Lymphoid enhancer‐binding factor 1 (LEF‐1) overexpression has been recently remarkably reported in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and has shown utility in distinguishing CLL/SLL from other B‐cell lymphomas. CLL has a well‐defined immunophenotype, yet, some cases of CLL demonstrate atypical morphology/ phenotype reflected by low Matutes score (atypical CLL). Till date, LEF1 expression has not been systematically studied in cases of CLL with atypical features.

In this study, LEF‐1 expression was assessed by two different techniques, (immunohistochemistry and flow cytometry), to investigate the expression profile of LEF‐1 in cases of CLL/SLL, in comparison with other low‐grade B‐lymphomas and CLL with atypical features, including atypical immunophenotype and CLL with increased prolymphocytes or morphologically atypical cells.

We found that LEF‐1 expression is downregulated in CLL with atypical immunophenotype/features compared to classic CLL; Chi‐Square P < .0001. The ratio for LEF‐1 expression in malignant B‐cells/NK (by flow cytometry) in CLL/SLL with classic immunophenotype was higher than atypical CLL and is significantly higher in other small B‐cell lymphomas (P < .01). Absence of LEF‐1 expression in CLL/SLL is correlated (P < .05) with downregulation of CD5, CD23, CD200, expression of FMC7, brighter expression of CD79b, brighter expression of surface light chain, increased prolymphocytes and lower Matutes score.

As downregulation of LEF‐1 expression is well correlated with atypical CLL, we suggest adding LEF‐1 to Matutes score as a beneficial marker to differentiate classic from atypical CLL LEF‐1 could also serve as a potential prognostic indicator for CLL clinical course.