{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T21:03:14Z","timestamp":1792184594211,"version":"4.4.0"},"reference-count":27,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T00:00:00Z","timestamp":1752105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Scientific and Technological Research Council of Turkey","award":["323S159"],"award-info":[{"award-number":["323S159"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and Objectives: Thyroid nodules are a common endocrine disorder, with 10\u201315% exhibiting malignancy. Accurate differentiation of malignant and benign nodules is crucial for optimizing treatment outcomes. Current diagnostic tools, such as the Bethesda classification and fine-needle aspiration biopsy (FNAB), are limited in sensitivity and specificity, particularly in indeterminate cases. Tumor-infiltrating immune cells (TIICs) in the tumor microenvironment (TME) play a significant role in thyroid cancer progression. CD66b+ neutrophil-like monocytes constitute a novel subset of myeloid cells that are implicated in the modulation of anti-tumor immune responses, but their role in thyroid cancer remains unclear. Materials and Methods: Peripheral blood and thyroid nodule tissue samples were obtained from 24 patients with papillary thyroid carcinoma, and from 10 patients who underwent surgery for symptoms of tracheal compression due to benign thyroid nodules. Myeloid cell populations were assayed by flow cytometric immunophenotyping with CD45, HLA-DR, CD14, and CD66b. The data were statistically analyzed with the clinical properties of the patients. Results: The neutrophil-like monocytes, which were determined as HLA-DR+CD14+CD66b+ cells, found in the circulation (11.9 \u00b1 2.4% of total mononuclear immune cells) of the patients with papillary thyroid carcinoma, were significantly elevated (p &lt; 0.001). Accordingly, these cells were more frequently detected in tumor tissues (21.1 \u00b1 2.1% of total tumor-infiltrating immune cells) compared to non-tumor thyroid tissues (p = 0.0231). The infiltration levels of neutrophil-like monocytes were significantly higher in malignant nodules as well as in the peripheral blood of the papillary thyroid carcinoma patients compared to the samples obtained from the patients with benign nodules. The tumor tissues exhibited increased immune cell infiltration and harbored CD66b-expressing neutrophil-like HLA-DR+CD14+ monocytic cells, which indicates an inflammatory milieu in malignant thyroid cancer. Conclusions: This study identifies neutrophil-like monocytes as a potential biomarker for differentiating malignant and benign thyroid nodules. Elevated levels of this novel subtype of immune cells in malignant tissues suggest their role in tumor progression and their utility in enhancing diagnostic accuracy. Incorporating these findings into clinical practice may refine surgical decision-making and improve outcomes through personalized diagnostic and therapeutic strategies, particularly for radioiodine-refractory thyroid cancer.<\/jats:p>","DOI":"10.3390\/medicina61071256","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T15:36:58Z","timestamp":1752161818000},"page":"1256","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["CD66b+ Tumor-Infiltrating Neutrophil-like Monocytes as Potential Biomarkers for Clinical Decision-Making in Thyroid Cancer"],"prefix":"10.3390","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1066-552X","authenticated-orcid":false,"given":"Hamdullah","family":"Yanik","sequence":"first","affiliation":[{"name":"Department of Basic Oncology, Cancer Institute, Hacettepe University, Ankara 06230, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4670-0876","authenticated-orcid":false,"given":"Ilgin","family":"Demir","sequence":"additional","affiliation":[{"name":"Department of General Surgery, University of Health Sciences Gulhane Training and Research Hospital, Ankara 06010, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9982-192X","authenticated-orcid":false,"given":"Ertugrul","family":"Celik","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Health Sciences Gulhane Training and Research Hospital, Ankara 06010, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ece","family":"Tavukcuoglu","sequence":"additional","affiliation":[{"name":"Department of Basic Oncology, Cancer Institute, Hacettepe University, Ankara 06230, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9417-3866","authenticated-orcid":false,"given":"Ibrahim Burak","family":"Bahcecioglu","sequence":"additional","affiliation":[{"name":"Department of Surgical Oncology, University of Health Sciences Gulhane Training and Research Hospital, Ankara 06010, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0777-8934","authenticated-orcid":false,"given":"Adile Begum","family":"Bahcecioglu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Gulhane Research and Training Hospital, University of Health Sciences, Ankara 06010, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1137-8803","authenticated-orcid":false,"given":"Mehmet Mert","family":"Hidiroglu","sequence":"additional","affiliation":[{"name":"Department of General Surgery, University of Health Sciences Gulhane Training and Research Hospital, Ankara 06010, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5069-1872","authenticated-orcid":false,"given":"Sumeyra","family":"Guler","sequence":"additional","affiliation":[{"name":"Department of Surgical Oncology, University of Health Sciences Gulhane Training and Research Hospital, Ankara 06010, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nese","family":"Ersoz Gulcelik","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Gulhane Research and Training Hospital, University of Health Sciences, Ankara 06010, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8967-7303","authenticated-orcid":false,"given":"Mehmet Ali","family":"Gulcelik","sequence":"additional","affiliation":[{"name":"Department of Surgical Oncology, University of Health Sciences Gulhane Training and Research Hospital, Ankara 06010, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerim Bora","family":"Yilmaz","sequence":"additional","affiliation":[{"name":"Department of General Surgery, University of Health Sciences Gulhane Training and Research Hospital, Ankara 06010, Turkey"},{"name":"Department of Medical and Surgical Research, Institute of Health Sciences, Hacettepe University, Ankara 06230, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunes","family":"Esendagli","sequence":"additional","affiliation":[{"name":"Department of Basic Oncology, Cancer Institute, Hacettepe University, Ankara 06230, Turkey"},{"name":"Department of Medical and Surgical Research, Institute of Health Sciences, Hacettepe University, Ankara 06230, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"81","DOI":"10.17925\/EE.2024.20.2.11","article-title":"The Horizon of Thyroid Imaging Reporting and Data System in the Diagnostic Performance of Thyroid Nodules: Clinical Application and Future Perspectives","volume":"20","author":"Sharafi","year":"2024","journal-title":"touchREV Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"791","DOI":"10.2214\/AJR.22.28556","article-title":"Diagnostic Performance of Six Ultrasound Risk Stratification Systems for Thyroid Nodules: A Systematic Review and Network Meta-Analysis","volume":"220","author":"Kim","year":"2023","journal-title":"AJR Am. 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