Evidence for distinct mechanisms of immune suppression in EBV-positive and EBV-negative Hodgkin lymphoma.

Epstein Barr Virus (EBV) has been recognized for its ability to transform B lymphocytes and for its association with different types of cancers including Hodgkin lymphoma. In addition, EBV may also modulate the microenvironment of HL. In this study, we aimed to investigate the prevalence of EBV among HL cases in Ethiopia and to assess the tissue cellular composition of EBV-related and EBV-unrelated cases. We constructed a tissue microarray (TMA) of 126 consecutive cases of classical HL (CHL) and nodular lymphocyte predominant HL (NLPHL) from a tertiary cancer centre, Tikur Anbessa Hospital, Addis Ababa, Ethiopia, and evaluated a panel of immunohistochemical markers. The quantification of immune cells was performed using HALO 2.3, a platform for image analysis from Indica Lab Inc. A total of 77/126 (61.1%) of HL cases expressed LMP1/EBER. Infiltration of CD8+, T-bet+ and FoxP3+ cells was higher in the microenvironment of EBV-related CHL, with P values of <0.001, <0.001 and <0.016, respectively. In contrast, the expression of PD1 was higher in the microenvironment of EBV-unrelated CHL cases (P < 0.001). Unlike in Western countries, the majority of HL cases in Ethiopia were associated with EBV. As FoxP3+ and PD1-expressing cells are thought to participate in down regulation of the immune response by different mechanisms, this finding highlights the previously unrecognized possibility that distinct immunosuppressive mechanisms may be ongoing within EBV positive and negative HL types. This may have important prognostic and therapeutic implications.

Clinical Characteristics and Histopathological Patterns of Hodgkin Lymphoma and Treatment Outcomes at a Tertiary Cancer Center in Ethiopia.

PURPOSE: In developing countries, Hodgkin lymphoma (HL) affects the young population. In Ethiopia, nearly 70% of the population are < 35 years of age. Therefore, this study aimed to elucidate the age distribution, histopathologic patterns, clinical characteristics and treatment outcomes of HL in Ethiopia. MATERIALS AND METHODS: Data from clinical records of 133 consecutive patients with HL between 2014 and 2019 were reviewed and collected. Formalin-fixed paraffin-embedded tissue blocks of HL cases were collected and used for subtype classification. RESULTS: A total of 68.4% (91) of the patients were male; male-to-female ratio was 2.2:1. The median age was 22 years. The age distribution was 57.1% (76), 30.8% (41), and 2.3% (3) for the age groups (10-29), (30-59), and (60-69) years, respectively. Thirteen percent (12) were associated with HIV. The majority of the cases, 50.4% (67), were of the mixed-cellularity (MCCHL) subtypes and 30% (40) nodular-sclerosis (NSCCHL). Most HIV-associated cases (60%, 6) were of the MCHL subtype. The 4-year overall survival (OS) was 83.1%. The 4-year OS of early-stage patients was 100% and advanced-stage patients with low-risk (International Prognostic Score [IPS] ≤ 2) and high-risk (IPS ≥ 3) were 94.1% and 62.9%, respectively. All patients who received combined-therapy survived, whereas those who received doxorubicin, bleomycin, vinblastine, and dacarbazine only showed a 4-year OS rate of 77.9%. CONCLUSION: HL affects the youngest and most productive population in Ethiopia. The treatment outcome is favorable in both HIV-associated and non-HIV-associated HL. However, the study population was likely a highly selected group as the majority of the Ethiopian population do not have access to specialized care.