Multifocality in papillary thyroid carcinoma (PTC) is a common finding, but the clonal relationship between individual tumors remains uncertain. While multiple synchronous tumor foci of PTC may develop through permeation of intraglandular lymph vessels of a single malignant clone, they can also arise from independent progenitor clones sustained by different genetic events. We report the case of a 37-year-old man who underwent total thyroidectomy after fine-needle aspiration of two bilateral thyroid nodules that yielded cytological findings consistent with atypia of undetermined significance/follicular lesion of undetermined significance. By next-generation sequencing of a large panel of thyroid carcinoma related genes, we found that the larger tumor harbored a mutation of the NRAS gene, while the contralateral tumor harbored a different mutation in the HRAS gene. Final pathology of the surgical specimen showed two encapsulated follicular variant papillary thyroid carcinomas of 16 and 6 mm in the right and the left lobes, respectively. To the best of our knowledge, this is the fourth case of multifocal PTC showing different HRAS and NRAS mutations, and highlights that mutational heterogeneity is also present in non-BRAF, non-RET genes, supporting the hypothesis that independent progenitor clones may explain multifocality in papillary thyroid carcinoma.

中文翻译：

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二代测序检测到具有不同RAS突变的乳头状甲状腺癌双侧滤泡变异：一例罕见病例报告及文献回顾

甲状腺乳头状癌 (PTC) 的多灶性是常见发现，但个体肿瘤之间的克隆关系仍不确定。虽然 PTC 的多个同步肿瘤病灶可能通过单个恶性克隆的腺内淋巴管的渗透而发展，但它们也可能来自由不同遗传事件维持的独立祖细胞克隆。我们报告了一例 37 岁男性，他在细针抽吸两个双侧甲状腺结节后接受了全甲状腺切除术，其细胞学检查结果与意义不明的非典型性/意义不明的滤泡性病变一致。通过对一大组甲状腺癌相关基因进行二代测序，我们发现较大的肿瘤存在NRAS基因突变，而对侧肿瘤的HRAS基因有不同的突变。手术标本的最终病理学显示，左右叶分别有两个 16 毫米和 6 毫米的包膜滤泡性甲状腺乳头状癌。据我们所知，这是多灶性 PTC 显示不同HRAS和NRAS突变的第四例，并强调突变异质性也存在于非BRAF、非RET基因中，支持独立祖细胞克隆可以解释多灶性的假设在甲状腺乳头状癌中。