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Introduction to Non-Hodgkin's Lymphomas (NHLs) LYMPHOMAS are 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 considered leukemias.          Plasma cell malignancies such as multiple myeloma are certainly lymphoid; but arbitrarily they often discussed separately. Another troublesome entity is Hodgkin's disease. Although sometimes called "Hodgkin's lymphoma," and evidence is building that some subtypes are indeed lymphomas, this entity is best discussed in its own section.

Non-Hodgkin's lymphoma, large cell Hodgkin's disease Multiple myeloma

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 more highly structured organs. 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: Immunophenotyping to determine what kind of surface molecules are present on the cells. Cytogenetics to identify any abnormal chromosomes. Molecular diagnostics including Southern blotting and the polymerase chain reaction to uncover clonal rearrangements of immune system genes or other genetic, subchromosomal evidence of malignancy.         Many attempts have been made to classify NHLs. Currently the most widely used is the Working Formulation. Based on only two criteria--1) the cytologic appearance of individual cells and 2) the follicular or diffuse nature of the proliferation-- NHLs are named and then categorized as low grade, intermediate grade, or high grade. These categories have clinical significance that was demonstrated in an initial study of over a thousand cases. Our discussion will use Working Formulation terminology, along with additional distinctions that postdate it.          For the patient and clinician the most important distinction is between low grade NHLs on the one hand and intermediate and high grade ones on the other. These 2 groups of NHLs have morphological, biological, and clinical differences that are discussed later. Epidemiology: In the United States the incidence of NHL in the last few years has been 17.9/100,00 in males and 11.5/100,000 in females. In 1998 an estimated 55,400 new cases will arise, and 24,900 deaths will occur. At this rate, it is the fifth or sixth most common cause of both new cases of cancer and cancer deaths. In comparison, 1998 will see 184,500 new cases of prostate cancer, 180,300 new cases of breast cancer, and 7,100 new cases of Hodgkin's lymphoma. The rate of NHL is twice as high in whites than in blacks.          Since the early 1970's the incidence of NHL has been increasing at the rate of 3-4% per year, which is impressive even after adjustment for the aging U.S. population and AIDS-related cases. The current aged-adjusted death rate for NHL is about 37% higher than it was 20 years ago, despite improved therapies that allow a 52% five-year survival rate compared to an earlier 41%. Only lung cancer in women and melanomas are increasing more rapidly. Unlike Hodgkin's 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 NHLs. 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. Table of Contents | Next section | Previous section