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Background
The polyoma virus is a commonly acquired infection with as many as 60-80% of adults in the U.S. testing positive for the virus. The kidney is one organ where the virus may lie dormant for many years. In the majority of patients, only a subclinical infection may resul. However, in immunocompromised patients, the virus may reactivate and cause significant disease.
OUTLINE
EPIDEMIOLOGY CHARACTERIZATION SYNONYMS INCIDENCE/
PREVALENCEAGE SEX GEOGRAPHY EPIDEMIOLOGIC ASSOCIATIONS
DISEASE ASSOCIATIONS CHARACTERIZATION KIDNEY TRANSPLANT
- Polyoma virus infection of renal allografts: relationships of the distribution of viral infection, tubulointerstitial inflammation, and fibrosis suggesting viral interstitial nephritis in untreated disease.
Meehan SM, Kadambi PV, Manaligod JR, Williams JW, Josephson MA, Javaid B.
Nephropathology Laboratory, Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
Hum Pathol. 2005 Dec;36(12):1256-64. Abstract quote
Whether polyoma virus (PV) infection of renal allografts induces an antiviral or antigraft immune reaction is unclear.
By examination of the relationships of tubular PV to graft inflammation and scarring, this study sought histological evidence of viral interstitial nephritis in allograft biopsies with untreated PV infection and compared the inflammatory indices to controls with acute rejection (AR).
Morphological features including viral cytopathic changes (VCCs) and modified Banff 97 histological indices were evaluated in sections of 28 diagnostic biopsies from a group of patients receiving prednisone, tacrolimus, and mycophenolate mofetil at constant dosage before biopsy. Two-micrometer paraffin sections were stained for PV large T antigen (TAg) and for C4d, by immunohistochemistry. Tubular profiles with 1 or more nuclei expressing TAg per x200 field were scored using an interval scale (0-10; none to 91-100%) by 2 observers. Controls with AR (n = 38, TAg negative) were matched for time after transplantation and severity of Banff 97 interstitial inflammation (i) and tubulitis (t) scores. Median t scores for tubules with VCC or TAg or both exceeded scores for tubules without VCC or TAg (3 versus 0, P = .001). Tubular TAg score correlated with i score (r = 0.58, P < .01) and sum ct + ci score (r = 0.61, P < .001). Atrophic tubules in scars had persistent VCC and/or TAg. Interstitial plasma cells (75% versus 21%) and neutrophils (32% versus 0%) were more frequent, and interstitial fibrosis was more severe (ci >1 in 54% versus 21%) in polyoma virus nephropathy (PVN) than in the group with AR (P < .01). Intimal arteritis (0% versus 35.7%), peritubular capillary C4d (0% versus 47.4%), and interstitial hemorrhage (4% versus 37%) were almost exclusively found in AR (P < .01). Tubular inflammation in untreated PVN involves infected tubular profiles with greater severity than those without evidence of infection. The extent of tubular PV infection is proportional to interstitial inflammation and scarring. Tubulointerstitial inflammation in PV infection has significant qualitative differences from AR.
Observations in these examples of untreated PVN suggest that the allograft inflammatory reaction may exhibit features of viral tubulointerstitial nephritis distinct from AR.
- Polyomavirus disease in renal transplantation Review of pathological findings and diagnostic methods.
Drachenberg CB, Hirsch HH, Ramos E, Papadimitriou JC.
Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Hum Pathol. 2005 Dec;36(12):1245-55. Epub 2005 Oct 19. Abstract quote
Up to 10% of renal transplant recipients can develop polyomavirus nephropathy (PVN) in the allograft, leading to premature graft failure. Recent studies have shown that early diagnosis of PVN before there is irreversible damage to the kidney can result in marked improvement of outcome with resolution of the infection in a large proportion of patients. Early histopathologic diagnosis is complicated by the subtle beginning of the infection and its multifocal nature.
This review presents a comprehensive set of guidelines for the effective clinical use of urine cytology and quantitation of viruria and viremia in conjunction with the renal biopsy findings. The morphological features of PVN are presented with specific emphasis on the patterns of PVN that are based on the histological progression of the disease and that correlate with clinical outcome.
Also discussed in the context of their clinical significance are the main virological and epidemiological aspects of the BK, JC, and SV40 polyomavirus infections.
Benjamin R. Kipp, MS, CT(ASCP)MP, etal.
Urinary polyomavirus subtype BK (BKV)-infected urothelial and renal tubular cells, "decoy cells," have been shown to be aneuploid with digital image analysis (DIA).
We wanted to determine whether decoy cells cause false-positive fluorescence in situ hybridization (FISH) results in BKV-infected urine samples.
Urine samples from 38 renal transplant recipients were split 3 ways and evaluated for number of decoy cells per 10 high-power fields by routine cytology, total nuclear DNA content by DIA, and chromosomal abnormalities by FISH. For DIA, Feulgen-stained cells were quantified with a CAS 200 image analyzer (Bacus Laboratories, Lombard, IL), and for FISH, the UroVysion probe set (Vysis, Downers Grove, IL) consisting of chromosome enumeration probes 3, 7, 17, and locus-specific identifier probe 9p21 (p16 gene) was used. Of the 38 specimens, 32 (84.2%) had evidence of BKV infection by routine cytology. DIA and FISH results were aneuploid/aneusomic in 30 (93.8%) and 4 (12.5%) cases, respectively. All aneusomic FISH specimens occurred in men older than 52 years of age and who also had 4 of the 6 highest PCR-BKV titers.
To date, no patient has clinical evidence of malignancy. The 6 specimens without decoy cells were DNA diploid/disomic by DIA and FISH. Abnormal FISH results of urinary decoy cells occur much less frequently than aneuploidy by DIA in renal transplant recipients and might merit close follow-up in some transplant recipients.
PATHOGENESIS CHARACTERIZATION GENERAL
- Cross-reactivity of T lymphocytes recognizing a human cytotoxic T-lymphocyte epitope within BK and JC virus VP1 polypeptides.
Krymskaya L, Sharma MC, Martinez J, Haq W, Huang EC, Limaye AP, Diamond DJ, Lacey SF.
Laboratory of Vaccine Research, Beckman Research Institute of the City of Hope, Duarte, CA 91010-3000, USA.
J Virol. 2005 Sep;79(17):11170-8. Abstract quote
A transgenic mouse model was used to identify an HLA-A*02-restricted epitope within the VP1 polypeptide of a human polyomavirus, BK virus (BKV), which is associated with polyomavirus-associated nephropathy in kidney transplant patients. Peptide stimulation of splenocytes from mice immunized with recombinant modified vaccinia virus Ankara expressing BKV VP1 resulted in expansion of cytotoxic T lymphocytes (CTLs) recognizing the sequence LLMWEAVTV corresponding to amino acid residues 108 to 116 (BKV VP1p108).
These effector T-cell populations represented functional CTLs as assessed by cytotoxicity and cytokine production and were cross-reactive against antigen-presenting cells pulsed with a peptide corresponding to the previously described JC virus (JCV) VP1 homolog sequence ILMWEAVTL (JCV VP1p100) (I. J. Koralnik et al., J. Immunol. 168:499-504, 2002). A panel of 10 healthy HLA-A*02 human volunteers and two kidney transplant recipients were screened for T-cell immunity to this BK virus VP1 epitope by in vitro stimulation of their peripheral blood mononuclear cells (PBMC) with the BKV VP1p108 peptide, followed by tetramer labeling combined with simultaneous assays to detect intracellular cytokine production and degranulation. PBMC from 4/10 subjects harbored CTL populations that recognized both the BKV VP1p108 and the JCV VP1p100 peptides with comparable efficiencies as measured by tetramer binding, gamma interferon production, and degranulation. CTL responses to the JCV VP1p100 epitope have been associated with prolonged survival in progressive multifocal leukoencephalopathy patients (R. A. Du Pasquier et al., Brain 127:1970-1978, 2004; I. J. Koralnik et al., J. Immunol. 168:499-504, 2002).
Given that both human polyomaviruses are resident in a high proportion of healthy individuals and that coinfection occurs (W. A. Knowles et al., J. Med. Virol. 71:115-123, 2003), our findings suggest a reinterpretation of this protective T-cell immunity, suggesting that the same VP1 epitope is recognized in HLA-A*02 persons in response to either BK or JC virus infection.
LABORATORY/
RADIOLOGIC/
OTHER TESTSCHARACTERIZATION RADIOLOGIC LABORATORY MARKERS POLYMERASE CHAIN REACTION
- Real-Time Polymerase Chain Reaction and Laser Capture Microdissection for the Diagnosis of BK Virus Infection in Renal Allografts.
Adeyi OA, Belloni DR, Dufresne SD, Schned AR, Tsongalis GJ.
Department of Pathology, Dartmouth-Hitchcock Medical Center, Lebanon, NH.
Am J Clin Pathol. 2005 Oct;124(4):1-6. Abstract quote
We used real-time polymerase chain reaction (PCR) technology to detect BK virus (BKV) in H&E-stained kidney biopsy sections, using laser capture microdissection. Renal allograft biopsy specimens from 4 patients with the histopathologic diagnosis of BKV-associated nephropathy (BKVAN; group 1) and 3 patients suspected to have BKVAN but without diagnostic histologic features (group 2) were retrieved. Diagnostic inclusion-bearing cells were microdissected by laser capture microscopy from group 1.
Renal tubular epithelial cells were microdissected randomly in group 2. DNA was extracted and real-time amplification performed using primers targeting the large "T" and small "t" regions of the BKV and JC virus genomes. Tubular epithelial cells from a case without evidence of BKV infection were used as negative controls in a similar reaction. BKV presence was demonstrated only in epithelial cells containing typical viral inclusions. Group 2 and negative control samples were confirmed as negative for BKVAN. Real-time PCR technology can be used to detect BKV in H&E-stained, paraffin-embedded tissue sections.
This technique detected BKV in tubular epithelial cells of renal allografts. To our knowledge, this is the first report of detecting BKV in laser capture microdissected renal biopsy specimens using real-time PCR.
- Detection and quantitation of BK virus DNA by real-time polymerase chain reaction in the LT-ag gene in adult renal transplant recipients.
Si-Mohamed A, Goff JL, Desire N, Maylin S, Glotz D, Belec L.
Laboratoire de Microbiologie, Unite de Virologie, Hopital Europeen Georges Pompidou, 20 rue Leblanc, 75908 Paris Cedex 15, France.
J Virol Methods. 2005 Aug 18; [Epub ahead of print] Abstract quote
Determination of polyomavirus BK (BKV) load in urine and plasma has been advocated for monitoring adult renal transplant recipients suffering from BKV-related nephropathy. An "in-house" real-time quantitative PCR assay was developed using the BKV-1/BKV-3 primers set in the large tumor antigen (LT-ag) region to quantitate BK virus loads in plasma and urine in renal transplant patients.
This assay was adapted to routine virology laboratory by evaluating two extraction procedures of nucleic acids from urine and plasma, one manual and the other using an automatic extractor, and by evaluating the Light Cycler versus Taqman apparatus. Both the manual and automatic extraction procedures and real-time PCR apparatus were equivalent. The Light Cycler and Taqman instruments allow similarly rapid, accurate, reproducible and specific quantitative detection of the three major BKV subtypes, with a detection limit of 10 BKV DNA copies/ml, and a range from 10(0) to 10(7)copies/ml. Of 855 renal transplant patients, 128 (15%) had BKV DNA in both plasma and urine samples with a mean viral load of 5.1log/ml in plasma and 6.8log/ml in urine and in 5 (4%) BKV-associated tubulo-interstitial nephropathy; 332 (39%) BKV DNA was found only in the urine, not in the plasma, without further development of nephropathy and 395 patients had no BKV in plasma and urine.
These observations emphasize the usefulness of real-time PCR to assess the BKV load by routine testing, and confirm the need to combine both plasma and urine determinations of the BKV DNA load in order to identify renal transplant patient at high risk for BKV-associated nephropathy.
GROSS APPEARANCE/
CLINICAL VARIANTSCHARACTERIZATION GENERAL VARIANTS GASTROINTESTINAL
- Frequent detection of polyomaviruses in stool samples from hospitalized children.
Vanchiere JA, Nicome RK, Greer JM, Demmler GJ, Butel JS.
Department of Pediatrics, Section of Infectious Diseases, Baylor College of Medicine, Houston, Texas, USA.
J Infect Dis. 2005 Aug 15;192(4):658-64. Epub 2005 Jul 12. Abstract quote
BACKGROUND. Infection with BK virus (BKV) generally occurs early during life, but its mode of transmission has not been clearly defined. We tested the hypothesis that polyomavirus shedding in stool may be a source of BKV exposure.
METHODS. Pediatric stool and rectal swab samples were tested for the presence of polyomavirus DNA by a polymerase chain reaction (PCR) assay that could detect a conserved region in the large T antigen gene of BKV, JC virus (JCV), and simian virus 40 (SV40). The specific viruses detected by this assay were confirmed by DNA sequence analysis of the PCR amplicons.
Results. Of 120 samples collected from 99 patients, 54 (45.0%) were positive for polyomavirus DNA. Of the 99 patients, 46 (46.5%) had at least 1 positive sample, with 38 (38.4%) positive for BKV and 8 (8.1%) positive for SV40. JCV was not detected. There was no association between polyomavirus fecal shedding and age, sex, race/ethnicity, immune status, or symptoms of gastrointestinal disease in the children studied. The BKV strains detected displayed polymorphisms in the T antigen sequence.
Conclusions. Polyomaviruses are frequently present in stool samples from hospitalized children. These findings suggest that fecal-oral transmission of BKV may play a role in the ubiquity of infection.
- Detection of JC virus DNA sequences in colorectal cancers in Japan.
Hori R, Murai Y, Tsuneyama K, Abdel-Aziz HO, Nomoto K, Takahashi H, Cheng CM, Kuchina T, Harman BV, Takano Y.
First Department of Pathology, Faculty of Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama, 930-0152, Japan
Virchows Arch. 2005 Jul 14;:1-8 [Epub ahead of print] Abstract quote
JC virus (JCV), a ubiquitous polyoma virus that commonly infects humans, was first identified as the etiologic agent for the fetal demyelinating disease, progressive multifocal leukoencephalopathy. Recently, a number of reports have documented detection of JCV in samples derived from several types of neural as well as non-neural human tumors. It has been suggested that oncogenicity of JCV depends on a T antigen having a strict structural homology to the T antigen of simian virus 40.
To clarify whether JCV might have a potential role with regard to colorectal cancers, we investigated the presence of its genome in a series of cases along with colorectal adenomas and normal colonic mucosa, targeting T antigen, VP and agnoprotein by nested polymerase chain reaction and Southern blotting and T antigen by immunohistochemistry. While VP and agnoprotein were not found in any of the samples examined, T antigen was detected in 6 of 23 colorectal cancers (26.1%) and 1 of 21 adenomas (4.8%), but none of 20 samples of normal colonic mucosa. No clear and diffuse staining with anti-T-antigen antibodies (1:100) could be detected, and there was no correlation with CD20-positive cells, which might have indicated JCV latent infection of B lymphocytes. Presence of T antigen did not influence clinicopathological variables, including survival. In one colonic cancer case positive for T antigen together with lymph node metastasis, DNA extracted from cancer cells in the lymph node revealed no detection of T antigen.
Our results are in the intermediate position between the high T antigen rate (81%) in one report and the lack of it (0%) in another focused on colon cancers. It was concluded that T antigen might be integrated in cancer cells in approximately one fourth of Japanese colon cancer cases without clear and diffuse expression of the protein, suggesting a possible role in oncogenesis which might involve a hit-and-run mechanism.
KIDNEY
- Detection of Polyomavirus BK and JC in Children With Kidney Diseases and Renal Transplant Recipients.
Muller A, Beck B, Theilemann K, Stapenhorst L, Licht C, Michalk D, Franzen C, Hoppe B.
From the *Department of Pediatrics, University of Bonn, Bonn, Germany; the daggerDepartment of Pediatrics, University of Cologne, Cologne, Germany; and the double daggerDepartment of Internal Medicine I, University of Regensburg, Regensburg, Germany.
Pediatr Infect Dis J. 2005 Sep;24(9):778-781. Abstract quote
BACKGROUND:: Reactivation of polyomavirus is a known reason for severe renal dysfunction in adult renal transplant recipients. Testing for polyomavirus DNA in plasma has been described as a sensitive and specific method to discover viral nephropathy in adult patients. We were now interested in polyomavirus status in a pediatric patient setting.
METHODS:: Plasma and urine samples were obtained from 80 children including 38 children after renal transplantation (group 1), 7 children with different kidney diseases receiving immunosuppressive treatment (group 2) and 35 children with different kidney diseases not receiving immunosuppressive treatment (group 3). A nested polymerase chain reaction method was used for amplification of polyomavirus DNA fragments. Differentiation between JC and BK virus was done by digestion with restriction endonucleases.
RESULTS:: Polyomavirus DNA was detected in the urine sample of 19 of 38 (50%) renal transplant recipients (group 1), of 1 of 7 (14%) patients from group 2 and in none of the 35 patients of group 3. Plasma samples from 3 (8%) of group 1 patients and from 1 child each of group 2 (14%) and group 3 (3%) were tested positive for polyomavirus DNA.
CONCLUSION:: Urinary polyomavirus excretion seems to be more frequent in pediatric patients with kidney diseases receiving immunosuppressive treatment and after renal transplantation than in children with various kidney diseases without immunosuppressive treatment.
Lytic JC Virus Infection in the Kidneys of AIDS Subjects.Boldorini R, Omodeo-Zorini E, Nebuloni M, Benigni E, Vago L, Ferri A, Monga G.
Dipartimento di Scienze Mediche, Facolta di Medicina e Chirurgia, Universita "Amedeo Avogadro" del Piemonte Orientale (RB, EO-Z, EB, GM), Novara, Italy.
Mod Pathol 2003 Jan;16(1):35-42 Abstract quote
Our objective was to investigate the role of the human polyomavirus JC virus as a possible cause of renal damage in AIDS subjects. Histology, immunohistochemistry, and molecular biology were used to evaluate the frequency of viral infection, genotypes, viral status, and the presence of rearrangements or point mutations in specific genomic regions of strains isolated from renal tissue.
Formalin-fixed, paraffin-embedded sections of postmortem renal specimens obtained from 111 unselected AIDS patients were stained for routine histology and with anti-SV40 antibody. The immunohistochemically positive specimens were further investigated by means of nested polymerase chain reaction for different polyomavirus genomic regions (large T, transcriptional control region, and viral protein 1).
Furthermore, the sequences of transcriptional control region and viral protein 1 were also analyzed. Immunohistochemistry was positive in seven cases (6.3%), four of which showed morphological evidence of viral replication (intranuclear inclusion bodies and/or intratubular cellular casts): in all seven cases, only epithelial tubular cells (with and without inclusion bodies) and cellular casts were stained. The JC virus genome was identified by polymerase chain reaction in five of the seven immunohistochemically positive cases; transcriptional control region and viral protein 1 were amplified in, respectively, three and four cases. Transcriptional control region sequence analysis revealed major rearrangements in all three cases, with duplications of all the transcriptional factor-binding sites, whereas no point mutations were found in the viral protein 1 region, which was characterized as Type 1A in all cases.
For the first time in AIDS subjects, this study shows that although rarely, JC virus can replicate in renal tissue. Molecular biology revealed major rearrangements in the transcriptional control region that, together with other unknown factors, could justify the increased pathogenicity of this human polyomavirus.
LUNGS
Hum Pathol. 2005 Sep;36(9):1031-4. Abstract quote
BK polyoma virus has a worldwide distribution in the human population. Primary BK infection takes place during childhood, with the virus remaining latent in many sites. Immunosuppressive states can lead to viral reactivation associated with many clinical sequelae.
We report a case of fatal BK-related pneumonia in a 69-year-old patient who was immunocompromised because of chemotherapy for chronic lymphocytic leukemia. Immunohistochemical, in situ hybridization, and polymerase chain reaction studies on paraffin-embedded lung tissue proved BK virus as the etiologic agent of pneumonia. The histological picture was remarkable for numerous intranuclear large basophilic viral inclusions with ground-glass appearance mainly in type II pneumocytes.
Similar to many other infectious agents, BK virus is emerging as an important pathogen in immunocompromised patients, making it important to consider in the differential diagnosis.PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY
- AIDS-Related Progressive Multifocal Leukoencephalopathy in the Era of HAART: Report of Two Cases and Review of the Literature.
Wyen C, Lehmann C, Fatkenheuer G, Hoffmann C.
University of Cologne, Cologne, Germany.
AIDS Patient Care STDS. 2005 Aug;19(8):486-94. Abstract quote
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system. It is caused by the JC virus (JCV), a human polyomavirus replicating in human glial cells. PML is the result of the reactivation of latent JCV infection that usually occurs in the setting of cellular immunodeficiencies such as HIV-1 infection.
Epidemiologic data suggest that the impact of highly active antiretroviral therapy (HAART) on the incidence of PML is less profound than seen with other opportunistic infections. Given the lack of an effective and specific therapy for PML, HAART remains the only therapeutic option in patients with PML. However, a significant number of cases appear unresponsive to antiretroviral therapy. Moreover, there is growing data on unexpected inflammatory cases of PML after initiation of HAART.
Thus, PML will remain a relevant cause of morbidity and mortality in HIV- 1-infected patients. Here we report two cases of PML, along with a concise review of the literature on this important disease.
HISTOLOGICAL TYPES CHARACTERIZATION GENERAL URINE Decoy cells
- Polyoma Virus-Associated Cellular Changes in the Urine and Bladder Biopsy Samples: A Cytohistologic Correlation.
Herawi M, Parwani AV, Chan T, Ali SZ, Epstein JI.
Departments of *Pathology daggerUrology double daggerOncology, Johns Hopkins University School of Medicine, Baltimore, MD section signDepartment of Pathology, University of Pittsburgh, Pittsburgh, PA.
Am J Surg Pathol. 2006 Mar;30(3):345-350. Abstract quote
Polyoma (BK) virus-type cellular changes are occasionally reported in urine specimens, yet rarely detected in histologic sections of bladder biopsies. A total of 762 predominantly voided urine specimens with a cytologic diagnosis of polyoma virus-type change were retrieved from the cytopathology files of the Johns Hopkins Hospital over a 15-year period (1988-2003).
Biopsies were available for 33 cases (29 patients) following or preceding the urinary cytology (mean interval, 210 days). The biopsies originated primarily from bladder (n=31) with one biopsy each from renal pelvis and urethra. Representative paraffin blocks were chosen from each case for immunoperoxidase staining with SV40 large T antigen. There were 22 males and 7 females with an age range of 34 to 79 years (mean, 64.7 years).
The histologic diagnoses of the 33 tissue biopsies were: benign urothelium (n=9), urothelial carcinoma (n=21) and 1 case each of dysplasia, small cell carcinoma, and chronic lymphocytic leukemia involving lamina propria of the bladder. Only 3 of 33 biopsies on hematoxylin-stained sections showed morphologic changes of polyoma virus, which lacked sufficient tissue to perform immunohistochemistry for SV40 large T antigen (LTag). Immunohistochemical staining for LTag was positive in 7 cases. Only 2 cases showed strong/diffuse and moderate/focal staining for LTag with both representing invasive high-grade urothelial carcinoma (where no inclusions were seen on hematoxylin and eosin-stained sections) and both demonstrating positive immunostaining for p53. One of these 2 cases was from an organ transplant recipient and the other from a patient with no known immunosuppression.
Our data lead to the following conclusions: 1) cytology appears to be more sensitive than histology in detecting cells with polyoma virus; 2) cytohistologic discordance might be due to: a) polyoma (BK) virus infected cells are shed from the tissue and collected in the urine; b) polyoma virus changes may be focal and not sampled in directed tissue biopsies; c) polyoma virus changes may originate from sites in the genitourinary tract other than the bladder; d) the lack of a "gold standard" to confirm the cytologic diagnoses of polyoma virus; and e) the discordance in time between the biopsy and cytology specimens in the current retrospective study. 3) Because some cytologically benign cases of polyoma virus were associated with malignant biopsies, careful morphologic evaluation is required to avoid false-negative urinary cytology samples. This investigation further examined the immunohistochemical staining pattern for SV40 LTag and p53 in noninvasive low-grade papillary urothelial carcinoma using a tissue microarray constructed from bladder biopsies of 79 randomly selected patients. Weak LTag staining was present in occasional neoplastic urothelial cells of 2 patients. The staining was present in only one of four samples from each tumor (0.63%; 2 of 316 tumor spots), which further illustrates the patchy and focal presence of virion containing cells. p53 staining in these two spots was also patchy and confined to rare nuclei.
- Periodic assessment of urine and serum by cytology and molecular biology as a diagnostic tool for BK virus nephropathy in renal transplant patients.
Boldorini R, Brustia M, Veggiani C, Barco D, Andorno S, Monga G.
Department of Medical Sciences, Faculty of Medicine and Surgery, Amedeo Avogdro University of East Piedmont, and Unit of Nephrology, Dialysis and Transplantation, Maggiore Hospital, Novara, Italy.
Acta Cytol. 2005 May-Jun;49(3):235-43. Abstract quote
OBJECTIVE: To investigate the significance of polyomavirus (PV) viruria and viremia by morphologic, immunohistochemical and molecular analysis (multiplex nested-polymerase chain reaction) in renal transplant patients.
STUDY DESIGN: Urine (n=328), serum (n= 53) and renal biopsies (n=24) from renal transplant patients (n=106) were studied.
RESULTS: Decoy cells were found in 53 samples (16%) from 19 patients (18%); viral DNA was amplified in all urinary samples and disclosed BK virus (BKV) (n=24), JC virus (JCV) (n=16), and JCV and BKV DNA (n=13). BKV was the prevailing genotype in patients with a high frequency of decoy cell excretion (p = 0.001). JCV excretion correlated with a low number (p = 0.01) and BKV with a high number of decoy cells (p=0.003). PV DNA was amplified from 30/53 serum samples (56.6%); BKV was the prevailing genotype (p = 0.04). On 24 renal biopsies (18 from the decoy cell-negative and 6 from the decoy cell-positive group) PV nephropathy (PVN) was identified and BKV DNA amplified in 4 biopsies, all from the group with a high frequency of decoy cell excretion. PVN was not identified in renal biopsies from the decoy cell-negative group.
CONCLUSION: PV infection is frequent in renal transplant patients. The BKV genotype in urine and serum is significantly related to a high frequency and high number of decoy cells. PVN occurs only in patients with BKV viremia and a high number and frequency of decoy cell excretion in urine. In the absence of decoy cells, PVN can be excluded. Cytologic analysis of urine is an important diagnostic tool for screening renal transplant patients at risk of PVN.
SPECIAL STAINS/
IMMUNOPEROXIDASE/
OTHERCHARACTERIZATION SPECIAL STAINS IMMUNOPEROXIDASE ELECTRON MICROSCOPY
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES
PROGNOSIS CHARACTERIZATION
TREATMENT CHARACTERIZATION GENERAL
Expert Rev Anti Infect Ther. 2005 Aug;3(4):629-40. Abstract quote
Progressive multifocal leukoencephalopathy is a fatal demyelinating disease caused by infection of oligodendrocytes by the human polyomavirus known as JC virus.
Over the past 10 years, the disease has been documented almost exclusively in AIDS patients, who constitute a rapidly growing population of immunosuppressed individuals. More recently, progressive multifocal leukoencephalopathy has also been described in patients undergoing solid organ or cell transplant, as a result of immunosuppressive therapy to avoid graft rejection.
Although there are several reports of successful treatment of progressive multifocal leukoencephalopathy, large-scale prospective trials have been few, and with mixed results.
As more is discovered about the biology of JC virus infection and advances are made in targeted parenchymal delivery of therapeutic agents, there is hope for the development of an effective therapy for progressive multifocal leukoencephalopathy.CIDOFOVIR
- Adjuvant low-dose cidofovir therapy for BK polyomavirus interstitial nephritis in renal transplant recipients.
Kuypers DR, Vandooren AK, Lerut E, Evenepoel P, Claes K, Snoeck R, Naesens L, Vanrenterghem Y.
Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Belgium.
Am J Transplant. 2005 Aug;5(8):1997-2004. Abstract quote
BK virus interstitial nephritis (BKVIN) is a serious complication after kidney grafting, necessitating drastic reduction of immunosuppressive therapy in order to enable viral clearance. Despite these measures, progressive graft dysfunction and graft loss occur in the majority of recipients.
We diagnosed BKVIN in 21 recipients grafted between 1998 and 2004. Eight of 21 patients were treated with weekly, adjuvant low-dose cidofovir in addition to reduction of immunosuppressive therapy. BKVIN caused irreversible deterioration of graft function in all patients but renal function stabilized after antiviral treatment (creatinine clearance: 51.8-32 mL/min; p=0.001) and no graft loss occurred in cidofovir-treated recipients during 24.8 (8-41) months follow-up.
Peak serum cidofovir concentrations were dose-dependent and attained approximately one-tenth of thein vitroEC50 for cidofovir against BK-virus, while pre-treatment with probenecid did not alter peak serum concentrations nor affected the incidence of nephrotoxicity. In fact, no cidofovir-related renal toxicity occurred; few patients had minor transient side effects (nausea, skin rash).
In contrast, 9 of 13 patient who received no adjuvant cidofovir therapy lost their graft after median 8 (4-40) months. In this selected group of recipients with BKVIN, the use of adjuvant low-dose cidofovir therapy resulted in prolonged graft survival and stabilized graft function.Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.
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