{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T19:11:31Z","timestamp":1780686691435,"version":"3.54.1"},"reference-count":12,"publisher":"Walter de Gruyter GmbH","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_cclm-2026-0251_abs_001\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Cervical lymph node metastases represent a key challenge in patients with differentiated thyroid carcinoma (DTC). Fine-needle aspiration cytology (FNAC) and thyroglobulin (Tg) measurement in fine-needle washout (FNA-Tg) are widely used but have recognized limitations. Cytokeratin 19 fragment 21-1 measurement in FNA washout (FNA-CYFRA 21-1) has recently emerged as a potential supplementary biomarker. We compared the diagnostic performance of FNAC, FNA-Tg and FNA-CYFRA 21-1 in a series of well characterized DTC patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_cclm-2026-0251_abs_002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this observational diagnostic accuracy study, 226 suspicious cervical lymph nodes were assessed by FNAC, FNA-Tg and FNA-CYFRA 21-1. The reference standard was histopathology or a predefined composite clinical follow-up. Receiver operating characteristic (ROC) analysis, logistic regression, and DeLong\u2019s test were applied.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_cclm-2026-0251_abs_003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 226 lymph nodes, 87 were metastatic and 139 benign. FNA-CYFRA 21-1 showed near-perfect discrimination (AUC 0.99, 95\u202f% CI 0.99\u20131.00), followed by FNA-Tg (AUC 0.97, 95\u202f% CI 0.94\u20130.98). FNAC demonstrated high specificity but lower sensitivity (positivity: 79.3\u202f% in metastatic vs. 3.6\u202f% in benign nodes). In multivariable models, adding washout Tg significantly improved discrimination over FNAC alone (AUC 0.98 vs. 0.91; p=0.0003). A model based solely on FNA-CYFRA 21-1 achieved the highest performance (AUC 0.99), comparable to FNAC combined with FNA-Tg (p=0.09). Diagnostic accuracy remained robust across anti-thyroglobulin antibody strata.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_cclm-2026-0251_abs_004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>FNA-CYFRA 21-1 provides excellent diagnostic accuracy for metastatic cervical lymph nodes in DTC and performs at least comparably to established approaches. Its integration into a multimodal strategy may enhance diagnostic confidence, particularly in cytologically indeterminate or Tg-challenging scenarios.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/cclm-2026-0251","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T12:50:36Z","timestamp":1773233436000},"page":"1687-1695","source":"Crossref","is-referenced-by-count":0,"title":["CYFRA 21-1 in lymph node fine-needle aspiration washouts: added value in differentiated thyroid cancer"],"prefix":"10.1515","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0177-939X","authenticated-orcid":false,"given":"Alfredo","family":"Campenni","sequence":"first","affiliation":[{"name":"Nuclear Medicine Unit, Biomedical, Dental Sciences and Morpho-Functional Imaging , University of Messina , Messina , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0282-405X","authenticated-orcid":false,"given":"Lilla","family":"Bonanno","sequence":"additional","affiliation":[{"name":"IRCCS Centro Neurolesi \u201cBonino-Pulejo\u201d , Messina , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1946-2128","authenticated-orcid":false,"given":"Petra","family":"Petranovi\u0107 Ov\u010dari\u010dek","sequence":"additional","affiliation":[{"name":"Department of Oncology and Nuclear Medicine , University Hospital Center Sestre Milosrdnice and School of Medicine, University of Zagreb , Zagreb , Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4849-3292","authenticated-orcid":false,"given":"Martin W.","family":"Huellner","sequence":"additional","affiliation":[{"name":"Nuclear Medicine , University Hospital of Z\u00fcrich , Z\u00fcrich , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8899-684X","authenticated-orcid":false,"given":"Rosaria Maddalena","family":"Ruggeri","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Clinical and Experimental Medicine , University of Messina , Messina , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0230-0974","authenticated-orcid":false,"given":"Luca","family":"Giovanella","sequence":"additional","affiliation":[{"name":"Nuclear Medicine , University Hospital of Z\u00fcrich , Z\u00fcrich , Switzerland"},{"name":"Nuclear Medicine and Thyroid Centre , Gruppo Ospedaliero Moncucco , Lugano , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2026,3,12]]},"reference":[{"key":"2026060518413034946_j_cclm-2026-0251_ref_001","doi-asserted-by":"crossref","unstructured":"Ringel, MD, Sosa, JA, Baloch, Z, Bischoff, L, Bloom, G, Brent, GA et al.. 2025 American thyroid association management guidelines for adult patients with differentiated thyroid cancer. 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