How can I differentiate Waldenström's Macroglobulinaemia from other causes of elevated IgM levels in a patient?

To differentiate Waldenström's macroglobulinaemia (WM) from other causes of elevated immunoglobulin M (IgM) levels, a combination of clinical, laboratory, and pathological assessments is essential.

Firstly, WM is characterised by a monoclonal IgM paraprotein detected on serum protein electrophoresis and immunofixation, whereas polyclonal IgM elevation suggests reactive or inflammatory causes rather than WM ¹.

Secondly, bone marrow biopsy in WM shows infiltration by lymphoplasmacytic lymphoma cells, which is a key diagnostic feature distinguishing it from other IgM elevations such as those seen in chronic infections or autoimmune diseases (Vijay and Gertz, 2007).

Thirdly, the presence of symptoms related to hyperviscosity, anaemia, or organomegaly supports WM diagnosis over benign IgM elevations ¹.

Additionally, molecular testing for the MYD88 L265P mutation, present in over 90% of WM cases, provides a highly specific marker to differentiate WM from other IgM-secreting disorders (Zanwar and Kapoor, 2024).

Finally, other causes of elevated IgM such as IgM monoclonal gammopathy of undetermined significance (MGUS) or other B-cell lymphoproliferative disorders require exclusion through comprehensive clinical and pathological evaluation ¹; (Zanwar and Kapoor, 2024).