Department of Otolaryngology-Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.
Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee.
JAMA Oncol. 2022 Sep 1;8(9):1323-1327. doi: 10.1001/jamaoncol.2022.1655.
Definitive diagnosis of a thyroid nodule in a child is obtained through diagnostic surgery. This is problematic because pediatric thyroid surgery is associated with higher rates of complications. In adults, preoperative molecular testing improves the management of thyroid nodules, but this has not been validated in children.
To determine whether the molecular landscape of pediatric thyroid nodules is amenable to detection by a multigene genomic classifier (GC) test (ThyroSeq v3; Sonic Healthcare USA).
DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective consecutive case series and GC testing of fine-needle aspiration (FNA) and formalin-fixed paraffin-embedded (FFPE) tissues from sequential pediatric thyroidectomies performed between January 2003 and December 2019 at a single tertiary academic medical center. The study included 95 patients (median [range] age, 16.3 [4.8 to 21.1] years; 75 [79%] female) who underwent surgery for a thyroid nodule.
A total of 118 thyroid nodule samples (95 FFPE, 23 companion FNAs) yielded informative next-generation sequencing data and multigene GC.
The primary outcome was the determination of the pediatric thyroid molecular landscape. The secondary outcome was the diagnostic accuracy of the GC test for pediatric thyroid nodules.
Of the 95 patients, 75 (79%) were female, and the median (IQR) age was 16.3 (14.0-17.3) years. Next-generation sequencing confirmed the unique molecular landscape of malignant pediatric thyroid nodules (compared with adults), which is dominated by gene fusions (most commonly RET and NTRK), rare BRAF/RAS alterations, and no TP53 or TERT promoter pathogenic variants. Several poorly differentiated thyroid cancers harbored DICER1 variants. Benign nodules appeared to be almost exclusively associated with TSHR and DICER1 alterations. The test demonstrated a 96% sensitivity (95% CI, 87%-99%) and 78% specificity (95% CI, 64%-88%). The negative predictive value was 95% (95% CI, 88%-98%) and the positive predictive value was 83% (95% CI, 74-89%). The concordance of GC between 23 pairs of matched FFPE and FNA tissues was 96%.
The study results of this retrospective consecutive case series suggest that the molecular landscape of pediatric nodules is unique but remains amenable to molecular classification. The multigene GC test, with high sensitivity and reasonably high specificity, represents a potential addition to the diagnostic workup of children with thyroid nodules and may decrease the use of diagnostic surgery.
儿童甲状腺结节的明确诊断需要通过诊断性手术获得。这是有问题的，因为儿科甲状腺手术与更高的并发症发生率有关。在成年人中，术前分子检测可改善甲状腺结节的管理，但尚未在儿童中得到验证。
确定儿童甲状腺结节的分子特征是否可通过多基因基因组分类器（GC）检测（ThyroSeq v3；Sonic Healthcare USA）检测到。
设计、地点和参与者：这是一项回顾性连续病例系列研究，对 2003 年 1 月至 2019 年 12 月期间在一家单一大三学术医疗中心连续进行的儿童甲状腺切除术的细针抽吸（FNA）和福尔马林固定石蜡包埋（FFPE）组织进行了 GC 检测。该研究包括 95 名患者（中位数[范围]年龄，16.3[4.8 至 21.1]岁；75[79%]为女性），因甲状腺结节接受手术。
共 118 个甲状腺结节样本（95 个 FFPE，23 个配对的 FNA）产生了信息丰富的下一代测序数据和多基因 GC。
主要结果是确定儿科甲状腺的分子特征。次要结果是 GC 检测对儿科甲状腺结节的诊断准确性。
95 例患者中，75 例（79%）为女性，中位（IQR）年龄为 16.3（14.0-17.3）岁。下一代测序证实了恶性儿科甲状腺结节（与成人相比）独特的分子特征，其特征是基因融合（最常见的是 RET 和 NTRK）、罕见的 BRAF/RAS 改变，以及没有 TP53 或 TERT 启动子致病性变异。一些低分化甲状腺癌含有 DICER1 变异体。良性结节似乎几乎仅与 TSHR 和 DICER1 改变有关。该检测显示出 96%的敏感性（95%CI，87%-99%）和 78%的特异性（95%CI，64%-88%）。阴性预测值为 95%（95%CI，88%-98%），阳性预测值为 83%（95%CI，74-89%）。23 对匹配的 FFPE 和 FNA 组织之间的 GC 一致性为 96%。
这项回顾性连续病例系列研究的结果表明，儿科结节的分子特征是独特的，但仍然可以进行分子分类。多基因 GC 检测具有较高的敏感性和相当高的特异性，代表了儿童甲状腺结节诊断的潜在补充方法，可能减少诊断性手术的使用。
