Clinical and Sonographic Differences between RET Fusion-Positive and BRAFV600E in Papillary Thyroid Carcinoma

Abstract Purpose This study aimed to describe the ultrasound characteristics of papillary thyroid carcinoma (PTC) harboring RET gene fusion and explore its clinical significance. Methods A retrospective study was conducted on 209 patients with PTC diagnosed between Aug 2021 and Jan 2024. All patients underwent ultrasound examination and were confirmed to be positive for RET fusion or BRAFV600E by pathological results. The differences in clinical characteristics and ultrasonography features between the two groups were analyzed. Results Among all PTCs (n=209), we detected 30 RET fusions, and 179 BRAFV600E. RET-fusion PTCs showed younger age (38.5(16.0-69.0) vs. 42.9(20.0-74.0) years, p<.05), larger tumor size (1.09(0.5-4.0) vs. 0.77(0.1-4.0) cm, p<.005), and more advanced N stage (p<.001) than BRAFV600E PTCs. RET-fusion PTCs were mainly classical and diffuse sclerosing subtypes. In terms of ultrasound performance, RET-fusion PTCs were mainly manifested as heterogeneous echogenicity (43.3%), ill-defined tumor margin (90.0%), irregular shape (83.3%) and intranodular microcalcification (83.3%), characterized by scattered microcalcification around the tumor/within thyroid gland (40.0%). In comparison, BRAFV600E PTCs were mainly characterized by hypoechogenicity (95.5%), round/oval shape (80.4%), and intranodular non-calcification (54.2%). Multivariate logistic regression analysis revealed that scattered microcalcification around the tumor/within the normal gland was an independent risk factor for lateral lymph node metastasis (LLNM) in RET-fusion PTCs (OR 9.79, 95% CI, 1.31, 72.93, P=.026). Conclusions Patients diagnosed with PTC harboring RET fusion presented with distinctive clinical characteristics and sonographic patterns, underscoring the unique diagnostic value of ultrasound examination. It can provide a preoperative non-invasive primary screening method for RET-fusion diagnosis, thus facilitating targeted patients with purposeful molecular sequencing to improve treatment outcomes.