Waldenström macroglobulinemia (WM) is a rare indolent B-cell lymphoma that most commonly occurs in older white men.
The pathophysiologic hallmark is monoclonal immunoglobulin M (IgM) production by a malignant lymphoplasmacytic clone that resides in the bone marrow.
Diagnosis is most often made following an incidental finding of an IgM paraprotein on a blood test.
Anemia (due to marrow infiltration), fatigue, and anorexia are the most common clinical features.
Lymphadenopathy, splenomegaly, and hyperviscosity (which can lead to skin and mucosal bleeding, thrombosis, retinopathy with visual disturbances, and neurologic symptoms such as headache, dizziness, and vertigo) are uncommon, but they are important clinical manifestations that require urgent treatment.
WM is incurable but median overall survival is long (approximately 8 years based on US data). Goals of treatment are to reduce symptoms, improve quality of life, and prolong survival. Treatment options include observation (for asymptomatic patients), plasmapheresis, chemotherapy, and targeted therapies (e.g., rituximab and ibrutinib).
There is no standard of care, mainly due to a lack of randomized trials in WM. Participation in clinical trials is recommended where possible.
Waldenström lymphoma can transform to aggressive high-grade lymphomas in around 5% of cases.
Waldenström macroglobulinemia (WM) is an indolent lymphoma in which malignant monoclonal plasmacytoid lymphocytes infiltrate bone marrow and visceral organs, and hypersecrete a monoclonal immunoglobulin M (IgM). It is often diagnosed following an incidental finding of an IgM paraprotein on a blood test.
Clinical manifestations are most commonly related to bone marrow infiltration by malignant cells (e.g., anemia, thrombocytopenia, pancytopenia). Clinical manifestations are less commonly related to organ infiltration (e.g., splenomegaly, hepatomegaly, and lymphadenopathy) and abnormal IgM properties and/or organ deposition (e.g., hyperviscosity syndrome, polyneuropathy, cryoglobulinemia, cold agglutinin hemolytic anemia, bleeding from the nose and gums, purpura, thrombosis [e.g., stroke, angina, myocardial infarction, pulmonary embolism, deep vein thrombosis], and kidney disease). The most common presenting symptoms are fatigue and anorexia. In contrast with multiple myeloma, bone lesions are not a feature of WM.
History and exam
Key diagnostic factors
- age >70 years
- male sex
- white ancestry
Other diagnostic factors
- history of IgM monoclonal gammopathy of undetermined significance (MGUS)
- family history of B-cell lymphoma or myeloma
- family history of WM with or without monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma
- peripheral neuropathy
- weight loss
- Raynaud phenomenon
- IgM component monoclonal gammopathy of undetermined significance (MGUS)
- family history of B-cell lymphoproliferative disease or multiple myeloma
- family history of WM
- hepatitis C virus (HCV)
1st investigations to order
- CBC with differential
- hematinic test (iron, vitamin B12, and folate)
- renal function panel
- high-resolution serum protein electrophoresis (SPEP) with immunofixation
- high-resolution urine protein electrophoresis (UPEP) and immunofixation
- serum free light chains
- cold agglutinins and cryoglobulins
- lactate dehydrogenase
- beta-2 microglobulin
- serum albumin
- relative serum viscosity
- bone marrow biopsy
- CT chest, abdomen, and pelvis
Investigations to consider
- lymph node biopsy
- 18-F-deoxyglucose (18F-FDG) PET/CT chest, abdomen, and pelvis
- quantitative immunoglobulins
- antimyelin-associated glycoprotein (MAG) antibodies
- antisulfatide IgM antibodies
- fat pad biopsy
- prothrombin time (PT) and activated partial thromboplastin time (APTT)
- viral serology (hepatitis B and C, and HIV)
- genetic mutation testing
symptomatic with low tumor burden
symptomatic with high tumor burden
responders to initial rituximab-containing treatment
relapse or refractory disease
- Multiple myeloma (MM)
- Low-grade B-cell lymphomas (e.g., follicular lymphoma)
- Chronic lymphocytic leukemia (CLL)
- NCCN clinical practice guidelines in oncology: Waldenström's macroglobulinemia/lymphoplasmacytic lymphoma
- Diagnosis and management of Waldenström macroglobulinaemia - a British Society for Haematology guideline
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