A subset of patients with
immunoglobulin M (
IgM)
monoclonal gammopathy of undetermined significance (MGUS) develop
IgM-related disorders (
IgM-RD) including
peripheral neuropathy,
cryoglobulinemia and/or
cold agglutinin disease (CAD). We examined the clinical and bone marrow pathologic findings in 191
IgM MGUS patients (2016 World Health Oragnization criteria). Clonal plasma cells were identified in 41 of 171 (24%) cases by immunohistochemistry (IHC) and clonal B cells in 43 of 157 (27%).
IgM-RD was identified in 82 (43%) cases, including
peripheral neuropathy (n=67, 35%),
cryoglobulinemia (n=21, 11%), and CAD (n=10, 5%). Cases of CAD showed distinctive features including lack of MYD88 mutations (P=0.048), supporting the concept of primary CAD as a distinct clinicopathologic disorder. Following exclusion of CAD, comparison of the remaining cases with (n=72) or without (n=109)
IgM-RD showed
IgM-RD to be more frequent in men than women (P=0.02) and to be more highly associated with MYD88 L265P (P=0.011). Cases with and without
IgM-RD otherwise showed similar features including serum
IgM concentrations, presence of lymphoid aggregates, clonal B cells by flow cytometry or clonal plasma cells by IHC. No differences were observed in overall survival between cases with and without
IgM-RD. No cases in this series met criteria for plasma cell type
IgM MGUS as defined in the 2022 International Consensus Classification of lymphoid
neoplasms. These results show
IgM-RD to be common in patients with
IgM MGUS. While CAD shows distinctive features, the remaining cases of
IgM-RD largely show pathologic findings similar to
IgM MGUS without
IgM-RD.