Low levels of monoclonal small B cells in the bone marrow of patients with diffuse large B-cell lymphoma of activated B-cell type but not of germinal center B-cell type.
BACKGROUND
Multiparameter flow cytometry allows the detection of minor monoclonal B-cell populations. Using this technique combined with morphology, we were struck by the presence of minor populations of small monoclonal B cells in bone marrows of patients with diffuse large B-cell lymphoma in routine diagnostic samples and performed a systematic retrospective study.


METHODS
Bone marrows of 165 patients with primary diffuse large B-cell lymphoma without histological evidence of concurrent non-Hodgkin's lymphoma were studied by routine microscopy of trephines and smears, immunohistochemistry and multiparameter flow cytometry.


RESULTS
Diffuse large B-cell lymphoma infiltration in marrows was documented in 11 of 165 patients. Morphological examination consistently revealed a higher tumor load than evidenced by flow cytometry. Of interest, only 3 of 119 patients with diffuse large B-cell lymphoma not otherwise specified, the largest subtype, showed marrow infiltration. By contrast, flow cytometry revealed a minor monoclonal B-cell population in 24 of 165 patients, none of whom showed diffuse large B-cell lymphoma infiltration by morphology. Of interest, morphological examination revealed the presence of small B cells in the marrows of those patients. Moreover, 11 of 39 (28.2%) of patients with diffuse large B-cell lymphoma not otherwise specified of ABC subtype and only 3 of 80 (3.7%) with the GCB subtype showed these monoclonal small B cells (P=0.0002). In addition 4 of 8 (50%), 4 of 15 (26.7%) and 2 of 3 (66.7%) patients with primary testicular, primary central nervous system and leg-type diffuse large B-cell lymphoma, respectively, showed monoclonal small B cells.


CONCLUSIONS
Bone marrow infiltration with diffuse large B-cell lymphoma in patients with diffuse large B-cell lymphoma not otherwise specified is rare at diagnosis. By contrast, a high number of diffuse large B-cell lymphoma not otherwise specified of the ABC subtype but not of GCB subtype is associated with monoclonal small B cells in the marrow. Whether these monoclonal small B cells are precursors of diffuse large B-cell lymphoma of the ABC type or arise in a common background that favors clonal B-cell expansion remains to be demonstrated.
Department of Pathology, The Norwegian Radium Hospital and University of Oslo, Montebello, N-0310 Oslo, Norway.
Anne M
AM
Tierens
Harald
H
Holte
Abdirashid
A
Warsame
Ida M
IM
Ikonomou
Junbai
J
Wang
Wing C
WC
Chan
Jan
J
Delabie
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D018951:Antigens, CD20 / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology*; D001483:Base Sequence; D001854:Bone Marrow Cells / Q000473:pathology*; D002999:Clone Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D015321:Gene Rearrangement; D018858:Germinal Center / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D016130:Immunophenotyping; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D012189:Retrospective Studies; D055815:Young Adult
D018951:Antigens, CD20; D007143:Immunoglobulin Heavy Chains