Summary
Waldenström macroglobulinemia (WM) is a B-cell lymphoproliferative disorder characterized by the accumulation of monoclonal cells in the bone marrow and peripheral lymphoid tissues, and associated with the production of an IgM serum monoclonal protein. The pathologic designation for WM is lymphoplasmacytic lymphoma, as proposed by the World Health Organization Classification of Tumors. WM has an overall incidence of 2.5/million/year and accounts for approximately 2% of all hematological malignancies. The median age at diagnosis is 63 years. WM has a wide clinical spectrum related to tumor infiltration, and the production and deposition of IgM in various tissues. The main clinical features are cytopenia, hepatosplenomegaly, lymphadenopathy, constitutional symptoms, oronasal bleeding and hyperviscosity syndrome. Fatigue related to normochromic normocytic anemia is the most common symptom. Visceral infiltration may target the stomach, small bowel, lungs, exocrine glands or skin. Retinal hemorrhage or serious neurologic complications may occur. Neurological presentations range from mild symptoms (headache, lightheadedness) to severe symptoms (mental confusion, stroke, focal neurological deficits, severe motor disease). Major complications include bone marrow failure, autoimmune cytopenia, large cell lymphoma and infections. WM clearly has a familial component, however, no susceptibility genes have yet been identified. Diagnosis is confirmed by the presence of an IgM (usually kappa) paraprotein and a bone marrow biopsy (showing infiltration by a lymphoplasmacytic lymphoma with a predominantly intertrabecular pattern, supported by appropriate immunophenotypic studies). Differential diagnosis includes multiple myeloma, chronic lymphocytic leukemia, non-Hodgkin lymphoma and amyloidosis (see these terms), as well as monoclonal gammapathies of undetermined significance (MGUS). Infections like hepatitis, AIDS, and various rheumatological disorders also raise IgM levels. Treatment includes cytostatics (alkylating agents, particularly chlorambucil), purine nucleoside analogs (fludarabine, cladribine), and most recently rituximab. Plasmapheresis with total plasma exchange is used for management of hyperviscosity and neuropathies. The median survival time is five years but in some cases the disease may progress slowly. *Author: Orphanet (February 2007)*.
