Burkitt Lymphoma: Association With Epstein-Barr Virus but Not HHV-8
Burkitt Lymphoma: Association With Epstein-Barr Virus but Not HHV-8
Burkitt lymphoma (BL) is a highly aggressive non-Hodgkin lymphoma, composed of a monomorphic population of medium-sized B cells with a high proliferation rate and a consistent MYC translocation. Epstein-Barr virus (EBV) has been associated with BL with different frequencies depending on the clinical variant. Kaposi sarcoma-associated herpesvirus, or human herpesvirus 8 (HHV-8), infects a wide range of normal cells, having a well-established role in the pathogenesis of various neoplasms, including Kaposi sarcoma, primary effusion lymphoma, multicentric Castleman disease (MCD) and MCD-associated plasmablastic lymphoma. In secondary immunodeficiencies, such as HIV-1 infection and organ transplantation, HHV-8 is considered an opportunistic pathogen linked to the development of lymphomas in patients with AIDS and HIV+ patients. We studied the association of EBV and HHV-8 by immunohistochemical analysis, in situ hybridization, and polymerase chain reaction in a large number of well-characterized BLs. EBV was present in 45.0% of all BL cases with higher incidence in the pediatric group; most cases were EBV type A. We found no association of BL with HHV-8 in EBV+ BL or in EBV- cases, including the HIV+ BL group.
Burkitt lymphoma (BL) is a highly aggressive non-Hodgkin lymphoma with endemic, sporadic, and immunodeficiency-associated clinical variants composed of a monomorphic population of medium-sized B cells with a high proliferation rate and having a consistent MYC translocation. Viral infections, in particular Epstein-Barr virus (EBV), have been associated with BL; it is well established that this association occurs with different frequencies depending on the clinical variant. EBV is present in the majority of endemic cases of BL and nearly 30% of cases of sporadic BL. In Brazil, a high association of EBV with BL has been demonstrated in tropical areas, especially in the northeast region.
Kaposi sarcoma-associated herpesvirus, or human herpesvirus (HHV)-8, is a virus able to infect mammalian cells, including lymphoid cells, dendritic cells, and fibroblasts. Several neoplasms have been associated with HHV-8, including Kaposi sarcoma, primary effusion lymphoma, multicentric Castleman disease (MCD), and MCD-associated plasmablastic lymphoma.
In the context of secondary immunodeficiencies, such as HIV-1 infection and organ transplantation, HHV-8 is considered an opportunistic pathogen that has been linked to the development of lymphoproliferative diseases, including lymphomas and related diseases. HHV-8 has also been reported in association with lymphomas in patients with AIDS and HIV+ patients. In common variable immunodeficiency, a primary immunodeficiency disorder of unknown etiology, patients have a high risk of B-cell lymphomas; HHV-8 has been identified in at least some of the associated lymphomas and is considered an important factor in their pathogenesis. Du et al demonstrated monotypic HHV-8+ plasmablasts in MCD and MCD-associated plasmablastic lymphomas.
HHV-8-associated lymphomas have included cases of naive cell origin, germinal center (GC) and post-GC cells, unlike EBV-associated lymphomas, which are generally more restricted to GC or post-GC origin. HHV-8 and EBV coinfection has been documented in primary effusion lymphoma and in the setting of Castleman disease, typically associated with an immunosuppressed state.
In the literature, there is scarce information on the association of HHV-8 with BL in HIV+ and HIV- patients, and it is generally limited to data concerning African populations. Lazzi et al, in a study of East African patients, evaluated 16 BL cases and detected HHV-8 in nonneoplastic lymphoid cells in 1 case of an HIV- patient with a lymph node partially involved by BL. The molecular analysis in microdissected HHV-8+ cells in this case showed absence of clonality. It is worth mentioning that in this BL case, there was no association with Kaposi sarcoma. In a previous study on HIV-associated malignant lymphomas, also in African patients, Lazzi et al analyzed 29 cases of BL, with none showing HHV-8 by polymerase chain reaction (PCR). In 10 cases of African BL, Tao and Ambinder did not find HHV-8 or HHV-7 but found HHV-6 in 3 cases studied.
We studied the association of EBV and HHV-8 in a large number of well-characterized BL cases in a Brazilian population.
Abstract and Introduction
Abstract
Burkitt lymphoma (BL) is a highly aggressive non-Hodgkin lymphoma, composed of a monomorphic population of medium-sized B cells with a high proliferation rate and a consistent MYC translocation. Epstein-Barr virus (EBV) has been associated with BL with different frequencies depending on the clinical variant. Kaposi sarcoma-associated herpesvirus, or human herpesvirus 8 (HHV-8), infects a wide range of normal cells, having a well-established role in the pathogenesis of various neoplasms, including Kaposi sarcoma, primary effusion lymphoma, multicentric Castleman disease (MCD) and MCD-associated plasmablastic lymphoma. In secondary immunodeficiencies, such as HIV-1 infection and organ transplantation, HHV-8 is considered an opportunistic pathogen linked to the development of lymphomas in patients with AIDS and HIV+ patients. We studied the association of EBV and HHV-8 by immunohistochemical analysis, in situ hybridization, and polymerase chain reaction in a large number of well-characterized BLs. EBV was present in 45.0% of all BL cases with higher incidence in the pediatric group; most cases were EBV type A. We found no association of BL with HHV-8 in EBV+ BL or in EBV- cases, including the HIV+ BL group.
Introduction
Burkitt lymphoma (BL) is a highly aggressive non-Hodgkin lymphoma with endemic, sporadic, and immunodeficiency-associated clinical variants composed of a monomorphic population of medium-sized B cells with a high proliferation rate and having a consistent MYC translocation. Viral infections, in particular Epstein-Barr virus (EBV), have been associated with BL; it is well established that this association occurs with different frequencies depending on the clinical variant. EBV is present in the majority of endemic cases of BL and nearly 30% of cases of sporadic BL. In Brazil, a high association of EBV with BL has been demonstrated in tropical areas, especially in the northeast region.
Kaposi sarcoma-associated herpesvirus, or human herpesvirus (HHV)-8, is a virus able to infect mammalian cells, including lymphoid cells, dendritic cells, and fibroblasts. Several neoplasms have been associated with HHV-8, including Kaposi sarcoma, primary effusion lymphoma, multicentric Castleman disease (MCD), and MCD-associated plasmablastic lymphoma.
In the context of secondary immunodeficiencies, such as HIV-1 infection and organ transplantation, HHV-8 is considered an opportunistic pathogen that has been linked to the development of lymphoproliferative diseases, including lymphomas and related diseases. HHV-8 has also been reported in association with lymphomas in patients with AIDS and HIV+ patients. In common variable immunodeficiency, a primary immunodeficiency disorder of unknown etiology, patients have a high risk of B-cell lymphomas; HHV-8 has been identified in at least some of the associated lymphomas and is considered an important factor in their pathogenesis. Du et al demonstrated monotypic HHV-8+ plasmablasts in MCD and MCD-associated plasmablastic lymphomas.
HHV-8-associated lymphomas have included cases of naive cell origin, germinal center (GC) and post-GC cells, unlike EBV-associated lymphomas, which are generally more restricted to GC or post-GC origin. HHV-8 and EBV coinfection has been documented in primary effusion lymphoma and in the setting of Castleman disease, typically associated with an immunosuppressed state.
In the literature, there is scarce information on the association of HHV-8 with BL in HIV+ and HIV- patients, and it is generally limited to data concerning African populations. Lazzi et al, in a study of East African patients, evaluated 16 BL cases and detected HHV-8 in nonneoplastic lymphoid cells in 1 case of an HIV- patient with a lymph node partially involved by BL. The molecular analysis in microdissected HHV-8+ cells in this case showed absence of clonality. It is worth mentioning that in this BL case, there was no association with Kaposi sarcoma. In a previous study on HIV-associated malignant lymphomas, also in African patients, Lazzi et al analyzed 29 cases of BL, with none showing HHV-8 by polymerase chain reaction (PCR). In 10 cases of African BL, Tao and Ambinder did not find HHV-8 or HHV-7 but found HHV-6 in 3 cases studied.
We studied the association of EBV and HHV-8 in a large number of well-characterized BL cases in a Brazilian population.
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