This is a heterogeneous group of Hodgkin lymphomas and non-Hodgkin lymphomas arising in persons with severe acquired immunodeficiency syndrome (AIDS) induced by infection with human immunodeficiency virus (HIV).

Lymphomas are the neoplasms most commonly associated with immune deficiencies of all types, congenital and acquired (1). After Kaposi sarcoma, lymphomas are the most common AIDS-related cancer (2).

Non-Hodgkin lymphomas in HIV-infected persons are considered AIDS-defining illnesses. They occur in 3% of patients with AIDS (3), who are thus at a risk for non-Hodgkin lymphoma that is 60 times greater than that of the general population (4). With the advent of the highly active antiretroviral therapy (HAART), HIV-associated morbidity and mortality have decreased significantly; however, the incidence of AIDS-related lymphomas has not decreased as much and remains a major therapeutic problem (5,6). Some studies show a continuing increase in the incidence of lymphomas among AIDS patients who now survive longer because of effective antiretroviral and antifungal therapies (7). In women, minorities, and persons originating outside the United States, AIDS-related lymphomas have increased significantly (6). In contrast to Kaposi sarcoma, which is far more common among homosexual AIDS patients than other patients with AIDS, non-Hodgkin lymphoma affects equally all AIDS risk groups including children (8). Hodgkin lymphoma is also more frequent in patients with AIDS, who carry a risk for this disease 10 times greater than patients without AIDS (9).

The high incidence of non-Hodgkin lymphomas in persons with AIDS parallels the increased frequency of these tumors in individuals with congenital immune deficiencies (see Chapter 80) (10,11) and in immunosuppressed recipients of organ transplants (see Chapter 81) (10,11,12). The AIDS-associated non-Hodgkin lymphomas are a group of heterogeneous neoplasms that are virtually all of B-cell type, but differ in their histologic type, location, and pathogenesis (13,14). The HIV, which is at the origin of AIDS, is not involved in the malignant transformation of B cells since no HIV sequences have been detected in the lymphoma cells (15). However, the HIV infection induces the production of a variety of cytokines and growth factors that play an important role in the activation and differentiation of B cells. The intense follicular hyperplasia of HIV lymphadenitis shows the active proliferation of B cells, which provides opportunities for cellular instability and molecular alterations such as mutations, translocations, or deletions of tumor suppressor genes (15,16,17,18,19). Thus, the excessive activation of B cells, the selection of B-cell clones carrying genetic alterations, and the cellular immune deficiency that inactivates the immune surveillance combine in the pathogenesis of AIDS-associated non-Hodgkin lymphomas (15). In the case of Burkitt lymphoma, which accounts for 30% of AIDS-associated non-Hodgkin lymphoma, the molecular pathway involves infection with Epstein-Barr virus (EBV), the activation of the c-MYC protooncogene, and the inactivation of the p53 tumor suppressor gene (15,16,17,18).

In contrast to the lymphomas found in the general population of young adults, in which Hodgkin lymphomas are more common, among the lymphomas of AIDS non-Hodgkin lymphomas are by far more frequent. Also contrary to the general population, lymphomas of AIDS more often originate in extranodal locations (20,21). In a study of 111 cases of AIDS-associated lymphomas, 11 were Hodgkin lymphoma and 100 were non-Hodgkin lymphoma (21). In the same study, of the 100 non-Hodgkin lymphomas, 61 originated in various internal organs, whereas only 49 were initially located in lymph nodes. Of these, the digestive tract (27 cases) and the central nervous system (CNS; 15 cases) were the most common primary sites. In a study from Kenya in which 65% of patients were in stage IV and 93% had high-grade lymphoma, the primary locations were quite similar: lymph nodes 30%, gastrointestinal tract 28%, and CNS 15%. A fairly large number had lymphoma in the chest wall (22). In most studies, patients with AIDS-related lymphomas present with advanced extranodal disease and CD4+ lymphocyte counts of less than 200/mm³. Two-thirds of lymphomas are of the diffuse large B-cell type and 25% to 30% of Burkitt type (23). The signs of EBV infection are found in about 30% of AIDS-Burkitt lymphomas and in over 70% of AIDS-diffuse large B-cell lymphomas (DLBCL), up to 100% in those located in the brain (1).

The lymph nodes within and around the salivary gland, particularly the parotid, are often involved in HIV infection, presenting as unilateral or bilateral often primary lymphadenitides (24) (see Chapter 43). Like lymph nodes in other locations, the salivary gland lymph nodes may also become the site of lymphomas. In both the lymphadenitides and lymphomas, the salivary glands are not directly involved (see Chapter 70A). The salivary gland lymphomas, as previously reported, are EBV-associated and may be synchronous or may succeed an HIV-associated salivary lymphadenitis (25). Regardless of their location, AIDS-associated lymphomas, which are in almost all cases of high histologic grades, exhibit great clinical aggressiveness (8,21,26). Hodgkin lymphomas in AIDS more often present in late stages III and IV, with noncontiguous lymph node progression and involvement of internal organs including bone marrow dissemination. Non-Hodgkin lymphomas in
AIDS are invariably of high histologic grades and present with early dissemination, resistance to treatment, frequent relapses, and short survivals (8,22,26,27,28).

In the HAART era, the decrease in opportunistic infections and improvement of immune deficiency have also affected the survival of AIDS-related lymphoma patients, which in many cases has become comparable to that of HIV-negative patients (29,30,31).