Malignant Lymphomas in Autoimmunity and Inflammation: A Review of Risks, Risk Factors, and Lymphoma Characteristics

Abstract

Certain autoimmune and chronic inflammatory conditions, such as Sjögren's syndrome and rheumatoid arthritis (RA), have consistently been associated with an increased risk of malignant lymphomas, but it is unclear whether elevated lymphoma risk is a phenomenon that accompanies inflammatory conditions in general. Likewise, it is debated whether the increased risk identified in association with some disorders pertains equally to all individuals or whether it varies among groups of patients with different phenotypic or treatment-related characteristics. It is similarly unclear to what extent the increased lymphoma occurrence is mediated through specific lymphoma subtypes. This update reviews the many findings on risks, risk levels, and lymphoma characteristics that have been presented recently in relation to a broad range of chronic inflammatory, including autoimmune, conditions. Recent results clearly indicate an association between severity of chronic inflammation and lymphoma risk in RA and Sjögren's syndrome. Thus, the average risk of lymphoma in RA may be composed of a markedly increased risk in those with most severe disease and little or no increase in those with mild or moderate disease. The roles of immunosuppressive therapy and EBV infection seem to be limited. Furthermore, RA, Sjögren's syndrome, systemic lupus erythematosus, and possibly celiac disease may share an association with risk of diffuse large B-cell lymphoma, in addition to well-established links of Sjögren's syndrome with risk of mucosa-associated lymphoid tissue lymphoma and of celiac disease with risk of small intestinal lymphoma. However, there is also obvious heterogeneity in risk and risk mediators among different inflammatory diseases. (Cancer Epidemiol Biomarkers Prev 2006;15(11):2069–77)

Management of Crohn's Disease in Adults

“…Pancreatitis, typically presenting several weeks a er initiating therapy, occurs in approximately 3 -15 % of patients and recurs with re-introduction of either azathioprine or mercaptopurine (17) . e risk of lymphoma related to purine analogs has been widely debated (15,17,216,217) . Aside from a potential risk of lymphoma (216) , neoplasia has not been observed with the use of purine analogs for in ammatory bowel disease (218,219) and it is accepted that the documented bene ts are most likely to o set a small increased risk (220) .…”

“…Aside from a potential risk of lymphoma (216) , neoplasia has not been observed with the use of purine analogs for in ammatory bowel disease (218,219) and it is accepted that the documented bene ts are most likely to o set a small increased risk (220) . Lymphomas that have occurred during thiopurine therapy have increasingly been recognized to be related to Epstein -Barr infections (216,217,221) . A rare form of natural killer cell, hepatosplenic lymphoma has recently been described associated with azathioprine therapy for CD either alone (222) or in combination with in iximab (223,224) .…”

Anti–tumor necrosis factor therapy and cancer risk in patients with autoimmune disorders

“…The reported range of relative risk for cancer in Hashimoto thyroiditis is 3-4 and for patients with celiac disease is 3-6. The modifying effect of anti-TNF agents on cancer susceptibility in patients with more than one cancer-predisposing condition is unknown (29).…”

“…This association is not surprising because hematologic malignancies and autoimmune diseases are likely to share a similar underlying inflammatory etiology (29). Ectopic germinal center formation like that that seen in the rheumatoid synovium provides a location for chronic immune stimulation and lymphomatogenesis where sustained B cell proliferation may lead the emergence of cancerous clones (29,39).…”

“…Ectopic germinal center formation like that that seen in the rheumatoid synovium provides a location for chronic immune stimulation and lymphomatogenesis where sustained B cell proliferation may lead the emergence of cancerous clones (29,39). Altered cytokine profiles that are common to both disease types may also be responsible for the shared risk phenotype.…”