Polyomavirus BK in the pathogenesis of bladder cancer.

Polyomaviruses are able to drive malignant transformation in rodent models, and have been implicated in the aetiology of a variety of human malignancies. However, the reports on this association in humans are strongly conflicting. Here we describe a renal transplant (RT) recipient with ureteral stenosis against the background of polyomavirus BK (BKV) activity. Six and a half years after transplantation, this patient developed metastasised bladder cancer. Prior to the diagnosis of cancer, atypical cells were detected in the urine that were denoted as 'decoy cells': virally infected epithelial cells that are frequently seen in the urine of RT recipients with BKV (re)activation, which may morphologically resemble malignant cells. Intriguingly, the primary urothelial carcinoma, as well as the mesenterial and two intestinal metastases, stained positive with antibodies against polyomavirus virus large T antigen protein, whereas the adjacent healthy tissue did not. This case suggests a role for BKV in the pathogenesis of bladder cancer, at least in the context of immunodeficiency.

BK virus infection in transplant recipients: clinical manifestations, treatment options and the immune response.

Polyomavirus BK (BKV) is ubiquitously present amongst the general population establishing a latent, seemingly asymptomatic infection in immunocompetent individuals. In transplant recipients, however, BKV reactivation is common and can lead to distinctive pathological entities in different patient groups: in renal transplant (RT) recipients, it is associated with nephropathy (BKVN) and ureteral stenosis, and in haematopoietic stem cell transplant (HSCT) recipients with haemorrhagic cystitis (HC). Furthermore, BKV employs several potentially oncogenic mechanisms to promote its replication in cells and has been inconsistently linked to the development of malignancies. BKVN is currently a major cause of allograft failure in RT recipients. HC causes prolonged hospital stay and increased mortality in HSCT recipients. Despite its discovery more than 40 years ago, few advances have been made with regard to therapeutic strategies. Current therapies aim to restore the impaired immune response, e.g. by lowering immunosuppressive agents in RT recipients. However, this is a double-edged sword since it also increases the chance of rejection. Therefore, more specific and effective treatment strategies are urgently needed. Here, we will review the current knowledge on the structure and lifecycle of BKV, characteristics of the BKV-specific immune response, its clinical manifestations and the strengths and limitations of available treatments Polyomavirus BK (BKV) is ubiquitously present amongst the general population establishing a latent, seemingly asymptomatic infection in immunocompetent individuals. In transplant recipients, however, BKV reactivation is common and can lead to distinctive pathological entities in different patient groups: in renal transplant (RT) recipients, it is associated with nephropathy (BKVN) and ureteral stenosis, and in haematopoietic stem cell transplant (HSCT) recipients with haemorrhagic cystitis (HC). Furthermore, BKV employs several potentially oncogenic mechanisms to promote its replication in cells and has been inconsistently linked to the development of malignancies. BKVN is currently a major cause of allograft failure in RT recipients. HC causes prolonged hospital stay and increased mortality in HSCT recipients. Despite its discovery more than 40 years ago, few advances have been made with regard to therapeutic strategies. Current therapies aim to restore the impaired immune response, e.g. by lowering immunosuppressive agents in RT recipients. However, this is a double-edged sword since it also increases the chance of rejection. Therefore, more specific and effective treatment strategies are urgently needed. Here, we will review the current knowledge on the structure and lifecycle of BKV, characteristics of the BKV-specific immune response, its clinical manifestations and the strengths and limitations of available treatments methods.

Vinblastine, rituximab and HAART, treatment of an HIV -positive patient with multicentric Castleman's disease.

An HIV-positive man from Somalia presented with severe malaise, weight loss, relapsing fever, lymphadenopathy and splenomegaly. An FDG-PET-scan-guided lymph node biopsy revealed the characteristic histological features of the plasma cell variant of Castleman's disease. A high HHV-8 viral load was detected in the serum (7980 copies/ml). Treatment with HAART, rituximab and vinblastine resulted in a full and rapid recovery and lowered HHV-8 viral load to undetectable levels.