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Historically, practice guidelines and various medical resources have combined follicular thyroid cancer (FTC) with papillary thyroid cancer (PTC) as if they were a single entity of “well-differentiated thyroid cancer.” Although they are derived from the same cell of origin, they are each driven by distinct genetic alterations which result in unique clinical characteristics. There are important differences in the diagnostic workup, cancer management, and prognosis between FTC and PTC. Future guidelines and studies should separate them as distinct clinical entities.

FTC can be stratified into low-risk, minimally invasive follicular thyroid carcinoma (MIFTC) and high-risk, widely invasive follicular thyroid carcinoma (WIFTC).1 MIFTC is characterized histologically by microscopic penetration of the tumor capsule without vascular invasion, and behaves similarly to benign follicular adenomas. Disease recurrence is extremely rare after complete surgical resection of MIFTC. In contrast, WIFTC is associated with a substantial risk of both local recurrence and hematogenous metastases. Controversies in the optimal management of FTC exist due to the lack of randomized controlled studies. Treatment of FTC should be based on individual risk assessment.


The overall incidence of thyroid cancer has increased in recent decades. This is a result of both increased detection and a true increase in disease incidence. FTC is the second most common subtype of thyroid carcinoma following PTC, and comprises approximately 10% of all thyroid cancers. FTC is more common in women than in men, with an approximate 3 to 1 ratio, although this varies depending on region. In Japan, the female to male ratio of FTC is as high as 13 to 1. FTC has a peak age of onset between 40 and 60 years old. In comparison, PTC has a peak age of onset between 30 and 50 years old.

Environmental factors may play a role in FTC development. FTC is more common in regions of iodine deficiency. Childhood exposure to ionizing radiation, whether therapeutic or environmental, is associated with an increased risk of both FTC and PTC. Lastly, both FTC and PTC are linked to genetic mutations.


Although specific genetic alterations have been observed in FTC, the genetic basis of oncogenesis remains poorly understood. RAS mutations are found in 40% to 50% of FTC, however up to a third of follicular adenomas also have RAS mutations. There is some evidence suggesting that follicular adenomas harboring RAS mutations may actually be precursors of FTC.2

In addition to RAS mutations, the PAX8/PPARϒ chromosomal rearrangement can be found in up to 30% of patients with FTC. Similar to RAS, the PAX8/PPARϒ rearrangement is not specific for FTC, as it is also found in a small percentage of follicular adenomas. RAS mutations and the PAX8/PPARϒ rearrangement are non-overlapping in FTC. RAS mutations or the PAX8/PPARϒ rearrangement are found in up to 70% of FTCs.


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