IgG-secreting lymphoplasmacytoid leukaemia: a B-cell disorder with extensively mutated V-H genes undergoing Ig isotype-switching frequently associated with trisomy 12

We investigated 16 patients with elevated serum monoclonal IgG and a leukae mic B-cell lymphocytic disorder different from multiple myeloma. Their clin ical history was that of a non-aggressive disease with dominant splenomegal y and long survival. Whereas abnormal blood and bone marrow cells were pred ominantly small lymphocytes with a few lymphoplasmacytoid cells, histopatho logical features included a lymphoplasmacytic infiltrate in eight cases. Mo st frequently, abnormal blood cells displayed a CD19(+)CD5(-)CD23(+/-) immu nophenotype different from that of chronic lymphocytic leukaemia, except in two cases with a CD19(+)CD5(+)CD23(+) phenotype. Interestingly, a coexiste nt serum monoclonal IgM and/or surface IgMG(+) with identical light chain w as identified in 10 patients, whereas in the remaining six patients only Ig G expression was determined. V-H gene analysis was performed in eight: pati ents to investigate the clonal origins of tumour cells. All cases utilized the V(H)3 family, with evidence of extensive somatic mutations and intraclo nal homogeneity in all cases. V-H gene analysis indicated a clonal relation ship between cells expressing IgM and IgG, with one case being biclonal. Cy togenetic evaluation showed a high incidence of trisomy 12 (60%) and 13q14 deletion (40%). In conclusion, we have described an unusual subset of low-g rade lymphoma with high-serum IgG and frequent lymphoplasmacytoid features in which tumour cells derive from post-follicular memory B cells undergoing isotype switching with some cases arrested at both the IgM and IgG stage a nd others as IgG-positive cells only.