MYD88L265P mutation is a highly specific marker for the nonGCB/ABC DLBCL molecular subtype

Mutations in the innate immune adapter MYD88 occur selectively in Lymphoplasmacytic lymphoma (LPL) of the IgM/WM subtype and ABC type DLBCL. We used MYD88L265P mutation detection based on AS-PCR using genomic DNA extracted from FFPE tissue and correlated with histopathological subtype, phenotype, Cell of origin classification based on IHC, tumor site and genetic features in a large cohort of 249 small B cell lymphoma and 204 DLBCL samples. In DLBCL MYD88 L265P mutation is found in 32% of cases and it is significantly more prevalent in cases with the non-GCB phenotype (OR 5.78 p value = 2.07 × 10⁻⁵) and in DLBCL of extranodal locations (OR = 5.44 p value p < 0.001), including, not only immuneprivileged sites but also the skin, breast, upper respiratory tract, adrenal gland and bone and soft tissues. MYD88L265P mutation is highly specific of the non-GCB type DLBCL, likely reflecting MCD/C5 genetic features in a subset of non-GCB/ABC DLBCL.