Plasma Cell Disorders

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Plasma Cell Disorders & MGUS - Gammopathy Genesis

  • Arise from clonal plasma cell proliferation, leading to monoclonal gammopathies.
  • Key feature: Secretion of monoclonal immunoglobulin (M-protein).
    • Identified by Serum Protein Electrophoresis (SPEP) showing an M-spike.
  • MGUS (Monoclonal Gammopathy of Undetermined Significance):
    • Earliest detectable, asymptomatic precursor lesion.
    • Criteria:
      • Serum M-protein < 3 g/dL.
      • Bone marrow clonal plasma cells < 10%.
      • No end-organ damage (CRAB: Hypercalcemia, Renal failure, Anemia, Bone lesions) or related symptoms.

    ⭐ MGUS progresses to MM or other lymphoproliferative disorders at a rate of approximately 1% per year. M-spike on serum protein electrophoresis

Multiple Myeloma - CRAB's Cruel Reign

Malignant proliferation of plasma cells in bone marrow (BM), producing monoclonal immunoglobulin (M-protein).

  • Key Diagnostic Markers:
    • Clonal BM plasma cells >10% or biopsy-proven plasmacytoma.
    • M-protein in serum and/or urine (IgG most common, then IgA).
    • Often: Bence Jones proteinuria (free light chains).
  • 📌 CRAB Criteria (Myeloma-Defining End-Organ Damage):
    • Calcium elevation: Serum Ca >11 mg/dL (or >0.25 mmol/L above ULN).
    • Renal insufficiency: Serum Creatinine >2 mg/dL (or CrCl <40 mL/min).
    • Anemia: Hb <10 g/dL (or >2 g/dL below normal).
    • Bone lesions: ≥1 lytic lesion on imaging (X-ray, CT, PET-CT).

⭐ Lytic bone lesions in Multiple Myeloma are characteristically 'cold' on technetium-99m bone scans because osteoblastic activity is suppressed.

Multiple Myeloma: Skull X-ray with Lytic Lesions

Myeloma's Kin & WM - Variant Vignettes

  • Smoldering Multiple Myeloma (SMM)
    • Asymptomatic; M-protein (IgG/IgA) ≥3 g/dL or urine ≥500 mg/24h.
    • BMPCs 10-60%.
    • NO CRAB.
    • Risk to MM: ~10%/yr (first 5 yrs).
  • Plasma Cell Leukemia (PCL)
    • Aggressive; PB plasma cells >20% or absolute >2x10⁹/L.
    • Primary (de novo) or secondary (from MM). Poor prognosis.
  • Waldenström Macroglobulinemia (WM)
    • LPL with IgM gammopathy.
    • BM: ≥10% LPL infiltration.
    • MYD88 L265P (>90%).
    • Clinical: Hyperviscosity (visual, neuro, bleeding), anemia, organomegaly. No lytic lesions.

⭐ Waldenström Macroglobulinemia is defined by IgM monoclonal gammopathy and ≥10% lymphoplasmacytic infiltration in bone marrow, often causing hyperviscosity. Bone marrow lymphoplasmacytic infiltrate

Diagnosis & Amyloidosis - Detect & Disrupt

  • Screening Tests:
    • Serum Protein Electrophoresis (SPEP): M-spike detection.
    • Serum Free Light Chain (FLC) Assay: Abnormal κ/λ ratio.
  • Definitive Diagnosis:
    • Immunofixation: M-protein typing.
    • Bone Marrow Biopsy: Plasma cell percentage (e.g., >10% in Myeloma).
  • AL Amyloidosis:
    • Light chain deposition disease; systemic.
    • Diagnosis: Tissue biopsy + Congo Red stain.

    ⭐ AL Amyloidosis demonstrates apple-green birefringence with Congo red stain under polarized light, pathognomonic for amyloid fibrils.

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High‑Yield Points - ⚡ Biggest Takeaways

  • Multiple Myeloma: Defined by CRAB criteria (Hypercalcemia, Renal failure, Anemia, Bone lesions), M-spike, and Bence Jones proteinuria.
  • Waldenström Macroglobulinemia: IgM hypersecretion causing hyperviscosity syndrome; no lytic bone lesions.
  • MGUS: Asymptomatic M-protein without end-organ damage; risk of progression to myeloma.
  • AL Amyloidosis: Monoclonal light chain deposition; Congo Red stain shows apple-green birefringence.
  • Rouleaux formation on peripheral smear is common in Multiple Myeloma.

Practice Questions: Plasma Cell Disorders

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What is the major fibril protein associated with Primary Amyloidosis?

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Flashcards: Plasma Cell Disorders

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Plasma cell tumors such as multiple myeloma are positive for CD_____

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Plasma cell tumors such as multiple myeloma are positive for CD_____

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