{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T05:41:40Z","timestamp":1774849300426,"version":"3.50.1"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Thyroid nodules with high-suspicion ultrasound features but benign cytologic findings remain a diagnostic challenge due to potential false-negative fine-needle aspiration (FNA) results. The BRAFV600E mutation, a hallmark of papillary thyroid carcinoma (PTC), may improve malignancy risk stratification. This study prospectively evaluated the diagnostic performance of BRAFV600E mutation testing in ultrasound-high-suspicion thyroid nodules with non-malignant cytology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A prospective observational study was conducted at the China\u2013Japan Union Hospital of Jilin University between January 2019 and July 2024, enrolling 562 ultrasound-high-suspicion thyroid nodules with non-malignant or indeterminate cytology (Bethesda II\u2013III). Preoperative BRAFV600E analysis was performed using PCR-based methods, and all nodules subsequently underwent surgical excision with definitive histopathology. Associations between mutation status, sonographic patterns, and final diagnoses were assessed through univariate and multivariable logistic regression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 562 nodules, 280 (49.8%) harbored the BRAFV600E mutation. Final pathology confirmed 390 PTCs (69.4%) and 172 benign lesions (30.6%). The BRAFV600E mutation was strongly associated with malignancy (66.2% vs. 12.8%, P\u00a0&amp;lt; 0.001). On multivariable analysis, BRAFV600E positivity independently predicted PTC (OR = 10.36, 95% CI = 6.18\u201317.35, P &amp;lt; 0.001). The test showed a sensitivity of 66.2%, specificity of 87.2%, positive predictive value of 92.1%, and overall accuracy of 72.6%.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>BRAFV600E mutation testing is a valuable molecular tool for evaluating high-suspicion thyroid nodules with cytologically benign or indeterminate findings. Its strong predictive value enables earlier identification of papillary thyroid carcinoma (PTC), but results should always be interpreted alongside clinicopathologic and imaging assessments to guide optimal diagnostic decisions. In this highly selected cohort, BRAFV600E testing added diagnostic value beyond high-suspicion ultrasound features, improving the distinction between true malignancy and benign mimics in a population with a 69.4% baseline cancer prevalence.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1803314","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T04:10:11Z","timestamp":1774843811000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["When cytology misses and ultrasound warns: the predictive role of BRAFV600E mutation in thyroid nodules"],"prefix":"10.3389","volume":"17","author":[{"given":"Liu","family":"Jie","sequence":"first","affiliation":[{"name":"Department of Thyroid Surgery, China-Japan Union Hospital of Jilin University, Jilin Provincial Key Laboratory of Thyroid Disease, Jilin Provincial Engineering Laboratory of Thyroid Disease Prevention and 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