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Non-Hodgkin Lymphoma

Non-Hodgkin Lymphoma

Overview

Non-Hodgkin lymphoma (NHL) is the seventh most commonly diagnosed cancer in both men and women in the United States. In 2013, it is estimated that there were 69,740 new cases of NHL (37,600 men and 32,140 women) and 19,020 deaths from NHL. The disease represents approximately 4.2% of all cancer diagnoses (4.4% in males and 4% in females). Notably, incidence rates of NHL almost doubled between 1970 and 1990 but have stabilized since the late 1990s among general populations. 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 (see sidebar).

Sidebar: Investigators from the National Institutes of Health showed that 5.9% of NHL cases diagnosed from 1992 to 2009 were in HIV-positive persons. Proportions of cases associated with HIV infection were highest for Burkitt lymphoma (26.9%), diffuse large B-cell lymphoma (7.8%), and peripheral T-cell lymphoma (3.2%). NHL rates among non–HIV-infected persons increased 1.4% per year during 1992 to 2009 (similar trends for diffuse large B-cell lymphoma and follicular lymphoma) and then stabilized thereafter (Shiels MS et al: Cancer Epidemiol Biomarkers Prev 22:1069-1078, 2013).

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. In the United States, incidence rates increased significantly during 2001-2010 for marginal zone lymphoma (2.2% per year) and mantle cell lymphoma (MCL) (1.9% per year) but decreased for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (−1.3% per year).

Epidemiology

Gender

The overall incidence of lymphoma is higher in men than in women. The age-adjusted incidence rate between 2006 and 2010 was about 45% higher in males (23.9 per 100,000) than in females (16.4 per 100,000). The overall NHL incidence rates remained unchanged during 2001-2010 among women but increased at the rate of 0.5% per year among men.

Age

The incidence of NHL overall and of most histologic subtypes rises exponentially with increasing age. In persons older than 65, the incidence was 91.4 per 100,000 persons in 2006-2010. 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 35 years. Substantially higher rates were observed for diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma among white and black men aged 25 to 54 years.

Race/Ethnicity

The incidence of NHL varies by race/ethnicity, with non-Hispanic whites (21 per 100,000 persons) at higher risk than blacks (14.3 per 100,000), Asian/Pacific Islanders (13.1 per 100,000), and Hispanics (17.8 per 100,000) during 2006-2010. Most histologies, particularly low-grade small lymphocytic and follicular lymphomas, are more common in whites than in blacks. Only peripheral T-cell lymphoma (PTCL), 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 lymphotropic 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 it 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 of Burkitt NHL in Africa (Nigeria and Tanzania) is 6 to 8, compared with 0.4 in the United States. Further, 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 rarely 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. PTCLs are more common in Europe and China than in North America. They represent 7% to 12% of lymphomas in Western countries.

Disease Sites

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, 70% to 80%; follicular, 8% to 10%), 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. Each of these sites may be involved singularly (ie, primary extranodal lymphoma) or as secondary extranodal sites concomitantly with other systemic disease.

Survival

The potential curability of NHL varies among the different histologic subtypes and is related in part to stage at presentation. The 5-year relative survival rate of patients with NHL increased from 47% between 1975 and 1977 to approximately 71% between 2003 and 2009. These improvements in survival occurred mainly in patients with intermediate- to high-grade histologies. The natural history (survival rates) for indolent lymphomas was unchanged from the 1950s to the early 1990s; however, Surveillance, Epidemiology, and End Results (SEER) and other data have shown improved overall survival rates for patients with follicular lymphoma.

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