BK virus–associated urinary bladder carcinoma in transplant recipients: report of 2 cases, review of the literature, and proposed pathogenetic model

Summary Despite strong experimental evidence, BK polyomavirus involvement in human cancers has been controversial. We report 2 cases of kidney ± pancreas transplant recipients with evidence of BK polyomavirus reactivation, who developed aggressive urinary bladder urothelial carcinomas with adenocarc...

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Published inHuman pathology Vol. 44; no. 5; pp. 908 - 917
Main Authors Alexiev, Borislav A., MD, Randhawa, Parmjeet, MD, Vazquez Martul, Eduardo, MD, Zeng, Gang, MD, PhD, Luo, Chunqing, PhD, Ramos, Emilio, MD, Drachenberg, Cinthia B., MD, Papadimitriou, John C., MD, PhD
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 01.05.2013
Elsevier Limited
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Abstract Summary Despite strong experimental evidence, BK polyomavirus involvement in human cancers has been controversial. We report 2 cases of kidney ± pancreas transplant recipients with evidence of BK polyomavirus reactivation, who developed aggressive urinary bladder urothelial carcinomas with adenocarcinomatous and/or micropapillary differentiation. Diffuse strong nuclear positivity for viral T antigen, p53, Ki-67, and p16 was observed in both malignancies. The BK polyomavirus role in promoting urothelial neoplasia in transplant recipients may be partly indirect, based on the demonstration by polymerase chain reaction in both tumors of BK polyomavirus with intact open reading frames and close phylogenetic clustering with known replication-competent strains, and viral capsid protein VP1 messenger RNA and intranuclear virions by electron microscopy in 1 tumor. No unique cancer-associated mutations were found, but some viral T antigen mutations were potentially associated with increased rate of viral replication and risk for “rare” carcinogenic events. The BK polyomavirus–induced profound effects on cell activation, cell cycle shift to proliferation, and apoptosis inhibition, in the context of marked immunosuppression, constitute a potentially ideal background for malignant transformation. The long time lapse between transplantation and tumor manifestation, 7 and 11 years, respectively, further supports the concept of multistep carcinogenesis cascade and long-term risk for these patients. We propose a model of changes ranging from viral reactivation to dysplasia to invasive carcinoma. Clinical vigilance is warranted for early diagnosis of BK polyomavirus–related urothelial malignancies in transplant recipients.
AbstractList Summary Despite strong experimental evidence, BK polyomavirus involvement in human cancers has been controversial. We report 2 cases of kidney ± pancreas transplant recipients with evidence of BK polyomavirus reactivation, who developed aggressive urinary bladder urothelial carcinomas with adenocarcinomatous and/or micropapillary differentiation. Diffuse strong nuclear positivity for viral T antigen, p53, Ki-67, and p16 was observed in both malignancies. The BK polyomavirus role in promoting urothelial neoplasia in transplant recipients may be partly indirect, based on the demonstration by polymerase chain reaction in both tumors of BK polyomavirus with intact open reading frames and close phylogenetic clustering with known replication-competent strains, and viral capsid protein VP1 messenger RNA and intranuclear virions by electron microscopy in 1 tumor. No unique cancer-associated mutations were found, but some viral T antigen mutations were potentially associated with increased rate of viral replication and risk for “rare” carcinogenic events. The BK polyomavirus–induced profound effects on cell activation, cell cycle shift to proliferation, and apoptosis inhibition, in the context of marked immunosuppression, constitute a potentially ideal background for malignant transformation. The long time lapse between transplantation and tumor manifestation, 7 and 11 years, respectively, further supports the concept of multistep carcinogenesis cascade and long-term risk for these patients. We propose a model of changes ranging from viral reactivation to dysplasia to invasive carcinoma. Clinical vigilance is warranted for early diagnosis of BK polyomavirus–related urothelial malignancies in transplant recipients.
Despite strong experimental evidence, BK polyomavirus involvement in human cancers has been controversial. We report 2 cases of kidney plus or minus pancreas transplant recipients with evidence of BK polyomavirus reactivation, who developed aggressive urinary bladder urothelial carcinomas with adenocarcinomatous and/or micropapillary differentiation. Diffuse strong nuclear positivity for viral T antigen, p53, Ki-67, and p16 was observed in both malignancies. The BK polyomavirus role in promoting urothelial neoplasia in transplant recipients may be partly indirect, based on the demonstration by polymerase chain reaction in both tumors of BK polyomavirus with intact open reading frames and close phylogenetic clustering with known replication-competent strains, and viral capsid protein VP1 messenger RNA and intranuclear virions by electron microscopy in 1 tumor. No unique cancer-associated mutations were found, but some viral T antigen mutations were potentially associated with increased rate of viral replication and risk for "rare" carcinogenic events. The BK polyomavirus-induced profound effects on cell activation, cell cycle shift to proliferation, and apoptosis inhibition, in the context of marked immunosuppression, constitute a potentially ideal background for malignant transformation. The long time lapse between transplantation and tumor manifestation, 7 and 11 years, respectively, further supports the concept of multistep carcinogenesis cascade and long-term risk for these patients. We propose a model of changes ranging from viral reactivation to dysplasia to invasive carcinoma. Clinical vigilance is warranted for early diagnosis of BK polyomavirus-related urothelial malignancies in transplant recipients.
Despite strong experimental evidence, BK polyomavirus involvement in human cancers has been controversial. We report 2 cases of kidney ± pancreas transplant recipients with evidence of BK polyomavirus reactivation, who developed aggressive urinary bladder urothelial carcinomas with adenocarcinomatous and/or micropapillary differentiation. Diffuse strong nuclear positivity for viral T antigen, p53, Ki-67, and p16 was observed in both malignancies. The BK polyomavirus role in promoting urothelial neoplasia in transplant recipients may be partly indirect, based on the demonstration by polymerase chain reaction in both tumors of BK polyomavirus with intact open reading frames and close phylogenetic clustering with known replication-competent strains, and viral capsid protein VP1 messenger RNA and intranuclear virions by electron microscopy in 1 tumor. No unique cancer-associated mutations were found, but some viral T antigen mutations were potentially associated with increased rate of viral replication and risk for "rare" carcinogenic events. The BK polyomavirus-induced profound effects on cell activation, cell cycle shift to proliferation, and apoptosis inhibition, in the context of marked immunosuppression, constitute a potentially ideal background for malignant transformation. The long time lapse between transplantation and tumor manifestation, 7 and 11 years, respectively, further supports the concept of multistep carcinogenesis cascade and long-term risk for these patients. We propose a model of changes ranging from viral reactivation to dysplasia to invasive carcinoma. Clinical vigilance is warranted for early diagnosis of BK polyomavirus-related urothelial malignancies in transplant recipients.
Author Vazquez Martul, Eduardo, MD
Drachenberg, Cinthia B., MD
Zeng, Gang, MD, PhD
Randhawa, Parmjeet, MD
Alexiev, Borislav A., MD
Luo, Chunqing, PhD
Ramos, Emilio, MD
Papadimitriou, John C., MD, PhD
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Issue 5
Keywords Adenocarcinoma
Micropapillary
Urothelial
Carcinogenesis
Polyomavirus
Language English
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Snippet Summary Despite strong experimental evidence, BK polyomavirus involvement in human cancers has been controversial. We report 2 cases of kidney ± pancreas...
Despite strong experimental evidence, BK polyomavirus involvement in human cancers has been controversial. We report 2 cases of kidney ± pancreas transplant...
Despite strong experimental evidence, BK polyomavirus involvement in human cancers has been controversial. We report 2 cases of kidney plus or minus pancreas...
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SubjectTerms Adenocarcinoma
Adenocarcinoma - etiology
Adenocarcinoma - virology
Adult
Antigens, Viral, Tumor - genetics
Automation
BK Virus - genetics
BK Virus - immunology
Bladder
Cancer
Carcinogenesis
Colleges & universities
Female
Health Insurance Portability & Accountability Act 1996-US
Humans
Immunosuppression - adverse effects
Kidney Transplantation - adverse effects
Male
Micropapillary
Microscopy
Middle Aged
Models, Biological
Mutation
Pathology
Polymerase chain reaction
Polyomavirus
Polyomavirus Infections - complications
Proteins
Review boards
Transplants & implants
Tumor Virus Infections - complications
Tumors
Urinary Bladder Neoplasms - etiology
Urinary Bladder Neoplasms - virology
Urogenital system
Urothelial
Virus Activation
Virus Replication
Title BK virus–associated urinary bladder carcinoma in transplant recipients: report of 2 cases, review of the literature, and proposed pathogenetic model
URI https://www.clinicalkey.es/playcontent/1-s2.0-S0046817712003632
https://dx.doi.org/10.1016/j.humpath.2012.09.019
https://www.ncbi.nlm.nih.gov/pubmed/23317548
https://www.proquest.com/docview/1327252938
https://search.proquest.com/docview/1642612058
Volume 44
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