Papillary Thyroid Carcinoma With Prominent Hobnail Features: A New Aggressive Variant of Moderately Differentiated Papillary Carcinoma. A Clinicopathologic, Immunohistochemical, and Molecular Study of Eight Cases

Abstract

Papillary thyroid carcinomas (PTC) are the most common thyroid tumors that usually have a good prognosis. Recurrence, metastases, and cancer death may occur in a few patients and are more commonly associated with more aggressive tumors, such as tall cell, columnar cell, or diffuse sclerosing variants of the PTC. We present the clinicopathologic, immunohistochemical, and molecular features of a rare aggressive variant of the PTC showing prominent hobnail features. The patients included 6 females and 2 males. Ages ranged from 28 to 78 years (mean 57.6). Patients presented with a neck mass and cervical lymphadenopathy. Tumor size ranged from 1.0 cm to 4.0 cm (mean 2.5 cm). The tumors were usually multifocal with variably sized complex papillary structures lined by cells with increased nuclear/cytoplasmatic ratios and apically placed nuclei that produced a surface bulge (hobnail appearance). Thyroglobulin, TTF-1, HBME-1, and p53 were positive in all cases, and there was membrane staining for beta-catenin and E-cadherin. The proliferative index with Ki67 ranged from 2% to 20% with a mean of 10%. BRAF mutation was present in 4/7 (57.1%) cases. Distant metastases to liver, lung, bone, brain, muscle, and pancreas developed in 5 patients. The average follow-up time was 77.2 months. Four patients died of disease after a mean of 42.8 months. Two patients are alive with disease after 4 and 87 months, respectively. Two patients are alive without disease after 120 and 236 months. PTC with a prominent hobnail pattern is a moderately differentiated PTC variant with aggressive clinical behavior and significant mortality.