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

Arch Pathol Lab Med. 2018 Jul;142(7):838-850. doi: 10.5858/arpa.2017-0118-OA. Epub 2018 Mar 27.

Abstract

Context: - Proposed noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTPs), formerly noninvasive encapsulated papillary carcinoma, follicular variant (PTC-FV), is an indolent tumor with follicular growth and frequent RAS mutations.

Objective: - To detect histologic and molecular differences separating NIFTP from follicular adenomas (FAs) and invasive carcinomas, particularly papillary carcinomas with extensive follicular growth (PTC-EFGs) and invasive encapsulated PTC-FV (IE-PTC-FV).

Design: - Sixty-one tumors were reviewed histologically and reclassified into 32 NIFTPs (52%), 4 IE-PTC-FVs (7%), 14 PTC-EFGs (23%), and 11 FAs (18%). Next-generation sequencing for mutations in 50 genes was performed. Clinical outcomes were recorded.

Results: - The NIFTPs and FAs were well circumscribed and unencapsulated. The FAs had bland nuclei, whereas the NIFTPs showed at least 2 of 3 (67%; sufficient) nuclear features (enlargement, irregular contours, chromatin clearing). The IE-PTC-FVs had follicular growth, sufficient nuclear features, and extensive capsular invasion. The PTC-EFGs had a median of 5% papillae with intrathyroidal invasion (broad-based, sclerotic, or small follicle growth patterns); intranuclear pseudoinclusions were present only in PTC-EFGs (9 of 14; 64%). Mutations included RAS in 20 of the 32 NIFTPs (62%), 4 of the 11 FAs (36%), and 3 of the 4 IE-PTC-FVs (75%); BRAF K601E in 1 NIFTP (3%); BRAF V600E in 5 PTC-EFGs (36%). No NIFTPs or FAs recurred or metastasized. All 4 IE-PTC-FVs (100%) had hematogenous metastasis. Two PTC-EFGs (14%) had lymphatic metastasis.

Conclusions: - The morphologic similarity and RAS mutations in FAs, NIFTPs, and IE-PTC-FVs supports the genetic similarity of those follicular neoplasms in contrast to the unique presence of BRAF V600E mutations in PTC-EFGs. Using strict diagnostic criteria supported by molecular testing, tumors with extensive follicular growth can be classified into follicular type or RAS-like (FA, NIFTP, IE-PTC-FV) versus papillary type or BRAF V600E-like (PTC-EFG).

MeSH terms

  • Adenoma / classification*
  • Adenoma / diagnosis
  • Adenoma / genetics
  • Adenoma / pathology
  • Adolescent
  • Adult
  • Aged
  • Carcinoma, Papillary / classification*
  • Carcinoma, Papillary / diagnosis
  • Carcinoma, Papillary / genetics
  • Carcinoma, Papillary / pathology
  • Cell Nucleus / pathology
  • Female
  • Humans
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Mutation
  • Proto-Oncogene Proteins B-raf / genetics
  • Thyroid Cancer, Papillary / classification*
  • Thyroid Cancer, Papillary / diagnostic imaging
  • Thyroid Cancer, Papillary / genetics
  • Thyroid Cancer, Papillary / pathology
  • Thyroid Neoplasms / classification*
  • Thyroid Neoplasms / diagnosis
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / pathology
  • Young Adult
  • ras Proteins / genetics

Substances

  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • ras Proteins