Epidemiology of the revised European-American lymphoma classification subtypes

Abstract

The epidemiology of precursor lymphoblastic leukemia/lymphoma has been advanced primarily by investigations into the occurrence of acute lymphocytic leukemia, which constitutes 85 percent of the cases that would fall under this rubric. Particularly salient characteristics of the disease are its bimodal age distribution and its relation to ionizing radiation exposure and a history of bone marrow transplantation. A number of additional hypotheses are also under study. Chronic lymphocytic leukemia/lymphoma consists of chronic lymphocytic leukemia, small lymphocytic lymphoma, and prolymphocytic leukemia. International differences in rates observed for small lymphocytic lymphoma and changes in risk with migration suggest an environmental component to the etiology, one that changes with migration. Although the disease has been related to farming and pesticide exposure, as well as a history of autoimmune disease, current understanding is limited. Follicular lymphoma is unusual in that its incidence is as high in women as in men. The disease also shows striking variation in relation to ethnic group and birthplace. In addition, exposure to hair dye, smoking, and occupational and chemical exposures have been associated with the disease, and its incidence is higher in the United States than in Japan. The epidemiology of marginal zone B-cell lymphoma has been poorly characterized, but the disease occurs much more frequently than expected among Sjogren's disease patients. A subtype, gastric MALT lymphoma, is widely believed to be a consequence of H. pylori infection, but epidemiologic evidence is limited. Hairy cell leukemia is a rare malignancy. It stands out for having a rapid age-related increase in incidence around middle age. Hairy cell leukemia has been associated with occupational factors, but epidemiologic study of the disease is difficult. The incidence of plasma cell myeloma is notable for being much higher in blacks than in whites, and the disease has been associated with ionizing radiation and agricultural exposures. Little is understood of the disease, but a better understanding of the causes of its precursor, monoclonal gammopathy, could shed light on its etiology. The etiology of diffuse large B-cell lymphoma is dominated by the role of immunodeficiency, not only by HIV infection, but also by other causes. AIDS-related diffuse large B-cell lymphoma and post-transplant lymphoproliferative disease currently comprise about half of the incidence in the United States. There is some evidence that Epstein-Barr virus is a cofactor in immunodeficiency-related diffuse large B- cell lymphoma, and Epstein-Barr virus genome incorporation may indicate an etiologically homogeneous subset of cases; but large, representative populations have not been studied. With respect to HIV-associated disease, the role of CD4 count has not been adequately described, nor has it been determined whether the recently introduced protease inhibitors, which increase CD4 counts, can prevent AIDS-related diffuse large B-cell lymphoma. It appears that approximately 1-5 percent of the more than 10,000 allogeneic transplants performed each year (United Network for Organ Sharing website) lead to post-transplant lymphoproliferative disease, but this relation has not been characterized well in relation to immunosuppressive regimen. Nor have the separate roles of Hodgkin's disease and its treatment been evaluated in relation to subsequent risk of diffuse large B-cell lymphoma. Burkitt's lymphoma and Burkitt-like lymphoma are also strongly related to HIV infection and, as with diffuse large B-cell lymphoma, risk should be characterized in relation to CD4 count and use of protease inhibitors. Epstein-Barr virus is hypothesized to be a cofactor in AIDS-related Burkitt's and Burkitt-like lymphoma, but large, representative samples of patients are needed to further evaluate this question. Outside of HIV infection, it is unclear whether other immunodeficiencies or a history of Hodgkin's disease is related to this disease. The remarkable peak in incidence among young white boys suggests a distinct causal pathway in this population. Mycosis fungoides/Sezary syndrome, a rare disease, is more common among blacks than among whites in the United States. There are no further clues about the disease. Progress in Hodgkin's disease has centered on the role of Epstein-Barr virus, and recent studies suggesting a role of immunodeficiency should be conducted in relation to the disease's histotypes. There is no information available about the following lymphoid malignancies: mantle cell lymphoma, large granular lymphocyte leukemia, and peripheral T- and natural killer-cell lymphoma (excluding adult T-cell lymphoma/leukemia).