CD5 Negative Mononuclear Lymphocytosis;a Precursor for Splenic Marginal Zone Lymphoma?

Abstract 3113

The natural history of patients with monoclonal B-cell lymphocytosis (MBL) who present with a lymphocytosis of <5×10⁹/l and an immunophenotype that is either CD5 negative or CD5 positive but atypical for CLL, and lacking an IGH/CCND1 translocation, is poorly understood. Six such patients under our care have evolved to typical SMZL. In order to clarify the biological relationship between non CLL/MCL-like MBL and SMZL we compared the lymphocyte morphology, immunophenotype, incidence of paraproteinemia, cytogenetic abnormalities and IGHV gene analysis in 47 local cases with a cohort of 61 patients diagnosed with SMZL. Results are shown in the table.

All 10 MBL cases for whom a CT or abdominal ultrasound scan was performed at or close to the time of presentation, showed no abnormality. None of the 47 cases has evolved into a chronic lymphoproliferative disorder other than SMZL. Lymphocyte morphology is often difficult to evaluate in cases with a slight lymphocytosis, but only 12 MBL cases did not show morphological features of SMZL in >10% of cells. MBL cases typically expressed moderate or strong surface IG and were CD5-, CD23-, CD79d+ and FMC7+, however, 9 expressed weak CD5. All had a Matutes CLL score of <3. The pattern of cytogenetic abnormalities was similar in both groups and del7q and the t(2;7) which are commonly associated with SMZL were found in the MBL cohort. The high incidence of TP53 loss associated with i(17q) in stable MBL cases contrasted with TP53 loss secondary to 17p deletion or translocation in cases of SMZL with aggressive disease and was not related to a differing incidence of TP53 mutations. IGHV gene usage was comparable between the 2 groups apart from a striking under-utilisation of IGHV1-2 and over-utilization of IGHV4-34 in the MBL cases. 1 case which has evolved to SMZL utilises IGHV4-34 and the single case among the MBL group utilising the 1–2 IGHV has the 1–2*04 allele found most frequently in SMZL.

There were no consistent differences in the biological features of those cases evolving to SMZL compared to those with stable MBL.

This data suggests that at least in a subset of cases, non CLL/MCL like MBL is a precursor of SMZL analogous to the relationship between CD5+ MBL and CLL. Differences in the IGHV gene repertoire and cytogenetic abnormalities may partially account for the differing clinical outcomes between MBL and SMZL.