Plasma Cell Disorders - Diagnosis and Management Summary
EVALUATION OF PLASMA CELL DISORDERS
Serum protein electrophoresis (SPEP): detects & quantifies monoclonal M-proteins
• M-protein (paraprotein, monoclonal protein): monoclonal Ig secreted by abnormally expanded clone of B-cells and plasma cells, seen in monoclonal B-cell proliferative disorders, cryoglobulinemia, and autoimmune disease (e.g. RA, SS)
Immunofixation (IF): confirms polyclonal or monoclonal nature of serum proteins, and determines the type of M-protein, based on its heavy (IgG, IgM, IgA) and light (κ/λ) chain composition
Serum free light chain (sFLC): detects polyclonal & monoclonal free light chains (κ/λ) (200-500x more sensitive than IF)
• Normal: κ & λ polyclonal light chains in a κ/λ ratio of 0.26-1.65 confirms normal B-cell differentiation
• Abnormal κ/λ ratio: monoclonal plasma (MM, primary amyloidosis) and B-cell (lymphomas) aberrations
• Polyclonal decrease: immunosuppression and immunodeficiency states
• ↑ sFLC & relatively unchanged κ/λ ratio: chronic infection, inflammatory disorders, polyclonal autoimmune disease
• NB: Renal failure results in increased sFLC levels with κ/λ ratio up to 3 due to ↓clearance of FLC→ determine urine Bence Jones protein (monoclonal light chains) by UPEP+IF κ/λ ratio 1.7-3.0, to determine if FLC are monoclonal
UPEP (24h): similar to SPEP but more sensitive in detecting FLC (BJP); if M protein detected, it is confirmed by IF
• SPEP & Ig levels: send if suspect primary hypogammaglobinemia (primary B-cell immunodeficiencies, e.g. CVID) or secondary immunodeficiencies (e.g. lymphoma, myeloma, immunosuppressive therapy, post-irradiation)
• SPEP+IF & sFLC: send if suspect clonal B-cell abnormalities (e.g. myeloma, Waldenstrom, amyloidosis, paraproteinemia)
• SPEP+IF alone is insensitive for primary amyloidosis, nonsecretory/oligosecretory myeloma, light-chain myeloma
• UPEP+IF: Not needed to screen for plasma cell disorders, as SPEP/IF/SFLC combination is sufficiently sensitive. Generally used after diagnosis is established to detect nephrotoxic FLC concentrations and monitor response to therapy.
TYPES OF PLASMA CELL DISORDERS
• MGUS: 3% population > age 50, 7.5% > age 85; abnl sFLC ratio predicts prog to MM (~1% progress/yr); SPEP in 6 mo, then yearly.
• MM (IgG or IgA): M-protein > 3 g/dL and/or 10-60% BM clonal cells + CRAB; or > 60% BM plasma cells, sFLC ratio > 100, or ≥1 focal lesion (plasmacytoma) on imaging w/o CRAB. [CRAB: Ca (>11 mg/dL), Renal dz (Cr >2 g/dL), Anemia (Hb <10 g/dL), Bone lesions (≥1 focal lesion on survey, CT, or PET)].
o Smoldering MM: absence of CRAB sx; treat if high risk (BM ≥ 10% with any M-protein, IgA, hypogammaglobulinemia, t(4;14), del(17p), MRI with bone marrow changes); 10% progress to full MM per year.
• Waldenstrom’s (IgM): Very rare; lymphoplasmacytic lymphoma in the bone marrow with IgM monoclonal gammopathy in the blood; anemia, mucocutaneous bleed, HSM, hyperviscosity (IgM = pentamer, thus more clumpedcheck viscosity), cryoglobulinemia.
• AL amyloidosis: 1) amyloid-related systemic syndrome, 2) (+) amyloid by Congo red, 3) amyloid is light-chain related, 4) monoclonal plasma cell d/o. Sx: cardiomyopathy, purpura, nephrotic syndrome, peripheral neuropathy, orthostasis, hepatomegaly, macroglossia.
• POEMS syndrome: (Polyneuropathy, Organomegaly, Endocrinopathy, M-protein, Skin changes), a/w ↑VEGF, sclerotic bone lesions, and Castleman’s disease.
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