Hashimoto's Thyroiditis Shows Sex- and Age-Dependent Inverse Associations with Papillary Thyroid Carcinoma Progression: A Propensity Score-Matched Analysis of 6963 Surgical Cases.

Introduction: The coexistence of papillary thyroid carcinoma (PTC) and Hashimoto's thyroiditis (HT) presents a clinically significant yet controversial association in endocrine pathology. This study aimed to systematically evaluate the potential inverse associations between HT and PTC progression through comprehensive clinicopathological analysis.

Methods: We conducted a retrospective cohort study of 6963 surgical PTC patients treated at our tertiary referral center between 2009 and 2023. Using propensity score matching to control for baseline confounders, we performed Chi-square tests and logistic regression analyses adjusted for key pathological parameters.

Results: Overall, 6963 patients were included in this study. Analysis revealed that male patients with PTC had a lower risk of concurrent HT (odds ratio [OR] 0.29, p < 0.001) and HT-positive patients were significantly younger than their HT-negative counterparts (p = 0.02). Propensity score-matched analysis demonstrated that HT served as a protective factor against lymph node metastasis (OR 0.802, p < 0.001), tumor capsular invasion (OR 0.86, p = 0.004), and BRAF V600E mutation (OR 0.579, p = 0.039). In subgroup analyses, the association between HT and PTC was exclusively observed in female patients, with its correlation with reduced lymph node metastasis primarily seen in the <55 years age group, while the inverse association with capsular invasion was more pronounced in the ≥55 years age group.

Conclusion: These findings suggest potential sex- and age-dependent associations between HT and less aggressive PTC characteristics, with the strongest correlations observed for reduced metastatic tendency in younger women and decreased local invasion in older patients. The observed BRAF mutation modulation suggests potential immune-mediated tumor microenvironment alterations warranting further molecular investigation.