B-Cell and Plasma Cell Clones with Identical Light Chain Expression by 8-Color Flow Cytometry and DNA Content Analysis: A Predictor of Diagnosis?
Flavia N Rosado, William G Morice, Rong He, Matthew T Howard, Ellen D McPhail. Mayo Clinic, Rochester, MN
Background: A number of low grade B-cell lymphomas involving the bone marrow (BM) can exhibit plasmacytic differentiation (LBCL-PC), including lymphoplasmacytic lymphoma (LPL)/Waldenstrom macroglobulinemia (WM) and marginal zone lymphomas (MZL). It is unclear whether flow cytometric (FC) DNA content analysis of B-cells and plasma cells (PC) has a role in distinguishing between these entities.
Design: Bone marrow samples containing Ig light chain identical PC and B-cell clones identified by FC were reviewed. Eight-color FC including DNA content analysis was performed in all cases and compared to the clinical findings.
Results: Sixteen LBCL-PC cases were identified being 12 LPL (all clinically WM), 3 LBCL-PC NOS, and 1 splenic MZL/large B-cell lymphoma). The monoclonal protein of the majority of the WM patients were IgM (n=10), but 1 was IgA and 1 was unknown. The LBCL-PC-NOS were IgG (n=2) or IgM (n=1), and the splenic MZL was IgM. Seven PCPD cases with a concurrent B-cell clone were identified, 6 were multiple myeloma (MM) and 1 was IgG monoclonal gammopathy of undetermined significance (MGUS). The MM cases were IgG (n=2), IgA (n=2), IgM (n=1) and unknown (n=1). By FC, the PC in the LBCL-PC group were frequently CD19+/CD45+ (8/16; 50%), while the PCPD cases were all negative. The single IgA WM case was CD19+/CD45+. A CD19+/CD45- phenotype was seen in 5/16 (31%) LBCL-PC and 1/7 (14%) PCPD, while a CD19-/CD45- phenotype was seen in 3/16 (19%) LBCL-PC and 6/7 (86%) PCPD, including the IgM MM. PCs in all LBCL-PC and in the single MGUS were diploid, while they were aneuploid in 4/6 (67%) MM. The B-cell population in both the LBCL-PC and PCPD groups had a low S-phase (0.2 and 0.1, respectively). The mean PC S-phase was as follows: MGUS, 0.9; LPL/WM, 1.3; LBCL-PC-NOS, 1.7; MM, 2.5; and splenic MZL/Large B cell lymphoma, 4.7.
Conclusions: Eight-color FC can be helpful in distinguishing between LBCL-PC and PCPDs with light chain identical B and PC clones by analyzing both PC phenotype, DNA content and S-phase. A CD19+/CD45+ PC phenotype is common in LBCL-PC (50%) but rare in PCPD (0%). A CD19-/CD45- PC phenotype, while common in PCPD (86%), is also present in a minority of LBCL-PC (19%). Aneuploidy is common in MM (67%) but rare in LBCL-PC (0%). PC S-phase tends to be higher in MM than in LBCL-PC (except for the single case of splenic MZL/large B-cell lymphoma). Finally, rare cases of non-IgM WM exist and have similar FC characteristics to other WM cases, raising the possibility that a broader definition of WM should be considered.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 216, Wednesday Afternoon