Abstract
Introduction. Expression of CD20 antigen is generally negative in patients (pts) with multiple myeloma (MM). However, a small number of MM pts (15-20%) can show CD20 positivity on neoplastic plasma cells (PC). The biologic and clinical features of pts with MM CD20+ are still a matter of debat.
Methods. From 1/2018 to 12/2023, all consecutive patients with MM newly diagnosed at our Center according to IMWG (International Myeloma Working Group) criteria were retrospectively evaluated. Immunophenotypic characterization of marrow PC was performed by multiparametric analysis with sequential gates through the expression of CD38/CD45, CD38/CD138 antigens. FISH was performed on isolated PC with probes from MM panel. Classical cytogenetic analysis using G-banding (GTG) was also done. Morphology of BM aspirate was independently reviewed by two different hematologists. Histology of BM was reviewed to define the grade of infiltration, type of infiltration, and intensity of CD20 positivity
Results. Among 104 evaluable pts, 23 (22,1%) were CD20+ and 81 (77.9%) CD20-: no significant differences were observed between CD20+ and CD20- pts as to the main clinical features at baseline. The main karyotypic and immunophenotypic features at diagnosis of the entire cohort and according to CD20 status are reported in Table 1. CD20+ pts presented a significant high rate of t(11;14) (43.5% vs 16.2%, p=0.006) and a trend for a lower rate of high-risk alterations (19.4% vs 37.8%, p=0.069). According to immunophenotype, CD20+ pts showed a significant higher co-expression of CD19 (22.7% vs 6.2%, p=0.020) and a trend for a lower co-expression of CD56 (52.2% vs 71.6%, p=0.080). Morphologic evaluation was done in 10 CD20+ pts, revealing a distinctive small-like lymphocyte morphology in more than 50% of PC in all 10 revised aspirates.
Conclusions. MM CD20+ pts seem to share distinctive features from classical MM. The presence of CD20 positivity, coupled with the common coexpression of CD19 and the predominant small lymphocyte–like morphologic features, suggests that neoplastic transformation could occur at a relatively more immature stage of differentiation than CD20- MM: in other words, CD20 positive MM could be considered as an intermediate phase between Waldenstrom disease and classic CD20 negative MM. Further studies are warranted to define the prognostic role of CD20 positivity and the possible utility of targeted therapies in this subset.

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