Immunophenotypic heterogeneity of normal plasma cells: Comparison with minimal residual plasma cell myeloma

Aims: Plasma cell myeloma (PCM) exhibits immunophenotypic aberrancies that can be used for minimal residual disease (MRD) detection after therapy. The authors sought to determine whether nonneoplastic plasma cells, especially in the bone marrow (BM) post various therapies, exhibit immunophenotypic variations interfering PCM MRD detection. Methods: The authors studied flow cytometric immunophenotypes of non-neoplastic plasma cells from 50 BM specimens, including 12 untreated BM and 38 BM specimens from patients with non-plasmacytic haematological malignancies undergoing various therapies, and compared the results with 59 BM specimens positive for PCM MRD. Results: Non-neoplastic plasma cells showed heterogeneous expression of CD45 (78% (41-100)) and CD19 (80% (52-97)), and nearly all negative for CD20 and CD117. CD56 was observed in a small subset (6% (0-37)) and CD28 in a larger subset (15% (0-59)) of non-neoplastic plasma cells, with CD28 more frequently expressed in post-treatment BMs (p=0.01). However, despite partial immunophenotypic overlap, PCM cells could be reliably discriminated from non-neoplastic plasma cells based on a higher number of aberrancies (median 3 (1-6) vs 0 (0-2)) and stronger intensity and uniformity of aberrant expression (p<0.001 in each marker using a cut-off value). Simultaneous assessment of cytoplasmic κ/λ with surface markers detected light chain restriction in all 59 PCM cases. Conclusion: Non-neoplastic plasma cells in BM are more immunophenotypically heterogeneous than previously understood; however, these immunophenotypic variations differ from those of PCM. With advances in multicolour flow cytometry and application of recently validated markers, PCM MRD can still be reliably distinguished from non-neoplastic plasma cells.