The incidence of non-Hodgkin lymphoma (NHL) increased by more than 80% between 1975 and 1991 in the United States, representing one of the largest increases of any cancer.1 While the overall NHL incidence rates began to stabilize in the late 1990s, the temporal trends varied by histologic subtype with the incidence of T/NK [natural killer]–cell lymphomas increasing 4% per year during 1992-2001 compared with 0.5% per year for B-cell lymphoma.2 Part of the overall steep increase in NHL incidence over the last several decades is due to human immunodeficiency virus (HIV) infection, although the incidence of NHL has been increasing irrespective of HIV status.3 Other pathogenic associations with NHL include viruses and bacteria (eg, human T-cell lymphotropic virus type 1,4 human herpesvirus 8,5 hepatitis C,6 and Helicobacter pylori7) and medications that cause extreme immunodeficiency. However, the etiology of NHL remains largely unknown. Furthermore, the significant geographic differences (eg, the incidence of NHL is 3-4 times more common in the United States vs Japan)8 and varying incidences by sex, age, and race in population registry data are unexplained.2,9
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The Rational Clinical Examination: Evidence-Based Clinical Diagnosis
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