Prevalence and clinical significance of the MYD88 (L265P) somatic mutation in Waldenström’s macroglobulinemia and related lymphoid neoplasms

Abstract

Key Points Using a sensitive method, the MYD88 (L265P) mutation is detectable in all patients with Waldenström’s macroglobulinemia, therefore representing a hallmark of the disease. MYD88 (L265P) is also found in a substantial proportion of patients with IgM-MGUS.

MYD88 L265P mutation contributes to the diagnosis of Bing Neel syndrome

“…High frequency of CD79A/CD79B mutation was also identified in PCNSL. Our current finding, that the MYD88 mutation was identified in the CSF of BNS without a BCR CD79-based activating mutation supports the concept that BNS might represent a pathogenetically distinct group of PCNSL (Montesinos-Rongen et al, 2011;Poulain et al, 2013b;Varettoni et al, 2013), and may help in the differential diagnosis as CD19 with K/L restriction is observed in the two diseases.…”

“…In our study, the increased level of detection of MYD88 L265P mutation was shown using high sensitive qPCR (allele-specific oligonucleotide-PCR) as compared to Sanger sequencing when present in a very limited number of cells, as exemplified by the higher level of detection of qPCR in IgM monoclonal gammopathy of undetermined significance, characterized with presence of a B lymphocyte cell clone at a very low level, and in minimal residual disease evaluation (Treon et al, 2012;Jimenez et al, 2013;Varettoni et al, 2013;Xu et al, 2013). High sensitive qPCR might also increase the chance to identify the presence of the MYD88 L265P mutation at a sub-clonal level, particularly in the context of low cellularity in the CSF following treatment.…”

MYD88 L265P mutation analysis helps define nodal lymphoplasmacytic lymphoma

“…19,20 Subsequent studies from multiple institutions have confirmed MYD88 L265P to be present in the majority of lymphoplasmacytic lymphoma/ Waldenstrom's macroglobulinemia, with reported incidence from 67 to 93%. 12,15,21 The mutation has also been found in 44-87% of IgM monoclonal gammopathy of undetermined significance. 12,15,22,23 In contrast, this abnormality has been found much less frequently in other small B-cell neoplasms, including 4-21% of cases diagnosed as splenic marginal zone lymphoma and 1-10% of chronic lymphocytic leukemia.…”

“…These results are similar to prior reports showing that MYD88 mutation is associated with higher serum IgM levels in bone-marrow-based lymphoplasmacytic lymphoma and IgM monoclonal gammopathy of undetermined significance. 12,15, 21 Ho et al 27 have also recently described MYD88 mutations to be associated with an IgM protein in nodal lymphomas as well.…”

“…This case displayed a prominently nodular growth pattern and cytology that appeared much more consistent with a diagnosis of nodal marginal zone lymphoma with plasmacytic differentiation. MYD88 L265P has also been described in a small percentage of chronic lymphocytic leukemia/small lymphocytic lymphoma, 15,21,25,26,40,41 emphasizing that MYD88 mutation status alone clearly cannot be used to define lymphoplasmacytic lymphoma. The MYD88 L265P abnormality has also been reported in a small percentage of cases diagnosed as extranodal marginal zone lymphoma, 19,20 although distinction between extranodal marginal zone lymphoma with plasmacytic differentiation and an extranodal lymphoplasmacytic lymphoma may be somewhat arbitrary, and the prior studies included insufficient clinical or histologic information to completely exclude extranodal lymphoplasmacytic lymphoma.…”