Immunophenotypic and molecular analysis of a B cell lymphoma with discordant light chain expression at different anatomic sites

Abstract

B cell lymphomas with discordant immunoglobulin light chain expression in the same patient are rare. We report a case of a 75-year-old woman with a high-grade B cell lymphoma with MYC and BCL2 rearrangements (HGBCL) with discordant immunoglobulin light chain restriction between a lymph node and a pleural fluid involved by lymphoma. Cytogenetic studies by FISH showed MYC and BCL2 rearrangement in both specimens. Immunoglobulin heavy chain and kappa light chain analysis demonstrated similar rearranged clonal peaks in the two specimens. A review of the literature revealed eight cases of B cell lymphoma with discordant immunoglobulin light chain expression (including our case). The light chain discrepancy occurred during a relapse in five cases, whereas in three other cases, the discrepancy was concomitant and present at the time of initial diagnosis. In most cases with relapse, the kappa light chain restriction preceded lambda light chain restriction. The B cell neoplasms with discrepant light chain expression showed similar histomorphologic features in four cases, whereas four cases were dissimilar (B cell lymphoma and plasmacytoma, follicular lymphoma and HGBCL, and two cases involving chronic lymphocytic leukemia and DLBCL). Immunoglobulin gene PCR and comparative sequencing confirmed the clonal relatedness of these lymphomas in 3 of the 8 cases. We conclude that flow cytometric evaluation has an important role in identifying B cell lymphomas with discordant light chain expression. Cytogenetic and molecular studies are essential to investigate the relationship between the two lymphomas in order to rule out independent lymphomas in the same patient and, ultimately, guide therapy.