Defining IgM multiple myeloma
Authors: Roger G Owen, Sylvia Feyler, Sheila JM O'Connor, Lee R Bond, Ruth M de Tute, Andy C Rawstron
Journal: American Journal of Hematology (2011)

We read with interest the recent report of Schuster et al. [1], who described the clinical presentation and outcome of 21 patients diagnosed with immunoglobulin M (IgM) multiple myeloma (MM). In this report, the authors defined IgM MM according to the following criteria—IgM monoclonal gammopathy, equal or greater than 10% bone marrow plasma cells and the presence of lytic bone disease and/or translocation t(11;14). We believe that this definition is restrictive and will fail to capture a proportion of patients particularly those with asymptomatic disease and other cytogenetic abnormalities. Ideally IgM MM should be defined according to principles identical to those used in standard MM. We have previously reported the clinicopathological features of 10 patients with IgM MM [2] and in this current report detail the features of two additional patients (Table I) to further clarify the immunophenotypic and genotypic characteristics of IgM MM. The cytogenetic characteristics of IgM MM were first evaluated by Avet-Loiseau et al. [3], who demonstrated the t(11;14) by fluorescence in situ hybridization in seven of eight cases (88%). Similarly, in our initial study, we demonstrated the translocation in 5/8 evaluable cases and have also demonstrated it in a further patient included in this current report (overall incidence 6/10, 60%). Schuster and coworkers demonstrated the translocation in a lower proportion of patients (38%), although a further report has failed to demonstrate it in two further cases [1, 4]. It is clear, therefore, that although the t(11;14) appears to occur at a higher frequency in IgM MM, it cannot be regarded as a defining abnormality. Similarly, we reported a patient with the t(4;14) in our original cohort and also include a patient with a t(14;16) in this current report (overall incidence 10% in each instance). Both patients have been reported in detail elsewhere [5, 6]. Myeloma plasma cells are characterized by distinct phenotypic differences, when compared to normal plasma cells, and these typically include loss of CD19, CD27, CD45 along with aberrant expression of CD56, CD20, CD117, and cyclin D1 [7]. In our original analysis, an aberrant plasma cell phenotype was demonstrable in 7/10 cases [2] and is also demonstrable in each of the additional cases included in this report confirming the applicability of extended plasma cell phenotyping by either flow cytometry or immunohistochemistry in the diagnosis of IgM MM. This is particularly useful in distinguishing IgM MM from Waldenstrom macroglobulinemia (WM). Our data would also suggest that the immunophenotypic profile of IgM MM differs from that of class-switched myeloma in that there appears to be a lower incidence of CD56 expression [2]. The presence of lytic bone disease was also included in the selection criteria used by Schuster et al. [1]. In our cohort of patients, bone disease was demonstrable in 5/8 (63%), whereas 2/10 (20%) showed neither the t(11;14) nor bone disease. It is interesting to note that the two patients, who lacked both bone disease and the t(11;14), were the patients with the t(4;14) and t(14;16). The inclusion of lytic bone disease and/or the t(11;14) as defining criteria will systematically exclude patients with asymptomatic disease as well as those with other distinct cytogenetic abnormalities. We would conclude that the immunophenotypic and genotypic characteristics of IgM MM are now better characterized and allow for more definitive diagnostic criteria. IgM MM should be defined by IgM monoclonal gammopathy and ≥10% bone marrow plasma cells. The plasma cells should express monotypic IgM and will frequently demonstrate aberrant expression of a range of antigens including CD19 and cyclin D1, although the incidence of CD56 expression appears lower than in standard MM. Similarly, IgM MM is characterized, in contrast to WM, by immunoglobulin heavy chain (IGH) translocations, and these include not only the t(11;14) but also the t(4;14) and t(14;16). Roger G Owen [email protected]*, Sylvia Feyler , Sheila JM O'Connor*, Lee R Bond , Ruth M de Tute*, Andy C Rawstron*, * HMDS Laboratory, St James's University Hospital, Leeds, United Kingdom, Department of Hematology, Calderdale and Huddersfield NHS Foundation Trust etc, Calderdale and Huddersfield NHS Foundation Trust, Huddersfield United Kingdom, Department of Hematology, York Teaching Hospitals NHS Foundation Trust etc, York Teaching Hospitals NHS Foundation Trust, York United Kingdom.