Plasma Cell Differentiation in CLL/SLL Tissue Sections Is Associated with Monoclonal Serum Free Light Chain and Better Clinical Outcome but Are Unrelated to MYD-88 Mutations
Daniel Martinez, Paola Castillo, Alejandra Martinez-Trillos, Carla Sole, Eva Gine, Armando Lopez-Guillermo, Elias Campo, Antonio Martinez. Hospital Clinic, Barcelona, Spain
Background: Plasma cell differentiation (PCD) is a frequent event in low grade B-NHL that may also occur in CLL although its biological meaning is unknown. Moreover, monoclonal free light chain component can be found in the serum from CLL/SLL patients making more difficult the distinction from lymphoplasmacytic lymphoma (LPL) in some cases. MYD-88 mutations can be rarely found in CLL but are a frequent genetic alteration in LPL. The aim of this study was to analyze the role of strong cytoplasmic light chain expression in a series of CLL/SLL patients.
Design: We have included 111 biopsies from CLL/SLL patients (72M/39F; median age 68 years) collected between 1994 and 2011. PCD was defined as strong cytoplasmic light chain expression by immunohistochemistry. The expression of the plasma cell transcriptions factors BLIMP1, IRF4 and the mutations for MYD-88, NOTCH1 and SF3B1 were also analyzed. The main clinico-biological features were recorded.
Results: Thirty cases (27%) fulfill the criteria for CLL/SLL with PCD. These cases were clinically similar to conventional CLL/SLL but had more frequently monoclonal paraprotein in serum (32% vs 14%). These tumors expressed strongly IRF4 and Blimp1. None of them had MYD-88 mutation and presented similar mutation rates for NOTCH1, SF3B1 and IGHV. CLL with PCD had a better overall survival: mean survival of 102 mo vs 67 mo (p=0.032).
|Patients (n=111)||Conventional CLL (n=81)||CLL with Plasma Cell Differentiation (n=30)||p-value|
|Median age (years)||71||62||n.s|
|Gender||52 Male / 29 Female||20 Male / 10 Female||n.s.|
|High LDH||12/59 (20.3%)||6/25 (24%)||n.s.|
|High B2||33/57 (40.7%)||11/23 (47.8%)||n.s.|
|ZAP70||27/54 (50%)||17/26 (65.4%)||n.s.|
|Unmutated IGHV||31/52 (61.5%)||17/24 (70.8%)||n.s.|
|Serum Monoclonal||9/66 (13.6%)||9/28 (32.1%)||0.037|
|Accelerated||13/81 (16%)||11/30 (37%)||0.019|
|Blimp1||15/55 (27.3%)||20/26 (76.9%)||<0.001|
|Irf4||22/54 (40.7%)||18/28 (64.3%)||0.043|
|NOTCH1||8/55 (14.5%)||2/23 (8.7%)||n.s.|
|MYD-88||0/53 (0%)||0/21 (0%)||n.s.|
|SF3B1||5/55 (9%)||2/19 (11%)||n.s.|
|Mean OS||67 mo||102 mo||0.032|