背景：最近的研究表明 DICER1 基因的致病性变异可能是某些儿童甲状腺结节改变的驱动因素，但数据仍然有限。本研究的目的是检测大量儿科甲状腺结节中 DICER1 基因的变异，然后将其与临床病理数据相关联，重点关注甲状腺癌患者的疾病预后。方法：这项回顾性队列研究由 350 名患有甲状腺结节的儿童和青年患者（年龄 2-21 岁）组成，收集了 275 份新鲜冷冻甲状腺结节样本和 92 份细针抽吸活检 (FNAB) 样本。在对甲状腺肿瘤主要遗传改变的变异进行分析后，使用下一代测序和多重连接依赖性探针扩增方法鉴定了 DICER1 基因的变异。对 DICER1 阳性肿瘤患者的外周血进行了分析。然后将遗传分析的结果与临床病理数据相关联。结果：总共 24/350 (6.9%; 95% CI [4.4;10.0]) 儿童和年轻成人患者中检测到 DICER1 基因变异，分别为 10/119 (8.4%; [4.1;14.9]) ) 良性新鲜冷冻组织患者、8/141 (5.7%; [1.9;9.5]) 甲状腺乳头状癌 (PTC) 患者和 6/86 (7.0%; [4.1;14.6]) FNAB 患者。在 DICER1 阳性样本中没有发现其他基因改变。在 11/24 (45.8%; [25.6;67.2]) 患者中发现了种系 DICER1 变异。在 9/24 (37.5%; [18.8;59.4]) 甲状腺结节中发现了 DICER1 基因的两个体细胞（双等位基因）变异。 2/24 (8.3%; [1.0;27.0]) 病例中发现至少 3 Mbp 长的体细胞缺失。 DICER1 阳性 PTC 与 PTC 的滤泡亚型 (p = 0.001)、包膜 (p = 0.006) 显着相关，并且尺寸较大 (p = 0.035)，但没有甲状腺外扩展 (p = 0.039)，且频率较低与 DICER1 阴性 PTC 相比，淋巴结转移 (p = 0.003)。 75% 的 DICER1 阳性 PTC 患者对治疗有良好的反应。结论：DICER1 基因的变异体常见于儿童和年轻成人患者的甲状腺结节中。在我们的患者中，DICER1 阳性 PTC 显示出低侵袭性。我们的研究结果支持考虑对 DICER1 阳性低风险 PTC 采取更保守的管理。

Background: Recent studies have suggested that pathogenic variants of the DICER1 gene could be a driver of alterations in some pediatric thyroid nodules, but data are still limited. The aim of this study was to detect variants in the DICER1 gene in a large cohort of pediatric thyroid nodules and then correlate them with clinicopathological data, with a focus on the disease prognosis in patients with thyroid carcinoma. Methods: This retrospective cohort study consisted of 350 pediatric and young adult patients (aged 2-21 years) with thyroid nodules, from whom 275 fresh-frozen thyroid nodule samples and 92 fine-needle aspiration biopsy (FNAB) samples were collected. After an analysis of variants in major genetic alterations of thyroid tumors, variants in the DICER1 gene were identified using next-generation sequencing and multiplex ligation-dependent probe amplification methods. Peripheral blood was analyzed from patients with DICER1-positive tumors. The results of genetic analysis were then correlated with clinicopathological data. Results: Variants in the DICER1 gene were detected in a total of 24/350 (6.9%; 95%CI [4.4;10.0]) pediatric and young adult patients, respectively, in 10/119 (8.4%; [4.1;14.9]) patients with benign fresh-frozen tissue, in 8/141 (5.7%; [1.9;9.5]) with papillary thyroid carcinoma (PTC) and in 6/86 (7.0%; [4.1;14.6]) patients with FNAB. No other gene alteration was found in DICER1-positive samples. Germline DICER1 variants were identified in 11/24 (45.8%; [25.6;67.2]) patients. Two somatic (biallelic) variants in the DICER1 gene were found in 9/24 (37.5%; [18.8;59.4]) thyroid nodules. Somatic deletions of at least 3 Mbp long were revealed in 2/24 (8.3%; [1.0;27.0]) cases. DICER1-positive PTCs were significantly associated with the follicular subtype of PTC (p = 0.001), encapsulation (p = 0.006) and were larger in size (p = 0.035), but with no extrathyroidal extension (p = 0.039), and less frequent lymph node metastases (p = 0.003) compared with DICER1-negative PTCs. Patients with DICER1-positive PTC had an excellent response to treatment in 75% of cases. Conclusions: Variants of the DICER1 gene are frequently found in the thyroid nodules of pediatric and young adult patients. In our patients, DICER1-positive PTCs showed low invasiveness. Our findings support considering more conservative management for DICER1-positive low-risk PTCs.