We retrospectively reviewed 21 lymphoid neoplasms occurring in the context of CVID and CVID-like disorders.
We correlated clinical, germline genetic and histopathological findings.
Median age at diagnosis of lymphoma was 38 years. Median time between onset of first symptoms attributed to CVID and lymphoma was 14 years. Non-infectious inflammatory and autoimmune manifestations had a higher prevalence in CVID patients with lymphoid malignancies compared to the CVID population in general. Next-generation sequencing revealed three CTLA4 mutation carriers, one TNFRSF13B variant, one BACH2 mutation, one STAT1 mutation and one NFKB2 variant of unknown significance. The most prevalent B-cell lymphoma subtypes were marginal zone lymphoma (MZL) and diffuse-large B-cell lymphoma (DLBCL). The majority of Hodgkin lymphomas occurred in germline CTLA4 mutation carriers and was EBV+ mixed cellularity classical subtype. T-cell lymphomas were less frequent and mostly T-cell large granular lymphocytic leukemia (T-LGLL). EBV association of DLBCL was more frequent compared to the general population and was accompanied by expression of PDL1 and PD1 suggesting a tolerogenic tumor environment. The prognosis of the CVID patients was predominantly determined by the underlying lymphoid neoplasm while toxicity of treatment had a minor impact.
Our data illustrate that an inflammatory environment facilitates the development of a distinct spectrum of lymphoid neoplasms in CVID. Hodgkin lymphoma occurring in the context of antibody deficiency should raise the suspicion of a CTLA4 mutation carrier status. Future studies will have to dissect the complex interplay between host and environmental factors facilitating the development of lymphoid neoplasms in CVID and CVID-like disorders.