Background/Objectives:Molecular testing of thyroid nodules enables the detection of genetic alterations, which can help assess the risk of malignancy and tumor behavior. While telomerase reverse transcriptase (TERTp) mutations are known to be associated with aggressive disease, their exact prognostic significance when occurring alone or with other molecular alterations remains underreported.Methods:This study examined patients with thyroid cancer treated at two tertiary care hospitals from 2017 to 2024. We compared tumor behavior in patients withTERTpmolecular alterations occurring alone and with concurrent molecular alterations. Aggressive histologic subtypes were defined as tall-cell, hobnail, and columnar variants of papillary carcinoma, as well as poorly differentiated and anaplastic carcinoma. High-risk disease was defined according to the 2015 ATA guidelines as gross extrathyroidal extension, lymph node metastasis >3 cm, postoperative elevated serum thyroglobulin, distant metastases, and/or positive resection margins. Statistical analysis was performed to assess differences between groups.Results:30 patients withTERTp-positive thyroid malignancies were included.TERTp/BRAF V600Ewas the most prevalent mutation combination (n= 13, 43.3%), followed byTERTpalone (n= 8, 26.7%) andTERTp/RAS(n= 7, 23.4%).TERTp/EIF1AX/GNASandTERTp/EIF1AX/PIK3CAwere the least common combinations (n= 1, 3.3% each). Nodules withTERTpand concurrent mutations were significantly more likely to be classified as high-risk (p= 0.006) and were more frequently associated with aggressive histologic subtypes (p= 0.003) compared to those withTERTpmutations alone, which tended to exhibit more benign behavior.Conclusions:Thyroid carcinomas harboring bothTERTpand concurrent molecular alterations are associated with more aggressive features and a higher likelihood of being classified as high-risk. In contrast,TERTpmutations occurring alone do not confer an elevated risk.
**背景/目的：** 甲状腺结节的分子检测能够识别基因改变，有助于评估恶性肿瘤风险及肿瘤行为。虽然端粒酶逆转录酶（TERTp）突变已知与侵袭性疾病相关，但其单独发生或与其他分子改变共存时的确切预后意义仍报道不足。 **方法：** 本研究纳入2017年至2024年在两家三级医院接受治疗的甲状腺癌患者。我们比较了仅存在TERTp分子改变与同时存在其他分子改变患者的肿瘤行为。侵袭性组织学亚型定义为高细胞型、鞋钉样及柱状细胞型乳头状癌，以及低分化和未分化癌。高风险疾病根据2015年美国甲状腺协会指南定义为：明显的甲状腺外侵犯、淋巴结转移＞3 cm、术后血清甲状腺球蛋白升高、远处转移和/或切缘阳性。通过统计分析评估组间差异。 **结果：** 共纳入30例TERTp阳性的甲状腺恶性肿瘤患者。TERTp/BRAF V600E是最常见的突变组合（n=13，43.3%），其次为单独TERTp突变（n=8，26.7%）和TERTp/RAS组合（n=7，23.4%）。TERTp/EIF1AX/GNAS和TERTp/EIF1AX/PIK3CA为最少见的组合（各n=1，3.3%）。与仅存在TERTp突变的结节相比，同时伴有其他突变的TERTp阳性结节更可能被归类为高风险（p=0.006），且更常与侵袭性组织学亚型相关（p=0.003）；而仅存在TERTp突变的结节往往表现出更良性的行为。 **结论：** 同时存在TERTp及其他分子改变的甲状腺癌具有更强的侵袭性特征，且更可能被归类为高风险。相比之下，单独发生的TERTp突变并未增加风险。
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