Clinical, laboratory, and histopathological features of subtypes of MCD
| . | MCD subtypes . | ||||
|---|---|---|---|---|---|
| . | POEMS-MCD . | HHV8-MCD . | iMCD . | ||
| iMCD-TAFRO . | iMCD-IPL . | iMCD-NOS . | |||
| Laboratory assessment | |||||
| CRP | +/++ | ++/+++ | +++ | ++ | +/++ |
| CBC‡ | Mild to moderate anemia, thrombocytosis | Moderate to severe anemia, thrombocytopenia | Moderate to severe anemia, severe thrombocytopenia | Mild to moderate anemia, severe thrombocytosis | Mild to moderate anemia, normal/mild thrombocytopenia or thrombocytosis |
| SPEP | Monoclonal paraprotein (small M-spike) | PHGG | Normal or mild PHGG | Severe PHGG | PHGG |
| IgG4 | Normal | Normal | Normal | Frequent in a subset of patients (but serum IgG4:IgG typically lower than IgG4-RD) | Normal |
| LFTs | Mild elevations can be observed | Mild elevations can be observed | Elevated ALP without hyperbilirubinemia and transaminase elevation | Mild elevations can be observed | Mild elevations can be observed |
| Other unique laboratory features | Endocrinopathy (variable: hypogonadism, adrenal insufficiency, hypothyroidism) | HHV8 infection, often in the setting of HIV infection | Renal insufficiency; elevated IL-6, VEGF (variable) | Renal insufficiency; elevated IL-6, VEGF (variable) | Renal insufficiency; elevated IL-6, VEGF (variable) |
| Clinical presentation | |||||
| Constitutional signs* | +/++ | ++/+++ | +++ | ++ | ++ |
| Primary LN pattern; % with LAD | Generalized; 100% | Generalized; 100% | Generalized; 100% | Generalized; 100% | Generalized; 100% |
| Other key symptoms/ organ involvement | Often associated with osteosclerotic myeloma; defining features: polyneuropathy (required), organomegaly (hepatosplenomegaly), endocrinopathy, monoclonal gammopathy (required), and skin changes; anasarca | Multiple (pulmonary symptoms, hepatosplenomegaly); anasarca | Multiple (hepatosplenomegaly, renal dysfunction, bone marrow reticulin fibrosis); anasarca; adrenal hemorrhages; eruptive cherry hemangiomas | Multiple (pulmonary symptoms, renal dysfunction) | Multiple (pulmonary, renal); additional autoimmune phenomena (autoimmune hemolytic anemia, paraneoplastic pemphigus, immune thrombocytopenia, etc) |
| Exposure history risk | N/A | Increased HIV exposure history | N/A | N/A | N/A |
| Key disease mimics | Multiple myeloma, plasmacytoma, lymphoma | HLH, primary effusion lymphoma, Kaposi sarcoma | HLH, sepsis, SLE | IgG4-RD | ALPS, Rosai-Dorfman |
| Histopathological features | |||||
| Lymph node histopathology | Plasmacytic with increased monoclonal plasma cells | HHV8 positive plasmablastic proliferation | Hypervascular or mixed subtype with germinal center regression, vascularity, and FDC prominence | Plasmacytic or mixed subtype with germinal center hyperplasia, vascularity, and increased plasma cells; frequently meets criteria for IgG4-RD lymphadenopathy | 3 potential histopathological subtypes (hypervascular, mixed, plasmacytic) |
| Bone marrow biopsy | Clonal plasma cells, megakaryocyte hyperplasia and atypia | HHV8 latent nuclear antigen (LNA) positive plasmablasts | Megakaryocyte hyperplasia, reticulin fibrosis | Hypercellularity, megakaryocytic atypia, and plasmacytosis (nonspecific) | Hypercellularity, megakaryocytic atypia, and plasmacytosis (nonspecific) |
| . | MCD subtypes . | ||||
|---|---|---|---|---|---|
| . | POEMS-MCD . | HHV8-MCD . | iMCD . | ||
| iMCD-TAFRO . | iMCD-IPL . | iMCD-NOS . | |||
| Laboratory assessment | |||||
| CRP | +/++ | ++/+++ | +++ | ++ | +/++ |
| CBC‡ | Mild to moderate anemia, thrombocytosis | Moderate to severe anemia, thrombocytopenia | Moderate to severe anemia, severe thrombocytopenia | Mild to moderate anemia, severe thrombocytosis | Mild to moderate anemia, normal/mild thrombocytopenia or thrombocytosis |
| SPEP | Monoclonal paraprotein (small M-spike) | PHGG | Normal or mild PHGG | Severe PHGG | PHGG |
| IgG4 | Normal | Normal | Normal | Frequent in a subset of patients (but serum IgG4:IgG typically lower than IgG4-RD) | Normal |
| LFTs | Mild elevations can be observed | Mild elevations can be observed | Elevated ALP without hyperbilirubinemia and transaminase elevation | Mild elevations can be observed | Mild elevations can be observed |
| Other unique laboratory features | Endocrinopathy (variable: hypogonadism, adrenal insufficiency, hypothyroidism) | HHV8 infection, often in the setting of HIV infection | Renal insufficiency; elevated IL-6, VEGF (variable) | Renal insufficiency; elevated IL-6, VEGF (variable) | Renal insufficiency; elevated IL-6, VEGF (variable) |
| Clinical presentation | |||||
| Constitutional signs* | +/++ | ++/+++ | +++ | ++ | ++ |
| Primary LN pattern; % with LAD | Generalized; 100% | Generalized; 100% | Generalized; 100% | Generalized; 100% | Generalized; 100% |
| Other key symptoms/ organ involvement | Often associated with osteosclerotic myeloma; defining features: polyneuropathy (required), organomegaly (hepatosplenomegaly), endocrinopathy, monoclonal gammopathy (required), and skin changes; anasarca | Multiple (pulmonary symptoms, hepatosplenomegaly); anasarca | Multiple (hepatosplenomegaly, renal dysfunction, bone marrow reticulin fibrosis); anasarca; adrenal hemorrhages; eruptive cherry hemangiomas | Multiple (pulmonary symptoms, renal dysfunction) | Multiple (pulmonary, renal); additional autoimmune phenomena (autoimmune hemolytic anemia, paraneoplastic pemphigus, immune thrombocytopenia, etc) |
| Exposure history risk | N/A | Increased HIV exposure history | N/A | N/A | N/A |
| Key disease mimics | Multiple myeloma, plasmacytoma, lymphoma | HLH, primary effusion lymphoma, Kaposi sarcoma | HLH, sepsis, SLE | IgG4-RD | ALPS, Rosai-Dorfman |
| Histopathological features | |||||
| Lymph node histopathology | Plasmacytic with increased monoclonal plasma cells | HHV8 positive plasmablastic proliferation | Hypervascular or mixed subtype with germinal center regression, vascularity, and FDC prominence | Plasmacytic or mixed subtype with germinal center hyperplasia, vascularity, and increased plasma cells; frequently meets criteria for IgG4-RD lymphadenopathy | 3 potential histopathological subtypes (hypervascular, mixed, plasmacytic) |
| Bone marrow biopsy | Clonal plasma cells, megakaryocyte hyperplasia and atypia | HHV8 latent nuclear antigen (LNA) positive plasmablasts | Megakaryocyte hyperplasia, reticulin fibrosis | Hypercellularity, megakaryocytic atypia, and plasmacytosis (nonspecific) | Hypercellularity, megakaryocytic atypia, and plasmacytosis (nonspecific) |
Anemia: mild (10-12 g/dL); moderate (8-10 g/dL); severe (<8 g/dL). Ranges provided for each disease are estimated but do not preclude patient subsets outside this range.
Fever, sweats, weight loss, malaise.
ALP, alkaline phosphatase; ALPS, autoimmune lymphoproliferative syndrome; HLH, hemophagocytic lymphohistiocytosis; LAD, lymphadenopathy; LNA, latent nuclear antigen; N/A, not applicable; PHGG, polyclonal hypergammaglobulinemia.