基于FNAB的分子检测技术在甲状腺结节诊断中的研究进展

随着各种检测技术的相继问世，甲状腺结节的检出率明显上升。尽管大多数甲状腺结节是良性的，但良恶性病变之间的判定仍然是临床医生面临的挑战。对于所有可疑甲状腺结节患者均应进行颈部超声检查。甲状腺超声可评估结节特征，某些甲状腺结节具有可疑恶性超声征象。然而，这些特征缺乏准确性，无法明确诊断结节的良恶性。目前的指南仍然推荐超声引导细针穿刺活检（FNAB）作为评估甲状腺结节良恶性的首选检查。FNAB是一种经济高效的诊断方法，由于其创伤小，敏感性和特异性较高，可用于术前评估甲状腺结节的性质，已成为临床不可或缺的检查手段之一。近年来国内关于FNAB的报道日益增多，国内外指南关于FNAB指征尚有争议，同时由于其自身存在一定的局限性，FNAB技术的全面实施需要严格把握指征及准确判读穿刺病理结果。FNAB虽然是术前评估甲状腺结节最常用的诊断技术，但仍有灰区结节需要进一步诊断研究。为了制定合理的手术方案及判断预后，指南推荐术前可测定促甲状腺激素（TSH）水平。FNAB作为一个简单且相对无创的技术，但也可产生相应的并发症，FNAB的并发症主要与甲状腺结节的位置、穿刺针的直径、穿刺医师的操作经验等因素相关，严重程度较轻，多呈自限性。对于FNAB无法诊断或意义不明确的非典型病变或滤泡性病变，学者们一直在努力寻找一种新的方法来精确地诊断甲状腺癌。分子生物学方法是目前的最佳选择。分子生物学方法通过检测特定甲状腺肿瘤易感基因的驱动突变来确认甲状腺肿瘤活检的恶性程度，如BRAF和RAS癌基因突变、RET/PTC重排和TERT突变检测，从而提高术前诊断效率。甲状腺乳头状癌最常见的转移部位是局部淋巴结，虽然FNAB对异常淋巴结有诊断价值，但小或囊性淋巴结可能由于缺乏肿瘤细胞而无法诊断。检测可疑颈部淋巴结细针穿刺活检冲洗液中甲状腺球蛋白含量可作为细胞学诊断的辅助手段。笔者认为FNAB联合分子生物学的多层次诊断体系可提高术前诊断的精准性，对指导治疗、判断预后具有重要价值。

Research progress of molecular detection technologies based on FNAB in diagnosis of thyroid nodules

With the advent of various detection technologies, the detection rate of thyroid nodules has increased significantly. Although most thyroid nodules are benign, the determination between benign and malignant lesions is still a challenge for clinicians. All patients with suspicious thyroid nodules should undergo neck ultrasound. Thyroid ultrasound can assess the characteristics of nodules, and some thyroid nodules have ultrasound signs of suspicious malignancy. However, these features lack accuracy and cannot clearly diagnose benign and malignant nodules. The current guidelines still recommend ultrasound-guided fine needle aspiration biopsy (FNAB) as the first choice for evaluating benign and malignant thyroid nodules. FNAB is a cost-effective diagnostic tool. Due to its small trauma, high sensitivity and specificity, it can be used to evaluate the nature of thyroid nodules before surgery and has become one of the indispensable clinical examination methods. In recent years, domestic reports about FNAB have been increasing. Domestic and foreign guidelines regarding FNAB indications are still controversial. At the same time, due to its own limitations, the full implementation of FNAB technology requires strict control of the indications and accurate interpretation of the pathological results of puncture. Although FNAB is the most commonly used diagnostic technique for preoperative evaluation of thyroid nodules, there are still gray area nodules that require further diagnostic studies. In order to formulate a reasonable surgical plan and judge the prognosis, the guidelines recommend that thyroid-stimulating hormone (TSH) levels can be measured before surgery. FNAB is a simple and relatively non-invasive technique, but it can also produce corresponding complications. The complications of FNAB are mainly related to the position of the thyroid nodule, the diameter of the puncture needle, and the operating experience of the puncture physician, of which, the severity is relatively light, and most are self-limiting. Scholars have been trying to find a new method to accurately diagnose thyroid cancer for atypical lesions or follicular lesions that cannot be diagnosed or whose meaning is not clear. Molecular biology methods are currently the best choice. Molecular biology methods confirm the malignancy of thyroid tumor biopsy by detecting driver mutations of specific thyroid tumor susceptibility genes, such as BRAF and RAS oncogene mutations, RET/PTC rearrangement and TERT mutation detection, thereby improving the efficiency of preoperative diagnosis. The most common metastatic site of papillary thyroid carcinoma is local lymph nodes. Although FNAB has diagnostic value for abnormal lymph nodes, small or cystic lymph nodes may not be diagnosed due to lack of tumor cells. Detection of thyroglobulin content in the washing fluid of fine needle aspiration biopsy of suspicious cervical lymph nodes can be used as an auxiliary means of cytological diagnosis. The author believes that the multi-level diagnostic system of FNAB combined with molecular biology can improve the accuracy of preoperative diagnosis and is of great value in guiding treatment and judging prognosis.