Received a pathology report confirming CD / iMCD features and need to conclude the diagnostic process?
Return to the diagnostic journey overviewIdiopathic MCD (iMCD) – Confirming a diagnosis
If you have received a pathology report identifying CD / iMCD features in your patients lymph node (and the patient has 2+ enlarged lymph nodes), it is possible they have iMCD – but first, you need to ADD two or more minor criteria and EXCLUDE potential mimics.
- Step one
- Step two
Add minor criteria
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)
- Fluid accumulation: oedema, anasarca, ascites or pleural effusion
- Large spleen and/or liver
- Eruptive cherry haemangiomatosis or violaceous papules
- Lymphocytic interstitial pneumonitis
2. Laboratory parameters
- Elevated CRP (> 10 mg/L) or ESR (> 15 mm/h)*
- Anaemia (haemoglobin < 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; 150 mg/24h or 10 mg/100 ml)
- Polyclonal hypergammaglobulinemia (total γ globulin or immunoglobulin G > 1700 mg/dL)
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)
- Diagnosis of disorders that have been associated with iMCD: paraneoplastic pemphigus, bronchiolitis obliterans organizing pneumonia, autoimmune cytopenias, polyneuropathy (without diagnosing POEMS†), glomerular nephropathy, inflammatory myofibroblastic tumour
*Evaluation of CRP is mandatory, and tracking is highly recommended, but ESR is acceptable where CRP is not avaiable.
Abbreviations: B2M, b-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 plasma cell disorder and skin changes;
sIL-2R, soluble interleukin 2 receptor; TAFRO, thrombocytopenia, anasarca, fever,
reticulin fibrosis, organomegaly; VEGF, vascular endothelial growth factor.
References: 1. Fajgenbaum DC, et al. Blood. 2017; 129: 1646–57.
Exclude potential mimics
Exclude all listed potential mimics to reach a diagnosis of iMCD.
1. Clinical symptoms
- 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's disease
- Juvenile idiopathic arthritis
- Autoimmune lymphoproliferative syndrome
Requires full clinical criteria, detection of autoimmune antibodies alone is not exclusionary
3. Malignant/lymphoproliferative
- Lymphoma (Hodgkin's and non-Hodgkin's)
- Multiple myeloma
- Primary lymph node plasmacytoma
- FDC sarcoma
- POEMS Syndrome (considered a disease ‘associated’ with CD)†
These disorders must be diagnosed before or at the same time as iMCD to be exclusionary.
†POEMS is considered to be a disease "associated" with CD. Because the monoclonal
plasma cells are believed to drive the cytokine storm, we do not consider it 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, immunohistochemical staining; iMCD, idiopathic Multicentric Castleman Disease; LANA-1,
latency-associated nuclear antigen; PCR, polymerase chain reaction;
POEMS, polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder and skin changes.
References: 1. Fajgenbaum DC, et al. Blood. 2017; 129: 1646–57.
