We have reported the case of a patient who presented with all the features of PEL that have been described elsewhere [14, 15]. This was the first AIDS defining illness in this patient even though she had very low CD4 counts.
The strong positivity for HHV-8 in this patient is similar to what other authors have found in studies on HIV-positive PEL patients [14, 16]. HHV-8, by definition, has to be present in the tumor cells in order to make a diagnosis of PEL . The co-infection of HHV-8 and EBV in this patient is interesting. Both HHV-8 and EBV are γ-herpes viruses and are closely related. While evidence of HHV-8 is essential for diagnosis of PEL, the role of HHV-8 in the pathogenesis is not clear. However, we know that EBV immortalizes B-cells while HHV-8 seems not to. It would, therefore, appear that HHV-8 by itself is not sufficient for the development of PEL. It seems that EBV causes unchecked proliferation of B-cells leading to development of PEL and, according to Fan and others, "once PELs have developed HHV-8 appears to be the driving force ." Recently, several cases of EBV negative PEL have been reported implying that HHV-8 plays a critical role in pathogenesis .
About 31 cases of HHV-8 independent PEL (HHV-8-unrelated PEL-like lymphoma) have been reported in the literature . This new entity is now referred to more precisely as HHV-8-unrelated large B-cell lymphomas because of the differences observed in its pathogenesis, morphology and immunophenotype (it expresses a B-cell phenotype unlike PEL), and is associated with hepatitis C virus infection in 30-40% of cases . The clinical behavior and prognosis are significantly different from that of PEL patients. The HHV-8-unrelated large B-cell lymphoma patients tend to have more indolent disease that has been observed to resolve spontaneously and, when treated, these patients have a much better prognosis than the HIV-positive, HHV-8 positive PEL patients - who have a very poor outcome . This therefore proves that the two are separate entities.
PEL, possibly uniquely, presents as serous effusions in the pleural, peritoneal and pericardial cavity without identifiable tumor masses or lymphadenopathy.
The morphological presentation is as a large B-cell neoplasm and the tumor cells contain KSHV/HHV-8 DNA and lack c-myc translocations. PEL most commonly affects male AIDS patients and was first recognized in men who have sex with men [20, 21]. However, a few cases have been reported in women. It is easily distinguished from other lymphomas because of its unusual morphology with large immunoblastic, plasmacytoid and/or anaplastic cells.
The immunophenotypical presentation of PEL cells is typically as a "null" lymphocyte phenotype, meaning that CD45 is expressed, but routine B-cell (including surface and cytoplasmic immunoglobulin, CD19, CD20, CD79a) and T-cell (CD3, CD4, CD8) markers are absent. Instead, various markers of lymphocyte activation (CD30, CD38, CD71, human leukocyte antigen DR) and plasma cell differentiation (CD138) are usually displayed .
PELs are of B-cell origin because they have clonal immunoglobulin gene rearrangements [17, 23].
Although immunohistochemical services are not routinely available in Uganda and other resource constrained countries, it is still possible to suspect PEL with available clinical and cytomorphologic criteria. These include lymphomatous effusions limited to the body cavities with no solid tumor or lymphadenopathy and pleomorphic large cells with immunoblastic, plasmacytoid and anaplastic variants .
Regarding PEL, no optimal treatment has yet been identified . Most HIV-positive PEL patients receive anthracycline-based multiagent chemotherapy (CHOP; cyclophosphamide, doxorubicin, vincristine, and prednisone) and antiretroviral therapy. Patients with HHV-8 negative large B-cell lymphomas have been shown to benefit from immunotherapy with rituximab since they display B-cell immunophenotype, pleurodesis and thoracocentesis . However, in resource poor settings such as Uganda only CHOP and antiretroviral agents are used . NF-kappa B plays a significant role in PEL oncogenesis. Studies using new drug regimens directed against NF-kappa B have shown positive results. These drugs are currently being developed for therapeutic use [26, 27].