What are the key clinical features and laboratory findings that suggest a diagnosis of Waldenström's Macroglobulinaemia?

Key clinical features suggesting Waldenström's macroglobulinaemia (WM) include symptoms related to bone marrow infiltration such as fatigue, anaemia, and bleeding tendencies, as well as hyperviscosity symptoms like blurred vision, headache, dizziness, and neurological deficits. Patients may also present with lymphadenopathy, hepatosplenomegaly, and constitutional symptoms such as weight loss and night sweats. Peripheral neuropathy is another notable clinical feature due to IgM paraprotein effects on nerves.

Laboratory findings critical for diagnosis include the presence of a monoclonal IgM paraprotein detected by serum protein electrophoresis and immunofixation. Bone marrow biopsy typically shows lymphoplasmacytic infiltration. Elevated serum viscosity may be observed in symptomatic patients. Additional laboratory abnormalities include anaemia, thrombocytopenia, and sometimes elevated beta-2 microglobulin. Molecular testing often reveals MYD88 L265P mutation, which supports diagnosis and risk stratification.

These clinical and laboratory features together form the basis for suspecting and diagnosing WM, as outlined in UK guidelines and supported by recent literature emphasizing the importance of integrating clinical presentation with detailed laboratory and molecular investigations for accurate diagnosis and management planning NICE NG35 Ghobrial et al. 2003Maqbool et al. 2020Zanwar & Kapoor 2024.