IgM multiple myeloma: More on a rare and heterogeneous disease
Authors: Quentin Cabrera, Sylvain Chantepie, Veronique Salaun, Xavier Levaltier, Xavier Troussard, Margaret Macro
Journal: American Journal of Hematology (2011)

IgM multiple myeloma (MM) is a rare disease, sharing clinical and biological manifestations with Waldenström macroglobulinemia (WM) that may lead to misdiagnosis [1]. The proper identification of IgM MM is crucial for the therapeutic approach and the long-term prognosis [2, 3]. A recent study by the Mayo Clinic group defined IgM MM with clinical and cytogenetic criteria [4] that all patients had IgM protein, regardless of size, more than 10% plasma cell infiltration in bone marrow, and lytic bone lesions with or without the presence of t(11;14) translocation. This translocation, leading to cyclin D1 dysregulation, was recently found to be present in some IgM MM but absent in WM [5]. However, the prevalence of the t(11;14) is low, only 38% in the Mayo Clinic study [4]. Flow cytometric immunophenotyping (FCI) of bone marrow plasma cells has substantial clinical relevance in differentiating MM from WM. All Plasma cells present a CD38+ (bright) CD138+ phenotype [6]. Myeloma plasma cells lack CD19, CD45, and CD27 expressions and are positive for CD56 (75%), CD117 (30%), and CD20 (30%) [6]. In WM, clonal B-cells express CD19, CD20, CD45, and a monoclonal profile for surface light chain. We report here three cases of IgM MM recorded in the last 3 years. Our goal is to underline the heterogeneity of the disease and to retain flow cytometry as a mandatory tool for IgM MM diagnosis. Patients' characteristics at diagnosis are shown in Table I. All patients had skeletal X-ray exam and vertebral MRI; only one (patient A) of three patients had bone lesions at diagnosis and presented cyclinD1 over expression. We believe that bone lesions can occur in IgM MM but do not represent major diagnostic criteria; two patients in the Mayo Clinic study were excluded a priori for that reason. In two patients with no bone lesion, there was no evidence of the t(11;14) by FISH or Cyclin-D1 over expression by RT-PCR. FCI of bone marrow plasma cells confirmed the diagnosis (Table II) and excluded a WM; all B-cells identified on the basis of scatter/CD45 characteristics and a Kappa/Lambda/CD19/CD5 gate were polyclonal with respect to the surface light chain expression. In the Mayo Clinic series, 15/21 patients had immunophenotyping analysis (71%) and five were CD20+, but no information was provided about the flow cytometric method or a complementary phenotype. Feyler et al. [7] considered an aberrant phenotype of IgM MM plasma cells as a diagnostic criterion: all 10 patients presented a CD56− and CD117− profile. However, patient B had a CD56+ CD117− different phenotype. We think that a heterogeneous phenotype can be found in IgM MM, as for clinical presentation. Furthermore, retaining bone lesions as a diagnostic criterion could miss true IgM MM cases even adding the t(11;14), which is not a sensitive tool. Bone marrow cells FCI is actually the most relevant method to affirm IgM MM. We confirm the clinical and immunophenotypic heterogeneous presentation of the disease in this series. Furthermore, we confirm, according to Feyler's series, the bad prognosis of IgM MM as 2/3 patients died at 2 and 6 months, despite new agents combination for first line therapy. Quentin Cabrera [email protected]*, Sylvain Chantepie*, Veronique Salaun , Xavier Levaltier , Xavier Troussard , Margaret Macro*, * Service d'Hématologie clinique, CHU de Caen, France, Service d'Hématologie biologique, CHU de Caen, France, Polyclinique du Parc, Caen, France.