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AIDS-related lymphomas: Clinical manifestations, diagnosis, and staging of systemic lymphoma

Authors
Lawrence D Kaplan, MD
Wei Ai, MD, PhD
Section Editor
Arnold S Freedman, MD
Deputy Editor
Alan G Rosmarin, MD

INTRODUCTION

Human immunodeficiency virus (HIV) infection results in impaired cellular immunity, a condition known to predispose persons to develop neoplasms [1-4]. As the lifespan of HIV-infected patients has increased, malignancies have become a known cause of morbidity and mortality in this population. Before the advent of antiretroviral therapy (ART), malignancies accounted for approximately 10 percent of HIV-related deaths. Since the routine implementation of ART, a cancer diagnosis is made in over 40 percent of HIV-infected patients during the course of the HIV infection [5], and over 28 percent of HIV-related deaths are attributable to malignancy [6,7].

There are three acquired immune deficiency syndrome (AIDS)-defining malignancies: Kaposi sarcoma, non-Hodgkin lymphoma (NHL) of high-grade pathologic type and of B cell or unknown immunologic phenotype, and invasive cervical carcinoma. In addition, non-AIDS-defining malignancies contribute to mortality in HIV-infected persons. (See "HIV infection and malignancy: Epidemiology and pathogenesis" and "HIV infection and malignancy: Management considerations".)

The clinical manifestations and diagnostic approach to AIDS-related systemic lymphoma will be reviewed here. The epidemiology, risk factors, pathobiology, and treatment of AIDS-related systemic NHL are discussed separately, as are the diagnosis of AIDS-related primary central nervous system lymphoma and primary effusion lymphoma. (See "AIDS-related lymphomas: Epidemiology, risk factors, and pathobiology" and "AIDS-related lymphomas: Treatment of systemic lymphoma" and "AIDS-related lymphomas: Primary central nervous system lymphoma" and "AIDS-related lymphomas: Primary effusion lymphoma".)

CLINICAL MANIFESTATIONS

General — The clinical presentation varies tremendously depending upon the type of lymphoma and the areas of involvement. Some behave indolently with lymphadenopathy waxing and waning over years. Others are highly aggressive, resulting in death within weeks if left untreated. Although indolent lymphoma may occur, most lymphoma in the human immunodeficiency virus (HIV)-seropositive population is clinically aggressive. Less common presentations of systemic lymphoma include abnormal laboratory results, such as unexplained cytopenias, hypercalcemia, elevated lactate dehydrogenase, or tumor lysis syndrome (ie, lactic acidosis, hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia). (See "Clinical presentation and diagnosis of non-Hodgkin lymphoma", section on 'Abnormal laboratory results' and "Tumor lysis syndrome: Definition, pathogenesis, clinical manifestations, etiology and risk factors".)

HIV-associated non-Hodgkin lymphoma (NHL) is most commonly diagnosed in patients with advanced HIV, a low CD4 count (often <100 cells/microL), high HIV viral load, and a prior diagnosis of acquired immunodeficiency syndrome (AIDS) [8-12]. Since the introduction of antiretroviral therapy (ART), the incidence of HIV-associated NHL has declined and the median CD4 count at diagnosis has increased [13-18]. The proportion of patients with stage IV disease (56 to 84 percent), bone marrow (13 to 22 percent) or leptomeningeal (6 to 16 percent) involvement has not changed [14-16,19-21]. Although the risk of NHL continues to be directly related to CD4 count, data from the UK Collaborative HIV Cohort demonstrate a median CD4 count >200/mm3 in those presenting with systemic NHL [22]. Hodgkin lymphoma (HL), a non-AIDS-defining malignancy, has a lower incidence with severe immunosuppression than with moderate immunosuppression [23]. While the incidence of AIDS-defining illnesses (ADI) has decreased overall since the introduction of ART, the proportion of AIDS defining illnesses attributable to NHL has increased [19,24]. NHL is one of the most common and most frequently fatal of the AIDS-defining illnesses [25], though survival has improved significantly since the introduction of ART [26]. HIV-associated lymphoma typically presents in an aggressive fashion, with diffuse large B cell lymphoma and Burkitt lymphoma comprising the majority of cases; low-grade (indolent) lymphomas are less common and typically occur in patients with relatively high CD4 counts [27].

             

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