Nuclear Protein Dysregulation in Lymphoplasmacytic Lymphoma/Waldenstrom Macroglobulinemia
MJ Roberts, A Chadburn, S Ma, LC Peterson. Northwestern University, Chicago, IL; Robert H. Lurie CCC, Northwestern University, Chicago, IL
Background: The cell of origin in LPL/WM is not fully characterized but is presumed to be a post-follicular B cell that differentiates to plasma cells. The expression pattern of proteins involved in germinal center lymphocyte maturation and plasma cell differentiation (PAX5, BLIMP1, MUM1) has not been clearly defined in LPL/WM. We evaluated the expression of these proteins in lymphocytes (LC) and plasma cells (PC) of LPL/WM to better characterize the role of transcription factors in the development of this neoplasm.
Design: Double immunohistochemical staining for CD22/PAX5, CD22/MUM1, CD138/PAX5 and CD138/MUM1 was performed on 23 pre-treatment bone marrow biopsies from patients with LPL/WM and 4 LPL/WM lesions (3 lymph nodes, 1 spleen). All of these tissues had monotypic CD20 and/or CD22 positive B LC and monotypic PC by IHC or flow cytometry. As controls, 8 plasma cell neoplasms (PCN: plasma cell myeloma/plasmacytomas), 6 marginal zone lymphomas (MZL: 2 BM, 3 LN, 1 gastric) and 5 normal tissues (3 tonsils, 2 BM) were studied. In addition, double stains for CD138/BLIMP1 and CD22/BLIMP1 were evaluated in 4 LPL/WM (3 LN, 1 spleen), 4 PCN, 4 MZL and 2 tonsils. 200 CD22+ and 200 CD138+ cells were counted in each case for each combination. More than 10% dual positive cells was considered positive.
Results: Co-expression of CD138 and PAX5 in PC (measured as the percentage of PAX5+ cells per 200 CD138+ cells) was negative in normal tissues (mean=1%), all MZL (mean=1%) and 7/8 PCN (mean=1%). The one positive CD138+/PAX5+ PCN (78% of CD138+ cells) was also dim CD20+. In contrast, 17/23 LPL/WM cases exhibited co-expression of CD138 and PAX5 in PC (mean=23%, p=0.016). Double staining was present with CD22/PAX5 (LC) and CD138/MUM1 (PC) and was negative with CD22/MUM1 in LPL/WM, PCN, MZL and normal tissues although occasional CD138-/MUM1+ cells with PC morphology were observed in LPL/WM. There was a trend to a lower number of CD138+/BLIMP1+ PC in LPL/WM lymph nodes (mean=80%) and spleen (73% of CD138+ cells) compared to PCN (99%), MZL (99%) and tonsils (100%), but the difference was not statistically significant (p=0.07).
Conclusions: Co-expression of CD138 and PAX5 in PC in LPL/WM is immunophenotypically abnormal and is increased in LPL/WM BM infiltrates when compared with PCN, MZL and normal tissues. The presence of this CD138+/PAX5+ PC suggests that dysregulation in nuclear protein expression during B cell differentiation may play a role in the pathogenesis of WM/LPL.
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 188, Monday Morning