Immunophenotypic and DNA content characteristics of plasma cells in multiple myeloma and monoclonal gammopathy of undetermined significance

In the present paper we review the immunophenotypic characteristics of plas ma cells (PC) and the PC DNA contents from multiple myeloma (MM) and monocl onal gammopathy of undetermined significance (MGUS), and its value for the differential diagnosis between both entities. The strong reactivity for CD3 8 and the positivity for CD138 are the two best markers for identifying PC. Myelomatous PC display an heterogeneous phenotype consistent with the fact that the neoplastic clone is able to undergo a certain degree of different iation. In addition, PC from MM patients usually lack surface expression of B-cell associated antigens and frequently display reactivity for markers w hich are not restricted to the B-cell lineage. In MGUS patients, two clearl y defined and distinct PC subpopulations can be identified. One of these PC subpopulations shows phenotypic characteristics identical to those of norm al PC, including a very strong reactivity for the CD38 antigen, intermediat e/low light scatter characteristics and positivity for CD19, in the absence of CD56, and corresponds to the residual normal bone marrow PC. The second PC subpopulation shows an immunophenotype similar to that of myelomatous P C, characterized by a slightly lower reactivity for CD38 and strong CD56 ex pression, on the absence of positivity for CD19, these PC corresponding to the clonal counterpart. Using a simultaneous staining for PC and DNA, aroun d 60% of MM and 73% of MGUS patients display DNA aneuploidy, the majority o f them being hyperdiploid. However, in contrast to MM patients, in MGUS pat ients two clearly different PC subsets can be discriminated in most cases ( 73%): a diploid and an aneuploid (hyperdiploid) subset, corresponding to no rmal and clonal PC, respectively. Upon comparing hyperdiploid with diploid patients in MM, the former display a better prognosis, in line with the hig her incidence of DNA hyperdiploidy in MGUS. A clear correlation between the percentage of S-phase PC and several prognosis features of MM has been fou nd. In spite of these findings, no significant differences in the percentag e of pathological S-phase PC are detected between MM and MGUS patients. Reg arding the differential diagnosis between MGUS and MM, multivariate analysi s shows that the ratio between the number of clonal and normal residual PC is the best single parameter.