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So, iMCD\u2010TAFRO is an aggressive subtype of iMCD with TAFRO syndrome and often hyper\u2010vascularized lymph nodes. Since we proposed diagnostic criteria of iMCD\u2010TAFRO in 2016, we have accumulated new insights on the disorder and additional cases have been reported worldwide. In this systematic review and cohort analysis, we established and validated a definition for iMCD\u2010TAFRO. First, we searched PubMed and Japan Medical Abstracts Society databases using the keyword \u201cTAFRO\u201d to extract cases. Patients with possible systemic autoimmune diseases and hematologic malignancies were excluded. Our search identified 54 cases from 50 articles. We classified cases into three categories: (1) iMCD\u2010TAFRO (TAFRO syndrome with lymph node histopathology consistent with iMCD), (2) possible iMCD\u2010TAFRO (TAFRO syndrome with no lymph node biopsy performed and no other co\u2010morbidities), and (3) TAFRO without iMCD or other co\u2010morbidities (TAFRO syndrome with lymph node histopathology not consistent with iMCD or other comorbidities). Based on the findings, we propose an international definition requiring four clinical criteria (thrombocytopenia, anasarca, fever\/hyperinflammatory status, organomegaly), renal dysfunction or characteristic bone marrow findings, and lymph node features consistent with iMCD. The definition was validated with an external cohort (the ACCELERATE Natural History Registry). The present international definition will facilitate a more precise and comprehensive approach to the diagnosis of iMCD\u2010TAFRO.<\/jats:p>","DOI":"10.1002\/ajh.26292","type":"journal-article","created":{"date-parts":[[2021,7,15]],"date-time":"2021-07-15T19:43:12Z","timestamp":1626378192000},"page":"1241-1252","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":133,"title":["Validated international definition of the thrombocytopenia, anasarca, fever, reticulin fibrosis, renal insufficiency, and organomegaly clinical subtype (TAFRO) of idiopathic multicentric <scp>Castleman<\/scp> disease"],"prefix":"10.1002","volume":"96","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0224-7501","authenticated-orcid":false,"given":"Yoshito","family":"Nishimura","sequence":"first","affiliation":[{"name":"Department of General Medicine Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences  Okayama Japan"},{"name":"Department of Medicine John A. 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