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Epidemiology, pathogenesis, clinical manifestations and diagnosis of Waldenström macroglobulinemia

S Vincent Rajkumar, MD
Section Editor
Robert A Kyle, MD
Deputy Editor
Rebecca F Connor, MD


The term "macroglobulinemia" refers to the production of excess IgM monoclonal protein that occurs in certain clonal lymphoproliferative disorders and plasma cell dyscrasias. This broad definition includes patients with monoclonal gammopathy of undetermined significance of the IgM type (IgM MGUS), smoldering Waldenström macroglobulinemia (SWM), Waldenström macroglobulinemia (WM), and a number of related disorders in which an IgM monoclonal protein is detected, such as chronic lymphocytic leukemia (CLL), a number of lymphoma variants, and primary (AL) amyloidosis.

WM is a distinct clinicopathologic entity demonstrating lymphoplasmacytic lymphoma (LPL) in the bone marrow with an IgM monoclonal gammopathy in the blood. Patients may present with symptoms related to the infiltration of the hematopoietic tissues or the effects of monoclonal IgM in the blood.

This topic review will limit discussion to the clinical manifestations and diagnosis of WM. The pathologic features of lymphoplasmacytic lymphoma and the prognosis and treatment of WM are discussed separately. (See "Treatment and prognosis of Waldenström macroglobulinemia" and "Clinical manifestations, pathologic features, and diagnosis of lymphoplasmacytic lymphoma" and "Clinical course and management of monoclonal gammopathy of undetermined significance", section on 'IgM MGUS'.)


Waldenström macroglobulinemia (WM) is a rare disorder with an incidence of approximately three per million people per year with 1400 new cases diagnosed in the United States each year [1,2]. The median age at diagnosis is 64 years; less than 1 percent of patients are under 40 years of age, and approximately 60 percent are males [3]. WM is much more common in Caucasians than in other ethnic groups [4]. Specifically, it is uncommon in Blacks, who make up approximately 5 percent of cases, and those of Mexican descent [1].

The majority of patients with the histopathologic finding of lymphoplasmacytic lymphoma (LPL) have a circulating monoclonal IgM consistent with the diagnosis of WM. In the past, LPL and WM have been arbitrarily differentiated from each other based on the level of the monoclonal IgM protein. Currently, the preferred terminology in cases of LPL with circulating monoclonal IgM is WM, rather than lymphoplasmacytic lymphoma, regardless of the size of the monoclonal IgM protein. (See 'Diagnosis' below.)


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Literature review current through: Sep 2016. | This topic last updated: Jul 26, 2016.
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