{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T22:44:49Z","timestamp":1787870689147,"version":"build-2784847793"},"reference-count":46,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T00:00:00Z","timestamp":1755734400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017559","name":"Recordati Rare Diseases","doi-asserted-by":"publisher","award":["080524"],"award-info":[{"award-number":["080524"]}],"id":[{"id":"10.13039\/100017559","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":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Idiopathic multicentric Castleman disease (iMCD) is a rare cytokine\u2010driven disorder characterized by systemic inflammation, organ dysfunction, and altered lymph node microscopic architecture. Over the past decade, diagnostic criteria have evolved significantly, integrating clinical, histopathological, and molecular biomarker advancements. Key drivers of iMCD pathogenesis, such as interleukin\u20106 dysregulation and other dysfunctional cytokine signaling, have been identified and led to the development of targeted therapies like siltuximab and tocilizumab. Histopathologic refinements have highlighted distinct subtypes, such as hypervascular, plasmacytic, and mixed histologic patterns, while molecular discoveries have unveiled potential paraneoplastic and clonal processes. Emerging technologies, including single\u2010cell sequencing, spatial transcriptomics, and digital pathology, offer promise in refining diagnostic precision and advancing personalized medicine. This review synthesizes historical frameworks, recent breakthroughs, and future directions in iMCD diagnostics, emphasizing the importance of multidisciplinary approaches for improved patient outcomes.<\/jats:p>","DOI":"10.1002\/ajh.70039","type":"journal-article","created":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T12:35:46Z","timestamp":1755779746000},"page":"2064-2073","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The Evolution and Recent Advances in Diagnostic Criteria for Idiopathic Multicentric Castleman Disease"],"prefix":"10.1002","volume":"100","author":[{"given":"FNU","family":"Alnoor","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of Miami Miller School of Medicine  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas C.","family":"Spies","sequence":"additional","affiliation":[{"name":"ARUP Laboratories, Department of Pathology University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jyoti","family":"Kumar","sequence":"additional","affiliation":[{"name":"Division of Pathology, Department of Diagnostic Medicine The University of Texas at Austin  Austin Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peyman","family":"Samghabadi","sequence":"additional","affiliation":[{"name":"Department of Pathology University of California  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Silva","sequence":"additional","affiliation":[{"name":"Department of Pathology Stanford University  Stanford California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1740-0724","authenticated-orcid":false,"given":"Matt X.","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1898-1252","authenticated-orcid":false,"given":"Karen M.","family":"Chisholm","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology University of Washington  Seattle Washington USA"},{"name":"Department of Laboratories Seattle Children's Hospital  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Zhang","sequence":"additional","affiliation":[{"name":"University of Colorado Anschutz Medical Campus  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Rangel","sequence":"additional","affiliation":[{"name":"Department of Pathology University of California  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8604-2073","authenticated-orcid":false,"given":"David","family":"Ng","sequence":"additional","affiliation":[{"name":"ARUP Laboratories, Department of Pathology University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4711-362X","authenticated-orcid":false,"given":"Peng","family":"Li","sequence":"additional","affiliation":[{"name":"ARUP Laboratories, Department of Pathology University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1881-3440","authenticated-orcid":false,"given":"Robert S.","family":"Ohgami","sequence":"additional","affiliation":[{"name":"ARUP Laboratories, Department of Pathology University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,21]]},"reference":[{"issue":"10","key":"e_1_2_9_2_1","first-page":"396","article-title":"Case Records of the Massachusetts General Hospital; Weekly Clinicopathological Exercises; Case No. 40351","volume":"251","author":"Castleman B.","year":"1954","journal-title":"New England Journal of Medicine"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(195607\/08)9:4<822::AID-CNCR2820090430>3.0.CO;2-4"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-10-746933"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-12-545087"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1159\/000505099"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020004016"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2023021992"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(197203)29:3<670::AID-CNCR2820290321>3.0.CO;2-#"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-198304000-00001"},{"issue":"8","key":"e_1_2_9_11_1","first-page":"626","article-title":"Systemic Lymphoproliferative Disorder With Morphologic Features of Castleman's Disease. Immunoperoxidase Study of Cytoplasmic Immunoglobulins","volume":"108","author":"Miller R. T.","year":"1984","journal-title":"Archives of Pathology & Laboratory Medicine"},{"key":"e_1_2_9_12_1","first-page":"55","article-title":"Idiopathic Plasmacytic Lymphadenopathy With Polyclonal Hyperimmunoglobulinemia: A Syndrome Related to Giant Lymph Node Hyperplasia of Plasma Cell Type","volume":"20","author":"Mori S.","year":"1980","journal-title":"Journal of the Japanese Society for Lymphoreticular Tissue Research"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-198404000-00006"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcp\/83.1.27"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000372-198306000-00015"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V86.4.1276.bloodjournal8641276"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11899-017-0367-0"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2018.04.001"},{"issue":"5","key":"e_1_2_9_19_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"},{"issue":"6","key":"e_1_2_9_20_1","article-title":"Biomarkers and Signaling Pathways Implicated in the Pathogenesis of Idiopathic Multicentric Castleman Disease\/Thrombocytopenia, Anasarca, Fever, Reticulin Fibrosis, Renal Insufficiency, and Organomegaly (TAFRO) Syndrome","volume":"12","author":"Sumiyoshi R.","year":"2024","journal-title":"Biomedicine"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.3960\/jslrt.53.57"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-022-01620-2"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-023-01962-5"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/hon.2969"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.17305\/bjbms.2017.1930"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2022007112"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.14740\/jh1343"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-12-4602"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2023010745"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-11-884577"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI126091"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-003566"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/biology10040251"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-021-00317-7"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keac481"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.16330"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2017009654"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-021-00950-3"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2021.280370"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2019-131367"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-61214-1"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.135031"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2021-eular.2246"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2412494"},{"issue":"2","key":"e_1_2_9_45_1","first-page":"153","article-title":"Automated Diagnosis of Lymphoma With Digital Pathology Images Using Deep Learning","volume":"49","author":"Achi H. E.","year":"2019","journal-title":"Annals of Clinical and Laboratory Science"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13102419"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2023010652"}],"container-title":["American Journal of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajh.70039","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T09:09:18Z","timestamp":1763975358000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajh.70039"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,21]]},"references-count":46,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1002\/ajh.70039"],"URL":"https:\/\/doi.org\/10.1002\/ajh.70039","archive":["Portico"],"relation":{},"ISSN":["0361-8609","1096-8652"],"issn-type":[{"value":"0361-8609","type":"print"},{"value":"1096-8652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,21]]},"assertion":[{"value":"2025-04-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}