Waldenström's macroglobulinaemia (WM) is a rare, low-grade, lymphoplasmacytic lymphoma characterised by the production of monoclonal IgM. The incidence rate of WM is approximately 5 cases per million persons per year, about 5 - 10% that of multiple myeloma (MM) . The median age at diagnosis is 65 years, and up to 70% of patients are male  Median survival is approximately 5 years (with 10% of patients still alive after 15 years); many die from unrelated causes . The majority of patients diagnosed with WM do not require immediate therapy as they are detected before symptoms occur .
Infiltration of bone marrow and extramedullary sites by malignant B-cells, and elevated serum IgM concentrations are responsible for the majority of symptoms associated with WM . Whilst the most common presenting symptom is fatigue related to anaemia, symptoms vary considerably among patients and may include night sweats, weight loss, bleeding tendency, polyneuropathy, lymphadenopathy, hepatosplenomegaly and symptoms relating to hyperviscosity (i.e. headaches, blurred vision, confusional episodes, epistaxis).
Cryoglobulinaemia (where monoclonal IgM reversibly precipitates at temperatures below 37 °C) affects up to 20% of patients, although <5% have symptoms (Section 34.2) . The presence of cryoglobulins makes serum collection and laboratory quantification of IgM difficult, as they need to be performed at elevated temperatures.
Attempts to standardise diagnostic criteria have been made by the World Health Organisation (WHO) and the Mayo Clinic (Table 32.1), but there are significant discrepancies between the two definitions .
|Mayo Clinic WM diagnostic criteria:|
▪ IgM monoclonal gammopathy (regardless of the size of the monoclonal protein).
▪ >10% bone marrow lymphoplasmacytic infiltration (usually inter-trabecular) by small lymphocytes that exhibit plasmacytoid or plasma cell differentiation.
▪ Tumour lymphocytes display a typical immunophenotype (surface IgM+, CD5-, CD10-, CD19+, CD20+, CD23-) that satisfactorily excludes other lymphoproliferative disorders, including chronic lymphocytic leukaemia and mantle cell lymphoma.