Villous Adenoma Arising in the Urethra of a Female with Bladder Augmentation History: A Case Report and Review of the Literature
Hale DEMIR1 , Selçuk CIN2, Sinharib CITGEZ3, Nesrin UYGUN4
1Department of Pathology, Amasya University, School of Medicine, AMASYA, TURKEY
2Bagcilar Training and Research Hospital, ISTANBUL, TURKEY
3Department of Urology, Istanbul University-Cerrahpasa, Cerrahpasa School of Medicine, ISTANBUL, TURKEY
4Department of Pathology, Istanbul University-Cerrahpasa, Cerrahpasa School of Medicine, ISTANBUL, TURKEY
Keywords: Villous adenoma, Urethra, Urinary tract, Bladder augmentation
Villous adenomas (VAs) in the female urethra are rare with only seven cases in the English literature to our knowledge. In patients with bladder
augmentation cystoplasty, the neoplasia development risk increases and most of these develop in the neobladder or anastomosis line. Only two
cases of VA developing from the native bladder mucosa have been reported. Physical examination of a 76-year-old female who had a history of
augmentation cystoplasty revealed a caruncula-like structure protruding from the urethral meatus. The urinary USG showed that the lesion had
no relation with the bladder. The lesion was excised. Microscopically, it consisted of villous structures covered with pseudostratified intestinal
type epithelium. Low-grade dysplasia was present in the epithelium but high-grade dysplasia or in-situ/invasive carcinoma was not observed.
Immunohistochemical study showed positivity for CK7, CK20, EMA, CEA and CDX2. The case was reported as VA of the urethra. We presented
the first VA case arising in the urethra of a female patient with intestinal bladder augmentation. Excision is curative for pure VAs. Transformation
to carcinoma or recurrence has not been reported. However, in one third of the cases, a malignant tumor may accompany the lesion. Therefore,
all excision material should be examined carefully. Routine endoscopic follow-up should be performed in cases with bladder augmentation.
Villous adenomas (VAs) of the urinary tract are rare
with only two case series and around 20 scattered
case reports in the literature (1-3). Histologically and
immunohistochemically, these tumors are similar to VAs of
the gastrointestinal system (1, 3). They are frequently seen
in elderly patients with a predilection for the urachus, dome
and trigone of the bladder (1, 4). Male predominance has
been reported (1, 2, 5). VAs of the female urethra are very
rare with only seven cases in the English literature to our
knowledge (Table I
) (1, 6-11).
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|Table I: Summary of our case and literature review of cases of villous adenoma arising in the female urethra.
In the etiology, it has been considered that urinary tract
VAs might develop from the cloacal remnants from which
the distal colorectum, bladder and urethra originate during
embryogenesis. On the other hand, they may also be a
product of the chronic irritation-metaplasia-dysplasiacarcinoma
In patients with bladder augmentation cystoplasty, it is
reported that the risk of carcinoma development increases
(4). Most of these carcinomas develop in the neobladder or
anastomosis line. Only 2 cases of VA that developed from
the native bladder mucosa have been reported (Table II) (4, 12). It is thought that the development of VA in patients
with bladder augmentation supports the second theory.
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|Table II: Villous adenoma arising from the urinary mucosa in the patients with a history of augmentation.
We present the first VA case arising in the urethra of a
female patient with intestinal bladder augmentation.
A 76-year-old female patient was hospitalized because
of high urea and creatinine levels. She had a history of
intestinal augmentation cystoplasty due to small capacity
hypersensitive bladder 30 years ago. The ileal segment
was augmented to the bladder dome. The bladder trigone
and urethra were not interfered with. Clean intermittent
catheterization (CIC) was recommended to the patient
after the first augmentation, but she did not do it regularly.
She was diagnosed as postrenal acute renal failure. A
catheter was inserted and the urea-creatinine levels began
to decrease. She had bilateral hydroureteronephrosis. After
4 months, physical examination revealed a carunculalike
structure protruding from the urethral meatus. The
urinary USG revealed that there was no relation with the
bladder. The urethral lesion was excised, and then the
bilateral hydroureteronephrosis regressed. CIC was not recommended for postoperative follow-up, as the patient
had no residual urine.
The macroscopic examination of the lesion revealed a
cream-white colored, fragile and polypoid mass, 4.5x2x1.5
cm in size. Its base was 1.5x1 cm in size, hemorrhagic and
brown colored. On the cut sections, it was composed of thin
papillary structures adhering to a fibrous core.
On microscopic examination, the tumor consisted of villous
structures covered with pseudostratified intestinal type
epithelium. Low-grade dysplasia and occasional squamous
metaplasia areas were present in the epithelium (Figure
1A-D). All material was investigated and high-grade
dysplasia or in-situ / invasive carcinoma was not observed.
Immunohistochemical study showed positivity for CK7,
CK20, EMA, CEA and CDX2 (Figure 2A-E).
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|Figure 1: Microscopic view of the urethral villous adenoma. A) A slide photograph shows thin papillary structures adhering to a fibrous
core (H&E; x4). B) Villous structures covered with pseudostratified intestinal type epithelium (H&E; x100). C) Squamous metaplasia
areas (H&E; x40). D) Low-grade dysplasia of adenomatous epithelium (H&E; x400).
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|Figure 2: Immunohistochemical panel.
Positivity for A) CK7 (IHC; x200),
B) CK20 (IHC; x200), C) EMA (IHC; x200),
D) CEA (IHC; x200), E) CDX2 (IHC; x200).
The case was reported as VA of the urethra. The adenomatous
epithelium was adjacent to the surgical margin. However,
there was no surgical recurrence in the 28-month followup.
During follow-up, there was no renal dysfunction or hydronephrosis. The patient stated that she was more
comfortable after the operation and could urinate.
Urinary tract VAs are benign glandular lesions which are
histologically and immunohistochemically similar to VAs
of the gastrointestinal tract (1, 3, 13). They are mostly
seen in patients aged 33 to 79 years with a mean age of
57 years (14). Male predominance has been reported (1,
2, 5). Patients usually present with hematuria, irritation
symptoms and rarely mucusuria (1, 15). Back or flank pain,
fever, abdominal discomfort and weight loss can be seen in
patients with pelvic VAs (16). There is no specific diagnostic
finding on the USG, CT, MRI or cystoscopy (17, 18).
In the past, various terms have been used to describe these
tumors as villous adenoma, tubulovillous adenoma, villous
metaplasia of the intestinal type with dysplasia, and enteric
adenoma. However, using the villous tumor or villous polyp
terms must be avoided because they can lead to confusion
with prostatic-type polyps (19).
Urinary tract VAs mostly arise in the urachus, dome, or
trigone of the bladder (1, 4). Cases located in the urethra,
renal pelvis, and ureter have also been reported (6, 20-22).
Dong et al. have reported that they found only 8 cases of
pelvic VA in the English literature and presented 2 additional
cases (22). Qin et al. also reported that they found only 11
cases with urethral VA between 1981 and 2003. Six of these,
and the case which they presented, were female (6). Our
presented case is therefore the eighth VA case arising in the
female urethra, as far as we are aware.
Two possibilities have been reported in the etiology of
VAs. According to the first theory, the distal colorectum,
bladder and urethra originate from the cloacal tissue
during embryogenesis, and these tumors may develop from
the cloacal remnants. This also explains the morphological
and cytogenetic similarity of the urinary tract lesions and
their counterparts in the gastrointestinal system. According
to the second theory, VAs are a product of the irritationmetaplasia-
dysplasia-carcinoma sequence (3). Intestinal
metaplasia of the urinary tract is often associated with
chronic inflammation, in particular infection, stones and
chemical injury (16). The presence of neutral mucins,
acidic sulfomucins, and sialomucins in both cystitis
glandularis and VA, and the similar genetic characteristics
in the dysplastic regions of the metaplastic mucosa and VA
support this theory (3, 23).
Augmentation cystoplasty using the colon, ileum or
stomach is an accepted reconstructive option for patients with intractable incontinence and poor bladder compliance
due to neurogenic and non-neurogenic disorders (6).
However, it has been reported that the risk of developing
bladder carcinoma increases 7-8 times with ileum and colon
segments, and 14-15 times with gastric segments (4, 12).
The most common histologic types are adenocarcinoma
and urothelial carcinoma (12). The incidence of VAs after
cystoplasty is very low and most of them develop in the
neobladder or anastomosis line (24). To our knowledge,
only 2 cases of VAs originating from the native bladder
mucosa have been reported (4, 12). It is thought that the
development of bladder VA in patients with a history of
augmentation supports the irritation-metaplasia-dysplasiacarcinoma
sequence theory (4, 12).
Our presented case had a history of intestinal augmentation
cystoplasty 30 years ago. However, VA had developed in the
urethral mucosa and protruded from the urethral meatus.
USG revealed that there was no relation with the bladder.
Our case is the first VA in a female urethra with a bladder
augmentation history. This case could also be another
example supporting the second theory.
Histologically, VAs consist of long villoglandular structures
with a central fibrovascular core and these structures are
lined by pseudostratified columnar epithelium (1, 13). The
epithelial cells display nuclear stratification, crowding,
hyperchromasia and occasional prominent nucleoli.
Variable mitotic figures are seen in situ and in the invasive
component (1). There is frequently a background of chronic cystitis and association with intestinal/squamous
metaplasia, cystitis cystica and cystitis glandularis (2).
Two-thirds of the cases may have simultaneous malignant
tumors such as urothelial carcinoma, and in situ or
infiltrative adenocarcinoma (2). Therefore, all of the
excision material should be examined carefully (2). In our
case, we investigated all excision material and there was no
high-grade dysplasia or in situ/invasive carcinoma focus.
Immunohistochemically, CK20 positivity was reported at a
rate of 100%, while CEA and EMA can be positive. CDX2
positivity is also reported (25). CK7 positivity is observed in
approximately half of the cases (1, 3, 26). Our case showed
positivity for all these markers.
Distinction from tumor metastasis of adjacent organs such
as colon, the female genital system, and the prostate is
important. For females with genital system adenocarcinoma,
Ca125, ER, PR can be helpful as diagnostic markers (6).
Morphological differential diagnosis between metastatic
adenocarcinoma of the gastrointestinal system and urinary
tract VAs is impossible. CK7 positivity can support VAs of
the urinary tract (3, 6). In the male urethra, morphological
features of prostatic ductal adenocarcinoma can easily
mimic VA (27). Expression of prostatic lineage markers
such as PSA and PSMA could be helpful to differentiate the
two entities (13).
Cytologically, it is difficult to distinguish VAs from other
glandular lesions. However, VAs must be considered in
the differential diagnosis when many glandular cells or
mucinous cells without atypia are recognized in the urine
Excision is curative for pure VAs. Carcinoma transformation
and recurrence were not reported in pure cases during a
mean follow up of 9.9 years (1). However, more aggressive
treatment may be indicated for the VAs coexisting with a
malignant tumor as adenocarcinoma to prevent recurrence
and metastasis (1, 6). In VAs of yjr calyx, the adenoma
may result in atypical hyperplasia and cancerization due
to continuous inflammation stimulation, and surgical
resection is therefore recommended (22). In the ureters,
tumor growth with mucus retention may be the main cause
of ureteral obstruction, and total excision of the tumor
prevents early obstruction (29). In patients with bladder
augmentation, long-term active surveillance is necessary in
terms of neoplasia development (12, 24). In our presented
case, the urethral tumor was excised. Although the
surgical margin was microscopically positive, there was no
recurrence in 28-month follow-up.
In conclusion, our case is the first VA arising in the female
urethra with a history of bladder augmentation. The present
case report supports the irritation-metaplasia-dysplasiacarcinoma
sequence theory. Excision is curative for pure
VAs. Transformation to carcinoma or recurrence has not
been reported. However, there may be an accompanying
malignant tumor such as adenocarcinoma, urothelial
carcinoma etc. in one-third of the cases. Therefore, all
excision material should be examined carefully. Routine
endoscopic follow-up should be performed in cases with
bladder augmentation. Further studies are needed to
establish the nature of urinary tract VAs.
CONFLICT of INTEREST
The authors declare no conflict of interest.
Concept: HD, Design: HD, NU, Data collection or
processing: HD, SC, SC, Analysis or Interpretation: HD,
NU, Literature search: HD, Writing: HD, Approval: NU.
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