Molecular Features of Follicular Variant Papillary Carcinoma of Thyroid: Comparison of Areas With or Without Classical Nuclear Features

Abstract

We aimed to compare the genetic background of different areas in follicular variant papillary thyroid carcinomas (FVPTC) with or without classical nuclear changes. Sixteen cases of FVPTC were included in our study. All tumors were well demarcated from surrounding thyroid tissue and had both areas with nuclear features (WNF) and areas without nuclear features (WONF) of papillary carcinoma. DNA is obtained by laser microdissection from WNF and WONF areas of each case. Point mutations for NRAS codon 61, HRAS codon 61, and BRAF were investigated by direct sequencing. In 11 cases, reverse transcription PCR was performed for the presence of PAX8-PPARɣ and RET/PTC1-3 gene rearrangements. Point mutation for NRAS codon 61 was also studied in 15 colloidal nodules. Seven cases (44 %) showed at least one mutation; two cases (13 %) revealed the same mutation in both WNF and WONF areas, while in the rest only WNF areas were mutated. None of the studied 11 cases demonstrated RET/PTC1-3 gene rearrangement and in only one case PAX8-PPARɣ gene rearrangement was found. Six cases (38 %) showed NRAS codon 61 mutation, involving only WNF areas in five cases and both WNF and WONF areas in one case. Neither HRAS codon 61 nor BRAF mutations were present. Fifteen colloidal nodules were also wild type for NRAS codon 61. Our findings suggest that NRAS codon 61 point mutations and PAX8-PPARɣ gene rearrangement play a role in the FVPTC pathogenesis and may be established before the morphological/phenotypical features fully develop.

Noninvasive Follicular Thyroid Neoplasms With Papillary-like Nuclear Features Are Genetically and Biologically Similar to Adenomatous Nodules and Distinct From Papillary Thyroid Carcinomas With Extensive Follicular Growth

“…13,36 In addition, although the number of NIFTPs we were able to test was relatively moderate (32), our numbers were slightly more or similar to other studies. 4,5,9,11 Our numbers were limited primarily by the relative rarity of PTC-FV and occasionally by difficulty in isolating quality DNA from thyroid tumors (7 PTC-FV), which were, therefore, excluded from this study. The number of IE-PTC-FVs tested was particularly limited (n ¼ 4) likely because of its even greater rarity, as well as by the design of our study (in which we did not search for FTCs with possible nuclear atypia).…”

“…Our findings coincide with those reported regarding the behavior and genetics of noninvasive, encapsulated PTC-FV (NIFTP) versus infiltrative PTC (PTC-EFG). 1,[4][5][6]9,11,12 Some authors suggest that encapsulated, noninvasive PTC-FVs (NIFTPs), because of their expected benign behavior, are best thought of as FAs with papillary-like nuclear features or atypia. 2,52 In this context, we contribute to the expanding body of knowledge by demonstrating histologic, genetic, and behavioral similarity of NIFTPs to benign FAs (never, to our knowledge compared in the same study before), and histologic, genetic, and behavioral similarity of IE-PTC-FV to FTC.…”

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

“…However, if at least three HPFs within a 3-mm linear area of tumor (diameter measure) showed these features, then the entire encapsulated nodule was diagnosed as an encapsulated follicular variant of papillary thyroid carcinoma, a convention used by others. 24,25 Other thyroid gland diseases were noted: adenomatoid nodules (78%) and chronic lymphocytic thyroiditis (42%). Parathyroid gland tissue was detected in 25%, confirming inadvertent removal is common.…”

Application of molecular pathology in endocrine pathology

“…younger age at presentation, smaller size, and more frequent vascular invasion. A small portion of follicular adenomas and follicular variant PTC also show this rearrangement (27,28). Furthermore, it has been reported that follicular adenomas showing this rearrangement demonstrate similar immunohistochemical profile with their malignant counterparts, which indicates that these lesions are probably early lesions of FTCs (29).…”