Collecting duct carcinoma arising in association with BK nephropathy post-transplantation in a pediatric patient. A case report with immunohistochemical and in situ hybridization study. Pediatr Transplant
Department of Pathology, University of Utah School of Medicine and Associated Regional and University Pathologists (ARUP) Laboratories, Salt Lake City, UT, USA. Pediatric Transplantation
(Impact Factor: 1.44).
08/2008; 12(5):600-5. DOI: 10.1111/j.1399-3046.2007.00855.x
The development of malignancy in a renal transplant graft is an uncommon phenomenon. A renal neoplasm developing in the adult donor kidney of a pediatric transplant recipient has only rarely been reported. We report a case of collecting duct carcinoma arising in association with BK virus nephropathy in an adult living-related donor renal allograft to a pediatric recipient. Our case is the second report of neoplasia occurring in association with BK virus nephropathy post-transplantation, suggesting that BK virus may play a role in oncogenesis. It has been proposed that the T-Ag protein encoded by the polyomavirus family of viruses disrupts chromosomal integrity, creating oncogenes, and inactivating tumor suppressor genes. In our study, immunohistochemical staining with antibody directed against BK virus large T antigen showed nuclear staining within urothelium, tubular epithelium, tubular intraepithelial neoplasia, and invasive carcinoma. In situ hybridization did not identify BK virus DNA within neoplastic cells. T-Ag protein expression has been shown to be tumor-specific in bladder, gastric, and colorectal cancers. The finding of T-Ag protein expression in both intraepithelial and invasive neoplastic tissues in our case raises the possibility of BK virus as a causative agent in oncogenesis.
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- "The high seroprevalence and high detection rate of BKV and JCV by sensitive molecular tools in healthy individuals complicates studies and require a rigorous re-evaluation of the published data. For BKV, the most convincing data of an oncogenic contribution have been presented in single case reports of urothelial malignancies and renal tubular malignancies, typically in the setting of kidney transplantation as illustrated by three reported single cases: (Emerson et al., 2008; Geetha et al., 2002; Narayanan et al., 2007). In other reports, BKV is not found convincingly in such tumors (Kausman et al., 2004; Loghavi and Bose, 2011). "
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ABSTRACT: Today the human polyomavirus (HPyV) family consists of 10 members, BK virus (BKV) and JC virus (JCV) isolated 40 years ago and the more recently identified KI virus (KIPyV), WU virus (WUPyV), Merkel cell polyomavirus (MCPyV), HPyV6, HPyV7, trichodysplasia spinulosa virus (TSPyV), HPyV9 and MWPyV. Serological studies suggest that HPyVs subclinically infect the general population with rates ranging from 35% to 90%. However, significant disease is only observed in patients with impaired immune functions. Thus, BKV has been linked to hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation and PyV-associated nephropathy (PyVAN) after kidney transplantation; JCV to progressive multifocal leukoencephalopathy (PML) in HIV-AIDS, hematological diseases and in autoimmune diseases treated with certain lymphocyte-specific antibodies. KIPyV and WUPyV have been found in the respiratory tract, HPyV6 and 7 in the skin, and HPyV9 in serum and skin, and MWPyV in stools and skin, but so far none of these PyVs have been linked to any disease. TSPyV, on the other hand, was identified in trichodysplasia spinulosa, a rare skin disease characterized by virus-induced lytic as well as proliferative tumor-like features that is observed in immune-suppressed transplant patients. In contrast to all the other HPyVs so far, MCPyV is unique in its association with a cancer, Merkel cell carcinoma, which is a rare skin cancer arising in the elderly and chronically immunosuppressed individuals. The discovery of the new HPyVs has revived interest in the Polyomaviridae and their association to human disease and cancer. In this review, we summarize knowledge about this expanding family of human pathogens.
Available from: Hendrik Paul Van Poppel
- "Besides the correlation between BKVN and graft failure, a small number of case reports suggest an association between BKV infection and the development of renal and bladder cancers in renal transplant recipients [7, 8, 9, 10, 11, 12, 13, 14] (table 1). Indeed, for more than 30 years, an oncogenic potential of BKV has been observed in vitro and in animal models [3, 15, 16]. "
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ABSTRACT: BK virus (BKV) is known to cause subclinical infection in childhood. The virus remains latent in the human body, mainly in the urinary tract epithelium. After initiation of an immunosuppressive treatment, reactivation can occur in renal transplant recipients. BKV can cause hemorrhagic cystitis, ureteral stenosis and BKV nephropathy in immunocompromised patients. Furthermore, a number of case reports suggest an association between BKV infection and the development of urinary tract cancer. So far, an oncogenic potential of BKV has been observed in vitro and in animal models; however, its oncogenic capacity in humans remains unclear. We report the case of a 59-year-old patient who developed a poorly differentiated renal cell carcinoma in her renal allograft, with pulmonary and abdominal metastasis. Surgical removal of the allograft and cessation of the immunosuppressive therapy resulted in complete resolution of the metastatic disease.
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