<i><scp>MYD</scp>88</i> wild‐type Waldenstrom Macroglobulinaemia: differential diagnosis, risk of histological transformation, and overall survival

Abstract

Summary MYD 88 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 MYD 88 ( MYD 88 WT ) WM cases. We systematically reviewed the clinical, pathological and laboratory studies for 64 suspected MYD 88 WT WM patients. World Health Organization and WM consensus guidelines were used to establish clinicopathological diagnosis. Up to 30% of suspected MYD 88 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 MYD 88 WT versus 90% (95% CI 82–95%) for mutated ( MYD 88 MUT ) WM patients (Log‐rank P &lt; 0·001). Multivariate analysis only showed MYD 88 mutation status ( P &lt; 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 MYD 88 WT and MYD 88 MUT patients, respectively (Odds ratio 23·3; 95% CI 4·2–233·8; P &lt; 0·001). Overall survival was shorter among MYD 88 WT patients with an associated DLBCL event (Log‐rank P = 0·08). The findings show that among suspected MYD 88 WT WM cases, an alternative clinicopathological diagnosis is common and can impact clinical care. WM patients with MYD 88 WT disease have a high incidence of associated DLBCL events and significantly shorter survival versus those with MYD 88 MUT disease.