细针穿刺细胞学与基因检测在甲状腺结节 诊疗中的研究进展
Advances in Fine-Needle Aspiration Cytology and Molecular Testing for the Management of Thyroid Nodules
DOI: 10.12677/acm.2026.1641649, PDF,   
作者: 何金航, 苏新良*：重庆医科大学附属第一医院乳腺甲状腺外科，重庆
关键词: 甲状腺结节；细针穿刺细胞学；基因检测；Thyroid Nodules； Fine-Needle Aspiration Cytology； Molecular Testing
摘要: 甲状腺结节在普通人群中具有极高的发病率，精准鉴别其良恶性并评估预后是目前甲状腺外科的核心挑战。尽管超声引导下细针穿刺细胞学(US-FNAC)是术前诊断的基石，但仍有20%~30%的结节表现为细胞学性质不确定(Bethesda III/IV类)，导致临床面临过度治疗或诊断延迟的困境。随着分子病理学的发展及2022版WHO甲状腺肿瘤分类的更新，术前基因检测已从单一的辅助诊断手段，演变为指导临床决策的核心工具。本文系统综述了细针穿刺细胞学FNAC与基因检测(包括多基因Panel、二代测序技术等)在甲状腺结节评估中的最新进展。文章深入探讨了甲状腺癌关键驱动基因突变(如BRAF、RAS、TERT等)的分子机制，对比了各类分子检测平台的临床效能，并重点论述了整合临床特征、影像学与分子标志物的模型在风险分层中的卓越表现。此外，本文还探讨了联合检测在指导个体化手术范围、术前预后评估、卫生经济学效益以及未来人工智能(AI)和液体活检技术在甲状腺精准医疗中的应用前景。
Abstract: Thyroid nodules are highly prevalent in the general population. Accurately differentiating between benign and malignant nodules and evaluating prognosis remain the core challenges in current thyroid surgery. Although ultrasound-guided fine-needle aspiration cytology (US-FNAC) serves as the cornerstone for preoperative diagnosis, approximately 20% to 30% of nodules yield cytologically indeterminate results (Bethesda categories III/IV), leading to clinical dilemmas of overtreatment or delayed diagnosis. Driven by advancements in molecular pathology and the updated 2022 WHO Classification of Thyroid Neoplasms, preoperative molecular testing has evolved from a mere adjunctive diagnostic tool into a core instrument for guiding clinical decision-making. This article systematically reviews the latest advancements in FNAC and molecular testing—including multi-gene panels and next-generation sequencing (NGS)—for the evaluation of thyroid nodules. The review thoroughly explores the molecular mechanisms underlying key driver mutations in thyroid carcinoma (e.g., BRAF, RAS, TERT), compares the clinical efficacies of various molecular testing platforms, and highlights the superior performance of risk-stratification models that integrate clinical characteristics, imaging features, and molecular biomarkers. Furthermore, this paper discusses the utility of combined testing in guiding personalized surgical extent and preoperative prognostic evaluation, along with its health economic benefits. Finally, we prospect the future applications of artificial intelligence (AI) and liquid biopsy technologies in the precision medicine of thyroid diseases.
文章引用：何金航, 苏新良. 细针穿刺细胞学与基因检测在甲状腺结节 诊疗中的研究进展[J]. 临床医学进展, 2026, 16(4): 3817-3824. https://doi.org/10.12677/acm.2026.1641649

参考文献

[1] Grani, G., Sponziello, M., Filetti, S. and Durante, C. (2024) Thyroid Nodules: Diagnosis and Management. Nature Reviews Endocrinology, 20, 715-728. [Google Scholar] [CrossRef] [PubMed]
[2] Alexander, E.K. and Cibas, E.S. (2022) Diagnosis of Thyroid Nodules. The Lancet Diabetes & Endocrinology, 10, 533-539. [Google Scholar] [CrossRef] [PubMed]
[3] Ovčariček, P.P., Campennì, A., Bongiovanni, M. and Giovanella, L. (2025) The Management of Cytologically Indeterminate Thyroid Nodules in Clinical Practice: A Contemporary Perspective with Focus on Molecular Imaging. Endocrine, 89, 710-716. [Google Scholar] [CrossRef] [PubMed]
[4] Fumagalli, C. and Serio, G. (2023) Molecular Testing in Indeterminate Thyroid Nodules: An Additional Tool for Clinical Decision-Making. Pathologica, 115, 205-216. [Google Scholar] [CrossRef] [PubMed]
[5] Vignali, P., Macerola, E., Poma, A.M., Sparavelli, R. and Basolo, F. (2023) Indeterminate Thyroid Nodules: From Cytology to Molecular Testing. Diagnostics, 13, Article 3008. [Google Scholar] [CrossRef] [PubMed]
[6] Raghunathan, R., Praw, S.S. and Livhits, M. (2023) Molecular Testing for Indeterminate Thyroid Nodules: Past, Present, and Future. Current Opinion in Endocrinology, Diabetes & Obesity, 30, 231-237. [Google Scholar] [CrossRef] [PubMed]
[7] Velez Torres, J.M., Tjendra, Y. and Kerr, D.A. (2023) A Triumvirate: Correlating Thyroid Cytopathology, Molecular Testing, and Histopathology. Surgical Pathology Clinics, 16, 1-14.
[8] Belovarac, B., Zhou, F., Sharma, J. and Brandler, T.C. (2023) Indeterminate Thyroid Nodules and Advances in Molecular Pathology. Seminars in Diagnostic Pathology, 40, 349-352. [Google Scholar] [CrossRef] [PubMed]
[9] Ito, Y. and Miyauchi, A. (2024) Prognostic Factors of Papillary and Follicular Carcinomas Based on Pre-, Intra-, and Post-Operative Findings. European Thyroid Journal, 13, e240196. [Google Scholar] [CrossRef] [PubMed]
[10] Lebrun, L. and Salmon, I. (2024) Pathology and New Insights in Thyroid Neoplasms in the 2022 WHO Classification. Current Opinion in Oncology, 36, 13-21. [Google Scholar] [CrossRef] [PubMed]
[11] Rossi, E.D. and Baloch, Z. (2023) The Impact of the 2022 WHO Classification of Thyroid Neoplasms on Everyday Practice of Cytopathology. Endocrine Pathology, 34, 23-33. [Google Scholar] [CrossRef] [PubMed]
[12] Staibano, P., Forner, D., Noel, C.W., Zhang, H., Gupta, M., Monteiro, E., et al. (2022) Ultrasonography and Fine-Needle Aspiration in Indeterminate Thyroid Nodules: A Systematic Review of Diagnostic Test Accuracy. The Laryngoscope, 132, 242-251. [Google Scholar] [CrossRef] [PubMed]
[13] Hlozek, J., Pekova, B., Rotnágl, J., Holý, R. and Astl, J. (2022) Genetic Changes in Thyroid Cancers and the Importance of Their Preoperative Detection in Relation to the General Treatment and Determination of the Extent of Surgical Intervention—A Review. Biomedicines, 10, Article 1515. [Google Scholar] [CrossRef] [PubMed]
[14] Richmond, B.K. and Gallimore, J. (2023) Genetic Considerations in the Tumorigenesis, Diagnosis, and Treatment of Differentiated Thyroid Cancer: Current State of the Science. The American Surgeon, 89, 4853-4859. [Google Scholar] [CrossRef] [PubMed]
[15] Ito, Y. and Miyauchi, A. (2026) Prognostic Factors Evaluated in Differentiated Thyroid Carcinomas. Endocrine Connections, 15, e250751. [Google Scholar] [CrossRef] 
[16] Silaghi, C.A., Lozovanu, V., Georgescu, C.E., Georgescu, R.D., Susman, S., Năsui, B.A., et al. (2021) Thyroseq V3, Afirma GSC, and Microrna Panels versus Previous Molecular Tests in the Preoperative Diagnosis of Indeterminate Thyroid Nodules: A Systematic Review and Meta-Analysis. Frontiers in Endocrinology, 12, Article 649522. [Google Scholar] [CrossRef] [PubMed]
[17] Vuong, H.G., Nguyen, T.P.X., Hassell, L.A. and Jung, C.K. (2021) Diagnostic Performances of the Afirma Gene Sequencing Classifier in Comparison with the Gene Expression Classifier: A Meta-Analysis. Cancer Cytopathology, 129, 182-189. [Google Scholar] [CrossRef] [PubMed]
[18] Liao, X., Van Den Heede, K., Lapauw, B., Huvenne, W., Ysebaert, D., Meert, V., et al. (2025) Comparing the Diagnostic Accuracy of Pre-Operative Genetic Testing for Thyroid Cancer on Fine Needle Aspiration Cytology Specimens: A Systematic Review and Meta-Analysis of Diagnostic Accuracy. Discover Oncology, 16, Article No. 1797. [Google Scholar] [CrossRef] 
[19] Ngo, H.T.T., Nguyen, T.P.X., Vu, T.H., Jung, C.K., Hassell, L., Kakudo, K., et al. (2021) Impact of Molecular Testing on the Management of Indeterminate Thyroid Nodules among Western and Asian Countries: A Systematic Review and Meta-Analysis. Endocrine Pathology, 32, 269-279. [Google Scholar] [CrossRef] [PubMed]
[20] Wu, J., Stewardson, P., Eszlinger, M., Khalil, M., Ghaznavi, S., Nohr, E., et al. (2025) Development of a Nomogram to Integrate Molecular Testing and Clinical Variables to Improve Malignancy Risk Assessment among Cytologically Indeterminate Thyroid Nodules. Thyroid, 35, 508-515. [Google Scholar] [CrossRef] [PubMed]
[21] Kim, N.E., Raghunathan, R.S., Hughes, E.G., Longstaff, X.R., Tseng, C., Li, S., et al. (2023) Bethesda III and IV Thyroid Nodules Managed Nonoperatively after Molecular Testing with Afirma GSC or Thyroseq V3. The Journal of Clinical Endocrinology & Metabolism, 108, e698-e703. [Google Scholar] [CrossRef] [PubMed]
[22] Schumm, M.A., Nguyen, D.T., Kim, J., Tseng, C., Chow, A.Y., Shen, N., et al. (2021) Longitudinal Assessment of Quality of Life Following Molecular Testing for Indeterminate Thyroid Nodules. Annals of Surgical Oncology, 28, 8872-8881. [Google Scholar] [CrossRef] [PubMed]
[23] Chowdhury, R., Hier, J., Payne, K.E., Abdulhaleem, M., Dimitstein, O., Eisenbach, N., et al. (2025) Impact of Molecular Testing on Surgical Decision-Making in Indeterminate Thyroid Nodules: A Systematic Review and Meta-Analysis of Recent Advancements. Cancers, 17, Article No. 1156. [Google Scholar] [CrossRef] [PubMed]
[24] Ontario Health (2022) Molecular Testing for Thyroid Nodules of Indeterminate Cytology: A Health Technology Assessment. Ontario Health Technology Assessment Series, 22, 1-111.
https://pmc.ncbi.nlm.nih.gov/articles/PMC9095064/
[25] Clinkscales, W., Ong, A., Nguyen, S., Harruff, E.E. and Gillespie, M.B. (2017) Diagnostic Value of RAS Mutations in Indeterminate Thyroid Nodules: Systematic Review and Meta-Analysis. Otolaryngology—Head and Neck Surgery, 156, 472-479. [Google Scholar] [CrossRef] [PubMed]
[26] Nabhan, F., Porter, K., Lupo, M.A., Randolph, G.W., Patel, K.N. and Kloos, R.T. (2018) Heterogeneity in Positive Predictive Value of RAS Mutations in Cytologically Indeterminate Thyroid Nodules. Thyroid, 28, 729-738. [Google Scholar] [CrossRef] [PubMed]
[27] Alzumaili, B.A., Instrum, R., Alabkaa, A., Sadow, P.M., Tuttle, M.R., Xu, B., et al. (2025) Pathological Diagnosis of Thyroid Nodules with Preoperatively Detected TERT Promoter Mutations in the Absence of BRAF V600E: A Bi-Center Series of 52 Cases. Thyroid, 35, 1145-1152. [Google Scholar] [CrossRef] [PubMed]
[28] Patel, S.G., Carty, S.E., McCoy, K.L., Ohori, N.P., LeBeau, S.O., Seethala, R.R., et al. (2017) Preoperative Detection of RAS Mutation May Guide Extent of Thyroidectomy. Surgery, 161, 168-175. [Google Scholar] [CrossRef] [PubMed]
[29] Kaya, C., Dorsaint, P., Mercurio, S., Campbell, A.M., Eng, K.W., Nikiforova, M.N., et al. (2021) Limitations of Detecting Genetic Variants from the RNA Sequencing Data in Tissue and Fine-Needle Aspiration Samples. Thyroid, 31, 589-595. [Google Scholar] [CrossRef] [PubMed]
[30] Bailey, G.E., Azadi, J., Russell, J.O., Cochand-Priollet, B. and Maleki, Z. (2025) Ultrasound-Guided Thyroid Fine-Needle Aspiration and Concurrent Core Needle Biopsy: A Comparative Study with Practical Clinical Scenarios. American Journal of Clinical Pathology, 164, 500-512. [Google Scholar] [CrossRef] [PubMed]
[31] Dutta, S., Tarafdar, S., Mukhopadhyay, P., Bhattacharyya, N.P. and Ghosh, S. (2021) Plasma Cell-Free DNA to Differentiate Malignant from Benign Thyroid Nodules. The Journal of Clinical Endocrinology & Metabolism, 106, e2262-e2270. [Google Scholar] [CrossRef] [PubMed]
[32] Negrelli, M., Frascarelli, C., Maffini, F., Mangione, E., Di Tonno, C., Lombardi, M., et al. (2025) Artificial Intelligence in Thyroid Cytopathology: Diagnostic and Technical Insights. Cancers, 17, Article No. 3525. [Google Scholar] [CrossRef] 
[33] Zhang, L., Wong, C., Li, Y., Huang, T., Wang, J. and Lin, C. (2024) Artificial Intelligence Assisted Diagnosis of Early TC Markers and Its Application. Discover Oncology, 15, Article No. 172. [Google Scholar] [CrossRef] [PubMed]

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