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persons include absence of prior AIDS diagnosis (20 versus 7 months) and a CD4 count >250/µL
(38 versus 11 months). The use of antiretroviral therapy (ART) can improve control of infection
and allow for more aggressive chemotherapy.[562,564]

NON-HODGKIN LYMPHOMAS.-- Persons infected with HIV develop non-Hodgkin
lymphoma (NHL) more frequently than the general population. The presence of the chemokine
receptor variant CCR5 delta32 appears to significantly lower the risk in persons with HIV-1
infection while presence of the SDF1-3'A chemokine receptor variant doubled the risk when
heterozygous and led to a fourfold increase in NHL in homozygotes.[565] The use of
antiretroviral therapy (ART) results in a reduction in the incidence of NHL in HIV infected
persons.[566]
AIDS-related lymphomas are thought to arise when a variety of predisposing factors
promote polyclonal B-cell proliferation. These factors include: diminished immunosurveillance
with decreasing CD4 lymphocyte counts, destruction of follicular dendritic cells leading to
interference with apoptosis and allowing B-cell clonal proliferation, chronic antigen stimulation
marked by polyclonal hypergammaglobulinemia, and cytokine deregulation. This B-cell
proliferation is best characterized clinically as persistent generalized lymphadenopathy (PGL).
Over time, B-cell oligoclonal expansions arise within this PGL pattern. A monoclonal
proliferation eventually arises from a single clone that has accumulated sufficient genetic
abnormalities.[561,567]
Viral infections with Epstein-Barr virus (EBV) and/or Kaposi sarcoma herpesvirus
(KSHV) commonly contribute to pathogenesis of most HIV-associated lymphomas. All are B
cell varieties. All diffuse large B-cell lymphomas and most Burkitt lymphomas, primary
effusion lymphomas, extracavitary solid primary effusion lymphomas, and plasmablastic
lymphomas of the oral cavity type are associated with EBV infection. All primary effusion
lymphomas and extracavitary solid primary effusion lymphomas occur with KSHV. All large B-
cell lymphomas associated with multicentric Castleman disease occur with KSHV.[568]
The clinical characteristics of non-Hodgkin lymphomas vary somewhat. About 80% of
NHL’s in AIDS arise systemically, either nodally or extra nodally, while 20% arise in the central
nervous system. AIDS patients with systemic lymphomas are likely to have had previous
opportunistic infections and be severely immunosuppressed with low CD4 lymphocyte counts at
the time of presentation. For persons with CNS lymphomas, presenting symptoms are often non-
localizing and include confusion, lethargy, and memory loss. Less frequent findings include
hemiparesis, aphasia, seizures, cranial nerve palsies, and headache. Radiographic findings with
either magnetic resonance imaging (MRI) or computed tomographic (CT) scans include single or
multiple discrete ring-enhancing lesions very similar to those seen with toxoplasmosis. In
contrast, patients presenting with systemic lymphomas are generally not as immunosuppressed,
but typically have widespread extranodal disease.[561,567]
Grossly, non-Hodgkin lymphomas with AIDS may appear as small infiltrates, focal
nodular lesions, or larger tumor masses. Multicentric lesions may appear in the same organ.
Smaller lymphomatous lesions appear white to tan with irregular borders, while larger masses
with definable margins are accompanied by necrosis and hemorrhage leading to appearance of a
variegated (red to brown-black to white) cut surface resembling a strawberry or chocolate
sundae.
Microscopically, systemic non-Hodgkin lymphomas with AIDS fall into two broad
categories, both of B-cell origin. About 30% are high-grade B-cell (small non-cleaved) Burkitt-