Caution in the Use of Immunohistochemistry for Determination of Cell of Origin in Diffuse Large B-Cell Lymphoma

TO THE EDITOR: The article by Nowakowski et al 1 reported the results from their phase II study, in which lenalidomide was administered in addition to standard first-line R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone) to 64 patients with diffuse large B-cell lymphoma (DLBCL). In that study, the authors compared the study cohort to an historical control group of 87 patients who received R-CHOP alone. They concluded that the additionoflenalidomide25mg(administeredfromday1today10)to R-CHOP overcomes the inferior prognosis associated with non‐ germinal center B-cell or activated B-cell (ABC) types of DLBCL treated with R-CHOP alone. The rationale for selecting the ABC subtype of DLBCL (ABCDLBCL) as a targeted subgroup for treatment with lenalidomide is strong,becausethisagentisaknowninhibitorofthenuclearfactorB pathway that is constitutively activated in ABC-DLBCL 2,3 ; however, we would advise caution in the interpretation of the results of Nowakowski et al. First, an historical control group was used for the comparison. Second and more important, the Hans algorithm, an immunohistochemistry(IHC)method,wasusedtodeterminethecell