[1587] 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%.

LEF-1 immunohistochemical staining characteristics in small B-cell lymphomas

Diagnosis (N)	Bone Marrow		Lymph Node/ Tissue
LEF-1:	Positive	Negative	Positive	Negative
CLL/SLL (30)	12	0	18	0
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

* One indeterminate case not scored due to high T-cell infiltrate


Conclusions: As shown in lymph node tissue previously, immunohistochemical staining for LEF-1 antibody is a promising new tool with high sensitivity and specificity for the diagnosis of CLL/SLL in bone marrow specimens. Because of the expression of LEF-1 in mature, benign T-cells, LEF-1 immunostaining must be correlated with CD3 and CD20 to determine the positivity of tumor cells. In difficult cases, a LEF-1/CD20 double-stain may prove useful.
Category: Hematopathology

Tuesday, March 20, 2012 11:30 AM

Platform Session: Section C, Tuesday Morning