## Immunophenotype of Myeloma Plasma Cells **Key Point:** The most common immunophenotype of malignant plasma cells in multiple myeloma is **CD38+, CD138+, CD19−**. ### Characteristic Markers | Marker | Expression | Significance | |--------|------------|-------------| | **CD138 (Syndecan-1)** | Positive | Plasma cell marker; nearly universal in MM | | **CD38** | Positive | Activation marker; prognostic significance | | **CD19** | Negative | B-cell marker; lost during plasma cell differentiation | | **CD45** | Negative | Pan-leukocyte marker; absent in mature plasma cells | | **CD20** | Negative | B-cell marker; typically lost in myeloma | | **CD27** | Variable | May be present or absent | | **CD56** | Positive (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-Yield:** 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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