Hematopathology / SURFACE IMMUNOGLOBULIN LIGHT CHAIN–NEGATIVE PERIPHERAL B-CELL LYMPHOMA Lack of Surface Immunoglobulin Light Chain Expression by Flow Cytometric Immunophenotyping Can Help Diagnose Peripheral B-Cell Lymphoma

We determined the prevalence and significance of finding B cells without surface immunoglobulin (SIg) light chain expression. The flow cytometry database at Johns Hopkins Medical Institutions was searched for cases in which immunoglobulin light chain staining was performed to rule out a B-cell malignant neoplasm between January 1994 and February 2000. We excluded plasma cell dyscrasias, precursor B-cell acute lymphoblastic leukemia/lymphomas, and hematogones. Cases with more than 25% of B cells lacking SIg light chain expression were retrieved. Polymerase chain reaction assays for immunoglobulin heavy chain gene rearrangements were performed in SIg-negative cases with available tissue blocks. We identified 36 cases; all represented lymphoma. Their diagnoses included diffuse large B-cell lymphoma (20), HIV-related lymphoma (5), follicular lymphoma (5), Burkitt lymphoma (2), monomorphic posttransplant lymphoproliferative disorder (1), chronic lymphocytic leukemia/small lymphocytic lymphoma (1), marginal zone B-cell lymphoma (1), and low grade B-cell lymphoma (1). Of the 17 SIg-negative cases with amplifiable DNAs, 12 (71%) showed a clonal immunoglobulin heavy chain gene rearrangement. SIgnegative B-cell lymphomas are rare. Complete absence of SIg light chain expression in a mature B cell proliferation can be used as a surrogate marker to help diagnose peripheral B-cell lymphoma. Malignant B-cell lymphomas derived from mature B cells encompass a spectrum of monoclonal proliferation of B cells at different stages of differentiation and comprise the majority of non-Hodgkin lymphomas in the Western populations. Except for plasma cells, mature B lymphocytes express either kappa or lambda immunoglobulin light chain proteins on their surface. The demonstration of surface immunoglobulin (SIg) light chain restriction by immunohistochemical or flow cytometric immunophenotyping (FCI) indicates monoclonality of the proliferating mature B cells, a feature that usually is used to support the diagnosis of malignant B-cell non-Hodgkin lymphomas. Previous studies have demonstrated that the neoplastic cells in up to one third of B-cell non-Hodgkin lymphomas did not express either kappa or lambda SIg light chain proteins.1 These early studies, however, were done using the relatively insensitive immunohistochemical method. Data obtained with the more sensitive FCI technique indicated that SIg-negative malignant B-cell non-Hodgkin lymphomas were rare.2-8 The frequency ranged from 3.4% to 12.2%, depending on the criteria used in the studies. Since the number of cases reported so far is limited, the true prevalence of SIg-negative non-Hodgkin lymphomas is still unknown. Furthermore, whether the absence of SIg light chain expression can be used as an indicator of peripheral B-cell lymphomas in the absence of demonstration of clonality remains to be determined. We retrospectively studied, by using FCI in a large referral laboratory, the frequency and significance of finding lymphoid proliferations in which B cells lacked SIg light chain expression. By correlating these findings with clinicopathologic and molecular genetic features of cases, we found Am J Clin Pathol 2002;118:229-234 229 © American Society for Clinical Pathology Li et al / SURFACE IMMUNOGLOBULIN LIGHT CHAIN–NEGATIVE PERIPHERAL B-CELL LYMPHOMA that complete lack of SIg light chain expression indicated an abnormal B-cell proliferation and can be used to support the diagnosis of malignant lymphoma. Material and Methods