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

We investigated 16 patients with elevated serum monoclonal IgG and a leukaemic B-cell lymphocytic disorder different from multiple myeloma. Their clinical history was that of a non-aggressive disease with dominant splenomegaly and long survival. Whereas abnormal blood and bone marrow cells were predominantly small lymphocytes with a few lymphoplasmacytoid cells, histopathological features included a lymphoplasmacytic infiltrate in eight cases. Most frequently, abnormal blood cells displayed a CD19(+)CD5(-)CD23(+/-) immunophenotype different from that of chronic lymphocytic leukaemia, except in two cases with a CD19(+)CD5(+)CD23(+) phenotype. Interestingly, a coexistent serum monoclonal IgM and/or surface IgMG(+) with identical light chain was identified in 10 patients, whereas in the remaining six patients only IgG expression was determined. V-H gene analysis was performed in eight: patients to investigate the clonal origins of tumour cells. All cases utilized the V(H)3 family, with evidence of extensive somatic mutations and intraclonal homogeneity in all cases. V-H gene analysis indicated a clonal relationship between cells expressing IgM and IgG, with one case being biclonal. Cytogenetic evaluation showed a high incidence of trisomy 12 (60%) and 13q14 deletion (40%). In conclusion, we have described an unusual subset of low-grade 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 and others as IgG-positive cells only.