{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T17:01:35Z","timestamp":1770742895107,"version":"3.49.0"},"reference-count":36,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T00:00:00Z","timestamp":1737936000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: The management of lymph node metastases of the central neck compartment (CNC) in differentiated thyroid carcinoma is debated. The intraoperative measurement of thyroglobulin (Tg) has gained attention in accurately detecting metastases, reducing unnecessary CNC dissections. Methods: A total of 37 patients underwent surgery. An intraoperative assay of thyroglobulin from fine needle aspiration (Tg-FNA) was performed on CNC lymph nodes, identified by blue dye injection in 15 patients (23 nodes, group A) and by palpation in 22 patients (35 nodes, group B). The Tg-FNA values were compared with histology to calculate the diagnostic accuracy. Results: In group A, the blue dye diffused widely, complicating lymph node identification: 2 were metastatic and 21 non-metastatic, with median Tg-FNA levels of 6236 ng\/mL and 99.20 ng\/mL, respectively. In group B, 8 were metastatic and 27 benign, with median Tg-FNA levels of 4063 ng\/mL and 121 ng\/mL (p &lt; 0.0001), respectively. ROC analysis identified 500 ng\/mL as a cutoff, achieving 100% sensitivity and 74% specificity in group B and 90% sensitivity and 70% specificity overall. Finally, among the non-metastatic lymph nodes, group A exhibited some cases of very high Tg-FNA values compared to group B, with lower accuracy for the cutoff, suggesting that colorant injection might lead to increased Tg-FNA levels. Conclusions: Blue dye injection showed low accuracy. Intraoperative Tg-FNA was reliable in detecting CNC metastases, although a higher cutoff is needed in this compartment compared to what has been reported for lateral lymph nodes. Lymphatic drainage and surgical manipulation might explain these findings. The careful interpretation of Tg-FNA in CNC should be adopted.<\/jats:p>","DOI":"10.3390\/cancers17030422","type":"journal-article","created":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T09:42:23Z","timestamp":1737970943000},"page":"422","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Detection of Central Compartment Lymph Node Metastasis of Thyroid Cancer: Usefulness of Intraoperative Thyroglobulin Measurement in Fine Needle Aspiration Washout with and Without Blue Dye Injection"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-5925-1866","authenticated-orcid":false,"given":"Chiara","family":"Mura","sequence":"first","affiliation":[{"name":"Endocrinology Unit, Department of Medical Sciences and Public Health, University of Cagliari, 09100 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3233-0269","authenticated-orcid":false,"given":"Gian Luigi","family":"Canu","sequence":"additional","affiliation":[{"name":"Surgery Unit, Department of Surgical Sciences, University of Cagliari, 09100 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9933-4040","authenticated-orcid":false,"given":"Giulia","family":"Lanzolla","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Medical Sciences and Public Health, University of Cagliari, 09100 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8101-8864","authenticated-orcid":false,"given":"Federico","family":"Cappellacci","sequence":"additional","affiliation":[{"name":"Surgery Unit, Department of Surgical Sciences, University of Cagliari, 09100 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9546-0178","authenticated-orcid":false,"given":"Fabio","family":"Medas","sequence":"additional","affiliation":[{"name":"Surgery Unit, Department of Surgical Sciences, University of Cagliari, 09100 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1208-7057","authenticated-orcid":false,"given":"Stefano","family":"Mariotti","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Medical Sciences and Public Health, University of Cagliari, 09100 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9637-1145","authenticated-orcid":false,"given":"Pietro Giorgio","family":"Cal\u00f2","sequence":"additional","affiliation":[{"name":"Surgery Unit, Department of Surgical Sciences, University of Cagliari, 09100 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9924-5192","authenticated-orcid":false,"given":"Francesco","family":"Boi","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Medical Sciences and Public Health, University of Cagliari, 09100 Cagliari, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1089\/thy.2012.0608","article-title":"A Systematic Review and Meta-Analysis of Prophylactic Central Neck Dissection on Short-Term Locoregional Recurrence in Papillary Thyroid Carcinoma after Total Thyroidectomy","volume":"23","author":"Lang","year":"2013","journal-title":"Thyroid"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2846","DOI":"10.1007\/s00268-018-4547-4","article-title":"Prophylactic Central Neck Dissection for Papillary Thyroid Carcinoma with Clinically Uninvolved Central Neck Lymph Nodes: A Systematic Review and Meta-Analysis","volume":"42","author":"Chen","year":"2018","journal-title":"World J. Surg."},{"key":"ref_3","unstructured":"Amin, M.B., Edge, S.B., Greene, F.L., Schilsky, R.L., Brookland, R.K., Washington, M.K., Gershenwald, J.E., Compton, C.C., Hess, K.R., and Sullivan, D.C. (2017). AJCC Cancer Staging Manual, American Joint Committee on Cancer (AJCC)."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"L7","DOI":"10.1530\/ERC-17-0453","article-title":"8th Edition of the AJCC\/TNM Staging System of Thyroid Cancer: What to Expect (ITCO#2)","volume":"25","author":"Lamartina","year":"2018","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1089\/thy.2017.0102","article-title":"Updated American Joint Committee on Cancer\/Tumor-Node-Metastasis Staging System for Differentiated and Anaplastic Thyroid Cancer (Eighth Edition): What Changed and Why?","volume":"27","author":"Tuttle","year":"2017","journal-title":"Thyroid"},{"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":"377","DOI":"10.1007\/s00423-012-1041-6","article-title":"The Number of Positive Lymph Nodes in the Central Compartment Has Prognostic Impact in Papillary Thyroid Cancer","volume":"398","author":"Rajeev","year":"2013","journal-title":"Langenbecks Arch. Surg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1089\/thy.2012.0043","article-title":"The Prognostic Significance of Nodal Metastases from Papillary Thyroid Carcinoma Can Be Stratified Based on the Size and Number of Metastatic Lymph Nodes, as Well as the Presence of Extranodal Extension","volume":"22","author":"Randolph","year":"2012","journal-title":"Thyroid"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1089\/thy.2012.0011","article-title":"Complications of Central Neck Dissection in Patients with Papillary Thyroid Carcinoma: Results of a Study on 1087 Patients and Review of the Literature","volume":"22","author":"Giordano","year":"2012","journal-title":"Thyroid"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Baud, G., Jannin, A., Marciniak, C., Chevalier, B., Do Cao, C., Leteurtre, E., Beron, A., Lion, G., Boury, S., and Aubert, S. (2022). Impact of Lymph Node Dissection on Postoperative Complications of Total Thyroidectomy in Patients with Thyroid Carcinoma. Cancers, 14.","DOI":"10.3390\/cancers14215462"},{"key":"ref_11","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_12","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.ejrad.2019.01.006","article-title":"Meta-Analysis of Ultrasound for Cervical Lymph Nodes in Papillary Thyroid Cancer: Diagnosis of Central and Lateral Compartment Nodal Metastases","volume":"112","author":"Zhao","year":"2019","journal-title":"Eur. J. Radiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1002\/lary.21227","article-title":"Efficacy of Preoperative Neck Ultrasound in the Detection of Cervical Lymph Node Metastasis from Thyroid Cancer","volume":"121","author":"Hwang","year":"2011","journal-title":"Laryngoscope"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1245\/s10434-021-10549-2","article-title":"Thyroglobulin Measurement Through Fine-Needle Aspiration for Optimizing Neck Node Dissection in Papillary Thyroid Cancer","volume":"29","author":"Jia","year":"2022","journal-title":"Ann. Surg. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1001\/archsurg.133.3.288","article-title":"Sentinel Lymphadenectomy in Thyroid Malignant Neoplasms","volume":"133","author":"Kelemen","year":"1998","journal-title":"Arch. Surg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1097\/00003072-199910000-00002","article-title":"Lymphoscintigraphy and Gamma Probe-Guided Surgery in Papillary Thyroid Carcinoma: The Sentinel Lymph Node Concept in Thyroid Carcinoma","volume":"24","author":"Gallowitsch","year":"1999","journal-title":"Clin. Nucl. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1007\/s002590000286","article-title":"Detecting the Sentinel Lymph Node in Patients with Differentiated Thyroid Carcinoma","volume":"27","author":"Rettenbacher","year":"2000","journal-title":"Eur. J. Nucl. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.biopha.2006.08.001","article-title":"Sentinel Node Mapping and Biopsy in Thyroid Cancer: A Surgical Perspective","volume":"60","author":"Pelizzo","year":"2006","journal-title":"Biomed. Pharmacother."},{"key":"ref_19","first-page":"483","article-title":"Sentinel Lymph Node (SLN) Procedure with Patent V Blue Dye in 153 Patients with Papillary Thyroid Carcinoma (PTC): Is It an Accurate Staging Method?","volume":"25","author":"Rubello","year":"2006","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1007\/s12020-018-1658-5","article-title":"Sentinel Lymph Node Biopsy in Small Papillary Thyroid Cancer. A Review on Novel Surgical Techniques","volume":"62","author":"Garau","year":"2018","journal-title":"Endocrine"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1016\/j.ejso.2020.02.007","article-title":"The Sentinel Lymph Node Biopsy Technique in Papillary Thyroid Carcinoma: The Issue of False-Negative Findings","volume":"46","author":"Garau","year":"2020","journal-title":"Eur. J. Surg. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1001\/archoto.2009.190","article-title":"The Role of Sentinel Lymph Node Biopsy in Differentiated Thyroid Carcinoma","volume":"135","author":"Anand","year":"2009","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1111\/cen.14993","article-title":"Lymph Node Imaging for Thyroid Cancer","volume":"100","author":"Holoubek","year":"2024","journal-title":"Clin. Endocrinol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Issa, P.P., Mueller, L., Hussein, M., Albuck, A., Shama, M., Toraih, E., and Kandil, E. (2022). Radiologist versus Non-Radiologist Detection of Lymph Node Metastasis in Papillary Thyroid Carcinoma by Ultrasound: A Meta-Analysis. Biomedicines, 10.","DOI":"10.3390\/biomedicines10102575"},{"key":"ref_25","first-page":"196","article-title":"Study on the Relationship between Ultrasonographic Features of Papillary Thyroid Carcinoma and Central Cervical Lymph Node Metastasis","volume":"40","author":"Wang","year":"2018","journal-title":"Zhonghua Zhong Liu Za Zhi"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1007\/s40618-017-0756-1","article-title":"Role of Sentinel Node in Differentiated Thyroid Cancer: A Prospective Study Comparing Patent Blue Injection Technique, Lymphoscintigraphy and the Combined Technique","volume":"41","author":"Gelmini","year":"2018","journal-title":"J. Endocrinol. Investig."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Huang, O., Wu, W.L., Wang, O.C., You, J., Li, Q., Huang, D.P., Hu, X.Q., Qu, J.M., Jin, C., and Xiang, Y.Q. (2011). Sentinel Lymph Node Biopsy Is Unsuitable for Routine Practice in Younger Female Patients with Unilateral Low-Risk Papillary Thyroid Carcinoma. BMC Cancer, 11.","DOI":"10.1186\/1471-2407-11-386"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1016\/j.ejso.2009.02.008","article-title":"Sentinel Lymph Node Biopsy in Papillary Thyroid Cancer: Comparison Study of Blue Dye Method and Combined Radioisotope and Blue Dye Method in Papillary Thyroid Cancer","volume":"35","author":"Lee","year":"2009","journal-title":"Eur. J. Surg. Oncol. (EJSO)"},{"key":"ref_29","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_30","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1007\/s00268-008-9657-y","article-title":"Sentinel Node Detection in Patients with Thyroid Carcinoma: A Meta-Analysis","volume":"32","author":"Raijmakers","year":"2008","journal-title":"World J. Surg."},{"key":"ref_31","first-page":"487","article-title":"Concentration of thyroxine, tri-iodothyronine and thyroglobulin in the thyroid lymph","volume":"142","author":"Persson","year":"1976","journal-title":"Acta Chir. Scand."},{"key":"ref_32","first-page":"489","article-title":"The release of thyroglobulin from the thyroid gland into thyroid lymphatics; the identification of thyroglobulin in the thyroid lymph and in the blood of monkeys by physical and immunological methods and its estimation by radioimmunoassay","volume":"12","author":"Daniel","year":"1967","journal-title":"Immunology"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Kolahdouzan, M., Sadeghi, M., Kalidari, B., Sanei, B., Mostafapour, E., and Aminorroaya, A. (2017). The Role of Intraoperative Thyroglobuline Level of Lymph Node in the Management of Papillary Thyroid Cancer (Determination of a Cutoff Point). Adv. Biomed. Res., 6.","DOI":"10.4103\/abr.abr_145_16"},{"key":"ref_34","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_35","doi-asserted-by":"crossref","first-page":"4435","DOI":"10.2147\/OTT.S140643","article-title":"Intraoperative Measurement of Thyroglobulin in Lymph Node Aspirates for the Detection of Metastatic Papillary Thyroid Carcinoma","volume":"10","author":"Wang","year":"2017","journal-title":"OncoTargets Ther."},{"key":"ref_36","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."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/3\/422\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T10:37:02Z","timestamp":1759919822000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/3\/422"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,27]]},"references-count":36,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["cancers17030422"],"URL":"https:\/\/doi.org\/10.3390\/cancers17030422","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,27]]}}}