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 MYD88, CD79B, CARD11, and BTK in a cohort of 116 patients, localized in the mediastinum (PMBL, n = 12), ear, nose and throat (ENT, n = 28), central nervous system (n = 29), testis (n = 7), breast (n = 4), stomach (n = 10), bone (n = 8), spleen (n = 2), and skin (n = 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 MYD88 and CD79B mutations in ENT lymphomas (46% and 50%, respectively). CARD11 mutations are rare but more frequently found in gastric lymphomas (30%), suggesting BTK resistance. Thirty‐four of 113 (30%) of the lymphomas harbored both MYD88 and CD79B mutations. Lower overall and progression‐free survival rates were found for cases with MYD88, CD79B, and BTK mutations. These data confirm the biologic singularity of PE‐DLBCLs and provide some suggestions for targeted therapies.