Aggressiveness of papillary thyroid carcinoma: a comprehensive analysis from molecular mechanisms to clinical applications

Papillary thyroid carcinoma (PTC) constitutes the predominant subtype among thyroid malignancies. Despite its generally favorable prognosis, certain aggressive subtypes, along with recurrent and metastatic manifestations, substantially affect patient survival outcomes. Recent advancementsin the diagnostic and therapeutic strategies for PTC have ushered in a new era, characterized by the integration of molecular mechanisms and imaging-based evaluations. This review offers an integrated perspective of the clinicopathological features, molecular genetic characteristics, epigenetic regulation, and the contribution of the immune microenvironment to the aggressiveness of PTC. Primary inve stigation targets include BRAF/RAS/RET-related molecular mechanisms and the functional significance of non-coding RNAs [especially long non-coding RNAs (lncRNAs) and microRNAs (miRNAs)] in molecular regulation. Additionally, the impact of clinical factors such as age, sex, obesity, and comorbidity with Hashimoto's thyroiditis on the aggressiveness of PTC is thoroughly examined. Furthermore, this review systematically synthesizes the clinical advances in the early detection and risk assessment of aggressive PTC by emerging imaging modalities such as conventional ultrasound, interventional ultrasound, ultrasound elastography, contrast-enhanced ultrasound, and artificial intelligence-assisted analysis. Looking ahead, multidisciplinary collaborations integrating pathology, genomics, and imaging are anticipated to enhance the precise evaluation of PTC aggressiveness and facilitate the development of individualized treatment strategies. This review serves as a comprehensive reference for mechanistic exploration and clinical translation in the study of PTC aggressiveness, and provides guidance for the progression of precision medicine and management models for PTC patients.