Malignancies in the acquired immunodeficiency syndrome

Abstract

Aside from opportunistic infections, several neoplasms have been identified as part of the spectrum of acquired immunodeficiency syndrome (AIDS) as defined by the Centers for Disease Control. Kaposi's sarcoma (KS) was the first such neoplasm to be recognized within the spectrum of AIDS. Although the classic form of Kaposi's sarcoma had been well recognized prior to the epidemic of AIDS, it was quite distinct from the illness that was seen in its “epidemic” form in young homosexual males. In this setting, Kaposi's sarcoma is an aggressive disease, with extensive involvement of skin and mucous membranes, early dissemination to lymph nodes, impressive development of extreme lymphedema, even in the absence of bulky adenopathy, and rapid spread to visceral organs, including lungs and gastrointestinal tract, among others. Although rapid clinical progression and short median survival have been the rule, a spectrum of disease has been seen such that some patients have survived for many years with disease limited to the skin. Certain clinical and laboratory features, such as presence of unexplained fever, night sweats, weight loss (“B” symptoms), or significant T-4-lymphocytopenia, have been identified as indicators of poor prognosis. Various therapeutic interventions have been employed in epidemic KS, and although partial and complete remissions have occurred, no regimen yet reported has significantly improved the survival of treated patients. High-dose recombinant alpha interferon has produced response rates in approximately 30% of treated patients, although toxicity has been observed in approximately 30% as well. Like-wise, vinblastine has produced similar response rates with no evidence of long-term efficacy or “cure”. Aside from Kaposi's sarcoma, lymphoma primary to the central nervous system was recognized early in the AIDS epidemic as a criterion for inclusion within AIDS in patients less than sixty years of age. Several years after the initial reports of disease, it became apparent that specific types of systemic lymphoma were also quite extraordinary, and the definition of AIDS was amended in June 1985 to include high-grade B-cell lymphomas in individuals who had positive serology or virology for the human immunodeficiency virus (HIV). The AIDS-related lymphomas are characteristic, both pathologically and clinically. The vast majority of these cases have been high-grade B-lymphoid tumors of either immunoblastic or small-non-cleaved type (also known as “undifferentiated,” Burkitt, or Burkitt-like). Approximately 80% of patients have presented with initial disease in extranodal sites, including unusual sites such as rectum, heart, kidneys, adrenals, and gastrointestinal tract. Initial involvement in the central nervous system (CNS) is found in approximately 30% of individuals, and relapse of disease within the CNS is not unusual, even in patients with no initial involvement of this site. The use of multiagent chemotherapy may provide short-lived remissions, and the majority of patients have died of recurrent lymphoma, development of opportunistic infection, or both, occurring far more frequently than would be seen in the “usual” patient with lymphoma receiving intensive chemotherapy. Newer therapeutic modalities employing less intensive regimens using immunomodulators, antiretroviral agents, or both, will be explored in future trials. Aside from these tumors, several cases of cloacogenic carcinoma of the anus, squamous cell carcinoma of the tongue, and other oropharyngeal malignancies have been reported in young homosexual males with HIV infection. Although these cancers have not demonstrated a statistical increase in frequency since the epidemic of AIDS began, they are most unusual, especially in these young patients, and may in fact be related to the current epidemic, induced perhaps by various viruses, with HIV serving to adversely affect the natural history of disease. Further observation may allow an understanding of the etiology of these unusual cancers, and may further define their specific relationship to AIDS.