Abstract Abstract 5092 Background The fact that monogenic interleukin (IL)-10 and IL-10 receptor deficiencies cause very early-onset, severe inflammatory bowel disease demonstrates the IL-10 pathway's crucial role in preventing microbiota-driven gut inflammation. However, no other severe complications of IL-10/IL-10R deficiencies have been reported to date. Methods A cohort of six patients with IL-10/IL-10R deficiency was retrospectively surveyed for phenotypic expression. The identification of a number of cases of lymphoma prompted an in-depth characterization of available biopsy material, with immunohistochemical staining, cytogenetic studies and gene expression profiling. Results Four patients (all with a complete IL-10R2 deficiency) had developed B cell non-Hodgkin's lymphoma between the ages of 5 and 6 years. Cytogenetic and IgH clonality analyses suggested that one of the patients developed at least 3 distinct lymphomas. The patients' tumors had the characteristics of diffuse large B cell lymphomas and contained monoclonal, Epstein-Barr-virus-negative germinal center B cells. Nuclear expression of the NF-κB factor c-REL was detected in all of the six lymphomas tested. Conclusions IL-10R deficiency is associated with a high risk of developing a B cell lymphoma with an unusual phenotype. Our results highlight an unexpected role of the IL-10R pathway in the control of lymphomagenesis. Disclosures: No relevant conflicts of interest to declare.