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Papillary Thyroid Carcinomas with Tall Cell Features: An Intermediate Entity Between Classic and Tall Cell Subtypes
Athanasios Bikas1, Kristine Wong2, Theodora Pappa1
1Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Summary
Papillary thyroid carcinomas with tall cell features (PTCtcf) represent an intermediate risk between classic PTC and tall cell PTC (tcPTC). This study clarifies their distinct clinicopathologic and genomic profiles, aiding in risk stratification.
Area of Science:
- Endocrinology
- Oncology
- Genomics
Background:
- Papillary thyroid carcinomas (PTCs) exhibit diverse subtypes, including classic PTC, tall cell PTC (tcPTC), and PTC with intermediate tall cell features (PTCtcf).
- The distinct clinicopathologic and genomic characteristics of PTCtcf relative to classic PTC and tcPTC require further elucidation for accurate risk assessment.
Purpose of the Study:
- To conduct an integrated clinicopathologic and genomic analysis comparing tcPTC, PTCtcf, and classic PTC.
- To define the spectrum of disease-specific risk and genomic drivers across these PTC subtypes.
Main Methods:
- Retrospective analysis of 292 patients with tcPTC, PTCtcf, and classic PTC (2005-2020).
- Comparison of clinicopathologic variables including AJCC stage, extrathyroidal extension, progression-free survival (PFS), and a composite adverse outcome.
- Targeted next-generation sequencing in a subset to analyze genomic alterations, focusing on TERT promoter mutations.
Main Results:
- PTCtcf exhibited an intermediate profile in advanced AJCC stage (8% vs. 13% tcPTC vs. 1% classic) and macroscopic extrathyroidal extension (14% vs. 38% tcPTC vs. 12% classic).
- Five-year PFS rates were 76.5% (tcPTC), 81.5% (PTCtcf), and 88.3% (classic PTC). The composite adverse outcome was significantly higher in tcPTC (40.2%) and PTCtcf (20.7%) compared to classic PTC (11.2%).
- Multivariable analysis identified tcPTC as an independent predictor of adverse outcomes (HR 4.3). tcPTC showed significantly higher TERT promoter mutations (44%) than PTCtcf (6%).
Conclusions:
- PTCtcf represents an intermediate entity in terms of clinicopathologic features and outcomes between tcPTC and classic PTC.
- These findings refine risk stratification for papillary thyroid carcinoma at presentation.
- The study highlights the genomic diversity among PTC subtypes, with TERT mutations being more prevalent in tcPTC.
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