{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T13:15:40Z","timestamp":1782738940011,"version":"3.54.5"},"reference-count":46,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Chang Gung Memorial Hospital-Kaohsiung Medical Center","award":["CMRPG8N0911"],"award-info":[{"award-number":["CMRPG8N0911"]}]},{"name":"Chang Gung Memorial Hospital-Kaohsiung Medical Center","award":["NSTC 113-2314-B-182A-138-MY2"],"award-info":[{"award-number":["NSTC 113-2314-B-182A-138-MY2"]}]},{"name":"National Science and Technology Council","award":["CMRPG8N0911"],"award-info":[{"award-number":["CMRPG8N0911"]}]},{"name":"National Science and Technology Council","award":["NSTC 113-2314-B-182A-138-MY2"],"award-info":[{"award-number":["NSTC 113-2314-B-182A-138-MY2"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Papillary thyroid carcinoma (PTC) frequently involves cervical lymph node (LN) metastases and is a major determinant of prognosis and recurrence. However, cytology alone has limitations. Fine-needle aspiration thyroglobulin (FNA-Tg) has emerged as a promising diagnostic marker, although its cutoff value remains controversial, particularly in patients with thyroglobulin antibodies (TgAbs). We retrospectively analyzed 63 LNs of 60 patients with PTC at a single medical center. Patients underwent FNA-Tg measurements and concurrent cytological evaluation. Diagnostic performance metrics, including sensitivity, specificity, positive and negative predictive value, and overall accuracy, were evaluated; the cutoff value was determined; and the potential influence of factors such as TgAb on FNA-Tg levels was investigated. A cutoff value of 4.23 ng\/mL for FNA-Tg achieved 100% sensitivity and 90.2% specificity, with an overall accuracy of 93.6%. TgAb positivity did not significantly affect the diagnostic performance in patients with FNA-Tg. FNA-Tg might be useful for detecting local LN recurrence and providing valuable diagnostic insights, particularly in patients with residual thyroid tissue or positive TgAbs.<\/jats:p>","DOI":"10.3390\/ijms26115340","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T11:40:32Z","timestamp":1748864432000},"page":"5340","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Clinical Implications of Lymph Node Thyroglobulin in Papillary Thyroid Carcinoma Metastases: Independent from Thyroglobulin Antibody Interference"],"prefix":"10.3390","volume":"26","author":[{"given":"Ping-Chen","family":"Kuo","sequence":"first","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Chieh","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Che","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun-Yu","family":"Chi","sequence":"additional","affiliation":[{"name":"Departments of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Hsiang","family":"Chiu","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Chen","family":"Yang","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen-Kai","family":"Chou","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan"},{"name":"College of Medicine, Chang Gung University, Kaohsiung 833, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/S2213-8587(21)00027-9","article-title":"Thyroid cancer incidence trends by histology in 25 countries: A population-based study","volume":"9","author":"Bray","year":"2021","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Fiorentino, V., Dell\u2019Aquila, M., Musarra, T., Martini, M., Capodimonti, S., Fadda, G., Curatolo, M., Traini, E., Raffaelli, M., and Lombardi, C.P. (2021). The role of cytology in the diagnosis of subcentimeter thyroid lesions. Diagnostics, 11.","DOI":"10.3390\/diagnostics11061043"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Lam, A.K. (2022). Papillary thyroid carcinoma: Current position in epidemiology, genomics, and classification. Papillary Thyroid Carcinoma: Methods and Protocols, Springer.","DOI":"10.1007\/978-1-0716-2505-7"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1158\/1055-9965.EPI-21-1440","article-title":"Epidemiology of thyroid cancer","volume":"31","author":"Kitahara","year":"2022","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1002\/jso.23967","article-title":"Postoperative recurrence of papillary thyroid carcinoma with lymph node metastasis","volume":"112","author":"Liu","year":"2015","journal-title":"J. Surg. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1177\/000313480507100907","article-title":"The implication of lymph node metastasis on survival in patients with well-differentiated thyroid cancer","volume":"71","author":"Podnos","year":"2005","journal-title":"Am. Surg."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/s00268-017-4279-x","article-title":"Papillary thyroid carcinoma (PTC) in children and adults: Comparison of initial presentation and long-term postoperative outcome in 4432 patients consecutively treated at the Mayo Clinic during eight decades (1936\u20132015)","volume":"42","author":"Hay","year":"2018","journal-title":"World J. Surg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1530\/EJE-07-0896","article-title":"Thyroid papillary microcarcinoma: A descriptive and meta-analysis study","volume":"159","author":"Roti","year":"2008","journal-title":"Eur. J. Endocrinol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1210\/jc.2012-3401","article-title":"Papillary thyroid cancer: Time course of recurrences during postsurgery surveillance","volume":"98","author":"Durante","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1159\/000354537","article-title":"2013 European thyroid association guidelines for cervical ultrasound scan and ultrasound-guided techniques in the postoperative management of patients with thyroid cancer","volume":"2","author":"Leenhardt","year":"2013","journal-title":"Eur. Thyroid J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1089\/thy.1999.9.105","article-title":"Role of thyroglobulin measurement in fine-needle aspiration biopsies of cervical lymph nodes in patients with differentiated thyroid cancer","volume":"9","author":"Frasoldati","year":"1999","journal-title":"Thyroid"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"382","DOI":"10.5455\/medarh.2019.73.382-385","article-title":"Fine needle aspiration cytology and thyroglobulin antibodies in preoperative diagnosis of thyroid malignancy","volume":"73","author":"Hasukic","year":"2019","journal-title":"Med. Arch."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1245\/s10434-016-5625-1","article-title":"Thyroglobulin measurement in fine-needle aspiration improves the diagnosis of cervical lymph node metastases in papillary thyroid carcinoma","volume":"24","author":"Strajina","year":"2017","journal-title":"Ann. Surg. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1002\/1097-0142(19890215)63:4<718::AID-CNCR2820630420>3.0.CO;2-N","article-title":"Sources of diagnostic error in fine needle aspiration of the thyroid","volume":"63","author":"Hall","year":"1989","journal-title":"Cancer"},{"key":"ref_15","first-page":"1401","article-title":"Detection of thyroglobulin in fine needle aspirates of nonthyroidal neck masses: A clue to the diagnosis of metastatic differentiated thyroid cancer","volume":"74","author":"Pacini","year":"1992","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1515\/cclm-2016-0543","article-title":"Measurement of thyroglobulin, calcitonin, and PTH in FNA washout fluids","volume":"55","author":"Trimboli","year":"2017","journal-title":"Clin. Chem. Lab. Med. (CCLM)"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1210\/jc.2012-3291","article-title":"Thyroglobulin in washout fluid from lymph node fine-needle aspiration biopsy in papillary thyroid cancer: Large-scale validation of the cutoff value to determine malignancy and evaluation of discrepant results","volume":"98","author":"Moon","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1007\/s12020-022-03213-6","article-title":"Optimal method for detecting cervical lymph node metastasis from papillary thyroid cancer","volume":"79","author":"Xiao","year":"2023","journal-title":"Endocrine"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1089\/thy.2013.0244","article-title":"Thyroglobulin in the washout fluid of lymph-node biopsy: What is its role in the follow-up of differentiated thyroid carcinoma?","volume":"24","author":"Torres","year":"2014","journal-title":"Thyroid"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1970","DOI":"10.1210\/jc.2014-1098","article-title":"Thyroglobulin in lymph node fine-needle aspiration washout: A systematic review and meta-analysis of diagnostic accuracy","volume":"99","author":"Grani","year":"2014","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Zhao, H., Wang, Y., Wang, M.J., Zhang, Z.H., Wang, H.R., Zhang, B., and Guo, H.Q. (2017). Influence of presence\/absence of thyroid gland on the cutoff value for thyroglobulin in lymph-node aspiration to detect metastatic papillary thyroid carcinoma. BMC Cancer, 17.","DOI":"10.1186\/s12885-017-3296-3"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1002\/kjm2.12173","article-title":"Clinical application of the ultrasound-guided fine needle aspiration for thyroglobulin measurement to diagnose lymph node metastasis from differentiated thyroid carcinoma-literature review","volume":"36","author":"Jiang","year":"2020","journal-title":"Kaohsiung J. Med. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1089\/thy.2015.0020","article-title":"2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: The American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid cancer","volume":"26","author":"Haugen","year":"2016","journal-title":"Thyroid"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1111\/coa.13103","article-title":"Reliable sonographic features for nodal thyroglobulin to diagnose recurrent lymph node metastasis from papillary thyroid carcinoma","volume":"43","author":"Jiang","year":"2018","journal-title":"Clin. Otolaryngol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.jss.2017.08.007","article-title":"Clinical predictors of lymph node metastasis and survival rate in papillary thyroid microcarcinoma: Analysis of 3607 patients at a single institution","volume":"221","author":"Xu","year":"2018","journal-title":"J. Surg. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1586\/eem.11.9","article-title":"Gender differences in thyroid cancer: A critical review","volume":"6","author":"Yao","year":"2011","journal-title":"Expert Rev. Endocrinol. Metab."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Lee, S., Lee, J.Y., Yoon, R.G., Kim, J.-h., and Hong, H.S. (2020). The value of microvascular imaging for triaging indeterminate cervical lymph nodes in patients with papillary thyroid carcinoma. Cancers, 12.","DOI":"10.3390\/cancers12102839"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1002\/jcu.23073","article-title":"The value of contrast-enhanced ultrasound for the diagnosis of metastatic cervical lymph nodes of papillary thyroid carcinoma: A systematic review and meta-analysis","volume":"50","author":"Li","year":"2022","journal-title":"J. Clin. Ultrasound"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Zhang, M.-B., Meng, Z.-L., Mao, Y., Jiang, X., Xu, N., Xu, Q.-H., Tian, J., Luo, Y.-K., and Wang, K. (2024). Cervical lymph node metastasis prediction from papillary thyroid carcinoma US videos: A prospective multicenter study. BMC Med., 22.","DOI":"10.1186\/s12916-024-03367-2"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"David, E., Grazhdani, H., Tattaresu, G., Pittari, A., Foti, P.V., Palmucci, S., Spatola, C., Greco, M.C.L., In\u00ec, C., and Tiralongo, F. (2024). Thyroid nodule characterization: Overview and state of the art of diagnosis with recent developments, from imaging to molecular diagnosis and artificial intelligence. Biomedicines, 12.","DOI":"10.3390\/biomedicines12081676"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1046\/j.1365-2265.2003.01681.x","article-title":"Laboratory medicine practice guidelines: Laboratory support for the diagnosis and monitoring of thyroid disease","volume":"58","author":"Demers","year":"2003","journal-title":"Clin. Endocrinol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5566","DOI":"10.1210\/jc.2005-0671","article-title":"Clinical impact of thyroglobulin (Tg) and Tg autoantibody method differences on the management of patients with differentiated thyroid carcinomas","volume":"90","author":"Spencer","year":"2005","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1530\/EJE-07-0749","article-title":"Significance of low levels of thyroglobulin in fine needle aspirates from cervical lymph nodes of patients with a history of differentiated thyroid cancer","volume":"158","author":"Borel","year":"2008","journal-title":"Eur. J. Endocrinol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1089\/thy.2004.14.959","article-title":"Detection of recurrent papillary thyroid carcinoma by thyroglobulin assessment in the needle washout after fine-needle aspiration of suspicious lymph nodes","volume":"14","year":"2004","journal-title":"Thyroid"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4278","DOI":"10.1210\/jc.2007-1075","article-title":"Serum thyroglobulin, high-resolution ultrasound, and lymph node thyroglobulin in diagnosis of differentiated thyroid carcinoma nodal metastases","volume":"92","author":"Snozek","year":"2007","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1515\/CCLM.2010.220","article-title":"Thyroglobulin measurement in fine-needle aspirates of lymph nodes in patients with differentiated thyroid cancer: A simple definition of the threshold value, with emphasis on potential pitfalls of the method","volume":"48","author":"Bournaud","year":"2010","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1007\/s12020-012-9636-9","article-title":"Usefulness of thyroglobulin measurement in needle washouts of fine-needle aspiration biopsy for the diagnosis of cervical lymph node metastases from papillary thyroid cancer before thyroidectomy","volume":"42","author":"Kim","year":"2012","journal-title":"Endocrine"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1007\/s00268-004-7701-0","article-title":"Usefulness of thyroglobulin measurement in fine-needle aspiration biopsy specimens for diagnosing cervical lymph node metastasis in patients with papillary thyroid cancer","volume":"29","author":"Uruno","year":"2005","journal-title":"World J. Surg."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/j.ejso.2022.12.007","article-title":"Lymph node thyroglobulin in the diagnosis of metastases of thyroid carcinoma with the thyroid in situ: A prospective intraoperative study","volume":"49","author":"Paladino","year":"2023","journal-title":"Eur. J. Surg. Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1210\/jc.2005-1705","article-title":"The diagnostic value for differentiated thyroid carcinoma metastases of thyroglobulin (Tg) measurement in washout fluid from fine-needle aspiration biopsy of neck lymph nodes is maintained in the presence of circulating anti-Tg antibodies","volume":"91","author":"Boi","year":"2006","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1002\/dc.20726","article-title":"The usefulness of detecting thyroglobulin in fine-needle aspirates from patients with neck lesions using a sensitive thyroglobulin assay","volume":"35","author":"Sigstad","year":"2007","journal-title":"Diagn. Cytopathol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"E21","DOI":"10.1002\/hed.21796","article-title":"Thyroglobulin measurement in fine-needle aspiration biopsy of metastatic lymph nodes after rhTSH stimulation","volume":"35","author":"Cappelli","year":"2013","journal-title":"Head Neck"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1590\/S0004-27302010000600007","article-title":"Thyroglobulin measurements in washout of fine needle aspirates in cervical lymph nodes for detection of papillary thyroid cancer metastases","volume":"54","author":"Zanella","year":"2010","journal-title":"Arq. Bras. Endocrinol. Metabol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"632","DOI":"10.3348\/kjr.2018.19.4.632","article-title":"2017 thyroid radiofrequency ablation guideline: Korean Society of Thyroid Radiology","volume":"19","author":"Kim","year":"2018","journal-title":"Korean J. Radiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.1016\/j.jfma.2021.09.026","article-title":"One year follow-up of US-Guided radiofrequency ablation for low-risk papillary thyroid microcarcinoma: The first experience in Taiwan","volume":"121","author":"Lin","year":"2022","journal-title":"J. Formos. Med. Assoc."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1089\/thy.2017.0500","article-title":"The 2017 Bethesda system for reporting thyroid cytopathology","volume":"27","author":"Cibas","year":"2017","journal-title":"Thyroid"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/11\/5340\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:45:52Z","timestamp":1760031952000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/11\/5340"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,1]]},"references-count":46,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["ijms26115340"],"URL":"https:\/\/doi.org\/10.3390\/ijms26115340","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,1]]}}}