Invasion rather than nuclear features correlates with outcome in encapsulated follicular tumors: further evidence for the reclassification of the encapsulated papillary thyroid carcinoma follicular variant

Abstract

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.

Ninety-four cases of encapsulated follicular variant of papillary thyroid carcinoma: A name change to Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features would help prevent overtreatment

“…In this cohort and in identical noninvasive tumors reported in the literature, there was no evidence of metastatic disease (structural or biochemical). 12 Follow-up (mean 11.2 years) showed a complete lack of latent or unrecognized disease and no need for prophylactic central lymph node dissection for this tumor type.…”

“…35 Previous studies have concluded that adequate therapy for encapsulated follicular variant of papillary thyroid carcinoma should be a lobectomy [35][36][37] without radioactive iodine. 1,12,14,15,29 Radioactive iodine should be employed only when a clinical benefit can be reasonably expected which cannot be shown for this tumor type, and thus should be avoided.…”

“…The encapsulated follicular variant of papillary thyroid carcinoma, characterized by an encapsulated (sometimes partial) noninvasive tumor with a nearly exclusive follicular pattern, focal to diffuse distribution of characteristic nuclear features of papillary carcinoma, a low risk of lymph node metastases, very low recurrence risk, and a strong association with RAS mutations, 1,[4][5][6][7] has an excellent prognosis. 1,[7][8][9][10][11][12][13][14][15][16][17][18][19][20] Recently, reclassification of this tumor as a non-malignant neoplasm has been proposed by an international group of thyroid gland specialists, using the term Noninvasive Follicular Thyroid Neoplasm With Papillary-Like Nuclear Features (NIFTP). 21 To date, there has not been a large, multi-institutional community practice evaluation of conservative management (surgery only without radioablative iodine or suppression therapy).…”

Noninvasive Follicular Variant of Papillary Thyroid Carcinoma and the Afirma Gene-Expression Classifier

“…Tumors with either capsular penetration or lymphovascular invasion would be designated as an encapsulated FVPTC with invasion. Approximately one third of encapsulated FVPTC are invasive (7)(8)(9)11,15). Encapsulated FVPTCs with invasion metastasize in a manner similar to FTC with distant metastases as opposed to lymph node metastases (8,15,16).…”

“…Approximately one third of encapsulated FVPTC are invasive (7)(8)(9)11,15). Encapsulated FVPTCs with invasion metastasize in a manner similar to FTC with distant metastases as opposed to lymph node metastases (8,15,16). Although rare, these patients can die of their disease (8,15).…”