Villous Adenoma Arising in the Urethra of a Female with Bladder Augmentation History: A Case Report and Review of the Literature

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.


INTRODUCTION
Villous adenomas (VAs) of the urinary tract are rare with only two case series and around 20 scattered case reports in the literature (1)(2)(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)(7)(8)(9)(10)(11).
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 sequence (3).
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.
We present the first VA case arising in the urethra of a female patient with intestinal bladder augmentation.

CASE REPORT
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

Villous Adenoma Arising in the Urethra of a Female with Bladder Augmentation History:
A Case Report and Review of the Literature hydronephrosis.The patient stated that she was more comfortable after the operation and could urinate.

DISCUSSION
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).
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).
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   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

Table I :
Summary of our case and literature review of cases of villous adenoma arising in the female urethra.
* The patient died 2 years later of a cerebral infarction.

Table II :
Villous adenoma arising from the urinary mucosa in the patients with a history of augmentation.