Case Report: Epstein-Barr-Virus negative diffuse large B-cell lymphoma detected in a peri-prosthetic membrane 

Primary lymphoma of the bone is rare, accounting for 3–7 % of malignant bone neoplasms and 4–5 % of extra-nodal Non-Hodgkin lymphomas [6]. Primary Non-Hodgkin lymphomas arising in the peri-prosthetic membrane around metallic implants are extremely rare. The carcinogenic effects of the metallic components and wear particles are not yet fully elucidated [7]. Most cases reported in this context are DLBCL associated with chronic inflammation and concomitant EBV infection [2, 7]. Campo et al. report, that in these lesions lymphomas-infected cells frequently express a latency type 3 with positivity for the viral proteins latent membrane protein 1 and EBV nuclear antigen 2, suggesting, that the lymphoid proliferation may be related primarily to a decrease in the host immune-surveillance [5]. Our described case of DLBCL, however, lacks EBV infection and is localized to the knee without any other site of involvement. A summary of our literature search (see Table 1) showed only one case of diffuse large B-cell lymphoma in association with a joint replacement without EBV association and was published in 2011 [2]. Another case was reported with negativity for the EBV in situ hybridization, but positivity for EBV in the polymerase chain reaction [7]. All reported cases did not show any signs of generalization [2, 7‐13].

In the context of our case we would like to challenge the concept that “DLBCL associated with chronic inflammation” is always associated with EBV infection. In our case EBV could clearly not be demonstrated by otherwise classic features of “DLBCL associated with chronic inflammation”. Although the pathogenesis in our case is not fully elucidated, we hypothesize that other factors may play a role in this context. Especially metallic ions are known to have carcinogenic potential. After a metal implantation a significant increased concentration of cobalt and chromium in the synovial fluid and blood could be measured. These metallic ions have mutagenic effects and have been described to potentially predispose to lymphomas [2]. In 2004 Landon et al. report about an increase in chromium and cobalt levels, an increased incidence of chromosomal translocation and an aneuploidy in the peripheral blood of patients within 2 years after metal-on-metal joint arthroplasty [14].

In addition a higher level of HBVc antibody was incidentally found in our patient. Gross et al. states that a negative HBV DNA does not rule out an HBV infection [15].

In the literature a connection between Hepatitis B virus infection and Non-Hodgkin lymphomas is described [16‐21]. It is suggested that HBV is not only a hepatotropic but also a lymphotropic disease and participates in the development of malignant lymphoproliferative disorders. For viral clearance the cellular and humoral immunity plays an important role for HBV infection and disease progression. The cellular and humoral immunity system gets activated after HBV infection. The immune system destroys the HBV infected cells and the host cells, which are infected by HBV [18]. However, the mechanisms are not fully elucidated [19, 20] and several theories are suggested. Proposed theories include [19]: