Influence of Chronic Lymphocytic Thyroiditis and BRAF V600E Mutation on Clinicopathological Features in Papillary Thyroid Carcinoma With Different Tumor Size.

Chronic lymphocytic thyroiditis (CLT) is recognized as the most prevalent inflammatory disorder of the thyroid, while the B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E mutation is the most frequently identified genetic alteration in papillary thyroid carcinoma (PTC). This study aims to explore the relationship between CLT and BRAF V600E mutation and to assess their combined impact on tumor behavior across different tumor sizes. We conducted a retrospective analysis of clinical and pathological data from 1474 patients who underwent surgical treatment for PTC. Univariate and multivariate logistic regression analyses were applied to identify independent factors influencing tumor characteristics. CLT was detected in 27.5% (405/1474) of the PTC cases. Multivariate analysis revealed that CLT was significantly associated with female sex; simultaneously, CLT was significantly negatively associated with BRAF V600E mutation, extrathyroidal extension (ETE), central lymph node metastasis (CLNM), and advanced disease stage (all p < 0.05). The BRAF V600E mutation was observed in 80.7% (1189/1474) of patients. Stratified analysis by tumor size showed that BRAF V600E mutation independently predicted CLT and advanced tumor-node-metastasis (TNM) stage in papillary thyroid microcarcinoma (PTMC); CLT, ETE, and CLNM in tumors 1-2 cm; CLT, ETE, CLNM, and lateral lymph node metastasis (LLNM) in tumors 2-4 cm; and CLT, ETE, vascular invasion, CLNM, and LLNM in tumors >4 cm (all p < 0.05). Notably, PTC patients without CLT but harboring BRAF V600E mutation showed a combined association with advanced TNM stage and aggressive features. The presence of CLT appears to exert a protective effect in PTC. However, the prognostic significance of BRAF V600E mutation varies with tumor size. While CLT-related inflammatory microenvironment may counteract tumor progression in small cancers, it seems insufficient to mitigate the aggressive behavior driven by BRAF V600E mutation in larger tumors.