Flow Cytometric Evaluation of Posttransplant B-Cell Lymphoproliferative Disorders

Context.-Posttransplant B-cell lymphoproliferative disorders (PTLDs) constitute a heterogeneous group that includes hyperplastic and unique polymorphic lesions at one end of the spectrum and monomorphic lymphoid proliferations indistinguishable morphologically from conventional B-cell non-Hodgkin lymphomas (NHLs) at the other end. Almost all the PTLDs are of B-cell origin, with only rare examples of T-cell phenotype described. Despite a plethora of information available on the morphologic spectrum, pathogenetic role of Epstein-Barr virus, and various treatment options, a detailed flow cytometric immunophenotypic evaluation of PTLDs is largely lacking. Objective.-To evaluate the immunophenotypic profiles of various PTLDs using multiparameter flow cytometric analysis to compare and contrast with conventional de novo B-cell lymphoproliferative disorders and to identify any immunophenotypic patterns useful in diagnosis. Design.-We retrospectively analyzed data on the immunophenotype of 25 cases of pediatric and adult PTLD (12 cases of monomorphic PTLD [m-PTLD] and 13 cases of polymorphic PTLD [p-PTLD]) using multiparameter flow cytometry in addition to routine morphologic and immunohistochemical evaluation. The flow cytometric immunophenotypic data were also compared and contrasted with 334 cases of various de novo B-cell NHLs during the same period as a control group. Results.-We observed a much higher incidence of lack of surface immunoglobulin light chains and CD20 expression in B-cell PTLDs using multiparameter flow cytometry in comparison with de novo B-cell NHL as a group (with the exception of small lymphocytic lymphoma). Four (16%) of 25 cases of PTLD (3 m-PTLD and 1 p-PTLD) showed almost complete lack (CD20%/CD19% ratio < 1: 9) of CD20 expression in contrast to only 8 (∼2%) of 334 cases of de novo B-cell NHL (P = .007). Several other cases of both m-PTLD and p-PTLD also showed partial and dim expression of CD20. Nine (36%) of 25 cases, including 5 cases of m-PTLD and 4 of p-PTLD, showed either an almost complete lack (light chains%/CD19% ratio < 1:9) or significant loss (>50% loss) of surface immunoglobulin light chains in contrast to less than 5% incidence of light-chain negativity in conventional de novo B-cell NHL. Immunoglobulin light-chain clonality was observed in 9 cases (5 m-PTLD and 4 p-PTLD). Seven cases (5 p-PTLD and 2 m-PTLD) had polyclonal expression of immunoglobulin κ and λ light chains. The m-PTLD showed expression patterns of CD5, CD10, and CD23 similar to their de novo counter-parts. Conclusions.-Both polymorphic and monomorphic PTLDs show a higher incidence of lack of CD20 and surface immunoglobulin light-chain expression. The lack of CD20 expression in these lesions may have therapeutic implications, since anti-CD20 antibody has increasingly become an important modality in the treatment of B-cell lymphoproliferative disorders, including posttransplant disorders.