The Risk Stratification of Papillary Thyroid Cancer With Bethesda Category III (Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance) by Thyroid Fine‐Needle Aspiration Could Be Assisted by Tumor Size for Precision Treatment

Abstract

PurposeTo investigate the clinical characteristics of papillary thyroid cancer (PTC) classified as Bethesda category III [atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS)] by fine-needle aspiration (FNA) for precision treatment.MethodsA total of 1,739 patients diagnosed with Bethesda category III (AUS/FLUS) by FNA were investigated, and 290 patients diagnosed with PTC were analyzed.ResultsThe rate of papillary thyroid microcarcinoma (PTMC) was 82.1% (238/290). The rates of lymph node metastases were 44.9% (22/49) and 25.2% (56/222) for PTC and PTMC, respectively (p = 0.006). The rates of extra-thyroid extension were 46.2% (24/52) and 19.8% (47/237) (p < 0.001). Compared with PTMC, PTC had significantly higher odds ratios (ORs) of 3.41 (1.81–6.44, p < 0.001), 2.19 (1.16–4.13, p = 0.016), and 2.51 (1.29–4.88, p = 0.007) for extra-thyroid extension, multifocality, and lymph node metastases, respectively, after adjustment for age and gender. The larger size and BRAF V600E mutation had a robust synergistic effect for invasive features. The rates of lymph node metastases, multifocality, and extra-thyroid extension were significantly increased with larger sizes harboring BRAF V600E mutation. Compared with PTMC harboring wild type (WT)-BRAF, PTC harboring BRAF V600E mutation had adjusted higher ORs of 3.01 (1.26–8.68, p = 0.015), 3.20 (1.22–8.42, p = 0.018), and 5.62 (2.25–14.01, p < 0.001) for lymph node metastases, multifocality, and extra-thyroid extension, respectively.ConclusionsIn this study, risk stratification was recommended for patients with Bethesda category III (AUS/FLUS) nodules with a size under 1 cm harboring WT-BRAF being regarded as low risk and should be recommended for active surveillance. Nodules with a size over 1 cm harboring WT-BRAF or those under 1 cm harboring BRAF V600E mutation could be regarded as moderate risk, and molecular testing should be recommended. However, those with a size over 1 cm harboring BRAF V600E mutation should be regarded as high risk, and a diagnostic surgery should be recommended.