Follicular variant of papillary thyroid cancer: encapsulated, nonencapsulated, and diffuse: distinct biologic and clinical entities

Arch Otolaryngol Head Neck Surg. 2012 Mar;138(3):227-33. doi: 10.1001/archoto.2011.1466.


Objective: To examine genotypic and clinical differences between encapsulated, nonencapsulated, and diffuse follicular variant of papillary thyroid carcinoma (EFVPTC, NFVPTC, and diffuse FVPTC, respectively), to characterize the entities and identify predictors of their behavior.

Design: Retrospective medical chart review and molecular analysis.

Setting: Referral center of a university hospital.

Patients: The pathologic characteristics of 484 consecutive patients with differentiated thyroid cancer who underwent surgery by the 3 members of the New York University Endocrine Surgery Associates from January 1, 2007, to August 1, 2010, were reviewed. Forty-five patients with FVPTC and in whom at least 1 central compartment lymph node was removed were included.

Main outcome measures: Patients with FVPTC were compared in terms of age, sex, tumor size, encapsulation, extrathyroid extension, vascular invasion, central nodal metastases, and the presence or absence of mutations in BRAF, H-RAS 12/13, K-RAS 12/13, N-RAS 12/13, H-RAS 61, K-RAS 61, N-RAS 61, and RET/PTC1.

Results: No patient with EFVPTC had central lymph node metastasis, and in this group, 1 patient (4.5%) had a BRAF V600E mutation and 2 patients (9%) had RAS mutations. Of the patients with NFVPTC, none had central lymph node metastasis (P > .99) and 2 (11%) had a BRAF V600E mutation (P = .59). Of the patients with diffuse FVPTC, all had central lymph node metastasis (P < .001), and 2 (50%) had a BRAF V600E mutation (P = .06).

Conclusions: FVPTC consists of several distinct subtypes. Diffuse FVPTC seems to present and behave in a more aggressive fashion. It has a higher rate of central nodal metastasis and BRAF V600E mutation in comparison with EFVPTC and NFVPTC. Both EFVPTC and NFVPTC behave in a similar fashion. The diffuse infiltrative pattern and not just presence or absence of encapsulation seems to determine the tumor phenotype. Understanding the different subtypes of FVPTC will help guide appropriate treatment strategies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Carcinoma, Papillary, Follicular / genetics*
  • Carcinoma, Papillary, Follicular / pathology*
  • DNA Mutational Analysis
  • Female
  • Genes, ras / genetics*
  • Genotype
  • Humans
  • Lymph Node Excision
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Proto-Oncogene Proteins B-raf / genetics*
  • Retrospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / pathology*


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