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January 25, 2026Cancers2 citationsOpen Access

Clinical Behavior of Aggressive Variants of Papillary Thyroid Carcinoma: A Retrospective Case–Control Study

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JIJovan IlicNSNikola SlijepčevićUniversity of BelgradeKTKatarina Tausanovic

Key Points

  • The study aims to evaluate the aggressiveness and clinical behavior of rare variants of papillary thyroid carcinoma compared to classic variants.
  • Analyzed 80 patients with rare PTC variants from 2009 to 2019
  • Compared clinicopathological characteristics and survival outcomes to classic PTC
  • Categorized variants into high-risk, intermediate-risk, and low-risk groups
  • Conducted multivariate analysis to identify predictors of recurrence
  • High-risk variants exhibited significantly more aggressive characteristics and worse survival compared to classic variants
  • Intermediate-risk variants showed no significant differences in clinicopathological characteristics or survival outcomes
  • Low-risk variants had excellent survival but were associated with several unfavorable characteristics
  • High-risk variant classification was the only independent predictor of recurrence

Abstract

Background/Objectives: Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. The classic variant (cPTC) is characterized by indolent behavior and excellent prognosis. However, rare subtypes of PTC most often exhibit adverse clinical behavior. The aim of the study was to assess the aggressiveness of rare variants of PTC by analyzing clinicopathological characteristics (CPCs) and survival outcomes. Methods: We analyzed 80 patients with rare PTC variants treated between 2009 and 2019 who were compared with cPTC and matched with a control group for age and tumor size. The variants were categorized into high-risk (HRV: tall cell, diffuse sclerosing, columnar cell, and hobnail variants), intermediate-risk (IRV: solid variant (SV)), and low-risk (LRV: oncocytic (OV) and Warthin-like (WLV)) variants. Different CPCs (capsule and blood vessel invasion, lymphonodal metastases, microscopic and macroscopic extrathyroid extension, multifocal and bilateral presentation) and survival outcomes—overall (OS), disease-specific (DSS), and disease-free survival (DFS) were compared. Results: HRVs exhibited significantly more aggressive CPCs and worse OS, DSS, and DFS compared to cPTC (p < 0.001). IRVs showed no significant difference in CPCs or survival outcomes compared to cPTC. LRVs showed excellent survival but were associated with several unfavorable CPCs. Multivariate analysis identified classification in HRVs as the only independent predictor of recurrence (p = 0.014). Conclusions: Tumors in the HRV group should retain their status as aggressive PTC variants due to unfavorable behavior and poorer prognosis. SVs, despite earlier assumptions, do not exhibit aggressive characteristics. Although the OV and WLV have similar survival to cPTC, their potential for adverse CPCs requires caution.

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Cite This Study

Ilic et al. (2026) studied this question.

synapsesocial.com/papers/6975b36bfeba4585c2d6eef0https://doi.org/10.3390/cancers18020345
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