What’s Your Diagnosis?

Abstract

What’s Your Diagnosis?What’s Your Diagnosis? Husn Frayha, MD, FRCPC Hadeel Al Mana, and MD Mohammed AkhtarMD, FCAP, FRCPA, FRCPath Husn Frayha Search for more papers by this author , Hadeel Al Mana Search for more papers by this author , and Mohammed Akhtar Search for more papers by this author Published Online:1 Sep 2003https://doi.org/10.5144/0256-4947.2003.337SectionsPDF ToolsAdd to favoritesDownload citationTrack citations ShareShare onFacebookTwitterLinked InRedditEmail AboutANSWERA needle biopsy of the kidney revealed extensive interstitial infiltration by lymphocytes and plasma cells. In addition, there was infiltration of several tubules by lymphocytes (Figure 1). This feature is termed tubulitis and is an important finding for the histopatholgoic diagnosis of acute cellular rejection. Another important morphologic finding in this biopsy was that some of the tubular epithelial cells had enlarged nuclei with characteristic smooth and gelatinous basophilic viral inclusions. In addition to the viral inclusions, the nuclei of tubular cells frequently showed marked hyperchromasia and marked variation in size. Some of the tubules contained necrotic cells desquamated within the lumina. The morphology of the intranuclear inclusions in this case is that of human polyoma viral infection (Figure 2). The presence of prominent tubulitis seen in this biopsy would suggest the possibility of concomitant acute cellular rejection although similar changes may also be considered part of the morphologic spectrum of human polyoma viral infection alone.Figure 1. Low magnification photomicrograph of the renal biopsy showing moderate interstitial infiltration by inflammatory cells along with tubular loss and fibrosis (Hematoxylin and eosin stain, x 100).Download FigureFigure 2. Photomicrograph showing several cells containing somewhat large nuclei with blue-grey inclusions (Hematoxylin and eosin stain, x 250).Download FigureDiagnosisRenal allograft biopsy with human polyoma viral infection.Human polyoma viruses include BK virus and CJ virus. Both viruses were first described in 1971 and assigned names according to the initials of the original patients. These viruses are non-enveloped with a diameter of 45 nanometers and a circular double-stranded DNA genome containing 5300 base pairs. Both viruses show 70% homology with each other and with simian virus 40 (SV40).1Human polyoma viruses are ubiquitous infections usually acquired early in childhood. Worldwide 60% to 80% of adults have antibodies to these viruses. The majority of infections are subclinical and lead to viral latency within the urogenital tract where the virus becomes incorporated in the genomic DNA of the tissue. Asymptomatic reactivation may occur spontaneously in immunocompetent persons, but is more frequent among those with altered cellular immunity such as pregnant women, patients with cancer receiving chemotherapy, patients with human immune deficiency virus (HIV-I) infection and recipients of renal and other transplants. Asymptomatic viruria occurs in 0.3% of immunocompetent patients, 3% of pregnant women, 10% to 45% of renal transplant recipients, and 50% of bone marrow transplant recipients. In patients with renal transplants, ureteric stenosis and gradual renal dysfunction have been temporally associated with viruria or seroconversion for polyoma virus. Recently there have been many reports of polyoma virus infection with renal allograft dysfunction, interstitial nephritis, tubulitis and ultimate graft loss in patients treated with FK506 and mycophenolate mofetil (MMF) based immunosuppression. The clinical presentation of these cases is indistinguishable from that of acute allograft dysfunction. A subset of patients with polyoma virus infection who have been treated with anti-lymphocyte agents present with rapid fall in GFR and graft failure.2Pathologic diagnosis of polyoma virus infection in renal transplant patients is primarily based on demonstration of characteristic intranuclear viral inclusions in renal biopsies. 3-5 However, demonstration of viral inclusions may be difficult in early cases and many of these may be diagnosed as acute rejection. Urine cytology is an extremely sensitive technique for demonstrating viral-infected transitional epithelial cells (decoy cells), but correlation with allograft function status and histologic findings of viral inclusions in renal biopsy is poor. Additional morphologic features such as more than 10 infected cells per cytospin preparation and presence of inflammatory changes in the sediments correspond closely to patients with acute allograft dysfunction and invariably to a biopsy specimen showing features of polyoma virus infection. Immunohistochemical staining of the allograft biopsy for a subset of lymphocyte may provide important clues. In biopsies with polyoma viruses there may be a marked increase in the numbers of CD20 positive B-lymphocytes and a decrease in the relative proportion of cytotoxic T cells.6 Electron microscopic examination of urinary sediment is an effective and confirmatory technique for demonstrating polyoma virus infection. In our case the urine examination revealed many infected epithelial cells (Figure 3) and electron microscopic examination of the urinary sediment revealed many cells with abundant intranuclear viral structures. (Figure 4) Immunohistochemical staining of virally infected cells using appropriate antibodies is also a useful technique. Similarly, the presence of virus in infected cells may also be demonstrated by in-situ hybridization. Nickeleit et al recently demonstrated detection of BK virus nephropathy compared to one of 25 transplant patients without nephropathy. The authors suggested that molecular diagnostic testing maybe a useful method for identifying and following patients who are at risk and those who are already infected.7,8Figure 3. Electron micrograph of a cell in urinary sediment showing loss of nuclear chromatin architecture due to the presence of numerous viral structures (Uranyl acidate and lead citrate, x 3000).Download FigureFigure 4. Higher magnification electron micrograph showing numerous viral structures (Uranyl acetal and lead citrate, x 15 000).Download FigureManagement of patients with polyoma virus nephropathy is problematic since no effective antiviral therapy is available. Until a safe antiviral therapy becomes available, reduction of immunosuppression is the only available course. The prognosis however is generally poor.ARTICLE REFERENCES:1. Butel JS, Arlington AS, Wong C, Lednicky JA, Finegold MJ. "Molecular evidence of simian virus 40 infections in children." J Infect Dis.. 1999; 180:884-887. Google Scholar2. Hussain S, Bresnahan BA, Cohen EP, Hariharan S. "Rapid kidney allograft failure in patients with polyoma virus nephritis with prior treatment with antilymphocyte agents." Clin Transplant.. 2002; 16:43-47. Google Scholar3. Drachenberg CB, Beskow CO, Cangro CB, Bourquin PM, Simsir A, Fink J, Weir MR, Klassen DK, Bartlett ST, Papadimitriou JC. "Human polyoma virus in renal allograft biopsies: Morphological findings and correlation with urine cytology." Hum Pathol.. 1999; 30(8):970-977. Google Scholar4. Purighalla , Shapiro R, McCauley J, Randhawa P. "BK virus infection in a kidney allograft diagnosed by needle biopsy." Am J Kidney Dis.. 1995; 26(4):671-673. Google Scholar5. Mathur VS, Olson JL, Darragh TM, Yen TSB. "Polymavirus-induced interstitial nephritis in two renal transplant recipients: Case reports and review of the literature." Am J Kidney Dis.. 1997; 29(5), 754-758. Google Scholar6. Ahuja M, Cohen EP, Dayer AM, Kampalath B, Chang C, Bresnahan BA, Hariharan S. "Polyoma virus infection after renal transplantation." Transplantation.. 2001; 71:896-899. Google Scholar7. Nickeleit V, Klimkait T, Binet IF, Dalquen P, Del Zeneiro V, Thiel G, Mihatsch MJ, Hirsch HH. "Testing for Polyomavirus type BK DNA in plasma to identify renal-allograft recipients with viral nephropathy." Massachusetts Medical Society.. 2000; 42(18):1309-1315. Google Scholar8. Cirocco R, Markou M, Rosen A, Goldsmith L, Cianco G, Roth D, Kupin W, Burke G, Esquenazi V, Tzakis A, Miller J. "Polyomavirus PCR monitoring in renal transplant recipients: Detection in blood is associated with higher creatinine values." Transplantation Proceedings. 2001: 33:1805-1807. Google Scholar Previous article FiguresReferencesRelatedDetails Volume 23, Issue 5September-October 2003 Metrics History Published online1 September 2003 InformationCopyright © 2003, Annals of Saudi MedicinePDF download