New and old knowledge on differentiated thyroid cancer epidemiology and risk factors.

Differentiated thyroid cancer (DTC) represents 1-2% of all human malignancies. The annual incidence varies among countries and it is estimated that 1.2-2.6 men and 2.0-3.8 women/100,000 individuals are affected worldwide. This incidence has been increasing in the last decades, likely due to an "over-diagnosis" of small cancers that would have remained occult and that have been likely revealed because of an increased diagnostic scrutiny rather than a real increase of incidence. The annual mortality rate for DTC is 0.5/100,000 both in men and women. DTC is 2-4 times more frequent in females than in males. The mean age at diagnosis is 40-45 yr for papillary tumors (PTC) and 50-55 yr for follicular tumors (FTC). They are very rare in children. Ninety percent of DTC are represented by PTC hystotype, mainly follicular and classical variants. In the last years it has been observed an important change in the oncogenic pattern of PTC with a significant reduction of RET/PTC rearrangements and an increase of BRAFV600E mutation suggesting a change in pathogenic events. The unique well-demonstrated risk factor of DTC is the exposure to external radiation which is also correlated with the presence of RET/PTC rearrangements. Recently, other environmental factors (i.e. living in a volcanic area or in a iodine- either deficient or rich area) or some eating habits leading to obesity have been considered as potential DTC risk factors. However, at present, the favorite hypothesis is that a complex interaction between genetic and environmental factors is required to develop DTC.