Received a pathology report confirming CD / iMCD features and need to conclude the diagnostic process?
Return to the diagnostic journey overviewIdiopathic multicentric Castleman disease (iMCD) – Confirming a diagnosis
- Step one
- Step two
Add minor criteria1
Add at least two minor criteria, including at least 1 laboratory abnormality.
1. Clinical symptoms
- Constitutional symptoms: night sweats, fever (> 38 °C), weight loss or fatigue (≥ 2 CTCAE lymphoma score for B-symptoms)
- Large spleen and/or liver
- Fluid accumulation: edema, anasarca, ascites or pleural effusion
- Eruptive cherry haemangiomatosis or violaceous papules
- Lymphocytic interstitial pneumonitis
2. Laboratory parameters*
- Elevated CRP (> 10 mg/L) or ESR (> 15 mm/h)†
- Anemia (hemoglobin < 12.5 g/dL for males, < 11.5 g/dL for females)
- Thrombocytopaenia (platelet count < 150 k/μL) or thrombocytosis (platelet count > 400 k/μL)
- Hypoalbuminaemia (albumin < 3.5 g/dL)
- Renal dysfunction (eGFR < 60 mL/min/1.73 m2) or proteinuria (total protein; 150 mg/24h or 10 mg/100 ml)
- Polyclonal hypergammaglobulinemia (total γ globulin or immunoglobulin G > 1700 mg/dL)
*Laboratory cutoff thresholds should be used as guidance as some laboratories have slightly different ranges. It is recommended to use the upper and lower ranges from the particular laboratory to determine if a patient meets a particular laboratory Minor Criterion.
†Evaluation of CRP is mandatory, and tracking is highly recommended, but ESR is acceptable where CRP is not available.
Abbreviations: B2M, β-2-microglobulin; CD, Castleman disease; CRP, C-reactive protein; CTCAE, common terminology criteria for adverse events; eGFR, estimated glomerular filtration rate; ESR, erythrocyte sedimentation rate; IgA, immunoglobulin A; IgE, immunoglobulin E; IL-6, interleukin-6; iMCD, idiopathic multicentric Castleman disease; LDH, lactate dehydrogenase; POEMS, polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes; sIL-2R, soluble interleukin 2 receptor; TAFRO, thrombocytopenia, anasarca/ascites, reticulin fibrosis in bone marrow, renal dysfunction, organomegaly; VEGF, vascular endothelial growth factor.
References: 1. Fajgenbaum DC, Uldrick TS, Bagg A, et al. International, evidence-based consensus diagnostic criteria for HHV-8-negative/idiopathic multicentric Castleman disease. Blood. 2017;129(12):1646-1657.
Exclude potential mimics1
Exclude all listed potential mimics to reach a diagnosis of iMCD.
1. Infection-related
- HHV-8 (infection can be documented by blood PCR; diagnosis of HHV-8 associated MCD requires positive LANA-1 staining by IHC, which excludes iMCD)
- Clinical EBV-lymphoproliferative disorders such as infectious mononucleosis or chronic active EBV (detectable EBV viral load not necessarily exclusionary)
- Inflammation and adenopathy caused by other uncontrolled infections (e.g. acute or uncontrolled CMV, toxoplasmosis, HIV, active tuberculosis)
2. Autoimmune/autoinflammatory
- Systemic lupus erythematosus
- Rheumatoid arthritis
- Adult-onset Still disease
- Juvenile idiopathic arthritis
- Autoimmune lymphoproliferative syndrome
Requires full clinical criteria, detection of autoimmune antibodies alone is not exclusionary.
3. Malignant/lymphoproliferative
- Lymphoma (Hodgkin and non-Hodgkin)
- Multiple myeloma
- Primary lymph node plasmacytoma
- FDC sarcoma
- POEMS Syndrome*
These disorders must be assessed at the same time as iMCD to be exclusionary.
Select additional features supportive of, but not required for diagnosis:
- Elevated IL-6, sIL-2R, VEGF, IgA, IgE, LDH, and/or B2M
- Reticulin fibrosis of bone marrow (particularly in patients with TAFRO syndrome [thrombocytopenia, anasarca/ascites, reticulin fibrosis in bone marrow, renal dysfunction, organomegaly])
- Diagnosis of disorders that have been associated with iMCD: paraneoplastic pemphigus, bronchiolitis obliterans organizing pneumonia, autoimmune cytopenias, polyneuropathy (without diagnosing POEMS* [polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes]), glomerular nephropathy, inflammatory myofibroblastic tumor
*POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes) is considered to be a disease “associated” with CD. Because the monoclonal plasma cells are believed to drive the cytokine storm, it is not considered iMCD, but rather “POEMS-associated MCD.”
Abbreviations: CD, Castleman disease; CMV, cytomegalovirus; EBV, Epstein-Barr virus; FDC, follicular dendritic cell; HHV-8, human herpesvirus 8; HIV, human immunodeficiency virus; IHC, immunohistochemistry staining; iMCD, idiopathic multicentric Castleman disease; LANA-1, latency-associated nuclear antigen; PCR, polymerase chain reaction; POEMS, polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes.
References: 1. Fajgenbaum DC, Uldrick TS, Bagg A, et al. International, evidence-based consensus diagnostic criteria for HHV-8-negative/idiopathic multicentric Castleman disease. Blood. 2017;129(12):1646-1657.
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