Phenotypic Profile of Waldenström Macroglobulinaemia B-Cells: Establishment of a Diagnosis Scoring System and Clinico-Biological Correlations

Waldenström Macroglobulinaemia (WM) is sometimes difficult to differentiate from marginal zone lymphoma (MZL), two entities with overlapping features for which no single marker assessed by multiparameter flow cytometry (MFC) is specific. The aim of this work was to establish a diagnostic phenotypic score for bone marrow (BM) and peripheral blood (PB) WM samples, to differentiate it from MZL and to improve the detection of small circulating WM clones. This study revealed a distinct phenotypic profile between WM and MZL B-cells. WM B-cells showed decreased expression of CD19, FMC7, CD22, CD27 and increased expression of CD79b and CD13. Supervised and unsupervised MFC analyses were used to define a phenotypic scoring system: a score of 3/6 or greater in BM or 4/7 or greater in PB samples supported the diagnosis of WM (sensitivity of 97.9% and 94.1% and specificity of 80.0% and 93.5%, respectively). These results were validated in a prospective cohort with very high sensitivity and specificity for the two scoring systems. Clinico-biological correlations showed that the absence or low expression of CD38 on BM WM B-cells was significantly associated with increased BM and PB infiltration (p < 0.0001 and p = 0.0024 respectively) and CXCR4 mutation (p < 0.0001). These results demonstrate that MFC can be used to differentiate WM from MZL with a scoring system that can be easily implemented in routine practice.