Serum-based BRAF V600E detection improves early diagnosis of papillary thyroid carcinoma: A prospective diagnostic accuracy study compared with ultrasound-guided cytology

Accurate preoperative diagnosis of papillary thyroid carcinoma (PTC) remains difficult, especially for small thyroid nodules and lesions with indeterminate cytology. This prospective diagnostic study evaluated the clinical value of serum-based v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) V600E mutation detection and its performance in combination with ultrasound-guided fine-needle aspiration cytology (US-FNAC). A total of 145 patients with thyroid nodules classified as TI-RADS 3 to 5 and measuring 3 cm or less were enrolled. All patients underwent US-FNAC and serum BRAF V600E testing using allele-specific quantitative PCR, with postoperative histopathology used as the reference standard. Among the enrolled patients, 64 were diagnosed with PTC and 81 had benign nodules. US-FNAC showed a sensitivity of 68.75% and specificity of 83.95%, while serum BRAF V600E testing showed a sensitivity of 62.50%, specificity of 81.48%, and an area under the curve (AUC) of 0.792. In patients with papillary thyroid microcarcinoma, serum BRAF V600E testing demonstrated higher sensitivity than US-FNAC, 94.12% versus 64.71%, with an AUC of 0.841. However, its diagnostic sensitivity remained limited in poorly differentiated PTC, at 57.14%. A combined model integrating US-FNAC and serum BRAF V600E testing improved diagnostic performance, with a sensitivity of 81.25%, specificity of 85.19%, and AUC of 0.873, significantly outperforming either method alone. These findings suggest that serum BRAF V600E detection is a useful complementary, minimally invasive approach for diagnosing PTC, particularly micro-PTC, and may improve early detection and risk stratification when combined with US-FNAC.