Diagnostics
Hashimoto Thyroiditis Modifies the Association Between Nuclear Atypia and Malignancy in Bethesda III Thyroid Nodules
By Adem Şentürk, Yusuf Öztürk, Emre Gönüllü and 5 others.
Abstract
Background
Nuclear atypia is associated with an increased risk of malignancy in Bethesda III thyroid nodules; however, reactive nuclear changes related to Hashimoto thyroiditis (HT) may complicate its interpretation. We investigated whether HT modifies the association between nuclear atypia and malignancy in Bethesda III nodules.
Methods
This retrospective single-center study included 426 surgically selected patients with Bethesda III nodules who underwent thyroidectomy between January 2015 and August 2026. HT was defined by postoperative histopathology. The association between nuclear atypia and malignancy was evaluated according to HT status. Effect modification was assessed using an HT × nuclear atypia interaction term in unadjusted and multivariable logistic regression models.
Results
HT was present in 199 (46.7%) patients. Malignancy was less frequent in patients with HT than in those without HT (26.1% vs. 38.8%, p = 0.006), whereas nuclear atypia was more frequent (91.0% vs. 45.8%, p < 0.001). In patients without HT, nuclear atypia was strongly associated with malignancy and remained an independent predictor after multivariable adjustment (adjusted OR 13.24, 95% CI 5.46–32.10; p < 0.001). In patients with HT, nuclear atypia was not associated with malignancy (OR 0.68, 95% CI 0.24–1.94; p = 0.466). The HT × nuclear atypia interaction was significant in both unadjusted (OR 0.040, p < 0.001) and adjusted models (OR 0.031, p < 0.001).