Clinical Lymphoma March 2005 • 285 Introduction Macroglobulinemia with lytic bone lesions was first reported in 1956. 1 This rare condition known as immunoglobulin (Ig) M myeloma has become recognized as an entity distinct from either Waldenström’s macroglobulinemia (WM) or multiple myeloma (MM). In a review of the literature, the authors found 20 cases that met the following criteria for diagnosis: IgM monoclonal protein, lymphoplasmacytic bone marrow infiltrates, and lytic bone lesions. 2-14 Reports on 8 other patients did not fulfill these criteria and were not included. 15-19 A patient with WM who developed lytic bone lesions 1 year after presentation provided the opportunity to investigate the potential mechanism for these findings. The purpose of this study was to confirm the diagnosis of IgM myeloma and to determine expression of cytokines known to be involved in pathogenesis of osteolytic disease in patients with plasma cell dyscrasias. Case Report The patient, a 58-year-old man, presented in March 2000 with a history of recurrent sinopulmonary infections, anemia, and an M-spike (6 g/dL) on serum protein electrophoresis. Physical examination disclosed retinal venous engorgement with “sausaging” on funduscopic examination. Bone tenderness, lymphadenopathy, and hepatosplenomegaly were absent. Hematocrit was 25% with serum viscosity of 4.7 (normal: 1.4- 1.8). A monoclonal IgM,κ protein was identified by serum immunofixation electrophoresis. Bone marrow examination disclosed a hypercellular specimen (85%) with 52% lympho- plasma cells in sheets and clusters. Flow cytometry on the marrow aspirate showed a cell population (32%) with monoclonal B-cell expansion, which was bright μ, κ, and CD38 + , CD45 + , CD56 + , and CD14 + ; and CD10 – , CD19 – , CD20 – , and human leukocyte antigen–DR–negative. The CD20 marker was variably expressed on subsequent determinations. Skeletal survey was negative for osteolytic lesions. The diagnosis of WM was made. Plasmapheresis was initiated for hyperviscosity syndrome, and the patient was started on alkylating agent and corticosteroid therapy. In March 2001, the patient complained of pain in the ribs. Radiographs showed rib fractures and lytic bone lesions in the parietal skull, proximal femora, pubic ramus, and right ischium. Treatment included multiple courses of alkylating agents, thalidomide, corticosteroids, pamidronate, erythropoietin, and plasmapheresis, with only transient improvement. A nonmyeloablative allograft was performed, but the patient continued to have elevated M- protein levels and serum viscosity. Repeat bone marrow examination showed 80%-90% plasma cells with IgM,κ restriction. Analysis by fluorescence in situ hybridization for the translocation t(11:14) (q13:32) was positive. The patient’s refractory disease was treated with pulse dexamethasone, arsenic trioxide, and bortezomib without success. He died in May 2003. Permission for an autopsy was not obtained. Immunoglobulin M Myeloma: Evaluation of Molecular Features and Cytokine Expression Kartik Konduri, 1 Surinder S. Sahota, 2 Gavin Babbage, 2 Alex W. Tong, 1 Padmasini Kumar, 1 Joseph T. Newman, 1 Marvin J. Stone 1 Immunoglobulin (Ig) M myeloma is a distinct entity with features of multiple myeloma (MM) and Waldenström’s macroglobulinemia (WM). The malignant cells in IgM myeloma have a distinctive chromosomal translocation that differentiates them from WM. These cells are postgerminal–center in origin with isotype-switch transcripts. They appear to be arrested at a point of maturation between that of WM and MM. Preliminary data indicate that a pattern of osteoclast-activating factor and osteoprotegerin expression similar to that observed in classic MM is present in IgM myeloma. Additional studies on patients with this rare tumor may provide further insight into the patho- genesis of bone disease in plasma cell dyscrasias. Clinical Lymphoma, Vol. 5, No. 4, 285-289, 2005 Key words: Osteoclast-activating factor, Osteoprotegerin, Plasma cell dyscrasias, Tumor V H gene Abstract Case Report Address for correspondence: Kartik Konduri, MD, Baylor Charles A. Sammons Cancer Center, 3535 Worth St, Dallas, TX 75246 Fax: 214-820-2780; e-mail: kartikkonduri@hotmail.com Submitted: Nov 11, 2004; Revised: Jan 20, 2005; Accepted: Jan 20, 2005 1 Baylor Charles A. Sammons Cancer Center, Dallas, TX 2 Southampton University Hospitals, Southampton, UK Electronic forwarding or copying is a violation of US and International Copyright Laws. Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by Cancer Information Group, ISSN #1526-9655, provided the appropriate fee is paid directly to Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923 USA 978-750-8400.