The Hobnail variant of Papillary Thyroid Carcinoma: Clinical/molecular characteristics of a large monocentric series and comparison with conventional histotypes.

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 with those of conventional papillary thyroid carcinoma (PTC). Methods: From 2010 to 2016, we treated 25 cases of HPTC, characterized clinically and molecularly (BRAF, RAS, TERT promoter and TP53), which were compared with 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, 12% had a mutation on the TERT promoter, 17% had a TP53 mutation (no RAS mutations were found). 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). By comparison with the PTC control group, the HPTC patients had larger tumors (30 mm versus 16 mm, p<0.001), more frequent lymph node involvement (68% versus 38%, p=0.01), and remote disease (16% versus 3%, p<0.0001), a similar prevalence of the BRAFV600E mutations (58% versus 59%), a higher prevalence of TP53 mutations (17% versus 1%, p<0.05) and a worse outcome (structural/biochemical disease: 32% versus 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.