Targetable Alterations in Primary Extranodal Diffuse Large B-cell Lymphoma

Primary extranodal diffuse large B-cell lymphoma (PE-DLBCL) is a heterogeneous subgroup of DLBCL. We investigated the prevalence and prognostic value of surface expression of PD-L1, PD1, and CD30, copy number of 9p24.1 (PD-L1 region), and mutations in , , , and in a cohort of 116 patients, localized in the mediastinum (PMBL,  = 12), ear, nose and throat (ENT,  = 28), central nervous system ( = 29), testis ( = 7), breast ( = 4), stomach ( = 10), bone ( = 8), spleen ( = 2), and skin ( = 16). PD-L1 expression is most frequent in PMBL (92%), followed by lymphomas originating in the stomach (57%), ENT (23%), and skin (18%). PD1 was expressed at low levels in less than 13% of PE-DLBCL, while CD30 expression was found in 58% of PMBL. Mutation analysis revealed an unexpectedly high frequency of and mutations in ENT lymphomas (46% and 50%, respectively). mutations are rare but more frequently found in gastric lymphomas (30%), suggesting BTK resistance. Thirty-four of 113 (30%) of the lymphomas harbored both and mutations. Lower overall and progression-free survival rates were found for cases with , , and mutations. These data confirm the biologic singularity of PE-DLBCLs and provide some suggestions for targeted therapies.