Alerts and Notices
SynopsisLymphoplasmacytic lymphoma (Waldenström macroglobulinemia; WM) is a rare clonal neoplastic disorder characterized by proliferation of lymphoplasmacytoid cells in the skin as well as proliferation of plasma cells and elevated immunoglobulin M (IgM). It is considered a low-grade non-Hodgkin lymphoma. WM is thought to have 3 phases: IgM monoclonal gammopathy of undetermined significance (MGUS, an increase in monoclonal proteins without symptoms), followed by smoldering WM, and finally WM.
WM has an incidence of 3.4 per million in men and 1.7 per million in women, with a higher prevalence in White patients, and accounts for 1%-2% of hematologic malignancies. The median age of onset is approximately 60 years. WM sometimes has familial clustering with multiple myeloma or other B-cell disorders.
Mutation in MYD88 L265P is seen in 80%-95% of patients, depending on detection method (eg, peripheral blood versus bone marrow). Five to ten percent of patients do not harbor the MYD88 L265P mutation; thus, its absence does not preclude the diagnosis.
In symptomatic disease, patients most often present with (in descending order of prevalence): anemia, cytopenia, B symptoms (fever, weight loss, night sweats; these symptoms are associated with increased plasma levels of inflammatory proteins and can be an indication for treatment), hyperviscosity syndrome, and neuropathy. Rarely, in less than 1%-2% of cases, patients may develop WM-related systemic amyloidosis, symptomatic cryoglobulinemia, and cold agglutinin disease. Bing-Neel syndrome is another rare complication, in which lymphoplasmacytic disease infiltrates the central nervous system and the orbits. It is associated with optic neuropathy.
Neuropathy is classically symmetric, starts distally / ascending and sensory, and is thought to be related to clonal antibodies to myelin-associated glycoproteins or other nerve sheath molecules.
High levels of monoclonal proteins can increase plasma viscosity, leading to hyperviscosity syndrome: headaches, blurred vision (with sausaging of retinal vessels and retinal petechiae and hemorrhage), nose bleeds, leg cramps, impaired mentation, and intracranial hemorrhages.
Light-chain components can cause proteinuria and renal failure. Autoantibodies to red cells (often cold agglutinins) can cause anemia, and hyperviscosity can be associated with Raynaud phenomenon, acrocyanosis, and livedo reticularis.
Skin lesions include the following:
- Raynaud phenomenon
- Vasculitis and cryoglobulinemia with purpura
- Acrocyanosis and livedo reticularis
- Acquired cutis laxa
- Cutaneous macroglobulinosis
- Blistering of the skin – Due to an immune response elicited by IgM antibodies against different molecules binding in the basement membrane zone. IgM antibodies can be detected by direct and indirect immunofluorescence testing.
- Schnitzler syndrome can be seen in WM along with other monoclonal disorders. Patients will manifest chronic urticarial eruptions, frequent fevers, arthralgias, and, frequently, increased neutrophils and sedimentation rates. Biopsy of the urticarial lesions shows a neutrophilic infiltrate that is different from most of the common forms of urticarial disease.
C88.0 – Waldenström macroglobulinemia
35562000 – Waldenstrom's macroglobulinemia
Differential Diagnosis & PitfallsWM should be differentiated from other monoclonal gammopathies and lymphomas:
- IgM MGUS
- Multiple myeloma
- Chronic lymphocytic leukemia
- Marginal zone lymphoma
- Mantle cell lymphoma
Differential diagnosis of palpable purpura –
- Leukocytoclastic vasculitis from an underlying infection, drug, autoimmune disease, or lymphoproliferative disorder or associated with cryoglobulinemia, IgA vasculitis, granulomatosis with polyangiitis (GPA), or eosinophilic GPA
- Papular mucinosis (see also lichen myxedematosus)
- Amyloidosis from other causes
- Metastatic carcinoma
- Lymphoma leukemia infiltration