远处转移性甲状腺乳头状癌分子病理特征

Genetic pathological features of papillary thyroid carcinoma with distant metastasis

远处转移性甲状腺乳头状癌(DM-PTC)是一种预后相对较差的疾病,严重影响病人的生存质量。这类肿瘤涵盖多种亚型,包括浸润性滤泡型、高细胞型、柱状细胞型、靴钉型、实体型和弥漫性硬化型。研究结果表明,儿童经典型和滤泡亚型甲状腺乳头状癌(PTC)的远处转移发生率远高于成人。在分子层面,这种肿瘤主要涉及22q缺失、BRAF、RAS突变或少数基因融合,常见的融合基因包括RET或NTRK3,且常伴有TERT启动子和(或)TP53基因的复合性改变。研究结果显示,远处转移性甲状腺乳头状癌的发病机制与多种分子标记物相关,其中TERT启动子突变、BRAFV600E基因突变和RAS突变是最常见的分子事件。这些分子标记物与病程的侵袭性和远处转移能力密切相关,尤其是TERT启动子突变,它通常与病程的严重性和较差的预后关联。此外,BRAFV600E突变与颈部淋巴结转移和局部复发的高发生率相关,而RAS突变的肿瘤则容易发生血管侵犯,并且对放射性碘治疗保持反应性。远处转移性甲状腺乳头状癌病人的主要死亡原因包括肺、骨和肝脏的转移,其中肺转移的病人相对有较高的5年生存率,而骨和肝脏转移的病人生存率则明显降低。这些临床特征突显了准确诊断和分型的重要性,以及基于疾病特点制定个性化治疗策略的必要性。因此,了解远处转移性甲状腺乳头状癌的分子病理特征对于优化治疗方案、改善病人预后具有重要意义。分子检测不仅有助于疾病的早期诊断和风险评估,还可指导针对特定分子标记物的靶向治疗,进一步推动精准医学在甲状腺癌治疗中的应用。

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.