ReviewChallenges in lymphoma diagnosis in HIV positive patients in the South African setting
Introduction
The majority of people (∼68%) living with HIV are in sub-Saharan Africa [1], with South Africa having the highest number of cases world-wide [2]. Estimates suggest the prevalence of HIV infection in South African adults (ages 15–49 years, 2009/2010) is 17–18% and approximately 300,000–350,000 new infections occur annually [3]. Although substantial improvements have been made in access to highly active antiretroviral therapy (from 4% of those requiring therapy in 2004 to 40–60% in 2009 and 75% in 2011) [4], [5], [6], therapy is started late in the course of the disease once significant immunosuppression has already occurred [4], [7], [8]. For this reason, end-stage organ damage is prevalent. Duration of detectable viraemia and both nadir and a prolonged period with a low CD4 count both increase the risk of HIV-related malignancies [9], [10], [11].
Lymphoma has been recognized as an AIDS-defining malignancy since the first descriptions of the disease in 1984 [12]. International data suggest an increased risk of more than a hundred fold for lymphoma development in the setting of HIV infection prior to the initiation of highly active anti-retroviral therapy (HAART) [13]. Possible aetiologic factors in the development of lymphoma include reduced immunosurveillance and immune dysregulation, new and reactivated oncogenic viral infections, possible direct oncogenic effect of HIV related proteins and chronic antigenic stimulation [11], [14], [15], [16].
HIV-infection has been associated with specific types of lymphoma. These are predominantly high grade B-cell tumours and include Burkitt leukaemia/lymphoma (BL), Diffuse large B-cell lymphoma (DLBCL), Plasmablastic lymphoma (PBL), Primary effusion lymphoma (PEL), Large cell lymphoma arising in HHV-8 associated multicentric Castleman’s disease and the recently added provisional category of B-Cell Lymphoma unclassifiable, with features intermediate between DLBCL and BL (BCLU) [17], [18].
In sub-Saharan Africa, accurate epidemiologic, aetiologic and clinical data is minimal. South African data, however, indicates that the incidence of lymphoma may be much lower in African settings than in the first world [19], [20], [21]. Preliminary studies conducted by our group suggest that HIV-related lymphomas in the Gauteng region of South Africa are increasing in number with increasing HIV prevalence and this is reflected by the high grade subtypes seen in state hospitals [22], [23]. In the 2007–2009 study periods, 62% of all patients diagnosed with lymphoma and greater than 90% of patients diagnosed with high grade B-cell lymphoma that were tested for HIV infection, were HIV infected [23].
In under-resourced environments, early diagnosis remains one of the best predictors of improved outcome. Accurate diagnosis remains a challenge, however, because of limited patient access to advanced diagnostic modalities, late patient presentation and atypical presentation [19]. In this review, we will discuss diagnostic predicaments which are common in our experience of the diagnosis of HIV-related lymphoma.
Section snippets
Reactive processes that mimic lymphoma
In the South African setting, many reactive processes are seen in the context of HIV infection which may mimic lymphoma pathologically and/or clinically. One of the most important processes to exclude is Mycobacterium tuberculosis infection [24]. Of the estimated 8.8 million cases of tuberculosis reported globally, approximately 26% are in Africa with South Africa ranking third highest in tuberculosis incidence worldwide (2011 figures) [25]. In South Africa, 60% of patients with TB are
Conclusion
HIV related lymphoma has decreased in prevalence in well-resourced settings with improved access to antiretroviral therapy. This has not been reflected in our setting and HIV-related lymphomas continue to cause significant morbidity and mortality. They also represent a diagnostic dilemma for a number of reasons resulting in further delay in initiating patient therapy with a worse prognosis.
Acknowledgements
Dr. T.M. Wiggill is the recipient of a Fogarty International Centre Scholarship (National Institutes of Health: D43 TW000010-21S1) Dr. T.M. Wiggill and Dr. P. Willem have a Cancer Research Grant from CANSA (Cancer Association of South Africa).
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These authors contributed equally to this work.