The Utility of LEF-1 Immunohistochemical Stain in the Diagnosis of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Douglas W Warden, Sarah Ondrejka, Lisa Durkin, Juraj Bodo, Eric D Hsi. Cleveland Clinic, Cleveland, OH
Background: Overexpression of lymphoid-enhancer-binding factor 1 (LEF-1) has recently been shown in virtually all cases of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) but not in other small B-cell lymphomas, opening the door for its use as an adjunct in the diagnosis of CLL/SLL. The feasibility and utility of LEF-1 immunohistochemical staining as a tool for the diagnosis of small B-cell lymphomas in decalcified bone marrow biopsy specimens has not been delineated.
Design: We performed immunohistochemical staining with a rabbit monoclonal LEF-1 antibody (Epitomics, Burlingame, CA, clone EPR2029Y) in 78 bone marrow and 56 lymph node/tissue samples of various small B-cell leukemias/lymphomas. An automated immunostainer (Leica BondMax) and heat induced epitope retrieval was used. Cases were considered positive if >70% of B-cells demonstrated nuclear immunoreactivity. CD3 and CD20 stains were simultaneously evaluated in order to assist with LEF-1 interpretation when significant T-cell infiltrates were also present.
Results: LEF-1 expression was observed in all 30 cases of CLL/SLL. Among the 104 non-CLL small B-cell lymphoma cases, only one (a CD5-negative lymphoplasmacytic lymphoma) expressed LEF-1. One case of splenic marginal zone lymphoma was not scored due to a significant T-cell infiltrate, which precluded confident interpretation. The remaining cases were negative (see table below). In our hands, LEF-1 showed a sensitivity and specificity for CLL/SLL of 100% and 99%.
|Diagnosis (N)||Bone Marrow||Lymph Node/ Tissue|
|Atypical CLL (2)||0||2||0||0|
|Follicular Lymphoma (17)||0||7||0||10|
|Hairy Cell Leukemia [HCL] (16)||0||16||0||0|
|HCL variant (2)||0||2||0||0|
|Lymphoplasmacytic lymphoma (22)||1||10||0||11|
|Mantle Cell Lymphoma (14)||0||9||0||5|
|Marginal zone lymphoma (20)*||0||9||0||10|
|B-cell lymphoproliferative disorder, nos (11)||0||10||0||1|