clonal, uncontrollably expanding, destructive proliferations of lymphoid cells.
Although 25-40% of NHLs arise extra-nodally, lymphoma cells are most at home in lymph
nodes or other primary lymphoid organs, such as the spleen, thymus, Waldeyer's
ring, or mucosa-associated lymphoid tissue. Lymphoid neoplasms
that predominantly involve the bone marrow and peripheral blood are usually
Like carcinomas and sarcomas,
NHLs more or less resemble
the normal tissue from which they derive. What makes life for the diagnostician
more difficult is that normal lymphocytes go through many stages as they
develop from small, resting, inexperienced cells to larger,
atypical-appearing, proliferating cells. The stimulus for this change, of course, is exposure to antigen. Malignancies may arise from lymphoid cells arrested at any of these stages. Morphologically, immunophenotypically, and genetically, the NHLs
fall into categories with important therapeutic
and prognostic associations.
Both cytologically and architecturally, lymphoid proliferations may lack some of the morphological complexity seen in non-lymphoid organs with more obvious structure. In some cases, ancillary laboratory studies are necessary to determine if a lymphoid proliferation is benign or malignant or to identify its lymphoma subtype. These studies include:
For the patient and clinician the most important distinction is between low grade NHLs on the one hand and higher grade ones on the other. These 2 forms of NHL have morphological, biological, and clinical differences that are discussed on another page.
As far as trends go, the current 5-year survival (2006-2012) is 70.7% compared to 45.8% in 1975. The death rate in recent years (2004-2013) has fallen an average of 2.4%/year. The incidence of NHL was 11.1 cases/100,000 people in 1975, and the rate increased to about 18-19/100,000 in 1990, where it has remained steadily until the present. Unlike Hodgkin lymphoma, which has a bimodal age distribution, the incidence rate of NHL steadily and steeply increases after age 30 years, although childhood NHLs are not rare.
The 1980s saw a startling incidence of NHL among patients with AIDS, who have a particularly high rate of high grade, extra-nodal, or central nervous system NHL. In this setting these types of lymphomas occur 60 times more frequently than in the general population. In one study the rate of NHL, measured from the initiation of zidovudine therapy, was 12% at 2 years and 29% at 3 years.
NHLs are also very prevalent among patients with primary immunodeficiencies or with therapeutic immunosuppression such as transplantation regimes. In post-transplant patients, evidence of clonal Epstein-Barr virus infection can be found in most NHLs.
Besides immunodefects, risk factors for NHLs are hard to identify. The second strongest risk factor is a family history of the disease, which entails a 3-4 times greater risk to relatives. A weaker and not completely persuasive factor is occupational exposure, especially to pesticides and herbicides. Finally a weak, inconsistent association has been unearthed between NHLs and hair dye use.