Division of Endocrine and Metabolic Diseases, IRCCS IstitutoAuxologicoItaliano, 20149, Milan, Italy.
Department of Pathophysiology and Transplantation, University of Milan, P.le Brescia 20, 20149, Milano, Italy.
J Endocrinol Invest. 2020 Jun;43(6):703-716. doi: 10.1007/s40618-019-01164-w. Epub 2019 Dec 18.
The diagnosis of indeterminate lesions of the thyroid is a challenge in cytopathology practice. Indeed, up to 30% of cases lack the morphological features needed to provide definitive classification. Molecular tests have been developed to assist in the diagnosis of these indeterminate cases. The first studies dealing with the preoperative molecular evaluation of FNA samples focused on the analysis of BRAF or on the combined evaluation of two or three genetic alterations. The sensitivity of molecular testing was then improved through the introduction of gene panels, which became available for clinical use in the late 2000s. Two different categories of molecular tests have been developed, the 'rule-out' methods, which aim to reduce the avoidable treatment of benign nodules, and the 'rule-in' tests that have the purpose to optimize surgical management. The genetic evaluation of indeterminate thyroid nodules is predicted to improve patient care, particularly if molecular tests are used appropriately and with the awareness of their advantages and weaknesses. The main disadvantage of these tests is the cost, which makes them rarely used in Europe. To overcome this limitation, customized panels have been set up, which are able to detect the most frequent genetic alterations of thyroid cancer.
In the present review, the most recent available versions of commercial molecular tests and of custom, non-commercial panels are described. Their characteristics and accuracy in the differential diagnosis of indeterminate nodules, namely Bethesda classes III (Atypical follicular lesion of undetermined significance, AUS/FLUS) and IV (Suspicious for follicular neoplasm, FN/SFN) are fully analyzed and discussed.
甲状腺不定性病变的诊断是细胞病理学实践中的一个挑战。事实上，多达 30%的病例缺乏提供明确分类所需的形态特征。已经开发了分子测试来协助这些不定性病例的诊断。最早研究的是针对细针穿刺抽吸活检（FNA）样本的术前分子评估，这些研究集中在分析 BRAF 或同时评估两个或三个基因改变。随后，通过引入基因组合，分子检测的敏感性得到了提高，这些基因组合在 21 世纪初开始应用于临床。已经开发了两种不同类别的分子测试，一种是“排除”方法，旨在减少对良性结节的不必要治疗；另一种是“确定”测试，目的是优化手术管理。预测对甲状腺不定性结节进行基因评估将改善患者的治疗效果，特别是如果适当使用分子测试并了解其优势和局限性。这些测试的主要缺点是成本，这使得它们在欧洲很少使用。为了克服这一限制，已经建立了定制的基因面板，可以检测甲状腺癌最常见的基因改变。
在本次综述中，描述了商业性分子测试和非商业化定制基因面板的最新可用版本。对其在诊断不定性结节（Bethesda 分类 III 级：意义未明的滤泡性病变，AUS/FLUS；IV 级：滤泡性肿瘤可疑，FN/SFN）的鉴别诊断中的特点和准确性进行了全面分析和讨论。
