The utility of the Bethesda category and its association with BRAF mutation in the prediction of papillary thyroid cancer stage Augustas Beiša1, Mindaugas Kvietkauskas1, Virgilijus Beiša1, Mindaugas Stoškus2, Elvyra Ostanevičiūtė3, Eugenijus Jasiūnas4, Laimonas Griškevičius2,5, Kęstutis Strupas1 1 Centre of Abdominal Surgery, Vilnius University, Vilnius, Lithuania 2 Centre of Haematology, Oncology and Transfusion Medicine, Vilnius University, Vilnius, Lithuania 3 Centre of Laboratory Medicine, Vilnius University, Vilnius, Lithuania 4 Mykolas Romeris University, Vilnius, Lithuania 5 Centre of Internal, Family Medicine and Oncology, Vilnius University, Vilnius, Lithuania Introduction Approximately 10% of all thyroid cancers have a poor prognosis, making it important to identify clinicopathological factors that could facilitate better prediction of patient prognosis and planning of appropriate treatment. We hypothesized that preoperative determination of the Bethesda category of fine-needle aspiration (FNA) biopsy specimens and its association with BRAF mutation would be an informative for predicting the stage of papillary thyroid cancer (PTC), and it could assist in defining the optimal scope of initial surgical and medical managements for PTC. Figure 1. Flow diagram of study. 308 Patients from AUS/FLUS, FN/SFN, SMC, and PMC groups had a thyroid surgery 176 AUS/FLUS and FN/SFN patients underwent histological examination 132 SMC and PMC patients underwent histological examination 139 Were excluded: 131 Benign lesion 5 Follicular TC 1 Medullary TC 1 Anaplastic TC 1 Lymphoma   26 Were excluded: 14 Benign lesion 6 Follicular TC 5 Medullary TC 1 Anaplastic TC Methods A prospective study analyzed patients who had US suspicious thyroid nodules, underwent FNA and cytological examination, and were classified according to the Bethesda system. Patients from AUS/FLUS, FN/SFN, SMC, and PMC groups were examined for the BRAF mutation and had a thyroid surgery. Demographical, histological features (tumor size, extrathyroidal extension, lymphovascular invasion, lymph nodes metastases, R1 resection, multifocality, and PTC type) and stage of the disease were evaluated for PTC patients in accordance to the Bethesda category and its association with BRAF mutation. 37 Were diagnosed with PTC 106 Were diagnosed with PTC Table 2. Patients diagnosed with PTC demographics and histologic features according to the Bethesda category (n=143).   Bethesda Category Value of P Odds ratio (95% CI) AUS/FLUS and FN/SFN (n=37) SMC and PMC (n=106) Tumor size (cm) 1 (0.3-3.8) 1.5 (0.3-7) 0.028 0.49 (Eta) Extrathyroidal extension (n) 11 (29.7%) 50 (47.2%) 0.065 2.11 (0.95-4.7) Lymph node metastases (n) 5 (13.5%) 44 (41.5%) 0.002 4.54 (1.64-12.58) PTC stage (n) I-II III-IVA 30 (81.1%) 7 (18.9%) 58 (54.7%) 48 (45.3%) 0.005 3.55 (1.43-8.79) Results Three hundred eight of all patients underwent operation. One hundred forty-three (46.4%) of them were diagnosed with PTC (Figure 1). In 14 (9.8%) PTC cases, FNA biopsies were classified as AUS/FLUS, 23 (16.1%) as FN/SFN, 41 (28.7%) as SMC, and 65 (45.5%) as PMC. I-II stage of PTC was diagnosed for 88 (61.5%) patients and III-IVA for 55 (38.5%). Patients from the SMC and PMC groups had larger tumors, higher incidence of lymph node metastases, classical PTC type, BRAF positive, and III-IVA stage cancer, than patients from the AUS/FLUS and FN/SFN groups (Table 2). When comparing 27 (18.9%) BRAF negative patients from the AUS/FLUS and FN/SFN groups with 116 (81.1%) BRAF negative patients from the SMC and PMC groups and all BRAF positive patients, the prediction of more aggressive histological features and stage was slightly improved (Table 3). Table 3. Patients diagnosed with PTC demographics and histologic features according to association of the Bethesda category and BRAF mutation (n=143).   Groups Value of P Odds ratio (95% CI) AUS/FLUS and FN/SFN with BRAF negative (n=27) AUS/FLUS and FN/SFN with BRAF positive or SMC and PMC with any BRAF (n=116) Tumor size (cm) 0.8 (0.3-3.8) 1.5 (0.3-7) 0.105 0.46 (Eta) Extrathyroidal extension (n) 7 (25.9%) 54 (46.6%) 0.051 2.49 (0.98-6.34) Lymph node metastases (n) 2 (7.4%) 47 (40.5%) 0.001 8.51 (1.92-37.67) PTC stage (n) I-II III-IVA 23 (85.2%) 4 (14.8%) 65 (56%) 51 (44%) 0.005 4.51 (1.47-13.87) Conclusions Higher Bethesda categories are associated with higher stages of PTC. Association of the Bethesda category with BRAF mutation can slightly improve the value of stage prediction. Beiša, A., Kvietkauskas, M., Beiša, V. et al. The utility of the Bethesda category and its association with BRAF mutation in the prediction of papillary thyroid cancer stage. Langenbecks Arch Surg (2017). doi:10.1007/s00423-017-1560-2