Summary The prognosis of the encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) and its relationship to encapsulated follicular carcinoma (EFC) and follicular adenoma (FA) is subject to controversy. All EFVPTCs, EFCs, and FAs identified at a single institution between 1981 and 2003 were analyzed microscopically. A cohort of FAs from a different hospital was also examined. EFVPTCs were subdivided into noninvasive EFVPTC (NIEFVPTC) and invasive EFVPTC (IEFVPTC) displaying capsular/vascular invasion. There were 83 EFVPTCs (57 noninvasive, 26 invasive), 14 EFCs, and 52 FAs. Similar to FA, over a median follow-up of 9.5 years, none of the NIEFVPTCs manifested lymph node metastasis (LNM) or recurred. Furthermore, with a median follow-up of 10.5 years, none of 39 NIEFVPTCs without radioactive iodine therapy recurred. Four (15%) of 26 IEFVPTCs and none of 14 EFCs harbored distant metastasis (P = .29). There was no difference in LNM rate and degree of vascular or capsular invasion between IEFVPTC and EFC (P > .1). All 4 IEFVPTCs with adverse behavior presented with distant metastasis and no LNM. Sixteen percent of IEFVPTCs had poor outcome, whereas there was none in the NIEFVPTCs (P = .007). In conclusion, NIEFVPTC seems to behave similarly to FA, whereas IEFVPTC can metastasize and spread like EFC. Thus, invasion rather than nuclear features drives outcome in encapsulated follicular tumors. Non-IEFVPTC could be treated in a conservative manner sparing patients unnecessary total thyroidectomy and radioactive iodine therapy. The position of the EFVPTC in the classification of thyroid neoplasia should be reconsidered.

Factors that should be considered when studying the effect of dietary iodine in the development of thyroid cancer include pathological criteria, diagnostic techniques, screening programs, radioactive fallout, and standard of medical care in the studied population. In most surveys, papillary carcinoma forms the largest group of thyroid malignancies, both before and after iodine prophylaxis where an increase in the papillary:follicular carcinoma ratio is also noted. Undifferentiated carcinomas decrease after salt prophylaxis. In Salta, Argentina, the increasing incidence of clinically significant papillary thyroid cancer and the decrease of undifferentiated carcinoma after iodine prophylaxis are probably due to better access to health centers and consequent earlier detection of differentiated precursor tumors. Autoimmune focal and diffuse or Hashimoto's thyroiditis are linked to dietary iodine. Pathological studies made in different regions indicate that these types of thyroiditis occur more frequently in areas of iodine sufficiency than in areas of iodine deficiency, and increase after iodine prophylaxis both in non-goitrous and iodine-deficient areas like Salta, Argentina. An increase of lymphocytic thyroiditis could be linked to an increased incidence of primary thyroid lymphoma, and thyroiditis is more commonly associated with papillary carcinoma than with other types of thyroid follicular or C-cell derived carcinomas regardless of iodine intake.

This study was conducted to investigate the natural history of undifferentiated thyroid carcinoma (UTC) in the iodine-deficient province of Salta, Argentina, in relation to salt iodization and health care standards. Five hundred ninety-three thyroid cancers diagnosed from 1958 to2012 were reviewed based mainly on the WHO classification and grouped into three periods, one before and two after iodine prophylaxis. The incidence of UTC was analyzed in relation to changing concentrations of potassium iodide (KI) in salt during the prophylaxis period (from 40 to 33.3 mg KI/kg salt), establishment of primary health care centers throughout the region, and use of fine needle aspiration (FNA) cytology. Twenty-nine UTCs were found in the whole series. The frequency of UTC decreased from 15.2 % (9/59 cases) in the first period to 2.6 % (10/381 cases) well after salt iodination (x (2) Fisher's test, p < 0.0002), and the incidence from 1.4/10(6)/year to 0.1/10(6)/year (Student's t test, p < 0.06), respectively. The decline of UTC after iodine prophylaxis occurred even after decreasing concentrations of KI in salt and timely coincided with the establishment of primary health care centers throughout the region and routine use of FNA. The lower rate of UTC after iodine prophylaxis in the province of Salta is mostly related to earlier detection of more differentiated thyroid tumors rather than higher salt iodization.