Waldenström's macroglobulinemia overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Mirdula Sharma, MBBS [2]
Overview
Waldenström macroglobulinemia (WM) is a rare lymphoproliferative disorder characterized by the presence of a serum IgM paraprotein associated with infiltration of the bone marrow by lymphoplasmacytic lymphoma. Waldenström macroglobulinemia is a type of lymphoproliferative disease involving lymphocytes with IgM as the main attributing antibody, and shares clinical characteristics with the indolent non-Hodgkin lymphomas. Waldenström's macroglobulinemia was first discovered by Jan G. Waldenström, and represents 1% of all hematological cancers. Common causes of this disease include genetic, environmental, and autoimmune factors, while common risk factors include monoclonal gammopathy of undetermined significance, age >50 year old, white ethnicity, heredity, hepatitis C, and immune disorders. Genes involved in pathogenesis of Waldenström macroglobulinemia include MYD88-L265P, CXCR4 and chromosomes 6q, 13q, 3q, 6p and 18q. The hallmark of Waldenström's macroglobulinemia is hyperviscosity syndrome. If left untreated, patients with asymptomatic Waldenström's macroglobulinemia may progress to develop symptomatic disease. Common complications of Waldenström's macroglobulinemia include hyperviscosity syndrome, cold haemagglutinin disease, cryoglobulinemia, peripheral neuropathy, venous thromboembolism, primary amyloidosis, malabsorbtive diarrhea, and bleeding manifestations. Prognosis varies depending on the multiple factors involved. Five year survival rate is 87% for low-risk disease and 36% for high-risk disease. Signs and symptoms of patients with Waldenström's macroglobulinemias depend on the degree of tissue infiltration by malignant tumor cells, hyperviscosity syndrome, and accumulation of paraprotein. The diagnosis of Waldenström macroglobulinemia is based on bone marrow biopsy and serum protein analysis. Risk stratification determines the protocol of management used for Waldenström macroglobulinemia patients. Watchful waiting is recommended for asymptomatic Waldenström's macroglobulinemia. Symptomatic Waldenström's macroglobulinemia is treated with Rituximab +/- Chemotherapy.
Historical Perspective
Waldenström macroglobulinemia was first discovered by Jan G. Waldenström, a Swedish physician in 1944.
Classification
There is no established system for the classification of Waldenström's macroglobulinemia.
Pathophysiology
Waldenström macroglobulinemia is an uncontrolled clonal proliferation of terminally differentiated B lymphocytes, which are normally involved in humoral immunity. Genes involved in the pathogenesis of Waldenström macroglobulinemia include MYD88-L265P, and CXCR4.
Causes
The exact cause of Waldenström macroglobulinemia has not been identified; however, the diesease has been highly associated with somatic mutations in MYD88 and CXR4 genes. In addition, possible less common causes of the disease include chromosomal abnormalities and environmental factors.
Differentiating Waldenström's Macroglobulinemia from Other B Cell Lymphoid Neoplasms
Waldenström macroglobulinemia must be differentiated from multiple myeloma, chronic lymphocytic leukemia/small lymphocytic lymphoma, b-cell prolymphocytic leukemia, follicular lymphoma, mantle cell lymphoma, and marginal zone lymphoma.
Epidemiology and Demographics
The prevalence of Waldenström macroglobulinemia is estimated to be 1500 cases in United States annually. Waldenström's macroglobulinemia represents 1% of all hematological cancers.
Risk factors
Common risk factors in the development of Waldenström macroglobulinemia are monoclonal gammopathy of undetermined significance, heredity, hepatitis C, and autoimmune disorders.
Screening
According to the the U.S. Preventive Service Task Force (USPSTF), there is insufficient evidence to recommend routine screening for Waldenström macroglobulinemia.
Natural History, Complications and Prognosis
If left untreated, patients with asymptomatic Waldenström macroglobulinemia may progress to develop fatigue, weight loss, peripheral neuropathy and other symptoms of the disease. Common complications of Waldenström macroglobulinemia include hyperviscosity syndrome, cold haemagglutinin disease, cryoglobulinemia, peripheral neuropathy, primary amyloidosis, renal insufficiency, malabsorbtive diarrhea, and visual abnormalities. Prognosis varies depending on the various factors involved. Five year survival rate is 87% for low-risk disease and 36% for high-risk disease.
Diagnostic Study of Choice
The diagnosis of Waldenström macroglobulinemia is based on bone marrow biopsy and serum protein analysis.
History and Symptoms
Many patients with Waldenström macroglobulinemia are asymptomatic. The disease is subtle and symptoms are nonspecific. The most common symptoms of Waldenström macroglobulinemia include weakness, anorexia, blurry vision, peripheral neuropathy, and weight loss. Less common symptoms of the disease include bleeding and Raynaud phenomenon.
Physical Examination
Patients with Waldenström macroglobulinemia usually appear oriented to time, place, and person. Physical examination of patients with waldenström's macroglobulinemia is usually remarkable for various findings depending on the degree of tissue infiltration by malignant tumor cells, hyperviscosity syndrome, and accumulation of paraprotein.
Laboratory Findings
Laboratory findings consistent with the diagnosis of Waldenström's macroglobulinemia include any cytopenia, elevated LDH, and elevated Beta-2 microglobulin.
Bone marrow aspiration and biopsy
A bone marrow aspiration may be helpful in the diagnosis of Waldenström macroglobulinemia, while a bone marrow biopsy is diagnostic of Waldenström macroglobulinemia.
Electrophoresis and Immunofixation
Serum protein electrophoresis and immunofixation are important for the diagnosis of Waldenström's macroglobulinemia.
Chest x-ray
On chest x-ray, waldenström's macroglobulinemia may be characterized by pulmonary infiltrates, nodules, effusion, and congestive heart failure.
CT scan
In Waldenström macroglobulinemia, CT scan imaging of chest, abdomen, and pelvis may show evidences of lymphadenopathy, and hepatomegaly.
Other Diagnostic Studies
Other diagnostic studies for Waldenström macroglobulinemia include nerve conduction study, electromyography, funduscopy, and plasma viscosity.
Medical Therapy
Risk stratification determines the protocol of management used for Waldenström's macroglobulinemia patients. Watchful waiting is recommended for asymptomatic Waldenström's macroglobulinemia. Symptomatic Waldenström's macroglobulinemia is treated with Rituximab +/- Chemotherapy.