MYD88 wild-type Waldenstrom Macroglobulinaemia: differential diagnosis, risk of histological transformation, and overall survival

Abstract

MYD88 mutations are present in 95% of Waldenstrom Macroglobulinaemia (WM) patients, and support diagnostic discrimination from other IgM-secreting B-cell malignancies. Diagnostic discrimination can be difficult among suspected wild-type MYD88 (MYD88^WT ) WM cases. We systematically reviewed the clinical, pathological and laboratory studies for 64 suspected MYD88^WT WM patients. World Health Organization and WM consensus guidelines were used to establish clinicopathological diagnosis. Up to 30% of suspected MYD88^WT WM cases had an alternative clinicopathological diagnosis, including IgM multiple myeloma. The estimated 10-year survival was 73% (95% confidence interval [CI] 52-86%) for MYD88^WT versus 90% (95% CI 82-95%) for mutated (MYD88^MUT ) WM patients (Log-rank P < 0·001). Multivariate analysis only showed MYD88 mutation status (P < 0·001) as a significant determinant for overall survival. Diffuse large B-cell lymphoma (DLBCL) was diagnosed in 7 (15·2%) and 2 (0·76%) of MYD88^WT and MYD88^MUT patients, respectively (Odds ratio 23·3; 95% CI 4·2-233·8; P < 0·001). Overall survival was shorter among MYD88^WT patients with an associated DLBCL event (Log-rank P = 0·08). The findings show that among suspected MYD88^WT WM cases, an alternative clinicopathological diagnosis is common and can impact clinical care. WM patients with MYD88^WT disease have a high incidence of associated DLBCL events and significantly shorter survival versus those with MYD88^MUT disease.

Keywords: IgM myeloma; MYD88; Waldenström Macroglobulinaemia; overall survival; transformation.