Increased diagnostic sensitivity of palpation-guided thyroid nodule fine-needle aspiration cytology by BRAF V600E-mutation analysis

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer and its incidence is increasing. Preoperative diagnosis is warranted in order to avoid two-stage procedures that are associated with additional costs and higher radioactive iodine remnant uptake. In the setting of thyroid cancer, somatic BRAF V600E-mutations are highly specific for PTC and can be analyzed in aspirates from fine-needle aspiration cytology (FNAC). The gold standard to perform FNAC is ultrasound guidance. Here, we analyze whether adding BRAF V600E-mutation analysis could be of value in palpation-guided FNACs. A total of 430 consecutive patients were included. Ultrasound-guided FNACs were performed in 251 patients and 179 patients underwent palpation-guided FNACs. BRAF V600E-mutation analysis was performed using two methods, an allele-specific polymerase chain reaction (PCR) analyzed by capillary gel electrophoresis (PCR/Qiaxcel), and a droplet digital PCR (ddPCR) assay. A total of 80 patients underwent surgery, and histology revealed 25 patients to have PTC. Of the 25 PTCs, 23 (92%) showed a BRAF V600E-mutation. Both mutation analysis methods (PCR/Qiaxcel and ddPCR) produced concordant results. In the ultrasound-guided group, the preoperative diagnostic sensitivity of FNAC using the Bethesda classification alone was very high and additional BRAF V600E-mutation analysis added little to the preoperative diagnostic sensitivity. By contrast, in the palpation-guided group, by adding BRAF V600E-mutation analysis, eight instead of four patients were diagnosed of having PTC. This increase in the diagnostic sensitivity was statistically significant (p < 0.05). The costs per sample were as low as 62 USD (PCR/Qiaxcel and ddPCR) and 35 USD (PCR/Qiaxcel only). Ultrasound-guided FNAC should be aimed for when dealing with thyroid nodules. However, if palpation-guided FNAC cannot be avoided or may be required due to resource utilization, adding BRAF V600E-mutation analysis using the methods described in this study might significantly increase the proportion of preoperatively diagnosed PTCs. The additional costs can be considered very reasonable.Funding Agencies|Medical Research Council of Southeast SwedenUK Research & Innovation (UKRI)Medical Research Council UK (MRC) [FORSS-648671, FORSS-861891]