ANZ J. Surg.

2005; 75: 213–217

ORIGINAL ARTICLE
ORIGINAL ARTICLE

IS SURVEILLANCE NECESSARY FOR INVERTED PAPILLOMA IN THE

URINARY BLADDER AND URETHRA?

CHI WAI CHENG,* LUNG WAI CHAN,* CHI KWOK CHAN,* CHI FAI NG,* HO YUEN CHEUNG,*
SHU YIN EDDIE CHAN,* WAI SANG WONG* AND KA FAI TO†
Departments of *Surgery and †Anatomical and Cellular Pathology, Chinese University of Hong Kong,
Prince of Wales Hospital, Hong Kong

Background: A case series of inverted papilloma of the urinary bladder and urethra is presented, together with a review of the
literature with respect to multiplicity, recurrence rate and association with transitional cell carcinoma, and a discussion on surveil-
lance of the lesion.
Methods: Cases of inverted papilloma of the lower urinary tract in a single centre were reviewed. Patient and tumour character-
istics, recurrence and associated transitional cell carcinoma are reported.
Results: Twenty patients were included (18 male, two female). The mean age was 60.8 years (range 35–78 years). All had solitary
tumours ranging from 3 mm to 30 mm in size. Median cystoscopic follow up was 30 months (range 2–140 months). There was no
recurrence. One patient was associated with subsequent transitional cell carcinoma 44 and 76 months later. Together with the present
20 cases, review of the English literature with respect to inverted papilloma of the lower urinary tract identified a total of 322 cases
reported, with a recurrence rate of 3.85%. Moreover, 1.55%, 5.90% and 1.54% were associated with previous, simultaneous and
subsequent transitional cell carcinoma, respectively.
Conclusions: Recurrence is not uncommon and risk of subsequent transitional cell carcinoma is not rare, such that non-invasive
surveillance with flexible cystoscopy is recommended for inverted papilloma of the lower urinary tract.

Key words: bladder, inverted, papilloma, review, urethra.

Abbreviation: TCC, transitional cell carcinoma.

INTRODUCTION
A thorough review of the English literature identified 302 cases
of inverted papilloma of the lower urinary tract.1–62 The lesion
was first described in four cases as adenomatoid polyp in the
German literature by the Viennese urologist Paschkis in 1927.63
Potts and Hirst termed it ‘inverted papilloma’ in 1963.46 Other
names such as adeno-urothelioma6 and Brunnian adenoma52 were
also used to describe the same lesion. Moreover, in 1983 Kunze
et al. divided inverted papillomas into trabecular and glandular
types based on histological grounds.5
Most urologists and pathologists will recognize inverted papil-
loma as benign. However, the multiplicity, tendency of recur-
rence and association with transitional cell carcinoma (TCC)
reported in the literature raised suspicion or doubt concerning its
benign nature.
At Prince of Wales Hospital, Hong Kong, regular cystoscopic
surveillance was performed for inverted papilloma of the lower
urinary tract in view of the possible recurrence and association
with TCC. The aim of the present review was to combine the
C. W. Cheng FRCS (Edin), FRCSEd (Urol); L. W. Chan MBChB, FRCS
(Edin); C. K. Chan FRCS (Edin), FRCSEd (Urol); C. F. Ng FRCS (Edin),
FRCSEd (Urol); H. Y. Cheung MBChB, FRCS (Edin); S. Y. E. Chan
MBChB, MRCS (Edin); W. S. Wong MB BS, FRCS (Edin); K. F. To
MBChB, FRCPA.
Correspondence: Dr C. W. Cheng, Department of Surgery, Chinese Univer-
sity of Hong Kong, Prince of Wales Hospital, Hong Kong.
Email: drmcheng@hotmail.com
Accepted for publication 11 November 2004.
outcomes of the present cases with data from the literature, and to
discuss whether long-term surveillance is warranted for inverted
papilloma of the urinary bladder and urethra.
METHODS
All cases of inverted papilloma of the lower urinary tract diag-
nosed at Prince of Wales Hospital, Hong Kong were reviewed.
Attention was paid to patient characteristics (sex, age and symp-
toms), tumour characteristics (multiplicity, size, shape, site, intra-
operative diagnosis, histological type and urine cytology), and
any recurrence or associated TCC.
All the cases were diagnosed by transurethral biopsy or resec-
tion. Most of the patients had upper tract imaging to exclude
synchronous lesion. Bladder surveillance was done by cyst-
oscopy approximately 6 monthly. All histological slides were
reviewed by uro-pathologists.
Review of the English literature was performed for inverted
papilloma of the urinary bladder and urethra. The total number of
cases and the number with multiplicity, recurrence and associated
TCC were recorded.
RESULTS
From 1987 to 2002, there were 20 cases of inverted papilloma
of the lower urinary tract diagnosed at Prince of Wales Hospital.
No inverted papilloma of the upper urinary tract was ever
found. The male : female ratio was 9:1. The age ranged between
35 and 78 years, with a mean of 60.8 years. Common symptoms
included haematuria, irritative lower urinary tract symptoms and
214 CHENG ET AL.

obstructive lower urinary tract symptoms. Two patients had acute investigated by imaging, 15 by intravenous urogram, two by
urinary retention. One female patient presented with a urethral ultrasonogram and one by bilateral ascending ureterogram, and
mass. Another patient presented with an incidental finding of all were negative for upper tract tumours.
bladder mass on imaging. Table 1 summarizes the symptoms. All The time of follow up ranged from 2 to 140 months, with a
patients had no previous history of TCC. median of 30 months. No recurrence of inverted papilloma was
All were solitary tumours ranging from 3 mm to 30 mm in
size. Nine cases were described as papillary under cystoscopy,
eight cases as pedunculated and three cases as both. All tumours
were situated between the interureteric bar and the bladder neck,
except one tumour that was located on the posterior bladder wall
and another in the prostatic urethra. The intraoperative impres-
sion was a malignant lesion in 15 cases and benign in the remain-
ing five cases. The histological diagnosis was inverted papilloma
in all cases, without any synchronous TCC. Fifteen cases
belonged to the trabeculated type and five cases were the glandu-
lar type. Figures 1,2 show the typical cystoscopic and histological
appearances of inverted papillomas. Eight patients had urine
cytology showing atypical cells while the others were negative
for atypia or malignancy. The one with subsequent TCC had
urine cytology showing atypia before the diagnosis of inverted
papilloma and TCC. Table 2 summarizes these tumour charac-
teristics. Eighteen of the 20 patients had their upper tract

Table 1. Symptoms of patients with inverted papilloma of the

urinary bladder and urethra in the present study
Symptoms Patients
n (%)
Fig. 2. Histological appearance of an inverted papilloma, showing
Hematuria 14 (70) interconnected trabeculated pattern with overall inverted growth (HE,
Irritative LUTS 9 (45) original magnification ×40).
Obstructive LUTS 7 (35)
AROU 2 (10)
Urethral mass 1 (5)
Incidental finding 1 (5) Table 2. Tumour characteristics of inverted papillomas of the
urinary bladder and urethra in the present study
LUTS, lower urinary tract symptoms; AROU, acute retention of urine.
Tumour characteristics Patients
n (%)

No. tumours
Single 20 (100)
Multiple 0 (0)
Size (mm)
3–10 9 (45)
11–20 6 (30)
21–30 4 (20)
Unspecified 1 (5)
Macroscopic feature
Papillary 9 (45)
Pedunculated 8 (40)
Both 3 (15)
Site
Posterior bladder wall 1 (5)
Trigone 18 (90)
Prostatic urethra 1 (5)
Intraoperative diagnosis
Malignant 15 (75)
Benign 5 (25)
Microscopic feature
Trabeculated type 15 (75)
Glandular type 5 (25)
Urine cytology
Positive 8 (40)
Negative 12 (60)
Fig. 1. Cystoscopic appearance of an inverted papilloma.
SURVEILLANCE OF INVERTED PAPILLOMA
ever found. One patient was associated with subsequent TCC.
This patient was a 60-year-old man who presented with gross
haematuria. Cystoscopy showed a 1-cm papillary lesion at the
trigone. Histological examination revealed a trabeculated type
of inverted papilloma. Subsequently, there was an asymptomatic
1-cm TaG1 TCC and two asymptomatic 0.3–0.5-cm TaG1 TCC
44 months and 76 months after the initial diagnosis of inverted
papilloma, respectively.
DISCUSSION
Inverted papillomas are generally recognized as benign. How-
ever, the multiplicity, tendency of recurrence and association with
TCC reported in the literature raises suspicion or doubt concern-
ing its benign nature. Surveillance is hence generally recom-
mended. However, after reviewing 277 cases from the upper and
lower urinary tract in the literature up to 1997, Witjes et al.
concluded that inverted papilloma did not seem to be a risk factor
for TCC of the urinary tract as a whole, and frequent and long-
term follow up was not advocated if there was no doubt with
regard to the diagnosis.3
The association of inverted papilloma and TCC was reported
to be stronger in the upper urinary tract,64 and the frequency of
synchronous malignancy in ureteric inverted papilloma was
reported to be threefold that found in similar lesions in the
bladder (18% vs 6%).65 The purpose of the present review is to
examine, with the available data in the literature, whether
inverted papilloma of the lower urinary tract is even more neg-
ligible as a risk factor for TCC, and to discuss whether surveil-
lance might not be necessary.
We hence extended the literature review up to the year 2002
and focused on the bladder and the urethra. Attention was paid
particularly to the number of cases, multiplicity, recurrence and
association with TCC. The surveillance of inverted papilloma of
the lower urinary tract will also be discussed.
Number of cases
Review of the English literature with respect to inverted papil-
loma known to be arising from the lower urinary tract produced
302 cases,1–62 282 cases in the bladder, 17 cases in the urethra and
three cases in both.3 Cheville et al. also described 51 cases of
inverted papilloma with the sites unspecified, which were hence
not included in this review, although recurrence and associated
TCC were also reported in that review.66 Witjes et al. analysed 37
cases of inverted papilloma of the bladder and urethra, which
were devoid of any previous or synchronous TCC.3 Another 16
cases in the same review were associated with previous or syn-
chronous TCC, but had the locations of the inverted papillomas
unspecified, and were again excluded from this review. We
reported 19 more cases in the bladder and one more case in the
urethra, making up a total of 322 cases of inverted papilloma of
the lower urinary tract reported in the English-language literature.
Inverted papilloma should be distinguished from TCC with
inverted growth pattern; the latter, either reported as such44,60 or
reported as inverted papilloma,67 was also excluded from this
review.
Multiplicity
Of these 322 cases of inverted papilloma of the lower urinary
tract, 14 cases (4.35%) had multiplicity.3,9–11,15,21,28,31,36,45 The
215
present series did not include a single case of multiple inverted
papillmas. The rate of multiplicity previously quoted in the litera-
ture was 5.4–8.1%.3
Recurrence
Out of the 260 patients mentioned to have follow up,1–38 inclusive
of the present 20 patients, at least 10 patients (3.85%) were
reported to have recurrence.3–11 It was ‘at least’ because in one
patient the exact site of the original inverted papilloma was not
mentioned.5 The median time to recurrence was 22 months (range
7–120 months). Again we did not find any recurrence during
follow up in the present series. Rate of recurrence previously
quoted in the literature was from < 1% to 5.4%.3,22 The low rate
of < 1% was quoted from an earlier report in 1978.22
Previous transitional cell carcinoma
Out of the total 322 patients, five patients (1.55%) had previous
history of TCC.1,2,7,36 As stated here, Witjes et al. mentioned 16
patients associated with previous or synchronous TCC, but the
locations of the inverted papillomas were unspecified.3
Synchronous transitional cell carcinoma
At least 19 of the 322 patients (5.90%) had synchronous
TCC.1,2,5,6,8,11,16,21,28,34,36,37,39–44 It is ‘at least’ because in one patient
the exact site of the inverted papilloma was not mentioned.5 We
did not have any case associated with previous or synchronous
TCC in the present series. The rate of synchronous TCC previ-
ously quoted in the literature was 11.1–33%.3,68
Subsequent transitional cell carcinoma
With those 260 patients mentioned to have follow up, seven
patients (2.69%) were reported to have subsequent TCC,1–4
including a patient from the present series. The median time to
subsequent TCC was 44 months (range 6–96 months). The site of
the subsequent TCC was the bladder in six cases and the upper
urinary tract in one case.4 Three patients were known to be
associated with previous or synchronous TCC, which might
contribute to the occurrence of the subsequent TCC.1,2 If these
three patients were excluded, the rate of subsequent TCC was
1.54%. Witjes et al. reported that the rate of subsequent TCC
was 2.7% in their series and was 5% in the literature, although
80% of the latter had previous history of TCC.3
Surveillance of inverted papilloma
Whether surveillance is needed mainly depends on the rate of
recurrence and subsequent TCC, which as mentioned here, are
3.85% and 1.54%, respectively, the latter figure representing
those patients without any previous or synchronous TCC.
Although these figures are lower than those previously reported
in the literature, and particularly lower than those reported by
Witjes et al. with respect to inverted papilloma of the whole
urinary tract,3 they still imply that one out of 26 cases will recur
and the rate of subsequent TCC is well above the incidence of
TCC in the general population. With the advent of flexible cyst-
oscopy, the procedure can be done in a few minutes under local
anaesthesia in a day-case setting. Urine cytology is not helpful for
surveillance for recurrence because inverted papilloma is usually
216
covered by normal urothelium, although it can be used for screen-
ing for subsequent TCC. Flexible cystoscopy remains the most
effective method for surveillance of inverted papilloma of the
lower urinary tract.
Half of the recurrences occurred at or before 22 months and
the longest time reported for its occurrence was as long as
120 months. The corresponding figures for subsequent TCC to
occur were 44 and 96 months, respectively. A surveillance proto-
col as frequent as the one suggested for TCC is not necessary. We
recommend a 6-monthly flexible cystoscopy for 4 years and then
yearly afterwards.
Routine surveillance of the upper urinary tract following
inverted papilloma of the lower tract is deemed not necessary.
Only one case of subsequent TCC in the upper tract has ever been
reported.4 A regular intravenous urogram programme is too inva-
sive for this rare occurrence.
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