Neoplasms in Acquired Immunodeficiency Syndrome

Abstract

Overview Immunodeficiency of multiple etiologies is associated with an increased risk of malignancy, particularly lymphoma. The risk is variable, depending on the severity and extent of the immunologic abnormality. In the setting of the acquired immunodeficiency syndrome (AIDS) secondary to human immunodeficiency virus type 1 (HIV‐1) infection, the range of tumor types is more extensive. Yet, the tumors are generally associated with oncogenic viruses and may be considered secondary, opportunistic neoplasms. Etiologic factors contributing to them include poor control of oncogenic viruses, altered cytokine regulation owing to HIV effects on immune cells and tissue stimulation from other AIDS‐associated events. The interplay of immunity, infection, and oncogenesis is central to AIDS‐related malignancies. The spectrum of the tumor types seen in the context of immunodeficiency extends beyond that of lymphoma, but is quite limited. There appears to be little interaction between the conditions that predispose to the emergence of epithelial malignancies seen in the general population and immunodeficiency. Rather, immunodeficiency tumors represent a narrow subset of neoplasms, some of which are seen with only very low incidence in the general population. For example, primary central nervous system (PCNS) lymphoma and Kaposi sarcoma (KS) are extremely rare entities in all but the immunodeficient population, where they compose a large proportion of tumors. In addition, the incidence of specific tumor types varies according to the immunodeficient state. Non‐Hodgkin lymphoma (NHL) is a common theme among all of the immunodeficiencies, yet in AIDS there is a broader spectrum of histologic subtypes than are seen in other immunodeficient states. KS is increased in subgroups of patients with HIV‐related and pharmacologically induced immunodeficiency. Cutaneous tumors are common in many immunodeficient states, but the increase in squamous cell tumors of the skin is higher in the post solid‐organ‐transplantation population than in those with HIV‐related immunodeficiency. In the latter, papillomavirus‐related squamous cell neoplasia of the anogenital region predominates. Shared among the tumors related to immunodeficient states is the frequent association with an infectious pathogen. The presence of Epstein–Barr virus (EBV) in immunodeficiency‐related lymphomas is well known and likely a result of the direct stimulation that the virus provides to B‐cell proliferation. In the absence of effective immunologic targeting of cells expressing EBV latency gene products, the overgrowth of cells may proceed unchecked, with the subsequent emergence of a transformed cell. This model for the direct ability of viruses to induce cell proliferation is a paradigm that may be applied to human papilloma virus (HPV)‐related tumors as well. However, the model is less easily applied to the KS‐associated herpesvirus/human herpesvirus‐8 (KSHV/HHV8)‐related tumors. The tumors associated with KSHV/HHV8 are more varied and are of less clear pathophysiologic relationship to viral gene products issues that are discussed in greater depth in sections that follow. In general, the tumors that do emerge in immunodeficiency are those in which a secondary pathogen can be implicated. Immunodeficiency further leads to a failure of innate host tumor surveillance. In essence, the concept of inadequate immunologic control provides a unifying mechanism, and these tumors may be considered opportunistic malignancies, much the way in which specific infections are considered opportunistic infections. Indeed, the opportunistic malignancies of the immunocompromised patient represent the overlap between infectious diseases and oncology and provide unique insight into the intersection of immune function and tumor development.