What is the pathophysiology of Waldenström macroglobulinemia?

Updated: May 29, 2020
  • Author: Karen Seiter, MD; Chief Editor: Emmanuel C Besa, MD  more...
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The clinical manifestations of this disorder result from 2 important factors. First, secretion of the IgM paraprotein leads to hyperviscosity and vascular complications because of physical, chemical, and immunologic properties of the paraprotein. These complications include the following:

  • Hyperviscosity syndrome
  • Cryoglobulinemia types 1 and 2
  • Coagulation abnormalities
  • Sensorimotor peripheral neuropathy
  • Cold agglutinin disease and anemia
  • Primary amyloidosis
  • Tissue deposition of amorphous IgM in the skin, GI tract, kidneys, and other organs

Second, neoplastic lymphoplasmacytic cells infiltrate the bone marrow, spleen, and lymph nodes. Less commonly, these cells can infiltrate the liver, lungs, GI tract, kidneys, skin, eyes, and central nervous system (CNS). Infiltration of these organs causes numerous clinical symptoms and signs.

Occasionally, IgM paraprotein has (1) rheumatoid factor activity, (2) antimyelin activity that can contribute to peripheral neuropathy, and (3) immunologically related lupus anticoagulant activity.

A study by Pasricha et al found that bone marrow features, particularly the degree of plasma cell infiltration, correlates with IgM paraprotein concentration at diagnosis. Thus, evaluation of the plasma cell compartment in the bone marrow at baseline and after therapy may be helpful. [8]

Jalali et al reported that levels of soluble programmed cell death protein 1 (PD-1) ligands are elevated in patients with Waldenström macroglobulinemia and, in addition to surface-bound ligands in bone marrow, could regulate T-cell function. These authors propose that soluble PD-1 ligands have the potential to promote disease progression in Waldenström macroglobulinemia. [9]

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