Departments of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Genes (Basel). 2023 Jun 22;14(7):1314. doi: 10.3390/genes14071314.
Thyroid nodules are quite common, and the determination of a nodule of concern is complex, involving serum testing, radiology and, in some cases, pathological evaluation. For those nodules that raise clinical concern of neoplasia, fine needle aspiration biopsy is the gold standard for evaluation; however, in up to 30% of cases, results are indeterminate for malignancy, and further testing is needed. Advances in molecular testing have shown it to be of benefit for both diagnostic and prognostic purposes, and its use has become an integral part of thyroid cancer management in the United States and in several global nations. After The Cancer Genome Atlas (TCGA) consortium published its molecular landscape of papillary thyroid carcinoma (PTC) and reduced the "black matter" in PTC from 25% to 3.5%, further work ensued to clarify the remaining fraction not neatly attributed to the -like or -like phenotypes of the TCGA. Over the past decade, commercial molecular platforms have been refined as data accrues, and they increasingly cover most genetic variants of thyroid carcinomas. Molecular reporting focuses on the nodule tested, including related clinical information for that nodule (size of nodule, Bethesda category, etc.). This results in a comprehensive report to physicians that may also include patient-directed, clear language that facilitates conversations about nodule management. In cases of advanced or recurrent disease, molecular testing may become essential for devising an individual therapeutic plan. In this review, we focus on the evolution of integrated molecular testing in thyroid nodules, and how our understanding of tumor genetics, combined with histopathology, is driving the next generation of rational patient management, particularly in the context of emerging small, targetable therapeutics.
甲状腺结节很常见，确定有问题的结节的过程很复杂，需要进行血清检测、影像学检查，在某些情况下还需要进行病理评估。对于那些临床怀疑为肿瘤的结节，细针穿刺活检是评估的金标准；然而，在多达 30%的病例中，结果不能明确为恶性肿瘤，需要进一步检查。分子检测的进展表明，它在诊断和预后方面都有帮助，其应用已成为美国和一些全球国家甲状腺癌管理的一个组成部分。在癌症基因组图谱（TCGA）联盟发表了其甲状腺乳头状癌（PTC）的分子图谱，并将 PTC 的“黑箱”从 25%减少到 3.5%后，进一步的工作随之展开，以阐明尚未明确归因于 TCGA 的 -样或 -样表型的剩余部分。在过去的十年中，随着数据的积累，商业分子平台得到了改进，它们越来越多地涵盖了甲状腺癌的大多数遗传变异。分子报告侧重于所检测的结节，包括该结节的相关临床信息（结节大小、Bethesda 分类等）。这为医生提供了一份全面的报告，其中可能还包括针对患者的、清晰的语言，以促进关于结节管理的对话。在晚期或复发性疾病的情况下，分子检测可能对制定个体化治疗计划变得至关重要。在这篇综述中，我们重点介绍了甲状腺结节中综合分子检测的发展，以及我们对肿瘤遗传学的理解与组织病理学相结合，如何推动下一代合理的患者管理，特别是在新兴的、可靶向的治疗方法的背景下。
