The incidence rates of non-Hodgkin lymphoma (NHL) in the United States have almost doubled between 1970 and 1990, representing one of the largest increases of any cancer. Although the overall incidence rates of NHL began to stabilize in the late 1990s, the temporal trends varied by histologic subtype. Some of this increase may be artifactual, resulting from improved diagnostic techniques and access to medical care, or directly related to the development of NHL in 25- to 54-year-old men with human immunodeficiency virus (HIV) infection. However, additional factors must be responsible for this unexpected increase in frequency of NHL that has been observed throughout the United States.
The incidence of NHL per 100,000 persons rose from 8.8 in 1972− 1974 to 19.5 in 2002− 2006 (all histologic subtypes) in the United States. The increases have been more pronounced in whites, males, the elderly, and those with NHL diagnosed at extranodal sites. Similar findings have been reported in other developed countries. NHL rates have decreased among American males aged 25 to 54 years in the middle to late 1990s (6% to 16% per year), although this may be in part due to improved HIV treatment.
Currently, NHL represents approximately 4.6% of all cancer diagnoses (4.8% in males and 4.4% in females), being the fifth most common cancer in women and the sixth in men. Estimates from the American Cancer Society indicate that in 2009, some 65,980 new cases of NHL will be diagnosed in the United States and approximately 19,500 people will die of this disease.
Epidemiology
Gender The overall incidence of lymphoma is higher in men than in women. The incidence rate (per 100,000 population) between 2002 and 2006 was 40% higher in males than in females. Only thyroid NHL is more common in women than in men.
Age Overall, the incidence of NHL rises exponentially with increasing age. In persons older than age 65, the incidence is 87.2 per 100,000 population. Except for high-grade lymphoblastic and Burkitt lymphomas (the most common types of NHL seen in children and young adults), the median age at presentation for all subtypes of NHL exceeds 50+ years. Low-grade lymphomas account for 37% of NHLs in patients between the ages of 35 and 64 years at diagnosis but for only 16% of cases in those younger than age 35.
Race The incidence varies by race, with whites at higher risk than blacks and Asian-Americans (incidence rates increased 40% to 70% in whites compared with blacks). Most histologies, particularly low-grade small lymphocytic and follicular lymphomas, are more common in whites than in blacks. Only peripheral T-cell lymphoma, mycosis fungoides, and Sézary syndrome are more common in blacks than in whites.
Geography NHL is most common in developed countries, with the United States having the highest rate worldwide. The lowest NHL rates are found in Eastern and south central Asia (2 to 3 per 100,000 population). Certain endemic geographic factors appear to influence the development of NHL in specific areas.
Human T-cell lymphotrophic virus-1 (HTLV-1)-associated adult T-cell lymphoma/leukemia (ATLL) occurs more frequently where HTLV-1 is endemic, in southern Japan and the Caribbean, and occurs sporadically in Brazil, sub-Saharan Africa, the Middle East, and the southeastern United States. The seroprevalence in southwest Japan is 16%, although the lifetime risk of ATLL for these persons is 2% to 6%.
The incidence (per 100,000 population) of Burkitt NHL in Africa (Nigeria and Tanzania) is 6 to 8, as compared with 0.1 in the United States. The clinical features of Burkitt lymphoma in Africa differ from those of cases reported to the American Burkitt Lymphoma Registry. Etiologic endemic factors include malaria as a source of chronic B-cell antigenic stimulation and Epstein-Barr virus (EBV)-induced immortalization of B lymphocytes.
Heavy-chain disease is a disorder of B-lymphoid cells characterized by diffuse thickening of the small intestine due to a lymphoplasmacytic infiltrate with secretion of incomplete IgA heavy chains. Pathologically, it is a mucosa-associated lymphoid tissue (MALT) lymphoma of the small bowel. This clinicopathologic entity is ray encountered in individuals other than those of Mediterranean ethnic origin.
Follicular lymphomas are more common in North America and Europe but are rare in the Caribbean, Africa, China, Japan, the Middle East, and Latin America.
Peripheral T-cell lymphomas are more common in Europe and China than in North America. They represent 7% to 12% of lymphomas in Western countries.
Disease site The NHLs are a heterogeneous group of neoplasms that usually arise or present in lymphoid tissues, such as lymph nodes, spleen, and bone marrow, but they may arise in almost any tissue. The most frequent sites for extranodal lymphomas, which constitute about 20% to 30% of all lymphomas (peripheral T-cell NHL 80%; extranodal, follicular 9%), are the stomach, skin, oral cavity and pharynx, small intestine, and central nervous system (CNS). Although primary CNS lymphomas are rare, there has been a threefold increase in incidence, even if patients with HIV infection and other types of immunosuppression are excluded.
Survival The 5-year ative survival rate of patients with NHL increased from 28% between 1950 and 1954 to 63% between 1990 and 2003. These improvements in survival occurred mainly in patients with intermediate-high-grade histologies. The potential for cure varies among the different histologic subtypes and is ated in part to stage at presentation and response to initial therapy. The natural history (survival rates) for indolent lymphomas has been unchanged from the 1950s to the early 1990s, although recent data including an analysis from Iowa of Surveillance, Epidemiology, and End Results (SEER) data (1979− 1999) shows improving survival rates of patients with follicular lymphoma.
