BACKGROUND 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 BRAFV600E 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. CONCLUSIONS 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.

中文翻译：

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分子标记不确定的甲状腺结节的分子标记。

背景技术甲状腺的不确定病变的诊断是细胞病理学实践中的挑战。实际上，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帮助诊断这些不确定的病例。有关FNA样品术前分子评估的第一批研究侧重于对BRAFV600E的分析或对两个或三个遗传变异的综合评估。然后，通过引入基因面板提高了分子测试的敏感性，该基因面板在2000年代后期开始可用于临床。已经开发出两种不同类型的分子测试方法，即“排除规则”方法（旨在减少可避免的良性结节的治疗）和“排除规则”方法。旨在优化手术管理的测试。不确定的甲状腺结节的遗传评估有望改善患者的护理，特别是如果适当地使用分子检测并且了解其优缺点的话。这些测试的主要缺点是成本高，这使得它们在欧洲很少使用。为了克服这个限制，已经建立了定制的面板，其能够检测最常见的甲状腺癌基因改变。结论在本综述中，描述了商业分子测试和定制的非商业小组的最新可用版本。它们的特征和准确性可用于不确定结节的鉴别诊断，即Bethesda III类（意义不明的非典型卵泡病变，