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Squamous cell carcinoma in situ in a female urethral diverticulum.

Abstract: There have been less than 100 reported cases of carcinoma in a female urethral diverticulum, with only 10 of these cases being squamous cell carcinoma (SCC). The course of this disease is frequently aggressive, despite multimodality treatment, and most patients die within 2 to 3 years. To our knowledge, carcinoma in situ of the female urethral diverticulum has not been reported to date, and thus, optimal treatment is not well defined. A 41-year-old woman was found to have SCC in situ without evidence of invasive carcinoma after diverticulectomy. She elected close observation and remains disease-free at 2 years. A brief overview is given of the presentation, management, and outcomes of urethral diverticular carcinoma.

Key Words: urethral diverticulum, squamous cell carcinoma, carcinoma in situ

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Urethral carcinoma in a woman is rare and carcinoma in a urethral diverticulum is even more uncommon. To date, less than 60 cases have been reported, with adenocarcinoma outnumbering both transitional cell carcinoma (TCC) and squamous cell carcinoma (SCC) combined. (1) While SCC typically follows an aggressive course, to our knowledge, SCC in situ has yet to be described and, thus, the optimum treatment is unclear. The case of a woman with urethral SCC in situ without evidence of invasive carcinoma after diverticulectomy is described.

Case Report

A 41-year-old woman presented with a two-year history of dysuria, recurrent urinary tract infections, urinary incontinence, and dyspareunia. An anterior vaginal wall mass was discovered on examination. A voiding cystoure-throgram (VCUG) confirmed a large urethral diverticulum without calculi or filling defects (Fig. 1). Video urodynamics revealed occult stress urinary incontinence with high Valsalva leak-point pressures. Cystourethroscopy revealed a narrow ostium to the diverticulum, which could not be entered. The remainder of the bladder and urethra were free of lesions. The patient underwent a urethral diverticulectomy with complete excision of the diverticulum and an autologous rectus fascia pubovaginal sling. Her immediate recovery was uneventful and a VCUG at two weeks confirmed complete healing of the urethra. Pathologic examination revealed SCC in situ with no evidence of invasive SCC (Fig. 2a, 2b). Options, including radical cystourethrectomy and radiotherapy, were discussed with the patient and she opted for close observation. At two years of follow-up, she is asymptomatic and continent. Her pelvic examination reveals no evidence of active disease and cystourethroscopy is negative.

Discussion

The female urethra is composed of five layers: mucosa, submucosa and three muscle layers. The mucosa is lined primarily with nonkeratinized stratified squamous epithelium which gradually becomes transitional cell epithelium near the bladder. Many small mucous glands open into the urethra and distally, these glands group into Skene glands, which empty through two small ducts near the urethral meatus. While there is no distinct adventitial layer to separate the urethra from the vagina, a functional point of separation exists within the periurethral fascia, or fascia of the urethropelvic ligament. (2) Urethral diverticula are mucosalized outpouchings of the urethra within the confines of the periurethral fascia. Although some may be congenital, most cases are thought to be acquired secondary to rupture of infected periurethral glands into the urethral lumen. (3)

[FIGURE 1 OMITTED]

Urethral carcinoma in women is uncommon, with SCC outnumbering all other pathologic subtypes combined (60% versus 40%). (1) The most significant prognostic factor for local control and survival is the anatomic location and extent of the tumor, with low-stage distal urethral tumors having a better prognosis than high-stage proximal urethral tumors. (4) Cancer in a urethral diverticulum is extremely rare and less than 60 cases are reported worldwide. (5,6) Over 50% of women with diverticular cancer presented with urethral bleeding, the most common symptom. (6) Other frequent symptoms are localized irritation and pain. In one large review, 56% of diverticular cancers were adenocarcinoma, while TCC and SCC comprised 29% and 15%, respectively. (6) The distinct predominance of adenocarcinoma may support the "acquired" nature of most female diverticula and their origin from the periurethral glands. The histologic subtype appears to have a correlation with prognosis as 75% of patients with adenocarcinomas and 56% of those with TCC exhibited no evidence of disease (NED) after aggressive therapy. (6) Conversely, only three of ten patients with SCC in a urethral diverticulum (30%) achieved NED status, and the rest died less than three years after diagnosis, despite radical surgery (cystourethrectomy and urinary diversion) and radiation. (6,7) Diverticulectomy alone is an uncommon therapy for SCC in a urethral diverticulum and has revealed mixed results. (6) Of the two patients who underwent local excision, one died as a result of her disease at two years while another was alive and NED after four years of follow-up. (6)

Urethral carcinoma in situ is a therapeutic dilemma. As the lesion is confined to the mucosa, it appears to be a candidate for complete local resection. On the other hand, it is typically considered a high-grade cancer and frequently warrants aggressive multimodality therapy. As this lesion has not, to date, been described, its optimal treatment and ultimate outcome are also unknown. Our patient elected observation and nonoperative management after definitive diverticulectomy and is NED at a postoperative interval of two years. Close follow-up is ongoing with annual pelvic examinations and cystourethroscopies to continue to monitor for local recurrence.

[FIGURE 2 OMITTED]

Conclusion

Carcinoma in a female urethral diverticulum often follows an aggressive, and frequently fatal, course. The optimum chance for survival typically follows radical surgery and radiotherapy. Carcinoma in situ has yet to be described and its prognosis after diverticulectomy alone is equally unknown. Our patient, whom we believe to be the first reported case, is currently disease free at 2 years, and close surveillance continues.

References

1. Donat SM, Cozzi PJ, Herr HW. Female urethral cancer. In: Walsh PC, Retik AB, Vaughan ED Jr, Wein AJ (eds). Campbell's Urology, 8th ed. Philadelphia, WB Saunders Co, 2003, pp 2996-2998.

2. Brooks JD. Anatomy of the lower urinary tract and male genitalia. In: Walsh PC, Retik AB, Vaughan ED Jr, Wein AJ (eds). Campbell's Urology, 7th ed. Philadelphia, WB Saunders Co, 1998, p 117.

3. Leach GE, Trockman BA. Surgery for fistulas and diverticulum. In: Walsh PC, Retik AB, Vaughan ED Jr, Wein AJ (eds). Campbell's Urology,. 7th ed. Philadelphia, WB Saunders Co, 1998, pp 1146-1147.

4. Dalbagni G, Zhang ZF, Lacombe L, et al. Female urethral carcinoma: an analysis of treatment outcome and a plea for a standardized management strategy. Br J Urol 1998;82:835-841.

5. Gonzalez MO, Harrison ML, Boileau M. Carcinoma in diverticulum of female urethra. Urology 1985;26:328-332.

6. Clayton M, Siami P, Guinan P. Urethral diverticular carcinoma. Cancer 1992;70:665-670.

7. Shalev M, Mistry S, Kernen K, et al. Squamous cell carcinoma in a female urethral diverticulum. Urology 2002;59:773.
The desire to take medicine is perhaps the greatest feature which
distinguishes man from animals.
--Sir William Osler


Diane Young, MD, Seth Bilello, MD, and Alex Gomelsky, MD

From the Departments of Urology and Pathology, Louisiana State University Health Sciences Center, Shreveport, LA.

Reprint requests to Dr. Alex Gomelsky, Department of Urology, LSU Health Sciences Center--Shreveport, 1501 Kings Highway, Shreveport, LA 71130. Email: agomel@lsuhsc.edu

Accepted September 5, 2006.

RELATED ARTICLE: Key Points

* Carcinoma in a female urethral diverticulum is rare and the typical course is aggressive.

* Optimum treatment usually involves radical surgery and adjuvant therapy.

* Prognosis depends on histology, stage, and grade of the cancer.

* Despite its high grade, carcinoma in situ may be completely excised with the diverticulum, and thus, cure may be possible without radical surgery.
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Title Annotation:Case Report
Author:Gomelsky, Alex
Publication:Southern Medical Journal
Article Type:Disease/Disorder overview
Date:May 1, 2007
Words:1245
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