Lymphoma and other lymphoproliferative disorders in inflammatory bowel disease: A review

Abstract

The lymphoproliferative disorders (LDs) are a heterogeneous group of at least 70 conditions that result from the clonal proliferation of B, T, and NK cells. Inflammatory bowel disease (IBD)‐associated lymphomas are typically B‐cell LD, while T‐cell or Hodgkin's lymphomas are rare. In IBD patients not on immunosuppression, the risk of LD seems to be similar or slightly higher than the background population risk. Thiopurine therapy is associated with an increased risk: the relative risk is increased four‐ to sixfold and the absolute risk varies between 1 in 4000–5000 for those aged 20–29 to 1 in 300–400 in those over 70. It is difficult to quantify the risk of anti‐ tumor necrosis factor (TNF) therapy alone; however, it appears to be less than for thiopurines alone. There is particular concern regarding the development of post‐transplant‐like LD in those with latent epstein‐barr virus (EBV) infection exposed to immunosuppressives, the occurrence of hepatosplenic T cell lymphoma in patients treated with combination anti‐TNF and thiopurine therapy, and the development of hemophagocytic lymphohistiocytosis in those who acquire a primary EBV or other infections while on immunosuppressive medication. There are currently no guidelines for monitoring EBV (or other virus) status in patients on immunosuppression, although it could be used to monitor those who have a prior history of lymphoma and are about to start a thiopurine or anti‐TNF agent. In discussing the risks of lymphoproliferative disorders associated with agents used for the treatment of IBD, patients can often be reassured that the benefits of such therapy still outweigh the small, but real, risks.

Pathogenesis of Crohn’s disease: Bug or no bug

“…Epidemiological data indicate that frequency of infection is similar in IBD patients and healthy controls, both approximately 100% [99] . The intensity of replication has been related to increased bowel inflammation [100] and to serious complications such as lymphomas [95,101] . Therefore, as with CMV, a modulating function, rather than an etiological implication, was determined.…”

Primary CNS lymphoma in a patient treated with azathioprine

“…PCNSL is a rare condition accounting for around 2% of all cerebral malignancies in immunocompetent patients 6. Most cases are aggressive diffuse large B-cell lymphomas with a poor prognosis.…”

Extra-intestinal malignancies in inflammatory bowel diseases: An update with emphasis on MDCT and MR imaging features

“…There are some studies that suggest an association between Epstein-Barr virus (EBV) infection and hepatosplenic T-cell lymphoma in IBD patients receiving an association of TNF-alpha inhibitors and thiopurine [85,86,[90][91][92].…”