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.
ABSTRACT 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). "
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.Virology 01/2013; 437(2). DOI:10.1016/j.virol.2012.12.015 · 3.28 Impact Factor
- Pediatric Transplantation 08/2008; 12(5):499-502. DOI:10.1111/j.1399-3046.2008.00960.x · 1.63 Impact Factor
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ABSTRACT: In the last 10 years, better immunosuppression drugs have decreased the rates of acute rejection in kidney transplantation but have also led to the emergence of polyomavirus-associated nephropathy (PVAN). This occurs in 1% to 10% of patients with kidney transplantion and is caused by BK virus in more than 95% of cases. Less than 5% of cases are attributed to the JC virus. Initially, lack of recognition or late diagnosis of PVAN resulted in rapid loss of graft function in more than 50% of patients. In recent years, it has become clear that early diagnosis and timely reduction in immunosuppression is the only proven measure, which significantly affects the outcome of PVAN. Diverse interventions have been explored including the adjunctive use of cidofovir, leflunomide, fluoroquinolones, and intravenous immunoglobulins. Allograft histology is needed to definitively establish the diagnosis of PVAN, but is of limited sensitivity in the early stage of disease. Well-established techniques and protocols for systematic screening by urine cytology and quantitative molecular-genetic techniques allow now for timely intervention before irreversible parenchymal changes occur. Moreover, preemptive reduction in immunosuppression is most effective in presumptive PVAN as defined by surrogate markers (i.e., high BK virus viremia). In this setting, preservation of graft function can be considered the rule. Nevertheless, the recovery of BK virus-specific T-cell immunity may require prolonged periods during which cytopathic damage may continue to accumulate. Despite remarkable progress in the field, important challenges remain, such as the rare patient with PVAN refractory to any intervention and the newly recognized association of PVAN with urogenital tumors.Transplantation 04/2009; 87(5):621-30. DOI:10.1097/TP.0b013e318197c17d · 3.78 Impact Factor