Uncovering clinically relevant phenotypic variations in malignancies: CD23 in mantle cell lymphoma.

An important consequence of the robust, multiparam-eter approach to the definition of lymphoma subtypes introduced in the Revised European and American Lymphoma classification in 1994, 1 continued in the 2001 World Health Organization classification, 2 has been that some established disease entities are now appreciated to have much broader phenotypic (morphologic, immunophenotypic, and clinical) variability than was previously appreciated. A case in point is mantle cell lymphoma (MCL). Since Banks et al 3 initially proposed this term in 1992 to encompass lymphomas previously designated as intermediately differentiated lympho-cytic lymphoma, centrocytic lymphoma, and mantle zone lymphoma, our concept of what this lymphoma can look like, stain like, and behave like has steadily expanded. 4-11 Even the t(11;14), resulting in overexpression of cyclin D1, the absolutely necessary genetic lesion in MCL, is no longer necessary 12 ; as with other types of non-Hodgkin lymphoma, there appear to be multiple molecular pathways that produce the same disease. Fortunately, robust multiparameter disease definitions can accommodate such variability. Immunophenotypically, MCL is CD5+/CD10–/ FMC7+/CD23–/CD20(bright)/CD79b+ and surface immunoglobulin(bright). The problem, of course, is that it often is not. 6,7 Being able to recognize the exceptions to the rules is one of the fundamental challenges of diagnostic pathology. Once we recognize these variations, though, the next logical step is to ask, " What do they mean? " The goal is to be able to predict how a particular tumor is going to behave and, ultimately, individualize therapy to achieve maximum clinical benefit. One such immunophenotypic variation in MCL is the expression of CD23. In the current issue of the Journal, Kelemen et al 6 report detection of this antigen at diagnosis in about one quarter of patients. These authors then ask, in a carefully performed, retrospective clinical study, " What does CD23 expression mean in MCL? " Since CD23 expression in conjunction with CD5 is a diagnostic hallmark of chronic lymphocytic leukemia/small lymphocytic lympho-ma (CLL/SLL), in the past it meant a diagnostic pitfall; it is likely that many CD23+ MCLs were previously diagnosed as CLL/SLL. In these authors' hands, the answer is that while CD23– and CD23+ MCLs are similar in most ways, they differ in that CD23+ MCLs more often manifest with disease in extranodal sites (exclusive of gastrointestinal tract and bone marrow) and less often manifest bulky disease. Most important, CD23 expression is associated with superior event-free and overall survival in a univariate analysis. These results …