Plasma cell disorder
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Plasma cell disorders |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Nazia Fuad M.D.
Overview
Plasma cell disorders are a diverse type of blood disorders characterized by the presence of a monoclonal paraprotein in the serum or urine. Monoclonal plasma cells are present in the bone marrow or, rarely, in other tissues. Plasma cell disorders include monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM), lymphoplasmacytic lymphoma/ Waldenstrom macroglobulinemia (LPL/WM), lymphoproliferative disorders, smoldering multiple myeloma (SMM); solitary or extramedullary plasmacytoma, amyloidosis, and POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, and Skin changes).The plasma-cell disorders are characterized by the proliferation of a single clone of plasma cells that produces a homogeneous monoclonal (M) protein. these disorders have been defined by the International Myeloma Working Group.1 In 2006.
Classification
Monoclonal gammopathies of undetermined significance (MGUS)
- Benign (IgG, IgA, IgD, IgM, and, rarely, free light chains)
- Associated neoplasms or other diseases not known to produce monoclonal proteins
- Biclonal and triclonal gammopathies
- Idiopathic (Bence Jones proteinuria)
Malignant monoclonal gammopathies
- Multiple myeloma (IgG, IgA, IgD, IgE, and free light chains)
- Symptomatic multiple myeloma
- Smoldering multiple myeloma
- Plasma-cell leukemia
- Non-secretory myeloma
- IgD myeloma
- POEMS syndrome: polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes (osteosclerotic myeloma)
- Solitary plasmacytoma of bone
- Extramedullary plasmacytoma
- Malignant lymphoproliferative disorders
Chronic lymphocytic leukemia
Heavy-chain diseases (HCDs)
- γHCD
- αHCD
- μHCD
Cryoglobulinemia
Primary amyloidosis (AL)
Differential Diagnosis
| Disease | IgM | IgG | IgA | IgE | IgD | Monoclonal Ig level | SFLC | Bone marrow plasma cells | Other criteria |
|---|---|---|---|---|---|---|---|---|---|
| IgM MGUS | + | − | − | − | − | < 3gm/dl | N/A | <10% | No end-organ damage |
| Non igM MGUS | − | + | + | − | − | < 3gm/dl | N/A | <10% | No end-organ damage |
| Smoldering MM | − | + | + | − | − | > 3gm/dl | N/A | 10-60% | No myeloma-defining event or CRAB features |
| Light chain MGUS | − | − | − | − | − | <500 mg/24 hrs (urine) | Free kappa or lambda light chain
Abnormal ratio (<0.26 or >1.65) Increase in involved light chain concentration |
<10% | No end-organ damage |
| Active symptomatic MM | + | + | + | + | >3gm/dl | >100 | >60% | ≥1 myeloma-defining event
or CRAB features | |
| Waldenstrom macroglobulinemia | + | − | − | − | − | Variable | N/A | >10% | Evidence of organ?tissue damage.
anemia, hepatosplenomegaly |
| Solitary Plasmacytoma | + | − | − | − | − | <3mg/dl | Abnormal in 47% cases | Normal | Solitory bone lesion due to plasma cell tumor
Preserved levels of uninvolved immunoglobulins No anemia, hypercalcemia or renal disease |
| Primary amyloidosis | <3md/dl | <10% | No bone lesions, |
Myeloma-defining events: ≥60% clonal plasma cells on BM examination; serum involved:uninvolved FLC ratio of ≥100; >1 focal lesion on MRI ≥5 mm
CRAB features: elevated calcium (>11 mg/dL), renal insufficiency (serum creatinine >2 mg/dL or creatinine clearance <40 mL/min), anemia (Hb <10 g/dL or 2 g/dL < normal), bone disease (≥1 lytic lesions on skeletal radiography, CT, or PET-CT , SFLC: serum free light chains, kappa and lambda immunoglobulin light chains.
The normal κ:λ ratio is 0.26 to 1.65 (17,18). Because free light chains undergo glomerular filtration, the ratio, rather than the absolute level, is the relevant measurement in individuals with renal impairment. A κ:λ ratio of <0.26 strongly suggests the presence of a population of plasma cells that are producing clonal λ free light chains, whereas a ratio >1.65 suggests production of clonal κ free light chains.