The Hobnail Variant of Papillary Thyroid Carcinoma: Clinical/Molecular Characteristics of a Large Monocentric Series and Comparison with Conventional Histotypes

Thyroid. 2018 Jan;28(1):96-103. doi: 10.1089/thy.2017.0248. Epub 2018 Jan 2.

Abstract

Background: The hobnail variant of papillary thyroid carcinoma (HPTC) has an aggressive behavior. The aims of this prospective study were to define the clinical/molecular characteristics of HPTC, and to compare them to those of conventional papillary thyroid carcinoma (PTC).

Methods: From 2010 to 2016, 25 cases of HPTC, characterized clinically and molecularly (BRAF, RAS, TERT promoter, and TP53 mutations), were compared to a series of 165 consecutive cases of PTC. All patients underwent total thyroidectomy and received radioactive iodine treatment. Follow-up was available for 19 HPTC patients.

Results: Among the HPTC patients, 64% had a hobnail component ≥30%, and 64% had multifocal disease. The mean tumor size was 30 mm; 96% of tumors were angio-invasive; 68% were N1, and 12% were M1; 58% harbored the BRAFV600E mutation, 12% had a mutation in the TERT promoter, 17% had a TP53 mutation, and not had a RAS mutation. At a mean follow-up of 39 months, 32% of patients had biochemical and/or structural disease. Tumor size was the only significant difference between patients with persistent disease and those with an excellent response (40 mm and 24 mm, respectively; p = 0.02). Compared to the PTC control group, the HPTC patients had larger tumors (30 mm vs. 16 mm; p < 0.001), more frequent lymph node involvement (68% vs. 38%; p = 0.01), and remote disease (16% vs. 3%; p < 0.0001), a similar prevalence of the BRAFV600E mutation (58% vs. 59%), a higher prevalence of TP53 mutations (17% vs. 1%; p < 0.05), and a worse outcome (structural/biochemical disease: 32% vs. 9%; p < 0.0001).

Conclusions: HPTC is an aggressive variant, characterized by large tumor size, lymph node involvement, a tendency to metastasize, and a worse outcome.

Keywords: aggressive behavior; hobnail variant; molecular; papillary carcinoma; thyroid.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / genetics*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Promoter Regions, Genetic
  • Prospective Studies
  • Proto-Oncogene Proteins B-raf / genetics
  • Telomerase / genetics
  • Thyroid Cancer, Papillary / genetics
  • Thyroid Cancer, Papillary / pathology*
  • Thyroid Cancer, Papillary / surgery
  • Thyroid Neoplasms / genetics
  • Thyroid Neoplasms / pathology*
  • Thyroid Neoplasms / surgery
  • Thyroidectomy
  • Tumor Suppressor Protein p53 / genetics
  • Young Adult
  • ras Proteins / genetics

Substances

  • Biomarkers, Tumor
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • TERT protein, human
  • Telomerase
  • ras Proteins