Introduction

Waldenstrom's macroglobulinemia (WM) is a distinct clinicopathological entity resulting from the accumulation, predominantly in the bone marrow, of clonally related lymphocytes, lymphoplasmacytic cells, and plasma cells that secrete a monoclonal IgM protein (Figure 9.1). This condition is considered to correspond to lymphoplasmacytic lymphoma (LPL) as defined by the World Health Organization classification system. Most cases of LPL are WM, with less than 5% of cases made up of IgA, IgG, and non-secreting LPL.

Epidemiology and etiology

WM is an uncommon disease, with a geometrical increase with age. The incidence rate for WM is higher among Caucasians, with African descendants representing only 5% of all patients. Genetic factors appear to be important to the pathogenesis of WM. A common predisposition for WM with other malignancies has been raised, and there have been numerous reports of familial predisposition, including clustering of family members with WM and other B-cell lymphoproliferative diseases. In a recent study, 28% of 924 serial WM patients presenting to a tertiary referral had a first or second degree relative with either WM or another B-cell disorder. Frequent familial associations with other immunological disorders in healthy relatives have also been reported. The role of environmental factors in WM remains to be clarified, but chronic antigenic stimulation from infections, certain drug and agent orange exposures remain suspect.