{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T11:10:22Z","timestamp":1780485022916,"version":"3.54.1"},"reference-count":9,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cytopathology"],"published-print":{"date-parts":[[2026,7]]},"abstract":"ABSTRACT<\/jats:title>\n \n Objective<\/jats:title>\n Conventional liquid biopsy primarily focuses on epithelial circulating tumour cells (CTCs). We previously demonstrated that a population of circulating cells in thoracic tumours express the vascular endothelial marker ERG. In this study, we defined these ERG\u2010positive cells with endothelial morphology in liquid\u2010based cytology (LBC) as \u201ccirculating tumor\u2010related endothelial\u2010like cells\u201d (CELCs). Our aim was to establish a morphological grading system to distinguish malignancy\u2010specific High\u2010Grade CELC from benign or reactive CELC populations.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Preoperative arterial blood samples from 28 patients (25 malignant and 3 benign cases) were processed using a soft\u2010microporous filtration system (S\u2010MPF). Captured cells were evaluated by Papanicolaou staining. CELCs were categorized based on LBC morphology into \u201cLow\u2010Grade\u201d (single cells or clusters <\u200915 cells) and \u201cHigh\u2010Grade\u201d (three\u2010dimensional morula\u2010like clusters \u2265\u200915 cells with marked nuclear pleomorphism).<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n CELCs were identified in 13 cases (46.4%). While Low\u2010Grade CELCs were observed in both cohorts (12 malignant, 1 benign), High\u2010Grade clusters\u2014representing definitive CTEC signatures\u2014were exclusively identified in 8 malignant cases (5 primary lung cancers, 2 metastatic tumours, and 1 thymic cancer). No High\u2010Grade features were detected in benign lesions, yielding a specificity of 100% (95% CI: 29.2%\u2013100%) for malignancy.<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Implementing an LBC\u2010based morphological threshold of \u2265\u200915 cells allows malignancy\u2010specific CELCs to be accurately distinguished from the broader population of CELCs. This grading system provides a practical and highly specific liquid biopsy framework, ensuring precise identification of tumour\u2010associated endothelial clusters even amidst reactive non\u2010malignant cells.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n UMIN Clinical Trials Registry (UMIN\u2010CTR, identifier: UMIN000058385)<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/cyt.70075","type":"journal-article","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T11:14:56Z","timestamp":1775646896000},"page":"344-352","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["High\u2010Grade Atypia in Circulating Tumour\u2010Related Endothelial\u2010Like Cells Serves as a Specific Marker for Malignant Thoracic Tumours"],"prefix":"10.1111","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4899-1005","authenticated-orcid":false,"given":"Noriyoshi","family":"Sawabata","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery Kawanishi City Medical Center Kawanishi Hyogo Japan"},{"name":"Department of Diagnostic Pathology Nara Medical University Nara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nagisa","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Kawanishi City Medical Center Kawanishi Hyogo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeru","family":"Nakane","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Kawanishi City Medical Center Kawanishi Hyogo Japan"},{"name":"Department of Thoracic Surgery Minoh City Hospital Minoh Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigenobu","family":"Tatsumi","sequence":"additional","affiliation":[{"name":"Department of Hospital\u2010Based Pathology Nara Medical University Hospital Nara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Nishikawa","sequence":"additional","affiliation":[{"name":"Faculty of Health Care Department of Clinical Laboratory Science Tenri University Nara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Pathology Kawanishi City Medical Center Kawanishi Hyogo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,8]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571\u2010019\u20100187\u20103"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3820"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1971"},{"key":"e_1_2_12_5_1","unstructured":"N.Sawabata \u201cMorphological Analysis of Circulating Tumor Cells in Thoracic Malignancy. KAKENHI Research Report (21H03021) \u201d(2025) https:\/\/kaken.nii.ac.jp\/ja\/file\/KAKENHI\u2010PROJECT\u201021H03021\/21H03021seika.pdf."},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.21873\/anticanres.15989"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.21873\/anticanres.16715"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2015.109"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102007\u201008\u2010105346"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.12251"}],"container-title":["Cytopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cyt.70075","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cyt.70075","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cyt.70075","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T10:39:15Z","timestamp":1780483155000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cyt.70075"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,8]]},"references-count":9,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1111\/cyt.70075"],"URL":"https:\/\/doi.org\/10.1111\/cyt.70075","archive":["Portico"],"relation":{},"ISSN":["0956-5507","1365-2303"],"issn-type":[{"value":"0956-5507","type":"print"},{"value":"1365-2303","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,8]]},"assertion":[{"value":"2025-12-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-08","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}