Aberrantly Sustained PAX5 Expression in Plasma Cell Differentiation Is a Frequent Feature in Lymphoplasmacytic Lymphoma but Not Marginal Zone Lymphoma in Bone Marrow
Yen-Chun Liu, Yifang Liu, Daniel M Knowles, Attilio Orazi, Wayne Tam. Weill Cornell Medical College, New York, NY
Background: Subclassification of low grade B cell lymphomas with plasmacytic differentiation can present as diagnostic challenges, especially in the bone marrow (BM). The major differential diagnoses include marginal zone lymphoma (MZL) and lymphoplasmacytic lymphoma (LPL). We hypothesize that the lymphoplasmacytic (LP) populations present in these two B cell lymphoma subtypes may differ in their spectrum of plasma cell differentiation. It is known that plasma cell differentiation is gradual and phenotypically defined. PRDM1/Blimp-1 expression is initiated in CD20+PAX5+ B cells that are destined to become plasma cells, and precedes CD138 expression. We compiled a series of MZL and LPL and utilized PRDM1/PAX5 and CD138/PAX5 double immunohistochemistry to characterize the LP populations in these two entities and to assess the differences between them.
Design: BM biopsy specimens of LPL (n=15) and MZL (n=14) were retrieved from the archives. All the MZL cases in the series had a corresponding extramedullary MZL diagnosis. Double immunohistochemical stains including PRDM1/PAX5 and CD138/PAX5 were performed on all cases. The percentage of PRDM1+PAX5+ cells of PRDM1+ cells and the percentage of CD138+PAX5+ cells of CD138+ cells were calculated and used for statistical analyses. Normal bone marrow and tonsil were also tested. Technically suboptimal stained sections were excluded.
Results: In the BM specimens, more CD138+PAX5+ cells were noted in LPL (mean:7.5% of the CD138+ cells, n=14) than in MZL (mean:2.2% of the CD138+ cells, n=13)(one-tailed t test p=0.058). Similar number of PRDM1+PAX5+ cells are noted in LPL (mean:10.3% of the PRDM1+ cells, n=11) and MZL (mean:7.6% of the PRDM1+ cells, n=8)(one-tailed t test p=0.28). No CD138+PAX5+ cells were found in either the tonsil or normal BM. PRDM1+PAX5+ cells were noted in the germinal centers (GC) on the tonsil section (∼10% of the intrafollicular PRDM1+ cells) but not in normal BM.
Conclusions: While plasma cell differentiation in MZL appears to recapitulate the normal pattern in GC in the vast majority of cases, PAX5 is aberrantly sustained in CD138+ cells in many LPL cases. These findings suggest that PAX5 deregulation may be a useful feature in distinguishing LPL from MZL in bone marrow. Identification of PRDM1+PAX5+ cells, which are found also in the GC, in LPL supports its post-GC derivation. Further molecular investigation into the nature of CD138+PAX5+ and PRDM1+PAX5+ cells may help to understand the pathobiology of LPL and MZL.
Monday, March 19, 2012 11:45 AM
Platform Session: Section C, Monday Morning