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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

¹ Department of Pathology and
² Department of Oncology, Oslo University Hospital and University of Oslo, Oslo, Norway and
³ Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska, USA

Correspondence: Jan Delabie, M.D., Ph.D., Department of Pathology, The Norwegian Radium Hospital and University of Oslo, Montebello, N-0310 Oslo Norway. Phone: international +0047.22934879. Fax: international +0047.22730164. E-mail: jan.delabie{at}medisin.uio.no

ABSTRACT

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 (DLBCL) in routine diagnostic samples and performed a systematic retrospective study.

Design and Methods: Bone marrows of 165 patients with primary DLBCL without histological evidence of concurrent non-Hodgkin lymphoma were studied by routine microscopy of trephines and smears, immunohistochemistry and multiparameter flow cytometry.

Results: DLBCL infiltration in marrows was documented in 11/165 patients. Morphological examination consistently revealed a higher tumour load than evidenced by flow cytometry. Of interest, only 3/119 patients with DLBCL, NOS, the largest subtype, showed marrow infiltration. By contrast, flow cytometry revealed a minor monoclonal B-cell population in 24/165 patients, none of which showed DLBCL infiltration by morphology. Of interest, morphological examination revealed the presence of small B-cells in the marrows of those patients. Moreover, 11/39 (28,2%) of patients with DLBCL, NOS of ABC subtype and only 3/80 (3,7%) with the GCB subtype showed these monoclonal small B-cells (MSBC) (p=0,0002). In addition 4/8 (50%), 4/15 (26,7%) and 2/3 (66,7%) of patients with primary testicular, primary central nervous system and leg-type DLBCL, respectively, showed MSBC.

Conclusions: Bone marrow infiltration with DLBCL in patients with DLBCL, NOS is rare at diagnosis. By contrast, a high number of DLBCL, NOS of the ABC subtype but not of GCB subtype is associated with MSBC in the marrow. Whether these MSBC are precursors of DLBCL of the ABC type or arise in a common background that favours clonal B-cell expansion remains to be demonstrated.

Key words: lymphoma, B-cell, lymphocytosis.