International Journal of Urology (2006) 13, 439–441
Blackwell Publishing AsiaMelbourne, AustraliaIJUInternational Journal of Urology0919-81722006 Blackwell Publishing Asia Pty LtdApril 2006134439441Case Report Polyoma virus infection of the bladder
Correspondence: David B. Weinreb, Mount Sinai School of
Medicine, 50 East 98th Street, Room 11C1, New York, NY
10029, USA. Email: firstname.lastname@example.org
Received 26 August 2005; accepted 8 November 2005.
Renal transplant patient with polyoma virus bladder infection and
subsequent polyoma virus nephropathy
DAVID B WEINREB,1 GARRETT T DESMAN,1 DAVID E BURSTEIN,1 STEVEN H DIKMAN1 AND
EDWARD M JOHNSON1,2
1Department of Pathology, and 2Department of Molecular, Cell and Developmental Biology and Oncological
Sciences, Mount Sinai School of Medicine, New York, USA
Abstract Polyoma virus nephropathy (PVN) is a significant cause of renal allograft dysfunction in transplant patients. A 58-year-
old male received a cadaveric renal transplant and 12 weeks later presented with fever, diarrhea, and dysuria. He was diagnosed
with a polyoma virus infection of the bladder by a transurethral bladder biopsy. One year post-transplant, he presented with renal
allograft dysfunction and was diagnosed by biopsy with PVN of the non-native kidney. The diagnosis of a polyoma virus infection
was confirmed by immunoreactivity to the polyoma T-antigen. We suggest that polyoma virus infection of the bladder be included
in the differential diagnosis of urinary dysfunction in post-transplant patients, as such infections might be an under-recognized
comorbidity in individuals with PVN.
Key words bladder, polyoma virus, renal transplant.
Polyoma virus nephropathy (PVN) is a widely recognized
cause of renal allograft dysfunction in transplant patients,
occurring with an approximate incidence of 5–8% in this
population.1 Additionally, polyoma virus infection is linked
to hemorrhagic cystitis and ureteral stenosis in immuno-
compromised individuals, predominantly bone marrow
transplant patients.1 Although there is an anecdotal report
of polyoma virus infection of the bladder in a renal trans-
plant patient with PVN, the extrarenal associations of PVN
have not been well-documented in the literature.2 A recent
case report describes a renal transplant patient with PVN
who subsequently developed metastatic urothelial carci-
noma of the bladder; polyoma virus infection was docu-
mented in nearly every cell of the primary tumor and its
metastases to the abdominal wall.3 Here, we present a case
of polyoma virus infection of non-cancerous bladder
mucosa preceding any clinical or histopathological evi-
dence of PVN.
A 58-year-old man with insulin-dependent diabetes melli-
tus and subsequent diabetic nephropathy underwent right
cadaveric renal transplantation at The Mount Sinai Hospi-
tal, New York. His postsurgical course was uneventful and
his antirejection therapy consisted of 1000 mg of
mycophenolate mofetil, b.i.d. At 4 and 6 weeks post-
transplantation, renal core biopsies (hematoxylin and
eosin) revealed minimal tubulitis and broad areas of orga-
nized infarction. Neither biopsy showed signs of interstitial
inflammation or viral inclusions. Immunohistochemical
reactivity to the SV40 T-antigen (monoclonal antibody;
Santa Cruz Biotechnology, Santa Cruz, CA, USA) was
negative in both specimens.
At 12 weeks post-transplantation, the patient developed
fever, dysuria, and diarrhea. Urine cytology analysis
revealed atypical epithelial cells with basophilic marginal-
ized chromatin, enlarged hyperchromatic nuclei, and
intranuclear inclusions of polyoma virus infection. A
transurethral urinary bladder biopsy revealed mucosal
ulceration with acute and chronic inflammation. The nuclei
of the mucosal cells adjacent to the ulcer exhibited aniso-
nucleosis and hyperchromasia with clumped chromatin
and prominent intranuclear inclusions characteristic of
polyoma virus infection (Fig. 1a). Strong nuclear immu-
noreactivity of the urothelial cells to the SV40 T-antigen
confirmed infection with polyoma virus (Fig. 1b).
As the transurethral urinary bladder biopsies revealed
no evidence of malignancy, the patient received no specific
therapy at this time. His immunosuppressive regimen was
At 32-weeks post-transplantation, a third renal core
biopsy revealed no evidence of tubulitis, acute rejection,
or viral inclusions. The immunoreactivity of the kidney
tubular cells was again negative to the SV40 T-antigen.
However, a fourth renal biopsy of the non-native kidney,
obtained 1 year post-transplant, showed extensive tubular
damage with eosinophilic intratubular debris, mitoses, cel-
440 DB Weinreb et al.
lular enlargement, and pleomorphism (Fig. 2a). In a mul-
tifocal and contiguous distribution, the cells lining the
collecting ducts exhibited multiple viral cytopathic intra-
nuclear inclusions. The tubular nuclei exhibited a strong
nuclear immunoreactivity to the SV40 T-antigen, consis-
tent with PVN (Fig. 2b).
Although allograft dysfunction due to polyoma virus infec-
tion of the non-native kidney is a widely reported sequela
of renal transplantation, extrarenal manifestations of PVN
have not been extensively described in the literature.
As the polyoma virus is now known to infect the blad-
der, ureter, and kidney, the initial site of infection might be
of clinical significance. Most of the infected tubular cells
lined the large collecting ducts, with relative sparing of the
more proximal segments of the nephron. This observation
of involvement of the large collecting ducts is consistent
with that of a previously published study.4 In addition, the
chronological sequence of events might also be significant
as the diagnosis of polyoma virus infection of the bladder
preceded the diagnosis of PVN by 9 months in this patient.
In summary, we suggest that polyoma virus infection of the
bladder might be under-reported in the post-transplant
population, and that the initial site of infection might be
the bladder urothelium, with the infection ascending in
the urinary tract. Therefore, any clinician with a post-
transplant patient presenting with hematuria or dysuria
should have polyoma virus infection of the bladder
included in the differential diagnosis. The early identifica-
tion of polyoma virus infection of the bladder might alert
clinicians to PVN or the subsequent development thereof.
This study was funded by a 2005 American Medical Asso-
ciation Foundation Seed Grant to Mr Weinreb.
iting anisonucleosis, hyperchromasia, and prominent intranu-
clear inclusions of polyoma virus infection. (b) Infection of
bladder urothelial cells by polyoma virus is confirmed by
strong nuclear immunoreactivity to the SV40 T-antigen (mon-
oclonal antibody; Santa Cruz Biotechnology, Santa Cruz, CA,
(a) Bladder mucosa (hematoxylin and eosin) exhib-
cells lining the collecting ducts that contain polyoma viral
intranuclear inclusions. (b) Infection of cells lining the col-
lecting ducts is confirmed by nuclear immunoreactivity to the
(a) Renal parenchyma (hematoxylin and eosin) with
Polyoma virus infection of the bladder441
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study of polyomavirus type BK replication and nephropathy
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maviruses in routine histologic tissue sections of animals
and man. Am. J. Clin. Pathol. 1980; 73: 795–7.
3 Geetha D, Tong BC, Racusen L, Markowitz J, Westra WH.
Bladder carcinoma in a transplant recipient: evidence to
implicate the BK human polyomavirus as a causal trans-
forming agent. Transplantation 2002; 73: 1933–6.
Nichkeleit V, Hirsch HH, Binet IF et al. Polyomavirus
infection of renal allograft recipients: from latent infection
to manifest disease. J. Am. Soc. Nephrol. 1999; 10: 1080–9.