CD180 as a Robust Immunophenotypic Marker for Differentiating Lymphoplasmacytic Lymphoma/Waldenström...

Precise differential diagnosis between lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM) and marginal zone lymphoma (MZL) remains a challenging issue because of overlapping clinicopathological and immunophenotypic features. In the present study, the differential diagnostic potential of CD180 was assessed by determining its expression patterns in patients with MZL and LPL/WM through flow cytometry. The results indicated that LPL/WM cases exhibited a complete absence of CD180 expression on malignant B cells, whereas MZL cases showed robust CD180 expression (P < .001). Receiver operating characteristic analysis demonstrated that CD180 expression percentage showed optimal diagnostic accuracy in LPL/WM and MZL cases (area under the curve = 0.998, sensitivity = 100%, and specificity = 98.0%), with a further improvement in differentiation potential by the CD180 mean fluorescence intensity ratio (lymphocytes/monocytes) of ≤ 0.47 (area under the curve = 0.937). Moreover, although the MYD88^L265P/CXCR4 mutation was not detected by next-generation sequencing in 2 LPL/WM cases, these cases still showed the absence of CD180 expression. Subsequently, droplet digital PCR revealed low-frequency MYD88^L265P mutations (0.95% and 1.6% variant allele frequency) in these CD180-negative cases, which confirmed the superior sensitivity of CD180 in identifying LPL/WM with low tumor burden. Overall, our findings establish CD180 as a novel, rapid, and precise flow cytometry-based biomarker with robust ability for the differential diagnosis of LPL/WM and MZL, particularly relevant in resolving diagnostically challenging cases and providing prompt tumor diagnosis in time-constrained situations.