Tan Gongxun, Wang Yuguo, Zhang Guoliang, Wang Xian, Ren Yongzhen, Gu Qian, Xu Feiju, Mao Zhenwei, Shi Chunhe, Wang Hui, Wu Ting, Wei Xi, Zhang Tengxu, Li Xiuying, Xu Ying, Ou Shengsheng, Wu Xinping, Jia Gaolei, Qian Xiaoqin
Department of Ultrasound, The Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, China.
Department of Ultrasound, Traditional Chinese Medicine Hospital of Nanjing Lishui District, Nanjing, Jiangsu, China.
Front Endocrinol (Lausanne). 2025 Aug 15;16:1603571. doi: 10.3389/fendo.2025.1603571. eCollection 2025.
Papillary thyroid carcinoma is the most common pathological subtype of thyroid cancer in both children/adolescents (TCCA) and adults (TCA). TCCA manifests more aggressive and invasive behaviors than TCA, which may be attributed to specific genomic alterations.
To better understand the specific molecular, pathological and clinical manifestations of TCCA, we retrospectively analyzed a cohort of 60 patients with sporadic papillary thyroid carcinoma, including 20 TCCAs and 40 TCAs. Fine-needle aspiration tissue samples from these cases were analyzed using next-generation sequencing. Demographics, ultrasound features, postoperative pathology and radiation exposure history were compared between TCCAs and TCAs. To validate our findings, we integrated data from 28 prior studies, resulting in a larger cohort of 1,483 sporadic TCCAs.
Multiple gene mutations were more prevalent in TCCAs than TCAs (p=0.013), such as coexisting with KMT2 family genes or PTEN. Although was the most common single nucleotide variant in TCCAs (25%, 5/20), its prevalence was significantly lower than in TCAs (95%, 38/40, p<0.0001). oncogenic fusions were detected exclusively in TCCAs, with an incidence of 20% (4/20). Compared with TCAs, TCCAs were associated with larger tumor diameters (p<0.001), more advanced tumor staging (T3-T4, p<0.001; N2, p=0.002), higher incidence of extrathyroidal extension (TCCA: 25%, TCA: 5%, p=0.036) and more frequent lymph node metastasis (TCCA: 70%, TCA: 27.5%, p=0.0024). Importantly, TCCAs harboring alongside other mutations (e.g., or family genes) exhibited more severe clinical manifestations, including larger tumors and higher rates of lymph node metastasis, compared with those harboring alone.
TCCAs exhibit more aggressive and invasive clinical manifestations than TCAs, particularly in cases with fusions or coexisting with other point mutations. Targeted comprehensive molecular profiling may aid in the diagnosis and treatment of TCCA.
甲状腺乳头状癌是儿童/青少年甲状腺癌（TCCA）和成人甲状腺癌（TCA）中最常见的病理亚型。与TCA相比，TCCA表现出更具侵袭性和侵犯性的行为，这可能归因于特定的基因组改变。
为了更好地了解TCCA的特定分子、病理和临床表现，我们回顾性分析了60例散发性甲状腺乳头状癌患者的队列，其中包括20例TCCA和40例TCA。使用下一代测序分析这些病例的细针穿刺组织样本。比较了TCCA和TCA之间的人口统计学、超声特征、术后病理和辐射暴露史。为了验证我们的发现，我们整合了28项先前研究的数据，从而形成了一个更大的包含1483例散发性TCCA的队列。
与TCA相比，多个基因突变在TCCA中更常见（p = 0.013），例如与KMT2家族基因或PTEN共存。虽然[此处原文缺失具体基因名称]是TCCA中最常见的单核苷酸变异（25%，5/20），但其发生率显著低于TCA（95%，38/40，p < 0.0001）。致癌融合仅在TCCA中检测到，发生率为20%（4/20）。与TCA相比，TCCA与更大的肿瘤直径相关（p < 0.001），肿瘤分期更晚（T3 - T4，p < 0.001；N2，p = 0.002），甲状腺外侵犯的发生率更高（TCCA：25%，TCA：5%，p = 0.036）以及更频繁的淋巴结转移（TCCA：70%，TCA：27.5%，p = 0.0024）。重要的是，与仅携带[此处原文缺失具体基因名称]的TCCA相比，同时携带[此处原文缺失具体基因名称]以及其他突变（例如[此处原文缺失具体基因名称]或[此处原文缺失具体基因名称]家族基因）的TCCA表现出更严重的临床表现，包括更大的肿瘤和更高的淋巴结转移率。
TCCA表现出比TCA更具侵袭性和侵犯性的临床表现，特别是在存在[此处原文缺失具体基因名称]融合或[此处原文缺失具体基因名称]与其他点突变共存的情况下。靶向全面分子谱分析可能有助于TCCA的诊断和治疗。
