Abstract
Papillary thyroid carcinoma (PTC) with hobnail areas above 30% is classified as hobnail variant (HVPTC). Although it is widely accepted that HVPTC has a worse outcome than classical PTC, it is unclear whether PTC with hobnail features below 30% is as aggressive as HVPTC. We gathered the largest mono-institutional series of PTC with hobnail areas and HVPTC to evaluate differences in terms of pathological features of aggressiveness, molecular profile, and treatment outcome. A total of 99 PTC with hobnail features above 5% were retrospectively selected; 34 of them met the criteria for HVPTC (0.4% of all PTC diagnosed at our institution). All tumors showed high rates of extra-thyroidal extension (40.4%), lymph node metastasis (68.1% of patients with lymphadenectomy), and vascular emboli (49.5%), with no differences according to the 30% cutoff. On the other hand, distant metastases were present in HVPTC only (9.4%). Also, advanced age, advanced disease stage, and TERT promoter mutation were associated with HVPTC. More than half of the patients with follow-up had structural or biochemical persistence after 1 year from surgery. Structural persistence was significantly more common in patients with HVPTC (37.5% vs. 8.7%), while no differences were observed considering structural and biochemical persistence together. The presence of hobnail features identifies locally aggressive tumors, and, consequently, it should be always acknowledged in the pathological report. However, tumors with more than 30% hobnail areas frequently present TERT promoter mutations, advanced disease stage, and structural persistence after radioiodine ablation.
Highlights
Thyroid carcinoma is the most common endocrine malignancy
The hobnail variant of papillary thyroid carcinoma (HVPTC) was firstly described by Kakudo et al in 2004, which noted loss of cell polarity, high nuclear/cytoplasmic ratio, and apical nuclear position that produce a surface bulge and confer the cell a hobnail appearance. The authors attributed these morphologic changes to poor cellular differentiation [5]. This suspicion was confirmed by a case series from the Mayo Clinic in 2010, which further described HVPTC and confirmed an aggressive clinical behavior including higher rates of distant metastases, radioiodine refractoriness, and mortality compared with classical variant Papillary thyroid carcinoma (PTC) (CVPTC) [6]
Since the latest World Health Organization (WHO) classification of endocrine tumors defines HVPTC by the presence of at least 30% of cells with hobnail features [1], it is not clear whether tumors with lower proportions of hobnail areas deserve to be classified as HVPTC
Summary
Thyroid carcinoma is the most common endocrine malignancy. The great majority of them are well-differentiated carcinomas, with papillary thyroid carcinoma (PTC) being the most common histotype [1]. The hobnail variant of papillary thyroid carcinoma (HVPTC) was firstly described by Kakudo et al in 2004, which noted loss of cell polarity, high nuclear/cytoplasmic ratio, and apical nuclear position that produce a surface bulge and confer the cell a hobnail appearance. The authors attributed these morphologic changes to poor cellular differentiation [5]. This suspicion was confirmed by a case series from the Mayo Clinic in 2010, which further described HVPTC and confirmed an aggressive clinical behavior including higher rates of distant metastases, radioiodine refractoriness, and mortality compared with classical variant PTC (CVPTC) [6]. Some authors have reported that patients with PTC presenting 10% to 30% of hobnail features have similar rates of aggressive pathological features and outcome to that of HVPTC patients [9, 12]
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