Aberrantly sustained PAX5 expression in plasma cell differentiation is a frequent feature in lymphoplasmacytic lymphoma but not marginal zone lymphoma in bone marrow

Subclassification of low-grade B cell lymphomas with plasmacytic differentiation can be a diagnostic challenge, especially in the bone marrow (BM). The major differential diagnoses include marginal zone lymphoma (MZL) and lymphoplasmacytic lymphoma (LPL). We hypothesize that the lymphoplasmacytic populations present in these two B cell lymphoma subtypes may differ in their spectrum of plasma cell differentiation. Plasma cell differentiation is gradual and phenotypically defined. PRDM1/Blimp-1 expression is initiated in B cells that are destined to become plasma cells, and precedes CD138 expression. We utilized PRDM1/PAX5 and CD138/PAX5 double immunohistochemistry to characterize and assess the differences of the plasmacytic populations in a series of MZLs, with or without plasmacytic differentiation, and LPLs. A higher percentage of CD138+ or PRDM1+ cells coexpressed PAX5 in LPL than in MZL without plasmacytic differentiation (p=0.013 and 0.06, respectively, two-tailed Mann-Whitney test). The percentage of CD138+ cells with PAX5 positivity also tends to be higher in LPL compared with MZL with plasmacytic differentiation (p=0.07, two-tailed Mann-Whitney test). A similar percentage of PRDM1+ cells coexpressing PAX5 were noted in LPLs and MZLs with plasmacytic differentiation. These results demonstrate that PAX5 is aberrantly sustained in a subset of CD138+ cells in many LPLs and suggest that PAX5 deregulation is a frequent feature of LPL. These findings may provide a novel area of investigation into the underlying pathogenesis of LPL.