Papillary and follicular cancers are rare in children and adolescents, and their incidence increases with age in adults. The median age at diagnosis is 45 to 50 years. Thyroid carcinomas are two to four times as frequent in women as in men.
Thyroid microcarcinomas (diameter, ั 1 cm) are found in 5 to 36 percent of adults at autopsy but are rare in children. The reported increase in the incidence of these small carcinomas in recent years can be attributed to an improvement in pathological techniques.
PATHOGENESIS
Oncogenes
Recent advances in molecular biology have improved our understanding of the pathogenesis of thyroid carcinomas. 5 Rearrangements of the tyrosine kinase domains of the RET and TRK genes with the amino-terminal sequence of an unlinked gene are P found in some papillary carcinomas. 6 RET rearrangements are found in 3 to 33 percent of papillary carcinomas unassociated with irradiation [7][8][9] and in 60 to 80 percent of those occurring after irradiation, diagnosed either in children in Belarus exposed to radiation after the nuclear accident in Chernobyl [10][11][12] or in patients who received external radiation treatment in childhood. 13 The frequency of TRK rearrangements is much lower. 8 Activating point mutations of the RAS genes are found with a similarly high frequency in thyroid adenomas and follicular carcinomas, suggesting that RAS mutations represent an early event in thyroid tumorigenesis. 5,14 Activating mutations of the genes encoding the thyrotropin receptor and the a subunit of the stimulatory G (G s ) protein have been reported in some follicular carcinomas. 14,15 Inactivating point mutations of the p53 tumor-suppressor gene are rare in patients with differentiated thyroid carcinomas but common in those with undifferentiated (anaplastic) thyroid carcinomas. 16,17