| 1. Presence of both major criteria |
| Lymph nodes with typical histology, and |
| lymph nodes enlarged >1 cm in at least 2 stations |
| 2. Presence of at least 2 of 11 minor criteria (including at least 1 laboratory criterion) |
| Clinical symptoms |
| 1. B symptoms (night sweats, fever over 38°C, weight loss, or fatigue) |
| 2. Splenomegaly and/or hepatomegaly |
| 3. Edema, anasarca, ascites, and pleural effusions |
| 4. Lymphocytic interstitial pneumonia |
| 5. “Eruptive” hemangiomatosis |
| Laboratory criteria |
| 1. Elevated CRP (>10 mg/L) or blood sedimentation (>15 mm/h) |
| 2. Anemia (hemoglobin <12.5 g/dL for men and <11.5 g/dL for women) |
| 3. Thrombocytopenia (platelet count, <150 per μL) or thrombocytosis (>400/μL) |
| 4. Hypoalbuminemia (<3.5 g/dL) |
| 5. Renal function impairment (eGFR, <60 mL/min per 1.73m2) or proteinuria (total protein, 150 mg/24 h or 10 mg/100 mL) |
| 6. Polyclonal hypergammaglobulinemia (>1700 mg/dL) |
| 3. Exclusion of other diseases with “Castleman-like” histology |
| Infection-associated diseases: HHV8 (PCR, serology, and/or LANA staining in the lymph node); infectious mononucleosis (EBV, otherwise no exclusion criterion); and lymphadenopathy due to HIV, CMV, toxoplasmosis, and tuberculosis. |
| Defined autoimmune diseases (detected antibodies alone do not exclude iMCD) such as systemic lupus erythematosus, rheumatoid arthritis, adult-onset Still disease, juvenile idiopathic arthritis, and autoimmune lymphoproliferative syndrome. |
| Malignant or lymphoproliferative diseases, diagnosed at the same time (Hodgkin and non-Hodgkin lymphomas, multiple myeloma, plasmacytoma localized primarily in the lymph node, and FDC sarcoma). |
| 1. Presence of both major criteria |
| Lymph nodes with typical histology, and |
| lymph nodes enlarged >1 cm in at least 2 stations |
| 2. Presence of at least 2 of 11 minor criteria (including at least 1 laboratory criterion) |
| Clinical symptoms |
| 1. B symptoms (night sweats, fever over 38°C, weight loss, or fatigue) |
| 2. Splenomegaly and/or hepatomegaly |
| 3. Edema, anasarca, ascites, and pleural effusions |
| 4. Lymphocytic interstitial pneumonia |
| 5. “Eruptive” hemangiomatosis |
| Laboratory criteria |
| 1. Elevated CRP (>10 mg/L) or blood sedimentation (>15 mm/h) |
| 2. Anemia (hemoglobin <12.5 g/dL for men and <11.5 g/dL for women) |
| 3. Thrombocytopenia (platelet count, <150 per μL) or thrombocytosis (>400/μL) |
| 4. Hypoalbuminemia (<3.5 g/dL) |
| 5. Renal function impairment (eGFR, <60 mL/min per 1.73m2) or proteinuria (total protein, 150 mg/24 h or 10 mg/100 mL) |
| 6. Polyclonal hypergammaglobulinemia (>1700 mg/dL) |
| 3. Exclusion of other diseases with “Castleman-like” histology |
| Infection-associated diseases: HHV8 (PCR, serology, and/or LANA staining in the lymph node); infectious mononucleosis (EBV, otherwise no exclusion criterion); and lymphadenopathy due to HIV, CMV, toxoplasmosis, and tuberculosis. |
| Defined autoimmune diseases (detected antibodies alone do not exclude iMCD) such as systemic lupus erythematosus, rheumatoid arthritis, adult-onset Still disease, juvenile idiopathic arthritis, and autoimmune lymphoproliferative syndrome. |
| Malignant or lymphoproliferative diseases, diagnosed at the same time (Hodgkin and non-Hodgkin lymphomas, multiple myeloma, plasmacytoma localized primarily in the lymph node, and FDC sarcoma). |
CMV, cytomegalovirus; EBV, Epstein-Barr virus; eGFR, estimated glomerular filtration rate; FDC, follicular dendritic cell; LANA, latency-associated nuclear antigen; PCR, polymerase chain reaction.
Adapted from Fajgenbaum et al4