{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:40:19Z","timestamp":1785404419181,"version":"3.56.0"},"reference-count":29,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T00:00:00Z","timestamp":1634083200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST110\u20102320\u2010B\u2010075\u2010003\u2010MY3"],"award-info":[{"award-number":["MOST110\u20102320\u2010B\u2010075\u2010003\u2010MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Cytopathology"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The studies on the cytomorphologic features of <jats:italic>NTRK<\/jats:italic>\u2010rearranged papillary thyroid carcinoma (PTC) are limited and some reported characteristics, such as frequent indeterminate diagnoses and presence of fibrotic fragments, are inconsistent in literature.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p><jats:italic>NTRK<\/jats:italic> gene rearrangements were detected in thyroidectomy specimens of PTC by either fluorescence in situ hybridization or next\u2010generation sequencing. All the cytologic slides of <jats:italic>NTRK<\/jats:italic>\u2010rearranged PTC were reviewed to evaluate the cytomorphologic features. The preoperative cytologic diagnoses of <jats:italic>NTRK<\/jats:italic>\u2010rearranged PTC were compared with those of <jats:italic>NTRK\/BRAF<\/jats:italic> wild\u2010type and <jats:italic>BRAF<jats:sup>V600E<\/jats:sup><\/jats:italic>\u2010positive PTC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Fourteen PTC cases were identified to harbor <jats:italic>NTRK<\/jats:italic> gene rearrangements. Most of them showed a mixed architectural pattern of cell fragments (n = 13, 92.9%) and microfollicles (n = 9, 64.3%) with relatively rare papillary structures (n = 4, 28.6%). Nuclear grooving was frequently present (n = 11, 78.6%) but was mostly subtle and limited. Seven cases (50.0%) showed rounded nuclei without discernible nuclear elongation, and only 3 (21.4%) cases presented with nuclear pseudoinclusions. Among these cases, 7 (50.0%) were diagnosed as The Bethesda System for Reporting Thyroid Cytopathology (TBS) category III, 2 (14.3%) were diagnosed as TBS IV, and 5 (35.7%) were diagnosed as TBS V. The rate of TBS III\u2010IV diagnoses for <jats:italic>NTRK<\/jats:italic>\u2010rearranged PTCs was significantly higher (64.3%) than that for the 25 consecutive <jats:italic>NTRK\/BRAF<\/jats:italic> wild\u2010type PTCs (20.0%, <jats:italic>P<\/jats:italic> = .013) and the 70 consecutive <jats:italic>BRAF<jats:sup>V600E<\/jats:sup><\/jats:italic>\u2010positive PTCs (7.1%, <jats:italic>P<\/jats:italic> &lt; .001) as selected.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p><jats:italic>NTRK<\/jats:italic>\u2010rearranged PTC demonstrated intermediate nuclear features, such as subtle nuclear grooving, infrequent nuclear elongation, and rare pseudoinclusions, resulting in a significantly higher rate of TBS III\u2010IV diagnoses compared to PTC with other molecular alterations.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncy.22522","type":"journal-article","created":{"date-parts":[[2021,10,17]],"date-time":"2021-10-17T04:12:25Z","timestamp":1634443945000},"page":"136-143","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["<i>NTRK<\/i>\u2010rearranged papillary thyroid carcinoma demonstrates frequent subtle nuclear features and indeterminate cytologic diagnoses"],"prefix":"10.1002","volume":"130","author":[{"given":"Yu\u2010Cheng","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Taipei Veterans General Hospital Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih\u2010Yi","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Taipei Veterans General Hospital Taipei Taiwan"},{"name":"School of Medicine National Yang Ming Chiao Tung University Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiung\u2010Ru","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Taipei Veterans General Hospital Taipei Taiwan"},{"name":"School of Medicine National Yang Ming Chiao Tung University Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4299-2784","authenticated-orcid":false,"given":"Jen\u2010Fan","family":"Hang","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Taipei Veterans General Hospital Taipei Taiwan"},{"name":"School of Medicine National Yang Ming Chiao Tung University Taipei Taiwan"},{"name":"Institute of Clinical Medicine National Yang Ming Chiao Tung University Taipei 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