Follicular variant of papillary thyroid carcinoma (FVPTC): histological features, BRAF V600E mutation, and lymph node status

J Cancer Res Clin Oncol. 2015 Oct;141(10):1749-56. doi: 10.1007/s00432-015-1939-9. Epub 2015 Feb 22.

Abstract

Purpose: Follicular variant of papillary thyroid carcinoma (FVPTC) is currently treated like conventional papillary thyroid carcinoma (cPTC). Recent reports indicate that encapsulated FVPTC behaves like follicular adenomas, while infiltrative FVPTC behaves like cPTC. This raises the possibility that histology and/or mutation status might help personalize management of FVPTC regarding extent of surgery, intensity of follow-up, and targeted therapy. This study correlates histological features, immunoreactivity for CK19, HBME, and Gal, and BRAF V600E mutation with lymph node (LN) metastasis and follow-up in FVPTC.

Methods: Forty-eight FVPTC (21 with regional lymph node metastasis [LN+] and 27 with negative lymph nodes [LN-]) were reviewed. Demographics, tumor focality, size, circumscription, follicular architecture, lymphovascular invasion, extrathyroidal extension (ETE), and margin status were charted. Macrodissected formalin-fixed paraffin-embedded sections from 47 (21 LN+ and 26 LN-) cases were analyzed for BRAF V600E (1799T>A) mutation using real-time PCR. Correlations between the variables and LN status were calculated.

Results: Sixty-two percent of cases with ETE demonstrated LN metastasis, while 59 % of cases with circumscribed tumors were LN-. In multivariable analysis, ETE and tumor size ≥1 cm were the best predictors of LN+ status, whereas in cases without ETE, the infiltrative pattern and tumor size provided the "best fit." Immunostains and BRAF mutation status were not helpful. All four tumors that recurred were LN+, with infiltrative borders, and lacked the BRAF mutation.

Conclusions: Tumor circumscription, extrathyroidal extension, and tumor size ≥ 1.0 cm are predictors of lymph node status in FVPTC.

MeSH terms

  • Adult
  • Aged
  • Carcinoma / genetics*
  • Carcinoma / pathology*
  • Carcinoma, Papillary
  • Carcinoma, Papillary, Follicular / genetics*
  • Carcinoma, Papillary, Follicular / pathology*
  • Female
  • Humans
  • Lymph Nodes / pathology*
  • Lymphatic Metastasis / genetics
  • Lymphatic Metastasis / pathology
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Proto-Oncogene Proteins B-raf / genetics*
  • Thyroid Cancer, Papillary
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / pathology*
  • Young Adult

Substances

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