- Short report
- Open Access
Primary bilateral adrenal B-cell lymphoma associated with EBV and JCV infection
© Barzon et al; licensee BioMed Central Ltd. 2009
- Received: 10 September 2008
- Accepted: 15 January 2009
- Published: 15 January 2009
Primary lymphoma of the adrenal gland is a rare and highly aggressive disease, with only a few reports in the literature. The pathogenesis is unknown, but detection of Epstein Barr virus (EBV) genome sequences and gene expression in some cases of primary adrenal lymphomas suggested the virus might be a causative agent of the malignancy. While investigating the presence of genome sequences of oncogenic viruses in a large series of adrenal tumors, both EBV and JC polyomavirus (JCV) DNA sequences were detected in a diffuse large primary bilateral B-cell non-Hodgkin lymphoma of the adrenal gland, which was diagnosed only at postmortem examination in a 77 year-old woman with incidentally discovered adrenal masses and primary adrenal insufficiency. The presence of both EBV and JCV genome sequences suggests the relevance of EBV and JCV coinfection in the pathogenesis of this rare form of B-cell lymphoma.
- Epstein Barr Virus
- Adrenal Mass
- Adrenocortical Carcinoma
- Primary Adrenal Insufficiency
- Primary Adrenal Lymphoma
Primary lymphoma of the adrenal gland is a rare and highly aggressive disease, with only a few reports in the literature [1–3]. It generally affects elderly individuals, especially those with a history of cancer, HIV infection, or autoimmune disorders, and, in about 50% of cases, it presents with symptoms of adrenal insufficiency due to bilateral adrenal involvement. Histologically, the most common type of primary adrenal lymphomas is diffuse large B-cell lymphoma . Treatment with chemotherapy according to the CHOP-regimen (cyclophosphamide, doxorubicin, vincristine, prednisone) alone or in combination with rituximab has led complete or partial remission is some patients, even though prognosis remains poor with death occurring within one year after diagnosis [3–5]. The pathogenesis is unknown, but detection of Epstein Barr virus (EBV) genome sequences and gene expression in 9 out of 20 cases of primary adrenal lymphomas suggested the virus might be the causative agent of the malignancy . While investigating the presence of genome sequences of oncogenic viruses in a large series of adrenal tumors and their potential association with malignancy , both EBV and JC polyomavirus (JCV) DNA sequences were detected in the case of primary bilateral adrenal B-cell lymphoma we are reporting here.
While EBV is a recognized causative agent of B-cell lymphomas, the association between JCV and hematologic malignancies is matter of debate. A potential implication of JCV in B-cell lymphomas is suggested by its oncogenicity in vitro and in animal models  and by its ability to infect B-lymphocytes , where it seems to cause chromosomal damage . Indeed, JCV DNA and gene expression have been detected in 4 of 63 (6%) non-Hodgkin lymphomas and in 1 of 20 (5%) Hodgkin lymphomas , in a primary B-cell lymphoma of the central nervous system occurring in a patient with AIDS and concurrent progressive multifocal leucoencephalopathy , and in 22 of 27 (81%) primary B-cell lymphomas of the central nervous system, including 14 which also contained EBV DNA . However, it remains unknown whether JCV has a causal role in human neoplasia. Our report of a primary adrenal B-cell lymphoma positive for both JCV and EBV DNA, even if it does not provide evidence for a causal relationship between viral infection and development of lymphoma, could support the hypothesis by Del Valle et al.  that JCV might act as a co-factor of EBV in B-cell transformation. However, since we did not evaluate whether the patient had systemic JCV infection before death, we cannot exclude a secondary involvement of lymphoma cells in the course of a systemic infection due to JCV reactivation in a terminally-ill patient. This is also suggested by the relatively low JCV DNA load (0.1 copies/cell) in tumor tissues.
In conclusion, we demonstrated the presence of both EBV and JCV genome sequences in a diffuse large B-cell non-Hodgkin lymphoma of the adrenal gland. Further studies in other cases are encouraged to clarify the relevance of EBV and JCV coinfection in the pathogenesis of this rare form of extranodal B-cell lymphoma.
This study was supported by grant no. RSF 271/07 from Veneto Region to Giorgio Palù.
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