March 2017 Case Cedars-Sinai Skip to content Close Select your preferred language English عربى 简体中文 繁體中文 فارسي עִברִית 日本語 한국어 Русский Español Tagalog English English عربى 简体中文 繁體中文 فارسي עִברִית 日本語 한국어 Русский Español Tagalog Translation is unavailable for Internet Explorer Cedars-Sinai Home 1-800-CEDARS-1 1-800-CEDARS-1 Close Find a Doctor Locations Programs & Services Health Library Patient & Visitors Community My CS-Link Education clear Go Close Academics Academics Faculty Development Community Engagement Calendar Research Research Areas Research Labs Departments & Institutes Find Clinical Trials Research Cores Research Administration Basic Science Research Clinical & Translational Research Center (CTRC) Technology & Innovations News & Breakthroughs Education Graduate Medical Education Continuing Medical Education Graduate School of Biomedical Sciences Professional Training Programs Medical Students Campus Life Office of the Dean Simulation Center Medical Library Program in the History of Medicine About Us All Education Programs Departments & Institutes Faculty Directory Anatomic and Clinical Pathology Residency Back to Anatomic and Clinical Pathology Residency Application Information Explore the Residency Training Curriculum Autopsy Pathology Rotation Bone and Soft Tissue Head and Neck Pathology Rotation Breast Pathology Rotation Cardiovascular Pathology Rotation Clinical Chemistry Rotation Coagulation Rotation Cytopathology Rotation Dermatopathology Rotation Forensic Pathology Rotation Frozen Section Rotation Gastrointestinal and Liver Pathology Genitourinary Pathology Rotation Genomic Pathology Rotation Gynecologic Pathology Rotation Hematopathology Rotation Laboratory Management Rotation Microbiology Rotation Neuropathology Rotation Pulmonary and Mediastinal Pathology Rotation Renal Pathology Rotation Transfusion Medicine Rotation Surgical Pathology Pathology Physician Scientist Training Program Residents Graduates Case of the Month Archive Publications Leadership Frequently Asked Questions March 2017 Case Authors Deepika Sirohi, MD (Fellow) and Daniel J. Luthringer, MD (Faculty) Subject Urologic Pathology Clinical History 66 year-old female, status post orthoptopic heart transplant 8 years ago for ischemic cardiomyopathy; presented with recent onset of urgency, frequency and dysuria of 6 weeks duration. She had multiple comorbidities significant amongst which were end stage renal disease and immunosuppressant therapy for heart transplant. Cystoscopic examination showed areas of papillary projections throughout the bladder and a transurethral resection was performed. For evaluation of end stage renal failure, a renal biopsy was performed 4 years ago. Diagnosis SV-40 associated invasive urothelial carcinoma, high grade with elements of micropapillary carcinoma and signet ring (mucinous) differentiation arising in a background of urothelial carcinoma in situ and surface papillary carcinoma with features of villoglandular differentiation. Discussion Human polyomaviruses are unenveloped DNA viruses that include the BK, JC and SV40 viruses. Most individuals acquire the infection during childhood that persists in a latent form. Shedding of the virus in urine is frequently seen in immunosuppressive states such as after organ transplant, chemotherapy and HIV infection. It is commonly diagnosed by urine cytology with the characteristic viral cytopathic changes of enlarged nuclei with basophilic ground glass appearance. However, urine cytology also happens to be a common cause of diagnostic error as the viral cytopathic changes can mimic malignant urothelial cell. Like many viruses, the role of BKV in oncogenesis has been postulated, with a putative role in urothelial carcinoma, ependymoma and mesothelioma. Studies have shown increased risk of urothelial carcinoma in renal transplant and BK viruric recipients with the latter cohort also showing a more rapid onset of malignancy. BK viruria, however is not always present. Literature review of reported cases of SV40 positive urothelial carcinomas occurring in post-transplant setting have been mostly high grade tumors with variant morphology, such as micropapillary or adenocarcinoma, presenting at high stage as seen in this case and have adverse outcomes. It is thought that BKV reactivation promotes dysplastic changes in the urothelium, though by itself is not sufficient for oncogenic transformation due to continuous cell death associated with lytic viral replication. With passage of time and acquisition of other mutations, the uncoupling of early and late viral genes prevents virion assembly and promotes oncogenesis. The exact role of BKV in causation of urothelial carcinoma is uncertain at present and an alternate explanation is that the positivity could be a consequence rather than cause of neoplastic transformation with the replicating cells providing a better milieu for viral replication. References 1. Roberts ISD, Besarani D, Mason P, Turner G, Friend PJ, Newton R. BK virus and bladder cancer in renal transplant recipients. British Journal of Cancer. 2008;99(9):1383 – 1386 2. Borislav A. Alexiev, Parmjeet Randhawa, Eduardo Vazquez Martul, Gang Zeng, Chunqing Luo, Emilio Ramos et al. BK virus–associated urinary bladder carcinoma in transplant recipients: report of 2 cases, review of the literature, and proposed pathogenetic model. Human Pathology. 2013; 44:908–917 3. Wang HH, Liu KL, Chu SH, Tian YC, Lai PC, Chaing YJ. BK virus infection in association with posttransplant urothelial carcinoma. Transplantation Proceedings. 2009; 41:165–166 4. Vajdic CM, McDonald SP, McCredie MR, van Leeuwen MT, Stewart JH, Law M et al. Cancer incidence before and after kidney transplantation. JAMA 2006;296:2823– 2831 Have Questions or Need Help If you have questions or would like to learn more about the Anatomic and Clinical Pathology Residency Program at Cedars-Sinai, please call or send a message to Academic Program Coordinator, LeeTanya Marion-Murray. Department of Pathology and Laboratory Medicine 8700 Beverly Blvd., Room 8709 Los Angeles, CA 90048-1804 310-423-6941 send a message Please ensure Javascript is enabled for purposes of website accessibility