关键词: 甲状腺乳头状癌, 远处转移, 分子病理特征, 遗传特征

Abstract: Genetic pathological features of papillary thyroid carcinoma with distant metastasis        LIU Zhi-yan, ZHAO Yi-wei. Department of Pathology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China
Corresponding author:LIU Zhi-yan, E-mail: zhiyanliu@shsmu.edu.cn
Abstract    Distant metastatic papillary thyroid carcinoma (DM-PTC) is a condition with a relatively poor prognosis that significantly impacts patient quality of life. This category of tumors encompasses various subtypes, including infiltrative follicular, tall cell, columnar cell, hobnail, solid, and diffuse sclerosing subtypes. Studies indicate that the rate of distant metastasis in classic and follicular variant pediatric PTC is significantly higher than that in adults. At the molecular level, these tumors primarily involve loss of 22q, BRAF and RAS mutation, or a few gene fusions, commonly including RET or NTRK3, often accompanied by complex changes in the TERT promoter and/or TP53 genes. Research demonstrates that the pathogenesis of distant metastatic papillary thyroid carcinoma is associated with multiple molecular markers, among which TERT promoter mutation, BRAFV600E mutation, and RAS mutation are the most prevalent molecular events. These molecular markers are closely linked to the aggressiveness of the disease course and the capacity for distant metastasis, particularly TERT promoter mutations, which are usually associated with severe disease progression and poorer prognosis. Moreover, BRAFV600E mutations are related to a higher incidence of cervical lymph node metastasis and local recurrence.   In contrast, tumors with RAS mutations tend to exhibit vascular invasion and maintain responsiveness to radioactive iodine treatment. The main causes of death in patients with distant metastatic papillary thyroid carcinoma include metastases to the lungs, bones, and liver, with patients having lung metastases showing relatively higher five-year survival rates, whereas those with bone and liver metastases have significantly reduced survival rates. These clinical characteristics highlight the importance of accurate histological diagnosis and subclassification and the necessity to develop personalized treatment strategies based on disease characteristics. Therefore, understanding the molecular pathological features of distant metastatic papillary thyroid carcinoma is crucial for optimizing treatment plans and improving patient outcomes. Molecular testing not only aids in early diagnosis and risk assessment but also guides targeted therapies specific to certain molecular markers, further advancing the application of precision medicine in treating thyroid cancer.

Key words: papillary thyroid carcinoma, distant metastasis, clinicopathological features, genetic features