{"id":10412,"date":"2024-07-16T19:37:54","date_gmt":"2024-07-16T19:37:54","guid":{"rendered":"https:\/\/medicalcriteria.com\/web\/?p=10412"},"modified":"2025-12-30T18:52:07","modified_gmt":"2025-12-30T18:52:07","slug":"imcd","status":"publish","type":"post","link":"https:\/\/medicalcriteria.com\/web\/imcd\/","title":{"rendered":"Diagnostic Criteria for Idiopathic Multicentric Castleman Disease (iMCD)"},"content":{"rendered":"<div class=\"99c380e4b4a7b96c35d7ddf7dcb434e8\" data-index=\"1\" style=\"float: none; margin:0px 0 0px 0; text-align:center;\">\n<script async src=\"https:\/\/pagead2.googlesyndication.com\/pagead\/js\/adsbygoogle.js\"><\/script>\r\n<!-- MC 2019- Horizontal -->\r\n<ins class=\"adsbygoogle\"\r\n     style=\"display:block\"\r\n     data-ad-client=\"ca-pub-0127150553352455\"\r\n     data-ad-slot=\"3806776041\"\r\n     data-ad-format=\"auto\"\r\n     data-full-width-responsive=\"true\"><\/ins>\r\n<script>\r\n     (adsbygoogle = window.adsbygoogle || []).push({});\r\n<\/script>\n<\/div>\n<p>Human herpesvirus-8 (HHV-8)\u2013negative, idiopathic multicentric Castleman disease (iMCD) is a rare and life-threatening disorder involving systemic inflammatory symptoms, polyclonal lymphoproliferation, cytopenias, and multiple organ system dysfunction caused by a cytokine storm often including interleukin-6. Accurate diagnosis is challenging, because no standard diagnostic criteria or diagnostic biomarkers currently exist, and there is significant overlap with malignant, autoimmune, and infectious disorders.<!--more--><\/p>\n<p><strong>Diagnostic Criteria for iMCD<\/strong><\/p>\n<p><strong>I. Major Criteria (need both):<\/strong><br \/>\n1. Histopathologic lymph node features consistent with the iMCD spectrum. Features along the iMCD spectrum include (need grade 2-3 for either regressive GCs or plasmacytosis at minimum):<\/p>\n<ul>\n<li>Regressed\/atrophic\/atretic germinal centers, often with expanded mantle zones composed of concentric rings of lymphocytes in an \u201conion skinning\u201d appearance<\/li>\n<li>Follicular dendritic cell (FDC) prominence<\/li>\n<li>Vascularity, often with prominent endothelium in the interfollicluar space and vessels penetrating into the GCs with a \u201clollipop\u201d appearance<\/li>\n<li>Sheetlike, polytypic plasmacytosis in the interfollicular space<\/li>\n<li>Hyperplastic GCs<\/li>\n<\/ul>\n<p>2. Enlarged lymph nodes (\u22651 cm in short-axis diameter) in \u22652 lymph node stations<\/p>\n<p><strong>II. Minor Criteria (need at least 2 of 11 criteria with at least 1 laboratory criterion)<\/strong><\/p>\n<p>Laboratory*<\/p>\n<ol>\n<li>Elevated CRP (&gt;10 mg\/L) or ESR (&gt;15 mm\/h)\u2020<\/li>\n<li>Anemia (hemoglobin &lt;12.5 g\/dL for males, hemoglobin &lt;11.5 g\/dL for females)<\/li>\n<li>Thrombocytopenia (platelet count &lt;150 k\/mL) or thrombocytosis (platelet count &gt;400 k\/mL)<\/li>\n<li>Hypoalbuminemia (albumin &lt;3.5 g\/dL)<\/li>\n<li>Renal dysfunction (eGFR &lt;60 mL\/min\/1.73m2) or proteinuria (total protein 150 mg\/24 h or 10 mg\/100 ml)<\/li>\n<li>Polyclonal hypergammaglobulinemia (total \u03b3 globulin or immunoglobulin G &gt;1700 mg\/dL)<\/li>\n<\/ol>\n<p>Clinical<\/p>\n<ol>\n<li>Constitutional symptoms: night sweats, fever (&gt;38\u00b0C), weight loss, or fatigue (\u22652 CTCAE lymphoma score for B-symptoms)<\/li>\n<li>Large spleen and\/or liver<\/li>\n<li>Fluid accumulation: edema, anasarca, ascites, or pleural effusion<\/li>\n<li>Eruptive cherry hemangiomatosis or violaceous papules<\/li>\n<li>Lymphocytic interstitial pneumonitis<\/li>\n<\/ol>\n<p><strong>III. Exclusion Criteria (must rule out each of these diseases that can mimic iMCD)<\/strong><\/p>\n<p>Infection-related disorders<\/p>\n<ol>\n<li>HHV-8 (infection can be documented by blood PCR, diagnosis of HHV-8\u2013associated MCD requires positive LANA-1 staining by IHC, which excludes iMCD)<\/li>\n<li>Clinical EBV-lymphoproliferative disorders such as infectious mononucleosis or chronic active EBV (detectable EBV viral load not necessarily exclusionary)<\/li>\n<li>Inflammation and adenopathy caused by other uncontrolled infections (eg, acute or uncontrolled CMV, toxoplasmosis, HIV, active tuberculosis)<\/li>\n<\/ol>\n<p>Autoimmune\/autoinflammatory diseases (requires full clinical criteria, detection of autoimmune antibodies alone is not exclusionary)<\/p>\n<ol>\n<li>Systemic lupus erythematosus<\/li>\n<li>Rheumatoid arthritis<\/li>\n<li>Adult-onset Still disease<\/li>\n<li>Juvenile idiopathic arthritis<\/li>\n<li>Autoimmune lymphoproliferative syndrome<\/li>\n<\/ol>\n<p>Malignant\/lymphoproliferative disorders (these disorders must be diagnosed before or at the same time as iMCD to be exclusionary):<\/p>\n<ol>\n<li>Lymphoma (Hodgkin and non-Hodgkin)<\/li>\n<li>Multiple myeloma<\/li>\n<li>Primary lymph node plasmacytoma<\/li>\n<li>FDC sarcoma<\/li>\n<li>POEMS syndrome\u2021<\/li>\n<\/ol>\n<p>Select additional features supportive of, but not required for diagnosis<\/p>\n<ol>\n<li>Elevated IL-6, sIL-2R, VEGF, IgA, IgE, LDH, and\/or B2M<\/li>\n<li>Reticulin fibrosis of bone marrow (particularly in patients with trombocytopenia, anasarca\/ascites, reticulin fibrosis in bone marrow, renal dysfunction, organomegaly (TAFRO))<\/li>\n<li>Diagnosis of disorders that have been associated with iMCD: paraneoplastic pemphigus, bronchiolitis obliterans organizing pneumonia, autoimmune cytopenias, polyneuropathy (without diagnosing POEMS\u2021), glomerular nephropathy, inflammatory myofibroblastic tumor<\/li>\n<\/ol>\n<p>B2M, b-2-microglobulin; CMV, cytomegalovirus; CTCAE, common terminology for adverse events; eGFR, estimated glomerular filtration rate; GC, germinal center; IHC, Immunohistochemistry; LANA-1, latency-associated nuclear antigen; LDH, lactate dehydrogenase; EBV, Epstein-Barr virus.<br \/>\n\u2020Evaluation of CRP is mandatory and tracking CRP levels is highly recommended, but ESR will be accepted if CRP is not available.<br \/>\n\u2021POEMS is considered to be a disease \u201cassociated\u201d with Castleman disease. Because the monoclonal plasma cells are believed to drive the cytokine storm, we do not consider it iMCD, but rather \u201cPOEMS-associated MCD.\u201d<\/p>\n<p>&nbsp;<\/p>\n<p><strong>References:<\/strong><\/p>\n<ol>\n<li>Fajgenbaum DC, Uldrick TS, Bagg A, Frank D, Wu D, Srkalovic G, Simpson D, Liu AY, Menke D, Chandrakasan S, Lechowicz MJ, Wong RS, Pierson S, Paessler M, Rossi JF, Ide M, Ruth J, Croglio M, Suarez A, Krymskaya V, Chadburn A, Colleoni G, Nasta S, Jayanthan R, Nabel CS, Casper C, Dispenzieri A, Foss\u00e5 A, Kelleher D, Kurzrock R, Voorhees P, Dogan A, Yoshizaki K, van Rhee F, Oksenhendler E, Jaffe ES, Elenitoba-Johnson KS, Lim MS. International, evidence-based consensus diagnostic criteria for HHV-8-negative\/idiopathic multicentric Castleman disease. Blood. 2017 Mar 23;129(12):1646-1657. <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/28087540\/\" target=\"_blank\" rel=\"noopener\">[Medline]<\/a><\/li>\n<li>Lang E, van Rhee F. Idiopathic multicentric Castleman disease: An update in diagnosis and treatment advances. Blood Rev. 2024 Mar;64:101161. <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/38087716\/\" target=\"_blank\" rel=\"noopener\">[Medline]<\/a><\/li>\n<\/ol>\n<p>&nbsp;<\/p>\n<p>Created Jul 03, 2024.<\/p>\n\n<div style=\"font-size: 0px; height: 0px; line-height: 0px; margin: 0; padding: 0; clear: both;\"><\/div>","protected":false},"excerpt":{"rendered":"<p>Sorry, this entry is only available in Espa\u00f1ol.<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_lmt_disableupdate":"no","_lmt_disable":"no","_exactmetrics_skip_tracking":false,"_exactmetrics_sitenote_active":false,"_exactmetrics_sitenote_note":"","_exactmetrics_sitenote_category":0,"footnotes":""},"categories":[171],"tags":[2659,16,15,14,13,51,50,65,64,2660,2658,2661],"class_list":["post-10412","post","type-post","status-publish","format-standard","hentry","category-hematology","tag-castleman","tag-criteria","tag-criterios","tag-diagnostic","tag-diagnostico","tag-disease","tag-enfermedad","tag-idiopathic","tag-idiopatica","tag-imcd","tag-multicentric","tag-multicentrica"],"modified_by":"Guillermo Firman","_links":{"self":[{"href":"https:\/\/medicalcriteria.com\/web\/wp-json\/wp\/v2\/posts\/10412","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/medicalcriteria.com\/web\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/medicalcriteria.com\/web\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/medicalcriteria.com\/web\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/medicalcriteria.com\/web\/wp-json\/wp\/v2\/comments?post=10412"}],"version-history":[{"count":13,"href":"https:\/\/medicalcriteria.com\/web\/wp-json\/wp\/v2\/posts\/10412\/revisions"}],"predecessor-version":[{"id":10430,"href":"https:\/\/medicalcriteria.com\/web\/wp-json\/wp\/v2\/posts\/10412\/revisions\/10430"}],"wp:attachment":[{"href":"https:\/\/medicalcriteria.com\/web\/wp-json\/wp\/v2\/media?parent=10412"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/medicalcriteria.com\/web\/wp-json\/wp\/v2\/categories?post=10412"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/medicalcriteria.com\/web\/wp-json\/wp\/v2\/tags?post=10412"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}