{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T16:18:13Z","timestamp":1792167493473,"version":"4.4.0"},"reference-count":24,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T00:00:00Z","timestamp":1750377600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour and Welfare","doi-asserted-by":"publisher","award":["JPMH23FC1025"],"award-info":[{"award-number":["JPMH23FC1025"]}],"id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP22K15405"],"award-info":[{"award-number":["JP22K15405"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP23K14476"],"award-info":[{"award-number":["JP23K14476"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP24KK0172"],"award-info":[{"award-number":["JP24KK0172"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP25K02476"],"award-info":[{"award-number":["JP25K02476"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Idiopathic multicentric Castleman disease (iMCD) is a rare lymphoproliferative disorder classified into three recognized clinical subtypes\u2014idiopathic plasmacytic lymphadenopathy (IPL), TAFRO, and NOS. Although clinical criteria are available for subtyping, diagnostically challenging cases with overlapping histopathological features highlight the need for an improved classification system integrating clinical and histopathological findings. We aimed to develop an objective histopathological subtyping system for iMCD that closely correlates with the clinical subtypes. Excisional lymph node specimens from 94 Japanese iMCD patients (54 IPL, 28 TAFRO, 12 NOS) were analyzed for five key histopathological parameters: germinal center (GC) status, plasmacytosis, vascularity, hemosiderin deposition, and \u201cwhirlpool\u201d vessel formation in GC. Using hierarchical clustering, we visualized subgroups and developed a machine learning\u2010based decision tree to differentiate the clinical subtypes and validated it in an external cohort of 12 patients with iMCD. Hierarchical cluster analysis separated the IPL and TAFRO cases into mutually exclusive clusters, whereas the NOS cases were interspersed between them. Decision tree modeling identified plasmacytosis, vascularity, and whirlpool vessel formation as key features distinguishing IPL from TAFRO, achieving 91% and 92% accuracy in the training and test sets, respectively. External validation correctly classified all IPL and TAFRO cases, confirming the reproducibility of the system. Our histopathological classification system closely aligns with the clinical subtypes, offering a more precise approach to iMCD subtyping. It may enhance diagnostic accuracy, guide clinical decision\u2010making for predicting treatment response in challenging cases, and improve patient selection for future research. Further validation of its versatility and clinical utility is required.<\/jats:p>","DOI":"10.1002\/ajh.27743","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T13:44:11Z","timestamp":1750427051000},"page":"1502-1512","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["International Consensus Histopathological Criteria for Subtyping Idiopathic Multicentric Castleman Disease Based on Machine Learning Analysis"],"prefix":"10.1002","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8433-4870","authenticated-orcid":false,"given":"Midori Filiz","family":"Nishimura","sequence":"first","affiliation":[{"name":"Department of Molecular Hematopathology Okayama University Graduate School of Health Sciences  Okayama Japan"},{"name":"The Research Program for Intractable Disease by Ministry of Health, Labor and Welfare, Castleman Disease TAFRO and Related Ddisease Research Group  Nagasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4366-3458","authenticated-orcid":false,"given":"Tomoka","family":"Haratake","sequence":"additional","affiliation":[{"name":"Department of Molecular Hematopathology Okayama University Graduate School of Health Sciences  Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0224-7501","authenticated-orcid":false,"given":"Yoshito","family":"Nishimura","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Mayo Clinic  Rochester Minnesota USA"},{"name":"Department of General Medicine Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences  Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1485-0527","authenticated-orcid":false,"given":"Asami","family":"Nishikori","sequence":"additional","affiliation":[{"name":"Department of Molecular Hematopathology Okayama University Graduate School of Health Sciences  Okayama Japan"},{"name":"The Research Program for Intractable Disease by Ministry of Health, Labor and Welfare, Castleman Disease TAFRO and Related Ddisease Research Group  Nagasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4814-7137","authenticated-orcid":false,"given":"Remi","family":"Sumiyoshi","sequence":"additional","affiliation":[{"name":"The Research Program for Intractable Disease by Ministry of Health, Labor and Welfare, Castleman Disease TAFRO and Related Ddisease Research Group  Nagasaki Japan"},{"name":"Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences Nagasaki University Graduate School of Biomedical Sciences  Nagasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Ujiie","sequence":"additional","affiliation":[{"name":"Department of Molecular Hematopathology Okayama University Graduate School of Health Sciences  Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuri","family":"Kawahara","sequence":"additional","affiliation":[{"name":"Department of Molecular Hematopathology Okayama University Graduate School of Health Sciences  Okayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2077-4428","authenticated-orcid":false,"given":"Tomohiro","family":"Koga","sequence":"additional","affiliation":[{"name":"The Research Program for Intractable Disease by Ministry of Health, Labor and Welfare, Castleman Disease TAFRO and Related Ddisease Research Group  Nagasaki Japan"},{"name":"Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences Nagasaki University Graduate School of Biomedical Sciences  Nagasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masao","family":"Ueki","sequence":"additional","affiliation":[{"name":"School of Information and Data Sciences Nagasaki University  Nagasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorottya","family":"Laczko","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Hospital of the University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8588-7138","authenticated-orcid":false,"given":"Eric","family":"Oksenhendler","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology H\u00f4pital Saint\u2010Louis  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7367-8184","authenticated-orcid":false,"given":"David C.","family":"Fajgenbaum","sequence":"additional","affiliation":[{"name":"Center for Cytokine Storm Treatment and Laboratory, Division of Translational Medicine and Human Genetics, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9959-1282","authenticated-orcid":false,"given":"Frits","family":"van Rhee","sequence":"additional","affiliation":[{"name":"Myeloma Center University of Arkansas for Medical Sciences  Little Rock Arkansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Kawakami","sequence":"additional","affiliation":[{"name":"The Research Program for Intractable Disease by Ministry of Health, Labor and Welfare, Castleman Disease TAFRO and Related Ddisease Research Group  Nagasaki Japan"},{"name":"Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences Nagasaki University Graduate School of Biomedical Sciences  Nagasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5234-6861","authenticated-orcid":false,"given":"Yasuharu","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Molecular Hematopathology Okayama University Graduate School of Health Sciences  Okayama Japan"},{"name":"The Research Program for Intractable Disease by Ministry of Health, Labor and Welfare, Castleman Disease TAFRO and Related Ddisease Research Group  Nagasaki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,20]]},"reference":[{"key":"e_1_2_10_2_1","volume-title":"WHO Classification of Haematolymphoid Tumours","author":"Tumour\u2010like lesions with B\u2010cell predominance","year":"2024"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2023.101161"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.27612"},{"key":"e_1_2_10_5_1","first-page":"55","article-title":"Idiopathic Plasmacytic Lymphadenopathy With Polyclonal Hyperimmunoglobulinemia: A Syndrome Related to Giant Lymph Node Hyperplasia of Plasma Cell Type [in Japanese]","volume":"20","author":"Mohri S. Mori, N.","year":"1980","journal-title":"Japanese Journal of Sociological Research"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/1066896908315812"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3960\/jslrt.22011"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms231810301"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.24242"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.26292"},{"key":"e_1_2_10_11_1","first-page":"320","article-title":"Thrombocytopenia With Mild Bone Marrow Fibrosis Accompanied by Fever, Pleural Effusion, Ascites and Hepatosplenomegaly","volume":"51","author":"Takai K.","year":"2010","journal-title":"Rinsh\u014d Ketsueki"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3960\/jslrt.53.57"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-07-862334"},{"key":"e_1_2_10_14_1","unstructured":"National Comprehensive Cancer Network Castleman Disease (Version 2. 2025)."},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-12-4602"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-020-04275-0"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25992"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-10-746933"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.modpat.2025.100782"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.3960\/jslrt.19037"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-016-1979-1"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2017.09.015"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0344-0338(97)80015-5"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2007.03.002"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.3960\/jslrt.21036"}],"container-title":["American Journal of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajh.27743","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T11:39:33Z","timestamp":1760701173000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajh.27743"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,20]]},"references-count":24,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1002\/ajh.27743"],"URL":"https:\/\/doi.org\/10.1002\/ajh.27743","archive":["Portico"],"relation":{},"ISSN":["0361-8609","1096-8652"],"issn-type":[{"value":"0361-8609","type":"print"},{"value":"1096-8652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,20]]},"assertion":[{"value":"2025-03-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}