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

Abstract

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 non-neoplastic plasma cells, especially in the bone marrow (BM) post various therapies, would exhibit immunophenotypic variations interfering PCM MRD detection. The authors studied the 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 with 59 BM specimens positive for PCM MRD. Non-neoplastic plasma cells showed heterogeneous expressions of CD45 (78% (41-100)) and CD19 (80% (52-97)), and were 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 the latter more frequently expressed in post-treatment BMs (p=0.01). However, despite a partial immunophenotypic overlap, PCM cells could be reliably discriminated from non-neoplastic plasma cells by the presence of a higher number of aberrancies (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). In addition, simultaneous assessment of cytoplasmic κ/λ with surface markers detected light chain restriction in all 59 PCM cases. In 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 may still be reliably distinguished from non-neoplastic plasma cells.

Consensus guidelines on plasma cell myeloma minimal residual disease analysis and reporting

“…That notwithstanding, it should be noted that appropriate multivariate analysis with 8 markers is required to reach such an applicability because it is now well recognized that minor subsets of normal BM PCs can express some markers with intensity levels previously considered to be aberrant (4,5,6). In this regard, Liu et al (5) and Tembhare et al (6) have proposed some helpful insights that can assist in the discrimination between normal versus neoplastic PCs, as described below.…”

“…In this regard, Liu et al (5) and Tembhare et al (6) have proposed some helpful insights that can assist in the discrimination between normal versus neoplastic PCs, as described below.…”

Consensus guidelines for myeloma minimal residual disease sample staining and data acquisition

“…In combination with CD38 and CD45, that can be aberrantly dim or absent, the lack of CD19 expression and/or strong CD56 expression differentiates neoplastic plasma cells from their normal counterpart in most cases. However, it should be noted that with improving outcomes and increased sensitivity of flow-MRD methods, it is now well-established that a subset of normal plasma cells can be CD19-and/or CD561 with even low/absent CD45 expression and there is strong evidence indicating that CD27, CD81, and CD117 are now also required for reproducible discrimination of neoplastic from normal plasma cells (1,(18)(19)(20). It should be noted that intracellular light chain evaluation does not provide additional information in greater than 97% of patients and therefore we would not recommend undertaking its routine detection (2,13,14,(20)(21)(22)(23).…”

Minimal residual disease testing in multiple myeloma by flow cytometry: major heterogeneity

“…3 In our survey, we found the definition of abnormal plasma cells to differ substantially between institutions (Table 1), with some relying on CD19 and CD45 negativity with or without CD56 positivity to determine the extent of MRD despite previous studies showing that normal plasma cell subpopulations can be negative for CD19 and CD45 or CD56 positive. 4,5 More specific antigens such as CD27, CD81, and CD117 were used by fewer than half of the institutions.…”