Primary diffuse large B-cell lymphoma associated with clonally-related monoclonal B lymphocytosis indicates a common precursor cell Bone marrow monoclonal small B-cell infiltration (MSBC) associated with monoclonal B lymphocytosis

Bone marrow monoclonal small B-cell infiltration (MSBC) associated with monoclonal B lymphocytosis (MBL), is present at a higher frequency in patients with diffuse large B-cell lymphoma (DLBCL). We have prospectively collected blood and bone marrow (BM) samples in patients with primary DLBCL at diagnosis to study the clonal relationship of MBL/MSBC with the paired DLBCL. MBL/MSBC were detected in 6 of 19 patients, of whom 5 presented DLBCL with activated Bcell origin (ABC) and one germinal center B-cell (GCB) origin. MBL/MSBC were clonally related to the paired DLBCL in 3 of 6 patients, as demonstrated by rearranged immunoglobulin heavy chain gene sequence analysis. MBL/MSBC in these 3 patients showed a chronic lymphocytic leukemia (CLL)-like, a non-CLL-like and a germinal center cell-like immunophenotype, respectively. The former two MBL/MSBC immunophenotypes were associated with DLBCL-ABC, and the latter with DLBCLGCB. Similar, but not identical, rearranged immunoglobulin genes were demonstrated for the 3 patients with MBL/MSBC and paired DLBCL and these were not clonally related. These results suggest that a subset of DLBCL may arise from MBL/MSBC. The most common type of DLBCL, DLBCL not otherwise specified (NOS) is subdivided according to cell of origin, either from activated B cells or from germinal center B cells. DLBCL-ABC is genetically different to DLBCL-GCB and is characterized by chronic active B-cell