Prevalence and prognostic value of MYD88and CD79Bmutations in ocular adnexal large B-cell lymphoma: a reclassification of ocular adnexal large B-cell lymphoma

AimsTo (1) reclassify ocular adnexal large B-cell lymphomas (OA-LBCLs) per 2016 WHO lymphoma classification and (2) determine the prevalence of MYD88and CD79Bmutations and their association with clinical parameters among OA-LBCLs.MethodsThis study is a retrospective analysis of all OA-LBCLs diagnosed in Denmark between 1980 and 2018. Medical records and tissue samples were retrieved. Thirty-four OA-LBCLs were included. Fluorescence in situ hybridisation and Epstein-Barr-encoded RNA in situ hybridisation were used for the reclassification. Mutational status was established by allele-specific PCR and confirmed by Sanger sequencing. Primary endpoints were overall survival, disease-specific survival (DSS) and progression-free survival (PFS).ResultsTwo LBCL subtypes were identified: diffuse large B-cell lymphoma (DLBCL) (27 of 32; 84%) and high-grade B-cell lymphoma (HGBL) with MYCand BCL2and/or BCL6rearrangements (5 of 32; 16%). cMYC/BCL2 double-expressor DLBCLs had a poorer DSS than non-double-expressor DLBCLs (5-year DSS, 25% vs 78%) (HR 0.23; 95% CI 0.06 to 0.85; p=0.014). MYD88mutations were present in 10 (29%) of 34 lymphomas and carried a poorer PFS than wild-type cases (5-year PFS, 0% vs 43%) (HR 0.78; 95% CI 0.61 to 0.98; p=0.039). CD79Bmutations were present in 3 (9%) of 34 cases.ConclusionOA-LBCL consists mainly of two subtypes: DLBCL and HGBL with MYCand BCL2and/or BCL6rearrangements. MYD88mutations are important drivers of OA-LBCL. MYD88mutations, as well as cMYC/BCL2 double-expressor DLBCL, appear to be associated with a poor prognosis. Implementing MYD88mutational analysis in routine diagnostics may improve OA-LBCL prognostication.