How can one distinguish chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) from mantle cell lymphoma (MCL) by flow cytometry?

It can be difficult to distinguish CLL/SLL from MCL. Both are CD5-positive chronic B-cell lymphoproliferative neoplasms of small size that have overlapping morphologic features. Furthermore, traditional reliance on CCND1 rearrangements and expression to diagnose MCL is not perfect, as there is increasing recognition of CCND1-negative variants of MCL.This distinction is critical because the clinical course and therapy are markedly different for these two diseases.
 Fortunately, there are a number of immunophenotypic features that allow differentiation of these two entities, although some are better than others. Thus, a global approach using multiple markers is warranted.

For many years, surface expression of CD23 was used as the most reliable distinguishing characteristic of these two lymphomas. CD23 is expressed by most CLL/SLL and is usually negative in MCL (Fig. 1A). However, in occasional cases, the CD23 expression may be intermediate or heterogenous, making the differentiation unclear. In these cases, examination of CD20 and surface light chain expression may help. Expression of both of these markers is often reduced or absent in CLL/SLL, but normal-to-bright in MCL (Fig. 1B). But there are exceptions to this as well. For example, CLL/SLL with trisomy 12 usually exhibits normal CD20 expression. Absence of FMC7 expression is also a hallmark of CLL/SLL. However, as it is now known to represent an epitope of CD20, is use may be redundant.
 

In recent years, additional markers that distinguish these two diseases have been described. A number of publications have demonstrated a role for CD200, which is a membrane glycoprotein normally expressed on thymocytes, activated B and T cells, and some dendritic cells, but not expressed on NK cells or myeloid lineage cells. It is typically bright in CLL/SLL and negative in MCL (Fig. 1C). Using these combinations of markers, flow cytometry can be an effective tool to make the clinical crucial distinction between these small B-cell lymphomas.

Further Reading:
 1. Matutes E, Owusu-Ankomah K, Morilla R, et al. (1994) The immunological profile of B-cell disorders and proposal of a scoring system for the diagnosis of CLL. Leukemia. 8:1640-1645.
 2. Challagundla P, Medeiros LJ, Kanagal-Shamanna R, Miranda RN, Jorgensen JL (2014) Differential expression of CD200 in B-cell neoplasms by flow cytometry can assist in diagnosis, subclassification, and bone marrow staging. Am J Clin Pathol. 142:837-844.
3. Sandes AF, de Lourdes Chauffaille M, Oliveira CRMC, et al. (2014) CD200 has an important role in the differential diagnosis of mature B-cell neoplasms by multiparameter flow cytometry. Cytometry B Clin Cytom. 86:98-105.