Specific genomic alterations and aggressive clinical features of sporadic thyroid carcinomas in children and adolescents: findings from an in-house cohort study

Gongxun Tan¹Yuguo Wang²Guoliang Zhang³Xian Wang¹Yongzhen Ren¹Qian Gu⁴Feiju Xu¹Zhenwei Mao⁵Chunhe Shi⁶Hui Wang⁷Ting Wu⁸Xi Wei⁸Tengxu Zhang⁹Xiuying Li¹⁰Ying Xu¹⁰Shengsheng Ou²Xinping Wu^11*Gaolei Jia^12*Qian Xiaoqin^1,13*

• ¹Department of Ultrasound, Jiangsu University Affiliated People's Hospital, Zhenjiang, China
• ²Department of Ultrasound, Traditional Chinese Medicine Hospital of Nanjing Lishui District, Nanjing, China
• ³Department of Thyroid Surgery, Jiangsu University Affiliated People's Hospital, Zhenjiang, China
• ⁴Department of Geriatrics, Jiangsu University Affiliated People's Hospital, Zhenjiang, China
• ⁵Laboratory Center, Jiangsu University Affiliated People's Hospital, Zhenjiang, China
• ⁶Department of Ophthalmology, Jiangsu University Affiliated People's Hospital, Zhenjiang, China
• ⁷Department of Endocrinology, Jiangsu University Affiliated People's Hospital, Zhenjiang, China
• ⁸Department of Pathology, Jiangsu University Affiliated People's Hospital, Zhenjiang, China
• ⁹Department of Cardiology, Jiangsu University Affiliated People's Hospital, Zhenjiang, China
• ¹⁰Nanjing D.A. Medical Laboratory, Nanjing, Liaoning Province, China
• ¹¹Department of Ultrasound, Jiangsu Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing, China
• ¹²Department of Vascular Thyroid Hernia Surgery, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, Xuzhou, China
• ¹³Department of Ultrasound Medicine, Northern Jiangsu People’s Hospital, Yangzhou, China

Papillary thyroid carcinoma in children/adolescents (TCCA) manifests more aggressive and invasive behaviors than those in adults (TCA). We retrospectively analyzed fine-needle aspiration samples from 60 patients with sporadic papillary thyroid carcinoma (20 TCCAs and 40 TCAs) using NGS and compared demographics, ultrasound features, postoperative pathology and gene mutations between the groups. Integrated data from 28 prior studies including 1,483 sporadic TCCAs were used to validate our findings. Multiple gene mutations were more prevalent in TCCAs than TCAs (p=0.013), such as BRAF V600E coexisting with KMT2 family genes or PTEN. Although BRA FV600E was the most common single nucleotide variant in TCCAs (45%, 9/20), its prevalence was significantly lower than in TCAs (95%, 38/40, p<0.0001). RET oncogenic fusions were detected exclusively in TCCAs (20%, 4/20).TCCAs were associated with larger tumors (p<0.001), more advanced tumor staging (T3-T4, p<0.001; N2, p=0.002), more extrathyroidal extension (TCCA: 25%, TCA: 5%, p=0.036) and lymph node metastasis (TCCA: 70%, TCA: 27.5%, p=0.0024) than TCAs. TCCAs harboring BRAF V600E alongside other mutations exhibited more severe clinical manifestations than those harboring BRAF V600E alone, including larger tumors and more lymph node metastasis. Overall, TCCAs exhibit more aggressive and invasive clinical manifestations than TCAs. Targeted comprehensive molecular profiling may inform TCCA diagnosis and treatment.