ESSENTIALS OF DIAGNOSIS
Monoclonal IgM paraprotein.
Infiltration of bone marrow by plasmacytic lymphocytes.
Absence of lytic bone disease.
L265P pathogenic variant in the gene MYD88.
Waldenström macroglobulinemia is a syndrome of IgM hypergammaglobulinemia that occurs in the setting of a low-grade non-Hodgkin lymphoma characterized by B cells that are morphologically a hybrid of lymphocytes and plasma cells. These cells characteristically secrete the IgM paraprotein, and many clinical manifestations of the disease are related to this macroglobulin.
This disease characteristically develops insidiously in patients in their 60s or 70s. Patients usually present with fatigue related to anemia. Hyperviscosity of serum may be manifested in a number of ways. Mucosal and GI bleeding is related to engorged blood vessels and platelet dysfunction. Other complaints include nausea, vertigo, and visual disturbances (eFigure 13–36). Alterations in consciousness vary from mild lethargy to stupor and coma. The IgM paraprotein may also cause symptoms of cold agglutinin disease (hemolysis) or chronic demyelinating peripheral neuropathy.
A: Hyperviscosity syndrome on funduscopic examination of a patient with Waldenström macroglobulinemia. Retinal findings include dilated retinal vessels, hemorrhages, and "venous sausaging." The whitish material lining the edge of the veins may be cryoglobulin. (Used with permission of Marvin J. Stone, MD.) B: Hyperviscosity syndrome as demonstrated by a fluorescein angiogram showing dilated arteries and veins. Also seen are microaneurysms and hemorrhages. (Reproduced with permission, from Riordan-Eva P, Augsburger JJ. Vaughan & Ashbury's General Ophthalmology. 19th ed. McGraw-Hill, 2018).
On examination, there may be hepatosplenomegaly or lymphadenopathy. The retinal veins are engorged. Purpura may be present. There should be no bone tenderness.
Anemia is nearly universal, and rouleaux formation is common, although the RBCs are agglutinated when the blood smear is prepared at room temperature. The anemia is related in part to expansion of the plasma volume by 50–100% due to the presence of the paraprotein. Other blood counts are usually normal. The abnormal plasmacytic lymphocytes may appear in small numbers on the peripheral blood smear. The bone marrow is characteristically infiltrated by the plasmacytic lymphocytes. The L265P pathogenic variant in MYD88 is detectable in more than 90% of patients.
The hallmark of macroglobulinemia is the presence of a monoclonal IgM spike seen on serum PEP in the beta-globulin region. The serum viscosity is usually increased above the normal of 1.4–1.8 times that of water. Symptoms of hyperviscosity usually develop when the serum viscosity is over four times that of water, and marked symptoms usually arise when the viscosity is over six times that of water. Because ...