波兰儿科分化型甲状腺癌临床表现变化：一项跨越45年的回顾性队列研究

背景：儿童分化型甲状腺癌（DTC）较为罕见；近年来的临床表现尚未完全描述。方法：本研究为一项回顾性队列研究，分析了1970年至2015年在波兰最大儿科DTC转诊中心——格利维采的玛丽亚·斯克沃多娃-居尼研究所（Maria Sklodowska-Curie National Research Institute of Oncology）中接受治疗的连续青少年患者的DEMOGRAPHIC和疾病特征。记录内容包括性别、年龄、组织病理学特征及DTC分期。旨在分析这些变量随时间的变化及其与淋巴结或远处转移的独立风险因素。采用Cochran-Armitage检验和Spearman相关分析趋势。采用多变量逻辑回归分析识别与淋巴结或远处转移相关的风险因素。结果：入选479名患者中的475名（99.2%），其中约一半年龄≥15岁，10%≤10岁。乳头状甲状腺癌（PTC）占88%，滤泡性甲状腺癌（FTC）占11%。≤2 cm的肿瘤占56%，>4 cm的占12%。多发性在37%的病例中观察到，甲状腺外侵犯在22%的病例中发现。淋巴结转移发生在59%，远处转移占16%。观察期内，病例的显著变化趋势包括：青少年≥15岁比例增加；肿瘤≤2 cm的频率增加；多发性率下降；PTC比例上升。甲状腺外侵犯率在1990年后5年子期间始终显著，范围为17%至28%。中央颈淋巴结转移显著增加，但在侧颈部持续常见；远处转移显著减少。多变量分析显示，多发性、甲状腺外侵犯和肿瘤大小与侧颈淋巴结转移显著相关；而多发性、大肿瘤和N1b远处转移也有关。结论：青少年诊断比例上升、原发肿瘤大小减小、多发性和远处转移频率下降，可能反映出早期检测到较少侵袭性的DTC患者。尽管如此，局部晚期疾病特征（多发性、甲状腺外侵犯和淋巴结转移）仍然普遍存在，且多变量分析显示这些特征与侧颈淋巴结及/或远处转移具有显著相关性。

Background: Differentiated thyroid carcinoma (DTC) in children is uncommon; clinical presentation over recent decades is incompletely characterized. Methods: This retrospective cohort study analyzed demographic and disease characteristics of consecutive juveniles with DTC treated from 1970 to 2015 at Poland's largest pediatric DTC referral center, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice, who had available records. Sex, age, histopathological characteristics, and DTC stage were documented. We aimed to identify changes in these variables over time and independent risk factors for lymph node or distant metastases. Trends in these variables were assessed using the Cochran-Armitage test and Spearman correlation. Multivariable logistic regression was performed to identify risk factors associated with lymph node or distant metastases. Results: 475 of 479 patients (99.2%) were included in the analysis; roughly half were age ≥15 years, 10%, <10 years. Papillary thyroid carcinoma (PTC) represented 88% of cases and follicular thyroid carcinoma (FTC) 11%. Tumors ≤2 cm constituted 56% of cases with relevant data; those >4 cm accounted for 12%. Multifocality was observed in 37% and extrathyroidal invasion in 22%. Lymph node metastases were noted in 59% and distant metastases in 16%. Over the observation period, significant trends among new cases included: increased proportion of adolescents >15 years; increased frequency of tumors ≤2 cm, decreased multifocality rates, and increased proportion of PTC versus FTC. Extrathyroidal invasion rates remained appreciable throughout, ranging from 17 to 28% during the 5-year study subperiods after 1990. Lymph node metastases significantly increased in frequency in the central neck, remaining consistently common in lateral sites; presence of distant metastases significantly decreased. In multivariable analysis, multifocality, extrathyroidal invasion, and tumor size were independently associated with lateral lymph node metastases and multifocality, larger tumor size, and N1b metastases with distant spread. Conclusions: Our observations of a rising proportion of diagnoses in adolescence, reductions in primary tumor size, and decreased frequency of multifocality and distant metastases may reflect increased detection of patients with less aggressive DTC at earlier disease stages. Nonetheless, we found persistently substantial rates of locoregionally advanced disease features (multifocality, extrathyroidal invasion, and lymph node metastases), which multivariable analyses suggested have significant associations with lateral lymph node and/or distant metastases.