| I. Major criteria (need both) |
- 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):
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- Regressed/atrophic/atretic germinal centers, often with expanded mantle zones composed of concentric rings of lymphocytes in an "onion skinning" appearance
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- Vascularity, often with prominent endothelium in the interfollicular space and vessels penetrating into the GCs with a "lollipop" appearance
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- Sheetlike, polytypic plasmacytosis in the interfollicular space
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- Enlarged lymph nodes (≥1 cm in short-axis diameter) in ≥2 lymph node stations
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| II. Minor criteria (need at least 2 of 11 criteria with at least 1 laboratory criterion) |
| Laboratory:* |
- Elevated CRP (>10 mg/L) or ESR (>15 mm/hour)¶
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- Anemia (hemoglobin <12.5 g/dL for males, hemoglobin <11.5 g/dL for females)
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- Thrombocytopenia (platelet count <150 k/microL) or thrombocytosis (platelet count >400 k/microL)
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- Hypoalbuminemia (albumin <3.5 g/dL)
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- Renal dysfunction (eGFR <60 mL/min/1.73 m2) or proteinuria (total protein 150 mg/24 hours or 10 mg/100 mL)
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- Polyclonal hypergammaglobulinemia (total gamma-globulin or immunoglobulin G >1700 mg/dL)
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| Clinical: |
- Constitutional symptoms: Night sweats, fever (>38°C), weight loss, or fatigue (≥2 CTCAE lymphoma score for B-symptoms)
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- Large spleen and/or liver
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- Fluid accumulation: Edema, anasarca, ascites, or pleural effusion
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- Eruptive cherry hemangiomatosis or violaceous papules
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- Lymphocytic interstitial pneumonitis
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| III. Exclusion criteria (must rule out each of these diseases that can mimic iMCD) |
| Infection-related disorders: |
- 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)
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- Clinical EBV-lymphoproliferative disorders such as infectious mononucleosis or chronic active EBV (detectable EBV viral load not necessarily exclusionary)
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- Inflammation and adenopathy caused by other uncontrolled infections (eg, acute or uncontrolled CMV, toxoplasmosis, HIV, active tuberculosis)
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| Autoimmune/autoinflammatory diseases (requires full clinical criteria, detection of autoimmune antibodies alone is not exclusionary): |
- Systemic lupus erythematosus
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- Rheumatoid arthritis
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- Adult-onset Still disease
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- Juvenile idiopathic arthritis
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- Autoimmune lymphoproliferative syndrome
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| Malignant/lymphoproliferative disorders (these disorders must be diagnosed before or at the same time as iMCD to be exclusionary): |
- Lymphoma (Hodgkin and non-Hodgkin)
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- Multiple myeloma
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- Primary lymph node plasmacytoma
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- FDC sarcoma
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- POEMS syndromeΔ
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| Select additional features supportive of, but not required for diagnosis: |
- Elevated IL-6, sIL-2R, VEGF, IgA, IgE, LDH, and/or B2M
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- Reticulin fibrosis of bone marrow (particularly in patients with TAFRO syndrome)
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- Diagnosis of disorders that have been associated with iMCD: Paraneoplastic pemphigus, bronchiolitis obliterans organizing pneumonia, autoimmune cytopenias, polyneuropathy (without diagnosing POEMSΔ), glomerular nephropathy, inflammatory myofibroblastic tumor
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