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    Subjects/Pathology/Multiple Myeloma
    Multiple Myeloma
    medium
    microscope Pathology

    A 62-year-old man with multiple myeloma undergoes bone marrow examination. Which is the most common immunophenotype of the malignant plasma cells?

    A. CD38−, CD138−, CD19+
    B. CD19+, CD20+, CD38+
    C. CD20+, CD138+, CD45+
    D. CD38+, CD138+, CD19−

    Explanation

    Immunophenotype of Myeloma Plasma Cells

    Key Point
    The most common immunophenotype of malignant plasma cells in multiple myeloma is CD38+, CD138+, CD19−.
    Characteristic Markers
    Table
    MarkerExpressionSignificance
    CD138 (Syndecan-1)PositivePlasma cell marker; nearly universal in MM
    CD38PositiveActivation marker; prognostic significance
    CD19NegativeB-cell marker; lost during plasma cell differentiation
    CD45NegativePan-leukocyte marker; absent in mature plasma cells
    CD20NegativeB-cell marker; typically lost in myeloma
    CD27VariableMay be present or absent
    CD56Positive (70%)NK cell marker; aberrantly expressed
    Pathophysiology of Marker Loss

    During normal B-cell to plasma cell differentiation, cells progressively lose B-cell associated antigens (CD19, CD20) while gaining plasma cell markers (CD138, CD38). In myeloma, this differentiation is arrested at the malignant plasma cell stage, resulting in the characteristic CD19−, CD20−, CD38+, CD138+ phenotype.

    High-YieldNEET PG
    CD138 positivity is used to isolate and enumerate plasma cells in flow cytometry. The absence of CD19 and CD20 helps distinguish myeloma from lymphoplasmacytic lymphoma or Waldenström macroglobulinemia.
    Clinical Pearl
    Flow cytometry with this immunophenotype panel is essential for diagnosis and monitoring of minimal residual disease (MRD) in myeloma patients.
    Why This Matters

    CD38 expression has prognostic significance—CD38+ myelomas may have different treatment responses compared to CD38− cases. Additionally, CD38 is a therapeutic target for monoclonal antibodies like daratumumab.

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