Angioimmunoblastic lymphadenopathy with dysproteinemia: emphasis on pathogenesis and treatment

Abstract

Angioimmunoblastic lymphadenopathy with dysproteinemia (AILD) is a rare lymphoproliferative disorder characterized by diffuse lymphadenopathy, fever, hepatosplenomegaly, hemolytic anemia, and polyclonal hypergammaglobulinemia. Morphologically, the involved lymph nodes demonstrate complete effacement of the normal architecture, prominent neovascularization and infiltration by immunoblasts and plasma cells. Other terms that have been used to describe this entity include diffuse plasmacytic sarcomatosis, immunoblastic lymphadenopathy, lymphogranulomatosis X, and immunologic aberrations in idiopathic reticulosis. Initially, AILD was thought to be a disease of B-cell origin that represented reactive immune response to unknown stimulus and high potential for malignant transformation. It is now evident that AILD in 80% of cases follows an aggressive course with short median survival, especially, if complete response with chemotherapy is not achieved. Immunologic and molecular studies have demonstrated that the majority of AILD cases are T-cell clonal disorders. Despite the numerous reports on the role of Epstein-Barr virus in this disorder, it is unknown whether the presence of this virus is associated with the immune defect that accompanies AILD, or whether it is a pathogenetic factor. In contrast to non-Hodgkin's lymphomas, a stage is not usually assigned to the patient since the disease is systemic in nature, subsequently, parameters such as extent of disease and tumor bulk used to identify high-risk patients with non-Hodgkin's lymphomas, do not appear to correlate with disease activity or prognosis in AILD. Treatment of AILD has been unsatisfactory, with approximately 25% of patients achieving complete and sustained remission when combined chemotherapy agents are used. This article is devoted to a discussion of the different manifestations, suggested pathogenesis, and treatment of AILD.