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

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<0001). Multivariate analysis only showed MYD88 mutation status (P<0001) as a significant determinant for overall survival. Diffuse large B-cell lymphoma (DLBCL) was diagnosed in 7 (152%) and 2 (076%) of MYD88(WT) and MYD88(MUT) patients, respectively (Odds ratio 233; 95% CI 42-2338; P<0001). Overall survival was shorter among MYD88(WT) patients with an associated DLBCL event (Log-rank P=008). 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.