Waldenstrom’s Macroglobulinemia

Abstract

Waldenström’s macroglobulinemia (WM) is a rare, distinct clinicopathological indolent B-cell lymphoproliferative disorder, first described in 1944 by Jan Gosta Waldenström (Incipient myelomatosis or essential hyperglobulinemia with fibrinogenopenia-a new syndrome? Acta Med Scand. 1944;117:216–47). The second international workshop on WM attempted to refine the working definition of the disease (Owen RG, Treon SP, Al-Katib A, Fonseca R, Greipp PR, McMaster ML, et al. Clinicopathological definition of Waldenstrom’s macroglobulinemia: consensus panel recommendations from the second international workshop on Waldenstrom’s macroglobulinemia. Semin Oncol. 2003;30(2):110–5). Diagnostic criteria include diffuse infiltration by lymphocytes, lymphoplasmacytic cells, and plasma cells and the presence of IgM regardless of the concentration. This condition is considered to correspond to the lymphoplasmacytic lymphoma (LPL) as defined by the World Health Organization classification system (Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127(20):2375–90).The diagnostic concept of Waldenström’s Macroglobulinemia (WM) has changed dramatically with the description of various recurrent mutations, including MyD88 and CXCXR4 mutations, leading to different clinical presentations, prognoses, and responses to treatment (Hunter ZR, Xu L, Yang G, Zhou Y, Liu X, Cao Y, et al. The genomic landscape of Waldenstrom macroglobulinemia is characterized by highly recurring MYD88 and WHIM-like CXCR4 mutations, and small somatic deletions associated with B-cell lymphomagenesis. Blood. 2014;123(11):1637–46; Treon et al., N Engl J Med 2012;367(9):826–33). Treatment initiation is only scheduled for symptomatic patients, including symptoms related to tissue infiltration by tumoral cells, such as cytopenias, bulky extra medullary disease, and IgM-related complications. Treatment options can be influenced by the genomic landscape of the tumor.KeywordsWaldenström’s macroglobulinemiaIndolent B-NHLIgMMonoclonal gammopathyMYD88CXCR4Ibrutinib