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Benign Female Periurethral Masses
0022-5347 /94/1526-1943$03. 00/0 11:frn JOURN.A..L OF UROLOGY Copyright© 1994 by AMERICAN UROLOGICAL
Vol. 152, 1943-1951, December 1994
Printed in U.S.A.
AssocJATION, INC.
Review Article BENIGN FEMALE PERIURETHRAL MASSES ROGER R. DMOCHOWSKI, K. GANABATHI, PHILIPPE E. ZIMMERN
AND
GARY E. LEACH*
From the Department of Urology, Kaiser Permanente Medical Center, Los Angeles, California KEY WORDS:
urethra, urethral neoplasms, embryology, anatomy
Benign female periurethral lesions encompass a spectrum of entities that have significance in clinical urology. Often unrecognized or incorrectly diagnosed, periurethral masses may be completely asymptomatic or may produce significant symptomatology with increasing size, such as urinary tract obstruction, irritative complaints or hematuria. Failure to identify these lesions correctly usually results from lack of familiarity. The goal of this review is to summarize concisely the embryology and anatomy of the female urethra and anterior vagina. Subsequent discussion will provide a practical approach to diagnostic recognition and appropriate treatments for periurethral lesions. EMBRYOLOGY
Urethra and anterior vaginal wall. The cloaca and internal genital ductal system develop in close apposition. This synopsis will review the internal ductal development initially, and subsequently review the process of cloacal transformation that gives rise to the urethra and anterior vaginal wall. The embryonic internal genital ductal system becomes identifiable at week 5 to 6 of gestation and remains sexually indifferent until week 10 of development. The mullerian or para-mesonephric duct is identifiable by week 6 of gestationo This duct lies in close apposition to the mesonephric duct during descent from the retroperitoneum to the true pelvis. The paired mullerian ducts assume a position lateral to the mesonephric (wolffian) system. With further differentiation, the mii.llerian ducts cross over the mesonephric ducts and fuse in the caudal midline. During week 8 of gestation the medial segments of the mesonephric system initiate fusion at the level of the bladder and form the uterovaginal primordium (mii.llerian tubercle). This process is completed by week 10. Development of the urogenital sinus proceeds parallel to formation of the internal ductal systemo Initially, septation of the primitive doacal membrane begins at 28 days. 1 By 50 days of gestation this process is complete (whether by subdivision due to ingrowth of the urorectal septum and plicae of Rathke or, instead, due to differential growth of various somatic components). As a byproduct of this division, the urogenital sinus becomes recognizable at week 6. Two subdivisions of the urogenital sinus are identified: a pelvic portion and a phallic portion. The pelvic subdivision of the urogenital sinus develops into the urethra and vagina. By week 11 ductular structures arise from the true urethra, which will eventually form Skene's glands. 1 The phallic portion of the urogenital sinus evolves into the vaginal vestibule. 2 The nonfused cranial portions of the mii.llerian ducts will give rise to the fallopian tubes. The fused uterovaginal primordium expands cranially to form the cervix and uterus. This process begins at week 12 and is complete by week 31, at * Requests for reprints: Department of Urology, Kaiser Permanente Medical Center, 4900 Sunset Blvd., Los Angeles, California 90027.
which time the uterus exhibits mural differentiation into myometrium and stroma. Caudal expansion of the uterovaginal primordium results in fusion with the dorsal wall of the urogenital sinus to form the uterovaginal canal (at the mii.llerian tubercle)o The caudal portion of the degenerating mesonephric ducts contributes mesodermal extensions and sinovaginal bulbs, which extend into the urogenital sinus creating the vaginal plate by week 16. This plate progressively canalizes and a vaginal cavity is formed by month 5. Therefore, at the completion of morphogenesis the vagina originates from 2 separate entities. The upper two-thirds of the vagina arises from the fused mii.llerian ducts, while the lower third arises from the urogenital sinus. 3 Gartner's duct. During miillerian development, mesonephric regression continues. Mesonephric remnants, however, may persist in close proximity to the evolving miillerian system. These remnants are found in a linear pattern that recapitulates the original location of the mesonephric system on either side of the internal female genitalia (Gartner's duct). This linear distribution begins caudally in the anterolateral vaginal wall and extends in a cephalad direction lateral to the uterus and fallopian tubes. These remnants are often microscopically present but can become clinically significant should cyst formation occur. Ectopia. During embryogenesis of the internal female genitalia, development of the urinary tract continues. The ureter forms as an evagination from the mesonephric duct at day 28. Delay in this process of evagination or the formation of a second evagination (or bud) results in a more cranial location for this budo As the mesonephric duct is incorporated into the trigone, this "ectopic" bud migrates caudally and inferiorly, and becomes incorporated at an aberrant location. This ectopic location may arise within the urinary tract, from the distal trigone to the urethra, or it may terminate out.side the urinary tract in the remnants of the mesonephric system inclusive of the vagina, cervix, uterus or Gartner's duct. 4 The incidence of ureteral ectopia is 1 in 125 cases and the femaleto-male ratio is 4:1. 5 ANATOMY
Cross sectional photomicrographs of the female urethra reveal an exuberant mucosal lining that covers a thick submucosa containing abundant vascularity (fig. 1). The submucosa contains not only a rich vascular network but also abundant connective tissue supplemented by elastic and smooth muscle fibers, which provide a natural seal effect to the urethral closure. Hormonal deprivation decreases the vascularity of the submucosa with loss of the mucosa! seal effect and also leads to increased fibrous tissue deposition. 6 Circumferential layers of smooth muscle bounded by fibroelastic tissue form the external component of the urethra. These tissues augment the seal effect of the mucosa and submucosa, and are additive to the sphincteric mechanism. Estrogens provide nutritive support to these tissues. 7 When viewed longitudinally, the urethra demonstrates
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}-e C
D
CROSS SECTION MID-URETHRA Fm. 1. Cross section offemale urethra. A, striated skeletal muscle fibers. B, smooth muscle layers, outer circular orientation, inner longitudinal. C, urethral lumen. D, paraurethral ligament. E, vaginal wall with fibromuscular wall and overlying epithelium.
variation in epithelial and muscular components. The distal urethra is lined by nonkeratinized stratified squamous epithelium, with the more proximal mucosa demonstrating pseudostratified and transitional components (the exact composition varies). With menopause, there is a gradual alteration from squamous to columnar cells associated with loss of estrogenic influence. 8 The urethral epithelium also shows significant variability associated with stage of the menstrual cycle. 9 The muscular wall of the urethra also varies with longitudinal location. 10 The inner layer of smooth muscle has a longitudinal and oblique orientation. External to this layer, a partial layer of smooth muscle in a circular arrangement can be detected. The relative diameters of these respective layers differ according to location along the urethra. Skeletal muscle, which has been termed the striated urinary sphincter (rhabdosphincter), is located around the smooth muscle layers. This layer of skeletal muscle is best defined in the middle third of the urethra, where it has a horseshoe-like configuration around the urethra. The external striated muscle extends proximally to the detrusor and distally to the perineal membrane (although this latter component is less well defined). 11 Age results in decreased density of these fibers. 12
Within the submucosa of the urethra lies an extensive network of glands. Two prominent glands just lateral to the meatus are known as Skene's glands. The ducts of these glands open into the urethral lumen at the urethral meatus. Proximal to these 2 paired glands, however, lies a complex of tubulo-alveolar glands with a ductular connection with the urethra in the posterolateral urethral wall. These glands are most numerous in the distal third of the urethra but they also occur more proximally and are usually the origin of urethral diverticula. 13 The lining of these ducts may be cuboidal or pseudostratified columnar. 14 The anterior vaginal wall lies in close juxtaposition with the urethra. The thickly rugated epithelium of the vaginal wall is composed of stratified squamous cells, which are also hormonally responsive. Beneath this epithelium lies a submucosal layer with abundant collagen and elastic fibers. External to this layer is a well developed fibromuscular layer, with smooth muscle bundles assuming an inner longitudinal and outer circular orientation. 15 These muscular layers are bounded by a thick fibrous capsule that contains a prominent element of elastic fibers. Beneath the anterior vaginal wall, the periurethral fascia forms a barrier between the vagina and urethra. PERIURETHRAL MASSES
The individual lesions are discussed on the basis oflocation along the urethra. Perimeatal lesions. Caruncle: A urethral caruncle usually presents as a soft, regular exophytic lesion of the urethral meatus, most commonly at the inferior margin. It is often pedunculated and may reach dimensions of 2 cm. or greater (fig. 2). Postmenopausal women who lack estrogenic supplementation are prone to suffer these excrescences. The incidence of urethral caruncle in the general population has not been established precisely. However, Marshall et al identified 356 caruncles in a series of 394 urethral lesions. In the same series they identified 22 urethral malignancies and 16 benign mesodermal tumors. 16 Walther reviewed 100 cases of urethral caruncle and identified 95 that were benign by pathological criteria. 17 Urethral caruncles may be completely asymptomatic, or they may be manifested by dysuria, bleeding, frank hematuria or, less commonly, obstructive symptoms. 16 Histologically, the lesion has a normal or hyperplastic squamous epithelial outer surface that covers a markedly edematous submucosa evincing abundant vascularity, inflammation and fibrosis. 17 Asymptomatic lesions with a benign appearance may be
Fm. 2. A, urethral caruncle. B, caruncle demonstrates mucosal ischemia
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FIG. 3. A, lateral and inferior location noted with Skene's gland abscesses. B, surgical dissection of Skene's gland shows ductular communication with urethra (arrow).
treated conservatively with sitz baths and topical estrogens. Symptomatic lesions or lesions that fail medical therapy should be excised. As noted by Marshall et al, all excised tissue must be histologically examined for occult carcinoma or dysplasia. 16 Skene's Gland Abscess: A Skene's gland abscess presents as a painful mass eccentric and lateral to the urethral meatus. Besides pain, the patient may also note dyspareunia, obstructive symptoms or dysuria. Cysts of Skene's duct have been reported in neonates. 18 - 20 Physical examination reveals a tender, erythematous, fluctuant mass inferolateral to the urethral meatus, with a dilated ductular opening often noted just inside the meatal opening (fig. 3). 18 Pressure on the mass may express fluid or pus from the ductular opening. Definitive therapy involves excision of the gland, including the ductular orifice. Palliative management with needle aspiration is useful with symptomatic abscesses. Judicious use of cystoscopy, voiding cystourethrography or excretory urography (IVP) may be necessitated before operative intervention if a urethral diverticulum or prolapsed ureterocele cannot be excluded by physical examination. Caution regarding proximal mucosal excision is necessary to avoid excessive removal of the urethral wall. Direct mucosa-to-mucosa reapproximation to close the resulting defect is required. Foley catheter drainage for 1 to 2 days postoperatively also is beneficial until distal urethral edema subsides. Small series have reported successful primary excision of a Skene's duct abscess. 18 ' 19 Kimbrough and Vaughan reported successful aspiration of a Skene's duct lesion in a neonate. 20 No complications due to treatment were noted in these reports. Mucosal Prolapse: Circumferential eversion of the distal urethral epithelium occurs in 2 distinct populations: prepubertal black girls and postmenopausal white women (fig. 4). Rare occurrence in neonates has been reported. 21 Causative factors may include Valsalva's maneuver, which results in separation of the muscular lamina of the urethral wall and atrophic vaginitis. 22 Presenting symptoms include hematuria or urethral bleeding, irritative voiding symptoms or a painless mass. Demonstration of complete circumferential eversion of the urethral mucosa is a vital diagnostic point of physical examination. 23 The mucosa covering the mass is often edematous, friable and occasionally ischemic. Management initially may be nonoperative with estrogen cream and sitz baths (and ensuring adequacy of bowel function).24-26 Redman managed a small cohort of patients in this fashion and although symptomatic improvement was
present the prolapsed urethral mucosa was still present months after the initial presentation. 23 Ligation of the prolapsed mass of mucosa around an indwelling catheter with delayed sloughing presents a prolonged approach. Primary circumferential excision and reapproximation of urethrovaginal margins, with an indwelling catheter postoperatively, result in the most definitive outcome. 27 ' 28 Cauterization, suture reduction without excision and suprapubic reduction have also been described but are less facile. 29 Jerkins et al reviewed 40 children undergoing different therapies for urethral prolapse. No recurrences or complications were experienced by 15 girls undergoing primary excision. Of 14 girls who underwent manual reduction and catheter placement 3 had recurrences and prolonged hospitalization (greater than 4 days). Of 6 patients managed conservatively 4 experienced recurrence. Two of 3 patients undergoing suture ligation had prolonged pain and catheter discomfort. 28 Devine and Kessel described suprapubic reduction but no specific followup was provided to assess the efficacy of this therapy. 29
FIG. 4. Circumferential, ischemic mucosa associated with urethral prolapse.
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Prolapse of Ureterocele: A prolapsed ureterocele presents as a lesion eccentric to the urethral meatus, covered with a smooth mucosal surface and occasionally discolored due to ischemia. The ureterocele may prolapse through the meatus or it may arise at a location external to the meatus (fig. 5). The prolapse may also be intermittent. Prolapsed ureteroceles should be considered in the differential diagnosis of meatal masses in children and, rarely, in adults (only 4 cases). 30 This lesion classically occurs in white patients. 31 Symptoms include hematuria, interrupted urinary stream or retention and pain. Of the ureteroceles 90% are associated with a duplex system and 10% with an ipsilateral single system. In 1 series 7% of these lesions were prolapsed at presentation. 32 Renal ultrasound or IVP will demonstrate renal duplication (or lack of visualization in the presence of a nonduplicated system). Rarely, direct injection of radiographic contrast medium into the lesion will be required to verify diagnostic suspicion. 33 A renal scan will allow functional assessment of the ipsilateral renal unit. Therapy of a prolapsed ureterocele is governed by the presence of obstruction or sepsis necessitating rapid decompression by cystoscopic incision or aspiration. Occasionally, manual decompression of the ureterocele may be necessary. 32 Williams and Woodard reported on 1 of 4 patients with a prolapsed ureterocele successfully managed by heminephrectomy and excision of the ureterocele. 33 Witherington and Smith reviewed 65 cases of female ureterocele prolapse and found a diversity of management strategies. 34 They proposed a treatment algorithm including an initial attempt at manual reduction, which if unsuccessful would be followed by ureterocele unroofing external to the meatus. Delayed management of the upper tract could then be pursued, predicated by the functional status of the involved renal unit. They argued against prior management strategies involving transvesical reduction, ureterocelectomy and reimplantation because of tissue friability. Miscellaneous Lesions: Miscellaneous benign lesions of the external meatus include polyps, 35 papillomas, condylomas, inclusion cysts, granulomas and hemangiomas. 36 Occasionally, polyps will be difficult to differentiate grossly from caruncles. Papillomas may be associated with other evidence of
urethral inflammation, including leukoplakia or cystitis cystica. 37 Pathological exclusion of malignancy is necessary for any papillary lesion of the meatus. Paraurethral inclusion cysts have been described, which emanate either from urethral or distal vaginal wall glands (including mesonephric remnants) and represent inclusion or retention cysts. 3 s These lesions are most commonly noted in neonates. The cyst is usually eccentric to the meatus and separate from the vagina. Among 5 neonates who presented with a paraurethral cyst excision was performed by Blaivas et al in 4, while spontaneous rupture occurred in 1. 38 Others have argued that intervention is rarely necessary given the asymptomatic and uniformly benign natural history of these cysts. 39 Condylomatous lesions are being increasingly recognized, and are a frequent source of urinary irritative symptomatology and/or hematuria. Viral lesions may exist solely around the meatus or they may be more extensive. According to Sand et al a third of the patients with genital condyloma will manifest urethral lesions. 40 Urethroscopy will delineate the proximal extent of lesions. Gynecological evaluation of the cervix is indicated in women with exposure to or established infection with papillomavirus. Physical examination of the genitalia of the male consort is also indicated. Biopsy of condylomatous lesions reveals exuberant epithelium with koilocytotic change and submucosal inflammatory infiltrate (fig. 6). Complete eradication of condylomatous lesions is often difficult. Topical therapy include 5 fluorouracil, liquid nitrogen or carbon dioxide laser ablation. 41 Krebs and Wheelock reported an 85% cure rate at 3 months using once weekly intravaginal instillation of 5-fluorouracil for 10 weeks followed by a second course in women who failed the initial therapeutic regimen. 42 Others reported 10% failure rates
FIG. 5. Ectopic ureterocele presenting as submeatal mass
FIG. 6. Meatal condyloma
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BENIGN FEMALE PERIURETHRAL MASSES TABLE
Lesion
1. Differential diagnosis of meatal and perimeatal lesions
Location
Presentation
Caruncle
Inferior to meatus
Skene's gland abscess
Inferior and lateral to meatus
Mucosa! prolapse
Circumferential mucosa! prolapse with central meatus Submeatal, prolapsed through meatus
Prolapsed ureterocele
Asymptomatic or dysuria/pain with ischemic mucosa! changes Painful, orifice of duct visible at urethral meatus Pain and dysuria, ischemic mucosa! changes Glistening mucosa, may be ischemic, may be asymptomatic
using an isolated 5-day course of the agent. 43 Local erosive vulvitis and urethritis may complicate even short duration therapy. 43 Carbon dioxide laser ablation approaches 90% successful lesion eradication rates, especially when multiple, repeated treatment cycles are used. Carbon dioxide laser ablation has been advocated for use in recurrent or drug resistant disease. 44 Neodymium:YAG laser treatment or 5-fluorouracil instillation can be considered for intraurethral lesions. Intralesional and systemic interferon therapy offers new avenues for management. Table 1 lists the differential diagnostic considerations for meatal lesions. Figure 7 depicts these lesions. Urethral lesions. Diverticula: A urethral diverticulum represents a cystic dilatation of a portion of the complex periurethral ductular system (fig. 8). Multilocular diverticula may represent a single dilated gland with septations or multiple glands in close proximity. Urethral diverticulum may occur on a congenital or acquired basis, with the acquired form being more common. Diverticula noted in newborns or young girls tend to form an anterior communication with the urethral lumen. 45 Congenital diverticula have also been noted at the insertion of an ectopic ureterocele. Colonic epithelial and Paneth cell metaplasia has been described microscopically in the congenital lesion, which further lends credence to a congenital origin for a minority of diverticula. 46 Although noted in the past, a racial predisposition to black patients has not been substantiated by recent reports. 47 The etiology of urethral diverticula is most commonly infectious. Infection leads to inflammation and enlargement of the involved periurethral gland. Progressive glandular dilatation is caused by ductular obstruction. Further occlusion leads to infection of the inspissated secretions and abscess formation within the occluded gland. The involved gland subsequently ruptures into the urethral lumen. 48 The resulting diverticulum often has an epithelial lining and fibrous wall adherent to surrounding structures. Other implicated
Comments Postmenopausal age group
Young girls or postmenopausal women
rvP to evaluate upper tract status
etiologies include trauma, sexually transmitted disease, instrumentation and multiparity. However, 15 to 20% of women who present with diverticula are nulliparous. 49 The incidence of urethral diverticula in the general population ranges from 1 to 5%. 50 Urethral diverticulum may be asymptomatic (4 to 20%) or it may exhibit a variety of symptoms, including irritative complaints, post-void dribbling, dyspareunia, anterior vaginal wall mass and recurrent infection. The diagnosis of urethral diverticulum hinges on a high degree of suspicion by the examiner. Physical examination may reveal a mass, urethral tenderness or induration indicative of stone or other intra-diverticular pathological condition. Of the cases 63% will be diagnosed in this fashion. 51 The presence and degree of genuine stress urinary incontinence
Ectopic ureteral orifice
Fm. 7. Meatal and perimeatal lesions. A, caruncle. B, mucosa! prolapse. C, Skene's duct cyst. D, ureterocele.
FIG. 8. Vaginal appearance of urethral diverticulum
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FIG. 9. Voiding cystourethrogram demonstrates multiloculated urethral diverticulum.
should also be evaluated and differentiated from coexistent urgency incontinence and paradoxical incontinence (leakage of pooled urine from the diverticulum related to stress maneuvers). The incidence of genuine stress urinary incontinence approximates 32% in patients who present with diverticula. 52 As a supplement to physical examination, voiding cystourethrography provides the most useful radiographic means to document the presence and extent of a diverticulum. Standard voiding cystourethrography detected diverticula in 60 of 63 patients in our previous series. 53 Using a standardized technique to perform voiding cystourethrography will provide documentation of the diverticulum and also the presence of associated genuine stress urinary incontinence.54 This technique will identify the majority of diverticular lesions. Retrograde positive pressure urethrography and vaginal ultrasonography provide ancillary diagnostic techniques if voiding cystourethrography fails to document a clinically suspected urethral diverticulum (fig. 9). 55 •56 Cystoscopy is essential in the evaluation of a urethral diverticulum to identify the site of communication between the diverticulum and urethral lumen. The communication site is usually identified in mucosal folds between the 4 and 8 o'clock positions. Localization of this site helps to ensure complete excision of the diverticulum during diverticulectomy and prevent recurrence. Urodynamic evaluation is crucial in patients with incontinence or symptoms of bladder dysfunction. Of the patients 60% will have abnormal findings on urodynamic evaluation. Stress incontinence alone (32.5%) or with detrusor instability (14.5%) is the most common finding. 53 Operative management of female urethral diverticula has included endoscopic57 and open surgical (marsupialization58 and diverticulectomy59 - 61 ) techniques. Formal diverticulectomy must excise all diverticular loculations completely. Subsequent 3-layer closure, using urethral wall, periurethral fascia and vaginal flap coverage, is accomplished. The select use of a Martius interposition graft and avoidance of overlying suture lines yield excellent results. In our prior series, applying the aforementioned principles of repair, the diverticulum recurrence rate was 3.6% and the urethrovaginal fistula rate was 1.8%. 53 Miscellaneous: A variety of lesions arising from the elements of the urethral wall and periurethral tissues have been reported, including fibromas and leiomyomas. 62- 64
These lesions are solid and evaluation confirms continuity with the urethral lumen. 65 Paraurethral leiomyomas have been reported in 29 patients to date, 60% of whom presented with dysuria, 50% with urinary tract infection and 30% with hematuria. Isolated cases of obstructive voiding symptomatology and stress incontinence have also been noted. The majority of leiomyomas have been excised through a transvaginal approach, although management has also included transurethral resection and excision through an abdominal approach. 63 Anterior vaginal wall lesions. Lesions arising from the anterior vaginal wall may be urethral or vaginal in origin. Vaginal Wall Cysts: Within the vaginal submucosa, cystic structures from several cell types have been described and classified according to histological appearance. These cysts may arise from mesonephric origin (nonciliated, nonsecretory cuboidal epithelium, that is Gartner' duct remnant), paramesonephric origin (tall columnar cells with abundant mucin, resembling cervical cells), endometriotic origin (columnar cells mimicking endometrial glands, often with pronounced hemorrhage) and epidermoid or implantation origin (stratified squamous lining, usually in areas of old trauma, either arising from iatrogenic or parturition etiologies that result in excluded vaginal wall epithelial elements). 66 The majority of these cysts are considered to be of paramesonephric or inclusion origin. Of 64 cysts Deppisch described 34 inclusion and 22 paramesonephric cysts. 67 Evans and Hughes noted 30 inclusion cysts in a series of 42 cystic vaginal lesions. 66 The increasing incidence of vaginal wall cysts with age indicates an etiological role for postpubertal hormonal changes. 68 These cysts may occur at any location on the anterior vaginal wall, from urethral meatus to cervix. The cysts may have no associated symptoms or they may cause obstructive or irritative urinary complaints. Evans and Hughes reported 3 paramesonephric type cysts that presented with bleeding or vaginal discharge. 66 The majority of the series of Deppisch consisted of asymptomatic lesions. 67 Dyspareunia may arise due to cyst size (fig. 10). 66 Evaluation should include history, physical examination and urinalysis. It is crucial to differentiate a vaginal cyst from a urethral diverticulum to avoid inadvertent extensive urethral injury. Voiding cystourethrography will aid in the diagnostic exclusion of a urethral diverticulum. Also, exclusion of ureteral ectopia with an IVP is necessary to avoid inadvertent creation of a ureterovaginal fistula. 69 Excision is performed with an indwelling urethral catheter to avoid urethral injury. With large or infected cysts, operative marsupialization into the vagina can represent an alternative to complete excision. Infantile paraurethral cysts can rupture spontaneously, as noted in 5 of 12 patients described in the literature. 38 Gartner's Duct Cysts: These cysts arise from embryonic remnants and are often diagnosed on the basis of location, which is anterolateral on the vaginal wall. The incidence of clinically detectable Gartner's duct lesions has been estimated to be approximately 1% of all female patients. 70 A left predilection has been reported. 71 Gartner's duct lesions can evolve into large masses that cause urinary tract obstruction or pelvic pain. Ureteral ectopia into the cyst, producing cyst expansion, can cause bladder outlet obstructive symptomatology. In a series of 16 patients Gotoh and Koyanagi noted dysuria in 6, incontinence in 6, vaginal discharge in 3 and abdominal pain in 2. 72 In addition, 7 lesions communicated with the vagina, 3 with the lower urinary tract, and 3 with the vagina and lower urinary tract. Of 22 patients reported on by Blackwell and McElin 19 were asymptomatic. 71 Ipsilateral renal nonfunction is most commonly associated with these cysts, although cases of functioning units associated with single system ectopia into Gartner's cyst have been noted. 73 Evaluation of Gartner's duct lesions should include upper
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FIG. 10. A, large anterior vaginal wall cyst. Two urethral sounds displace main cyst loculation to demonstrate aperture through which smaller loculation has spontaneously drained into vagina (arrow). B, septate anterior vaginal wall cyst.
tract assessment (anatomical and functional). Other methods of vaginal evaluation include transvaginal ultrasound, vaginoscopy74 or contrast vaginography 75 to assist in anatomical delineation. However, these methods are not crucial to diagnosis or operative planning. When upper tract evaluation reveals absence of a renal moiety, the vaginal lesion may be simply excised. No recurrence and only l febrile complication were noted by Blackwell and McElin using only simple transvaginal excision in 22 cases. 71 Marsupialization of isolated duct remnants has also been described occasionally. 75 · 76 With poorly functional renal parenchyma and ureteral ectopia into a Gartner's duct cyst, nephroureterectomy is performed and the vaginal component is allowed to decompress spontaneously. Gotoh and Koyanagi reported no complications in 5 patients undergoing this form of therapy. 72 They also reviewed 16 previously reported patients, 9 of whom underwent nephrectomy with all patients undergoing resection or unroofing of the vaginal component. Leiomyoma: Smooth muscle tumors of the vagina can occur at any location in the vagina, although they most commonly occur on the anterior vaginal wall (fig. U). These tumors may be completely asymptomatic, or they may cause obstruction to either urinary or genital systems and result in dystocia. 77 Leiomyomas may also show hormonal responsiveness, with recurrence after prior complete resection during pregnancy. 78 Evaluation should verify the solid or solid with cystic components of the tumor and also exclude a coexisting large uterine fibroma. 79 More than 250 cases have been reported. These lesions are usually solitary, although 3 multicentric lesions have been described. 79 Therapy involves local resection or enucleation of the entire tumor, since recurrence is possible. A total of 60 patients underwent local excision, with 5 local recurrences and 1 malignancy discovered (leiomyosarcoma). 80 Miscellaneous: Reports of vaginal masses have included fibromas, 81 histiocytomas, neural tumors (5 neurofibromas in 12 years, Armed Forces Institute of Pathology) and vascular lesions. 82 Vaginal varices can be identified in this area of the vaginal wall. Management of these lesions is predicated
FIG. 11. Large anterior wall vaginal leiomyoma. (Allis clamp is on reflected vaginal wall.)
by adequate delineation of the extent of the mass and any possible relationship to the urinary tract. Endometrioma occasionally will implant on the anterior vaginal wall in the presence oflesions elsewhere in the pelvis. These lesions may grow to significant size. Infectious masses include viral (condylomas) and microbial (vaginitis emphysematosa or etiology due to Hemophilus vaginalis) types. 83 Table 2 represents a summary of the differential diagnoses of urethral and vaginal lesions. Figure 12 depicts common anterior vaginal wall tumors.
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BENIGN FEMALE PERIURETHRAL MASSES TABLE
Lesion
2. Differential diagnostic considerations for urethral and anterior vaginal wall lesions Location
Symptoms, Physical Findings
Cystoscopic and Radiographic Findings Orifice of diverticulum visible on urethral floor, voiding cystourethrography opacifies lesion None or extrinsic compression
May be multilocular
None or extrinsic compression, IVP may indicate ectopic ureteral drainage None or extrinsic compression
Rule out ureteral ectopia before excision
Urethral diverticulum
Anterior vaginal wall, midline
Vaginal wall cyst Gartner's duct cyst
Anterior vaginal wall, midline or eccentric Anterolat. vaginal wall
Urinary tract infection, dysuria, dyspareunia, post-void dribbling, cystic mass Cystic mass may be multiloculated Cystic mass
Leiomyoma, hamartoma
Vaginal wall
Solid mass
Urethral diverticulum "
.'-' inclusion cyst
Gartner's duct cyst
Fm. 12. Urethral and anterior vaginal wall lesions. A, urethral diverticulum. B, vaginal wall inclusion cyst. C, Gartner's duct cyst.
Evaluation and management of periurethral and anterior vaginal wall lesions involve a systematic approach using a careful physical examination supplemented by specific diagnostic tests. Management of these tumors relies on definition of any possible communication with the urethra and delineation of upper tract status. Individualized therapy based on the presumptive diagnosis can then be performed and a successful outcome achieved. Dr. F. Y. Miyazaki supplied figure 1. REFERENCES
1. Stephens, F. D.: Congenital Malformations of the Urinary Tract. New York: Praeger Publishers, 1983. 2. Hamilton, W. J. and Mossman, H. W.: The urogenital system. In: Human Embryology: Prenatal Development of Form and Function, 4th ed. Baltimore: Williams & Wilkins, p. 377, 1976. 3. Waterman, R. E.: Human embryo and fetus. In: Atlas of Human Reproduction by Scanning Electron Microscopy. Edited by E. S. E. Hafez and P. Kenemans. Hingham, Massachusetts: Kluwer Boston, Inc., 1982. 4. Tanagho, E. A.: Embryologic basis for lower ureteral anomalies: a hypothesis. Urology, 7: 451, 1976. 5. Mandell, J., Bauer, S. B., Colodny, A. H., Lebowitz, R. L. and Retik, A. B.: Ureteral ectopia in infants and children. J.-uroL, 126: 219, 1981. 6. Huisman, A. B.: Aspects on the anatomy of the female urethra with special relation to urinary continence. Contr. Gynec. Obst., 10: 1, 1983.
Comments
Rule out malignancy
7. Staskin, D. R., Zimmern, P. E., Hadley, H. R. and Raz, S.: The pathophysiology of stress incontinence. UroL Clin. N. Amer., 12: 271, 1985. 8. Carlile, A., Davies, I., Faragher, E. and Brocklehurst, J. C.: The epithelium in the female urethra: a quantitative study. J. UroL, 138: 775, 1987. 9. Smith, P.: Age changes in the female urethra. Brit. J. UroL, 44: 667, 1972. 10. Delancey, J. 0.: Correlative study of paraurethral anatomy. Obst. Gynec., 68: 91, 1986. 11. Oelrich, T. M.: The striated urogenital sphincter muscle in the female. Anat. Rec., 205: 223, 1983. 12. Carlile, A., Davies, I., Rigby, A. and Brocklehurst, J. C.: Age changes in the human female urethra: a morphometric study. J. Urol., 139: 532, 1988. 13. Huffman, J. W.: The detailed anatomy of the paraurethral ducts in the adult human female. Amer. J. Obst. Gynec., 55: 86, 1948. 14. Tepper, S. L., Jagirdar, J., Heath, D. and Geller, S. A.: Homology between the female paraurethral (Skene's) glands and the prostate. Immunohistochemical demonstration. Arch. Path. Lab. Med., 108: 423, 1984. 15. Smout, C. F. V., Jacoby, F. and Lillie, E.W.: Gynaecological and Obstetrical Anatomy (Descriptive and Applied). Baltimore: Williams & Wilkins, 1969. 16. Marshall, P. C., Uson, A. C. and Melicow, M. M.: Neoplasms and caruncles of the female urethra. Surg., Gynec. & Obst., 110: 723, 1960. 17. Walther, H. W.: Caruncle of the urethra in the female with special reference to the importance of histological examination in the differential diagnosis. J. UroL, 50: 380, 1943. 18. Das, S. P.: Paraurethral cysts in women. J. Urol., 126: 41, 1981. 19. Kimbrough, H. M. and Vaughan, E. D.: Skene's duct cyst in a newborn: case report and review of the literature. J. UroL, 117: 387, 1977. 20. Miller, E. V.: Skene's duct cyst. J. UroL, 131: 966, 1984. 21. Peters, W. A., Jr.: Prolapse of the urethral mucosa. Amer. J. Obst. Gynec., 84: 862, 1962. 22. Lowe, F. C., Hill, G. S., Jeffs, R. D. and Brendler, C. B.: Urethral prolapse in children: insights into etiology and management. J. UroL, 135: 100, 1986. 23. Redman, J. F.: Conservative management of urethral prolapse in female children. Urology, 19: 505, 1982. 24. Richardson, D. A., Hajj, S. N. and Herbst, A. L.: Medical treatment of urethral prolapse in children. Obst. Gynec., 59: 69, 1982. 25. Klaus, H. and Stein, R. T.: Urethral prolapse in young girls. Pediatrics, 52: 645, 1972. 26. Morris, T. M.: Conservative management of urethral prolapse. Urology, 20: 351, 1982. 27. Venable, D. D. and Markland, C.: Urethral prolapse in girls. South. Med. J., 75: 951, 1982. 28. Jerkins, G. R., Verheeck, K. and Noe, H. N.: Treatment of girls with urethral prolapse. J. UroL, 132: 732, 1984. 29. Devine, P. C. and Kessell, H. C.: Surgical correction of urethral prolapse. J. UroL, 123: 856, 1980. 30. Miller, M. A. W., Comaby, A. J., Nathan, M. S., Pope, A. and Morgan, R. J.: Prolapsed ureterocele: a rare vulval mass. Brit. J. Urol., 73: 109, 1994. 31. Mandell, J., Colodny, A.H., Lebowitz, R., Bauer, S. B. and Retik, A. B.: Ureteroceles in infants and children. J. UroL, 123: 921, 1980. 32. Witherington, R. and Smith, A. M.: Management of prolapsed
BENIGN FEMALE P:SRIURETHRAL Mi\SSES ureterocele: past and present J. Urol., 121: 813, 1979. 33. Williams, D. I. and Woodard, J. R.: Problems in the management of ectopic ureteroceles. J. Urol., 92: 635, 1964. 34. Nussbaum, A. R. and Lebowitz, R. L.: Interlabial masses in little girls: review and imaging recommendations. AJR, 141: 65, 1983. 35. Klee, L. W., Rink, R. C., Gleason, P. E., Ganesan, G. S., Mitchell, M. E. and Heifetz, S. A.: Urethral polyp presenting as interlabial mass in young girls. Urology, 41: 132, 1993. 36. Radman, H. M.: Urethral hemangioma. J. Urol., 94: 580, 1965. 37. Grabstald, H.: Tumors of the urethra in men and women. Cancer, 32: 1236, 1973. 38. Blaivas, J. G., Pais, V. M. and Retik, A. B.: Paraurethral cysts in female neonate. Urology, 7: 504, 1976. 39. Cohen, H.J., Klein, M. D. and Laver, M. B.: Cysts of the vagina in the newborn infant. Amer. J. Dis. Child., 94: 322, 1957. 40. Sand, P. K., Shen, W., Bowen, L. W. and Ostergard, D. R.: Cryotherapy for the treatment of proximal urethral condyloma acuminatum. J. Urol., 137: 874, 1987. 41. Krebs, H.B.: Genital human papillomavirus infection. Management strategies. Clin. Obst. Gynec., 32: 200, 1989. 42. Krebs, H. B.: Treatment of vaginal condylomata acuminata by weekly topical application of 5-fluorouracil. Obst. Gynec., 70: 68, 1987. 43. Ferenczy, A., Mitao, M., Nagai, N., Silverstein, S. J. and Crum, C. P.: Latent papillomavirus and recurring genital warts. New Engl. J. Med., 313: 784, 1985. 44. Krebs, H. B. and Wheelock, J. B.: The CO2 laser for recurrent and therapy-resistant condylomata acuminata. J. Reprod. Med., 30: 489, 1985. 45. Silk, M. R. and Lebowitz, J. M.: Anterior urethral diverticulum. J. Urol., 101: 66, 1969. 46. Niemiec, T. R., Mercer, L. J., Stephens, J. K. and Hajj, S. N.: Unusual urethral diverticulum lined by colonic epithelium with Paneth cell metaplasia. Amer. J. Obst. Gynec., 160: 186, 1989. 47. Leach, G. E. and Bavendam, T. G.: Female urethral diverticula. Urology, 30: 407, 1987. 48. Davis, B. L. and Robinson, D. G.: Diverticula of the female urethra: assay of 120 cases. J. Urol., 104: 850, 1970. 49. Lee, R. A.: Diverticulum of the urethra. Clinical presentation, diagnosis, and management. Clin. Obst. Gynec., 27: 490, 1984. 50. Anderson, M. J. F.: The incidence of diverticula in the female urethra. J. Urol., 98: 96, 1967. 51. Davis, H.J. and TeLinde, R. W.: Urethral diverticula: an assay of 121 cases. J. Urol., 80: 34, 1958. 52. Bass, J. 8. and Leach, G. E.: Surgical treatment of concomitant urethral diverticulum and stress incontinence. Urol. Clin. N. Amer., 18: 365, 1991. 53. Ganabathi, K., Sirls, L., Zimmern, P. E. and Leach, G. E.: Operative management of female urethral diverticula. In: Advances in Urology. Edited by E. J. McGuire. Chicago: Year Book Medical Publishers, vol. 7, 1993. 54. Zimmern, P. E.: The role of voiding cystourethrography in the evaluation of the female lower urinary tract. Prob!. Urol., pp. 23-41, 1991. 55. Baert, L., Willemen, P. and Oyen, R.: Endovaginal sonography: new diagnostic approach for urethra diverticula. J. Urol., 147: 464, 1992. 56. Stewart, M., Bretland, P. M. and Stidolph, N. E.: Urethral diverticula in the adult female. Brit. J. Urol., 53: 353, 1981. 57. Lapides, J.: Transurethral treatment of urethral diverticula in women. J. Urol., 121: 736, 1979. 58. Spence, H. M. and Duckett, J. W., Jr.: Diverticulum of the female urethra: clinical aspects and presentation of a simple operative technique for cure. J. Urol., 104: 432, 1970.
1951
59. Moore, T. D.: Diverticu!um of female urethra: an improved technique of surgical excision. J. Urol., 68: 611, 1952. 60. Benjamin, J., Elliot, L., Cooper, J. and Bjornson, L.: Urethral diverticulum in adult female: clinical aspects, operative procedure, and pathology. Urology, 3: 1, 1974. 61. Leach, G. E., Schmidbauer, C. P., Hadley, H. R., Staskin, D.R., Zimmern, P. E. and Raz, S.: Surgical treatment of female urethral diverticulum. Sem. Urol., 4: 33, 1986. 62. Scholl, A. J. and Braasch, W. F.: Primary tumors of the urethra. Ann. Surg., 76: 246, 1922. 63. Fry, M., Wheeler, J. S., Jr., Mata, J. A., Culkin, D. J., St. Martin, E. and Venable, D. D.: Leiomyoma of the female urethra. J. Urol., 140: 613, 1988. 64. Shield, D. and Weiss, R. M.: Leiomyoma of the female urethra. J. Urol., 109: 430, 1973. 65. Cattolica, E. V., Klein, R. and Knigge, W.: Paraurethral leiomyoma-an imitator. Urology, 6: 605, 1976. 66. Evans, D. M. D. and Hughes, H.: Cysts of the vaginal wall. J. Obst. Gynaec. Brit. Comm., 68: 247, 1960. 67. Deppisch, L. M.: Cysts of the vagina: classification and clinical correlations. Obst. Gynec., 45: 632, 1975. 68. Sandberg, E. C.: The incidence and distribution of occult vaginal adenosis. Amer. J. Obst. Gynec., 101: 322, 1968. 69. Blacklock, A. R. E., Shaw, R. E. and Geddes, J. R.: Late presentation of ectopic ureter. Brit. J. Urol., 54: 106, 1982. 70. Gardner, H. and Kaufman, R. H.: Cystic tumors. Benign Diseases of the Vulva and Vagina. St. Louis: The C.V. Mosby Co., chapt. 5, pp. 70-97, 1969. 71. Blackwell, W. J. and McElin, T. W.: Vaginal cysts ofmesonephric duct origin (Gartner's duct cysts); report of 22 cases. Quart. Bull. Northwestern Univ. Med. Sch., 29: 94, 1955. 72. Gotoh, T. and Koyanagi, T.: Clinicopathological and embryological considerations of single ectopic ureters opening into Gartner's duct cyst: a unique subtype of single vaginal ectopia. J. Urol., 137: 969, 1987. 73. Kjaeldgaard, A., Fianau, 8., Thorgeirsson, T. and Ekman, P.: Single bifid ectopic left ureter presenting clinically as a vaginal cyst. Diag. Obst. Gynec., 3: 321, 1981. 74. Goldstein, A. I., Ackerman, E. S., Woodruff, R. and Poyas, J.: Vaginal and cervical communication with mesonephric duct remnants: relationship to unilateral renal agenesis. Amer. J. Obst. Gynec., 116: 101, 1973. 75. Currarino, G.: Single vaginal ectopic ureter and Gartner's duct cyst with ipsilateral renal hypoplasia and dysplasia (or agenesis). J. Urol., 128: 988, 1982. 76. Gadbois, W. F. and Duckett, J. W., Jr.: Gartner's duct cyst and ipsilateral renal agenesis. Urology, 4: 720, 1974. 77. Brown, R. C., Hawtrey, C. E. and Rose, E. F.: Leiomyoma of vesicovaginal septum causing urinary retention. Urology, 6: 379, 1975. 78. Rywlin, A. M., Simmons, R. J. and Robinson, M. J.: Leiomyoma of vagina recurrent in pregnancy: a case with apparent hormone deficiency. South. Med. J., 62: 1449, 1969. 79. Quan, A. and Birnbaum, S.: Vaginal leiomyoma: report of a case and review of the literature. Obst. Gynec., IS: 360, 1961. 80. Tavassoli, F. A. and Norris, H.J.: Smooth muscle tumors of the vagina. Obst. Gynec., 53: 689, 1979. 81. Freed, S. Z., Haleem, S. A., Wiener, I. and Feldman, J.: Bladder outlet obstruction caused by vaginal fibromyoma: the female prostate. J. Urol., 113: 30, 1975. 82. Kaufman, R. H. and Gardner, H. L.: Tumors of the vulva and vagina. Benign mesodermal tumors. Clin. Obst. Gynec., 8: 953, 1965. 83. Gardner, H. L. and Fernet, P.: Etiology ofvaginitis emphysematosa; report of22 cases and review ofliterature. Amer. J. Obst. Gynec., 88: 680, 1964.
Vol. 152, 1943-1951, December 1994
Printed in U.S.A.
AssocJATION, INC.
Review Article BENIGN FEMALE PERIURETHRAL MASSES ROGER R. DMOCHOWSKI, K. GANABATHI, PHILIPPE E. ZIMMERN
AND
GARY E. LEACH*
From the Department of Urology, Kaiser Permanente Medical Center, Los Angeles, California KEY WORDS:
urethra, urethral neoplasms, embryology, anatomy
Benign female periurethral lesions encompass a spectrum of entities that have significance in clinical urology. Often unrecognized or incorrectly diagnosed, periurethral masses may be completely asymptomatic or may produce significant symptomatology with increasing size, such as urinary tract obstruction, irritative complaints or hematuria. Failure to identify these lesions correctly usually results from lack of familiarity. The goal of this review is to summarize concisely the embryology and anatomy of the female urethra and anterior vagina. Subsequent discussion will provide a practical approach to diagnostic recognition and appropriate treatments for periurethral lesions. EMBRYOLOGY
Urethra and anterior vaginal wall. The cloaca and internal genital ductal system develop in close apposition. This synopsis will review the internal ductal development initially, and subsequently review the process of cloacal transformation that gives rise to the urethra and anterior vaginal wall. The embryonic internal genital ductal system becomes identifiable at week 5 to 6 of gestation and remains sexually indifferent until week 10 of development. The mullerian or para-mesonephric duct is identifiable by week 6 of gestationo This duct lies in close apposition to the mesonephric duct during descent from the retroperitoneum to the true pelvis. The paired mullerian ducts assume a position lateral to the mesonephric (wolffian) system. With further differentiation, the mii.llerian ducts cross over the mesonephric ducts and fuse in the caudal midline. During week 8 of gestation the medial segments of the mesonephric system initiate fusion at the level of the bladder and form the uterovaginal primordium (mii.llerian tubercle). This process is completed by week 10. Development of the urogenital sinus proceeds parallel to formation of the internal ductal systemo Initially, septation of the primitive doacal membrane begins at 28 days. 1 By 50 days of gestation this process is complete (whether by subdivision due to ingrowth of the urorectal septum and plicae of Rathke or, instead, due to differential growth of various somatic components). As a byproduct of this division, the urogenital sinus becomes recognizable at week 6. Two subdivisions of the urogenital sinus are identified: a pelvic portion and a phallic portion. The pelvic subdivision of the urogenital sinus develops into the urethra and vagina. By week 11 ductular structures arise from the true urethra, which will eventually form Skene's glands. 1 The phallic portion of the urogenital sinus evolves into the vaginal vestibule. 2 The nonfused cranial portions of the mii.llerian ducts will give rise to the fallopian tubes. The fused uterovaginal primordium expands cranially to form the cervix and uterus. This process begins at week 12 and is complete by week 31, at * Requests for reprints: Department of Urology, Kaiser Permanente Medical Center, 4900 Sunset Blvd., Los Angeles, California 90027.
which time the uterus exhibits mural differentiation into myometrium and stroma. Caudal expansion of the uterovaginal primordium results in fusion with the dorsal wall of the urogenital sinus to form the uterovaginal canal (at the mii.llerian tubercle)o The caudal portion of the degenerating mesonephric ducts contributes mesodermal extensions and sinovaginal bulbs, which extend into the urogenital sinus creating the vaginal plate by week 16. This plate progressively canalizes and a vaginal cavity is formed by month 5. Therefore, at the completion of morphogenesis the vagina originates from 2 separate entities. The upper two-thirds of the vagina arises from the fused mii.llerian ducts, while the lower third arises from the urogenital sinus. 3 Gartner's duct. During miillerian development, mesonephric regression continues. Mesonephric remnants, however, may persist in close proximity to the evolving miillerian system. These remnants are found in a linear pattern that recapitulates the original location of the mesonephric system on either side of the internal female genitalia (Gartner's duct). This linear distribution begins caudally in the anterolateral vaginal wall and extends in a cephalad direction lateral to the uterus and fallopian tubes. These remnants are often microscopically present but can become clinically significant should cyst formation occur. Ectopia. During embryogenesis of the internal female genitalia, development of the urinary tract continues. The ureter forms as an evagination from the mesonephric duct at day 28. Delay in this process of evagination or the formation of a second evagination (or bud) results in a more cranial location for this budo As the mesonephric duct is incorporated into the trigone, this "ectopic" bud migrates caudally and inferiorly, and becomes incorporated at an aberrant location. This ectopic location may arise within the urinary tract, from the distal trigone to the urethra, or it may terminate out.side the urinary tract in the remnants of the mesonephric system inclusive of the vagina, cervix, uterus or Gartner's duct. 4 The incidence of ureteral ectopia is 1 in 125 cases and the femaleto-male ratio is 4:1. 5 ANATOMY
Cross sectional photomicrographs of the female urethra reveal an exuberant mucosal lining that covers a thick submucosa containing abundant vascularity (fig. 1). The submucosa contains not only a rich vascular network but also abundant connective tissue supplemented by elastic and smooth muscle fibers, which provide a natural seal effect to the urethral closure. Hormonal deprivation decreases the vascularity of the submucosa with loss of the mucosa! seal effect and also leads to increased fibrous tissue deposition. 6 Circumferential layers of smooth muscle bounded by fibroelastic tissue form the external component of the urethra. These tissues augment the seal effect of the mucosa and submucosa, and are additive to the sphincteric mechanism. Estrogens provide nutritive support to these tissues. 7 When viewed longitudinally, the urethra demonstrates
1943
1944
BENIGN FEMALE PERIURETHRAL MASSES
}-e C
D
CROSS SECTION MID-URETHRA Fm. 1. Cross section offemale urethra. A, striated skeletal muscle fibers. B, smooth muscle layers, outer circular orientation, inner longitudinal. C, urethral lumen. D, paraurethral ligament. E, vaginal wall with fibromuscular wall and overlying epithelium.
variation in epithelial and muscular components. The distal urethra is lined by nonkeratinized stratified squamous epithelium, with the more proximal mucosa demonstrating pseudostratified and transitional components (the exact composition varies). With menopause, there is a gradual alteration from squamous to columnar cells associated with loss of estrogenic influence. 8 The urethral epithelium also shows significant variability associated with stage of the menstrual cycle. 9 The muscular wall of the urethra also varies with longitudinal location. 10 The inner layer of smooth muscle has a longitudinal and oblique orientation. External to this layer, a partial layer of smooth muscle in a circular arrangement can be detected. The relative diameters of these respective layers differ according to location along the urethra. Skeletal muscle, which has been termed the striated urinary sphincter (rhabdosphincter), is located around the smooth muscle layers. This layer of skeletal muscle is best defined in the middle third of the urethra, where it has a horseshoe-like configuration around the urethra. The external striated muscle extends proximally to the detrusor and distally to the perineal membrane (although this latter component is less well defined). 11 Age results in decreased density of these fibers. 12
Within the submucosa of the urethra lies an extensive network of glands. Two prominent glands just lateral to the meatus are known as Skene's glands. The ducts of these glands open into the urethral lumen at the urethral meatus. Proximal to these 2 paired glands, however, lies a complex of tubulo-alveolar glands with a ductular connection with the urethra in the posterolateral urethral wall. These glands are most numerous in the distal third of the urethra but they also occur more proximally and are usually the origin of urethral diverticula. 13 The lining of these ducts may be cuboidal or pseudostratified columnar. 14 The anterior vaginal wall lies in close juxtaposition with the urethra. The thickly rugated epithelium of the vaginal wall is composed of stratified squamous cells, which are also hormonally responsive. Beneath this epithelium lies a submucosal layer with abundant collagen and elastic fibers. External to this layer is a well developed fibromuscular layer, with smooth muscle bundles assuming an inner longitudinal and outer circular orientation. 15 These muscular layers are bounded by a thick fibrous capsule that contains a prominent element of elastic fibers. Beneath the anterior vaginal wall, the periurethral fascia forms a barrier between the vagina and urethra. PERIURETHRAL MASSES
The individual lesions are discussed on the basis oflocation along the urethra. Perimeatal lesions. Caruncle: A urethral caruncle usually presents as a soft, regular exophytic lesion of the urethral meatus, most commonly at the inferior margin. It is often pedunculated and may reach dimensions of 2 cm. or greater (fig. 2). Postmenopausal women who lack estrogenic supplementation are prone to suffer these excrescences. The incidence of urethral caruncle in the general population has not been established precisely. However, Marshall et al identified 356 caruncles in a series of 394 urethral lesions. In the same series they identified 22 urethral malignancies and 16 benign mesodermal tumors. 16 Walther reviewed 100 cases of urethral caruncle and identified 95 that were benign by pathological criteria. 17 Urethral caruncles may be completely asymptomatic, or they may be manifested by dysuria, bleeding, frank hematuria or, less commonly, obstructive symptoms. 16 Histologically, the lesion has a normal or hyperplastic squamous epithelial outer surface that covers a markedly edematous submucosa evincing abundant vascularity, inflammation and fibrosis. 17 Asymptomatic lesions with a benign appearance may be
Fm. 2. A, urethral caruncle. B, caruncle demonstrates mucosal ischemia
BENIGN FEMALE PERIURETHRAL MASSES
1945
FIG. 3. A, lateral and inferior location noted with Skene's gland abscesses. B, surgical dissection of Skene's gland shows ductular communication with urethra (arrow).
treated conservatively with sitz baths and topical estrogens. Symptomatic lesions or lesions that fail medical therapy should be excised. As noted by Marshall et al, all excised tissue must be histologically examined for occult carcinoma or dysplasia. 16 Skene's Gland Abscess: A Skene's gland abscess presents as a painful mass eccentric and lateral to the urethral meatus. Besides pain, the patient may also note dyspareunia, obstructive symptoms or dysuria. Cysts of Skene's duct have been reported in neonates. 18 - 20 Physical examination reveals a tender, erythematous, fluctuant mass inferolateral to the urethral meatus, with a dilated ductular opening often noted just inside the meatal opening (fig. 3). 18 Pressure on the mass may express fluid or pus from the ductular opening. Definitive therapy involves excision of the gland, including the ductular orifice. Palliative management with needle aspiration is useful with symptomatic abscesses. Judicious use of cystoscopy, voiding cystourethrography or excretory urography (IVP) may be necessitated before operative intervention if a urethral diverticulum or prolapsed ureterocele cannot be excluded by physical examination. Caution regarding proximal mucosal excision is necessary to avoid excessive removal of the urethral wall. Direct mucosa-to-mucosa reapproximation to close the resulting defect is required. Foley catheter drainage for 1 to 2 days postoperatively also is beneficial until distal urethral edema subsides. Small series have reported successful primary excision of a Skene's duct abscess. 18 ' 19 Kimbrough and Vaughan reported successful aspiration of a Skene's duct lesion in a neonate. 20 No complications due to treatment were noted in these reports. Mucosal Prolapse: Circumferential eversion of the distal urethral epithelium occurs in 2 distinct populations: prepubertal black girls and postmenopausal white women (fig. 4). Rare occurrence in neonates has been reported. 21 Causative factors may include Valsalva's maneuver, which results in separation of the muscular lamina of the urethral wall and atrophic vaginitis. 22 Presenting symptoms include hematuria or urethral bleeding, irritative voiding symptoms or a painless mass. Demonstration of complete circumferential eversion of the urethral mucosa is a vital diagnostic point of physical examination. 23 The mucosa covering the mass is often edematous, friable and occasionally ischemic. Management initially may be nonoperative with estrogen cream and sitz baths (and ensuring adequacy of bowel function).24-26 Redman managed a small cohort of patients in this fashion and although symptomatic improvement was
present the prolapsed urethral mucosa was still present months after the initial presentation. 23 Ligation of the prolapsed mass of mucosa around an indwelling catheter with delayed sloughing presents a prolonged approach. Primary circumferential excision and reapproximation of urethrovaginal margins, with an indwelling catheter postoperatively, result in the most definitive outcome. 27 ' 28 Cauterization, suture reduction without excision and suprapubic reduction have also been described but are less facile. 29 Jerkins et al reviewed 40 children undergoing different therapies for urethral prolapse. No recurrences or complications were experienced by 15 girls undergoing primary excision. Of 14 girls who underwent manual reduction and catheter placement 3 had recurrences and prolonged hospitalization (greater than 4 days). Of 6 patients managed conservatively 4 experienced recurrence. Two of 3 patients undergoing suture ligation had prolonged pain and catheter discomfort. 28 Devine and Kessel described suprapubic reduction but no specific followup was provided to assess the efficacy of this therapy. 29
FIG. 4. Circumferential, ischemic mucosa associated with urethral prolapse.
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BENIGN FEMALE PERIURETHRAL MASSES
Prolapse of Ureterocele: A prolapsed ureterocele presents as a lesion eccentric to the urethral meatus, covered with a smooth mucosal surface and occasionally discolored due to ischemia. The ureterocele may prolapse through the meatus or it may arise at a location external to the meatus (fig. 5). The prolapse may also be intermittent. Prolapsed ureteroceles should be considered in the differential diagnosis of meatal masses in children and, rarely, in adults (only 4 cases). 30 This lesion classically occurs in white patients. 31 Symptoms include hematuria, interrupted urinary stream or retention and pain. Of the ureteroceles 90% are associated with a duplex system and 10% with an ipsilateral single system. In 1 series 7% of these lesions were prolapsed at presentation. 32 Renal ultrasound or IVP will demonstrate renal duplication (or lack of visualization in the presence of a nonduplicated system). Rarely, direct injection of radiographic contrast medium into the lesion will be required to verify diagnostic suspicion. 33 A renal scan will allow functional assessment of the ipsilateral renal unit. Therapy of a prolapsed ureterocele is governed by the presence of obstruction or sepsis necessitating rapid decompression by cystoscopic incision or aspiration. Occasionally, manual decompression of the ureterocele may be necessary. 32 Williams and Woodard reported on 1 of 4 patients with a prolapsed ureterocele successfully managed by heminephrectomy and excision of the ureterocele. 33 Witherington and Smith reviewed 65 cases of female ureterocele prolapse and found a diversity of management strategies. 34 They proposed a treatment algorithm including an initial attempt at manual reduction, which if unsuccessful would be followed by ureterocele unroofing external to the meatus. Delayed management of the upper tract could then be pursued, predicated by the functional status of the involved renal unit. They argued against prior management strategies involving transvesical reduction, ureterocelectomy and reimplantation because of tissue friability. Miscellaneous Lesions: Miscellaneous benign lesions of the external meatus include polyps, 35 papillomas, condylomas, inclusion cysts, granulomas and hemangiomas. 36 Occasionally, polyps will be difficult to differentiate grossly from caruncles. Papillomas may be associated with other evidence of
urethral inflammation, including leukoplakia or cystitis cystica. 37 Pathological exclusion of malignancy is necessary for any papillary lesion of the meatus. Paraurethral inclusion cysts have been described, which emanate either from urethral or distal vaginal wall glands (including mesonephric remnants) and represent inclusion or retention cysts. 3 s These lesions are most commonly noted in neonates. The cyst is usually eccentric to the meatus and separate from the vagina. Among 5 neonates who presented with a paraurethral cyst excision was performed by Blaivas et al in 4, while spontaneous rupture occurred in 1. 38 Others have argued that intervention is rarely necessary given the asymptomatic and uniformly benign natural history of these cysts. 39 Condylomatous lesions are being increasingly recognized, and are a frequent source of urinary irritative symptomatology and/or hematuria. Viral lesions may exist solely around the meatus or they may be more extensive. According to Sand et al a third of the patients with genital condyloma will manifest urethral lesions. 40 Urethroscopy will delineate the proximal extent of lesions. Gynecological evaluation of the cervix is indicated in women with exposure to or established infection with papillomavirus. Physical examination of the genitalia of the male consort is also indicated. Biopsy of condylomatous lesions reveals exuberant epithelium with koilocytotic change and submucosal inflammatory infiltrate (fig. 6). Complete eradication of condylomatous lesions is often difficult. Topical therapy include 5 fluorouracil, liquid nitrogen or carbon dioxide laser ablation. 41 Krebs and Wheelock reported an 85% cure rate at 3 months using once weekly intravaginal instillation of 5-fluorouracil for 10 weeks followed by a second course in women who failed the initial therapeutic regimen. 42 Others reported 10% failure rates
FIG. 5. Ectopic ureterocele presenting as submeatal mass
FIG. 6. Meatal condyloma
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BENIGN FEMALE PERIURETHRAL MASSES TABLE
Lesion
1. Differential diagnosis of meatal and perimeatal lesions
Location
Presentation
Caruncle
Inferior to meatus
Skene's gland abscess
Inferior and lateral to meatus
Mucosa! prolapse
Circumferential mucosa! prolapse with central meatus Submeatal, prolapsed through meatus
Prolapsed ureterocele
Asymptomatic or dysuria/pain with ischemic mucosa! changes Painful, orifice of duct visible at urethral meatus Pain and dysuria, ischemic mucosa! changes Glistening mucosa, may be ischemic, may be asymptomatic
using an isolated 5-day course of the agent. 43 Local erosive vulvitis and urethritis may complicate even short duration therapy. 43 Carbon dioxide laser ablation approaches 90% successful lesion eradication rates, especially when multiple, repeated treatment cycles are used. Carbon dioxide laser ablation has been advocated for use in recurrent or drug resistant disease. 44 Neodymium:YAG laser treatment or 5-fluorouracil instillation can be considered for intraurethral lesions. Intralesional and systemic interferon therapy offers new avenues for management. Table 1 lists the differential diagnostic considerations for meatal lesions. Figure 7 depicts these lesions. Urethral lesions. Diverticula: A urethral diverticulum represents a cystic dilatation of a portion of the complex periurethral ductular system (fig. 8). Multilocular diverticula may represent a single dilated gland with septations or multiple glands in close proximity. Urethral diverticulum may occur on a congenital or acquired basis, with the acquired form being more common. Diverticula noted in newborns or young girls tend to form an anterior communication with the urethral lumen. 45 Congenital diverticula have also been noted at the insertion of an ectopic ureterocele. Colonic epithelial and Paneth cell metaplasia has been described microscopically in the congenital lesion, which further lends credence to a congenital origin for a minority of diverticula. 46 Although noted in the past, a racial predisposition to black patients has not been substantiated by recent reports. 47 The etiology of urethral diverticula is most commonly infectious. Infection leads to inflammation and enlargement of the involved periurethral gland. Progressive glandular dilatation is caused by ductular obstruction. Further occlusion leads to infection of the inspissated secretions and abscess formation within the occluded gland. The involved gland subsequently ruptures into the urethral lumen. 48 The resulting diverticulum often has an epithelial lining and fibrous wall adherent to surrounding structures. Other implicated
Comments Postmenopausal age group
Young girls or postmenopausal women
rvP to evaluate upper tract status
etiologies include trauma, sexually transmitted disease, instrumentation and multiparity. However, 15 to 20% of women who present with diverticula are nulliparous. 49 The incidence of urethral diverticula in the general population ranges from 1 to 5%. 50 Urethral diverticulum may be asymptomatic (4 to 20%) or it may exhibit a variety of symptoms, including irritative complaints, post-void dribbling, dyspareunia, anterior vaginal wall mass and recurrent infection. The diagnosis of urethral diverticulum hinges on a high degree of suspicion by the examiner. Physical examination may reveal a mass, urethral tenderness or induration indicative of stone or other intra-diverticular pathological condition. Of the cases 63% will be diagnosed in this fashion. 51 The presence and degree of genuine stress urinary incontinence
Ectopic ureteral orifice
Fm. 7. Meatal and perimeatal lesions. A, caruncle. B, mucosa! prolapse. C, Skene's duct cyst. D, ureterocele.
FIG. 8. Vaginal appearance of urethral diverticulum
1948
BENIGN FEMALE PERIURETHRAL MASSES
FIG. 9. Voiding cystourethrogram demonstrates multiloculated urethral diverticulum.
should also be evaluated and differentiated from coexistent urgency incontinence and paradoxical incontinence (leakage of pooled urine from the diverticulum related to stress maneuvers). The incidence of genuine stress urinary incontinence approximates 32% in patients who present with diverticula. 52 As a supplement to physical examination, voiding cystourethrography provides the most useful radiographic means to document the presence and extent of a diverticulum. Standard voiding cystourethrography detected diverticula in 60 of 63 patients in our previous series. 53 Using a standardized technique to perform voiding cystourethrography will provide documentation of the diverticulum and also the presence of associated genuine stress urinary incontinence.54 This technique will identify the majority of diverticular lesions. Retrograde positive pressure urethrography and vaginal ultrasonography provide ancillary diagnostic techniques if voiding cystourethrography fails to document a clinically suspected urethral diverticulum (fig. 9). 55 •56 Cystoscopy is essential in the evaluation of a urethral diverticulum to identify the site of communication between the diverticulum and urethral lumen. The communication site is usually identified in mucosal folds between the 4 and 8 o'clock positions. Localization of this site helps to ensure complete excision of the diverticulum during diverticulectomy and prevent recurrence. Urodynamic evaluation is crucial in patients with incontinence or symptoms of bladder dysfunction. Of the patients 60% will have abnormal findings on urodynamic evaluation. Stress incontinence alone (32.5%) or with detrusor instability (14.5%) is the most common finding. 53 Operative management of female urethral diverticula has included endoscopic57 and open surgical (marsupialization58 and diverticulectomy59 - 61 ) techniques. Formal diverticulectomy must excise all diverticular loculations completely. Subsequent 3-layer closure, using urethral wall, periurethral fascia and vaginal flap coverage, is accomplished. The select use of a Martius interposition graft and avoidance of overlying suture lines yield excellent results. In our prior series, applying the aforementioned principles of repair, the diverticulum recurrence rate was 3.6% and the urethrovaginal fistula rate was 1.8%. 53 Miscellaneous: A variety of lesions arising from the elements of the urethral wall and periurethral tissues have been reported, including fibromas and leiomyomas. 62- 64
These lesions are solid and evaluation confirms continuity with the urethral lumen. 65 Paraurethral leiomyomas have been reported in 29 patients to date, 60% of whom presented with dysuria, 50% with urinary tract infection and 30% with hematuria. Isolated cases of obstructive voiding symptomatology and stress incontinence have also been noted. The majority of leiomyomas have been excised through a transvaginal approach, although management has also included transurethral resection and excision through an abdominal approach. 63 Anterior vaginal wall lesions. Lesions arising from the anterior vaginal wall may be urethral or vaginal in origin. Vaginal Wall Cysts: Within the vaginal submucosa, cystic structures from several cell types have been described and classified according to histological appearance. These cysts may arise from mesonephric origin (nonciliated, nonsecretory cuboidal epithelium, that is Gartner' duct remnant), paramesonephric origin (tall columnar cells with abundant mucin, resembling cervical cells), endometriotic origin (columnar cells mimicking endometrial glands, often with pronounced hemorrhage) and epidermoid or implantation origin (stratified squamous lining, usually in areas of old trauma, either arising from iatrogenic or parturition etiologies that result in excluded vaginal wall epithelial elements). 66 The majority of these cysts are considered to be of paramesonephric or inclusion origin. Of 64 cysts Deppisch described 34 inclusion and 22 paramesonephric cysts. 67 Evans and Hughes noted 30 inclusion cysts in a series of 42 cystic vaginal lesions. 66 The increasing incidence of vaginal wall cysts with age indicates an etiological role for postpubertal hormonal changes. 68 These cysts may occur at any location on the anterior vaginal wall, from urethral meatus to cervix. The cysts may have no associated symptoms or they may cause obstructive or irritative urinary complaints. Evans and Hughes reported 3 paramesonephric type cysts that presented with bleeding or vaginal discharge. 66 The majority of the series of Deppisch consisted of asymptomatic lesions. 67 Dyspareunia may arise due to cyst size (fig. 10). 66 Evaluation should include history, physical examination and urinalysis. It is crucial to differentiate a vaginal cyst from a urethral diverticulum to avoid inadvertent extensive urethral injury. Voiding cystourethrography will aid in the diagnostic exclusion of a urethral diverticulum. Also, exclusion of ureteral ectopia with an IVP is necessary to avoid inadvertent creation of a ureterovaginal fistula. 69 Excision is performed with an indwelling urethral catheter to avoid urethral injury. With large or infected cysts, operative marsupialization into the vagina can represent an alternative to complete excision. Infantile paraurethral cysts can rupture spontaneously, as noted in 5 of 12 patients described in the literature. 38 Gartner's Duct Cysts: These cysts arise from embryonic remnants and are often diagnosed on the basis of location, which is anterolateral on the vaginal wall. The incidence of clinically detectable Gartner's duct lesions has been estimated to be approximately 1% of all female patients. 70 A left predilection has been reported. 71 Gartner's duct lesions can evolve into large masses that cause urinary tract obstruction or pelvic pain. Ureteral ectopia into the cyst, producing cyst expansion, can cause bladder outlet obstructive symptomatology. In a series of 16 patients Gotoh and Koyanagi noted dysuria in 6, incontinence in 6, vaginal discharge in 3 and abdominal pain in 2. 72 In addition, 7 lesions communicated with the vagina, 3 with the lower urinary tract, and 3 with the vagina and lower urinary tract. Of 22 patients reported on by Blackwell and McElin 19 were asymptomatic. 71 Ipsilateral renal nonfunction is most commonly associated with these cysts, although cases of functioning units associated with single system ectopia into Gartner's cyst have been noted. 73 Evaluation of Gartner's duct lesions should include upper
BENIGN FEMALE PERIURETHRAL MASSES
1949
FIG. 10. A, large anterior vaginal wall cyst. Two urethral sounds displace main cyst loculation to demonstrate aperture through which smaller loculation has spontaneously drained into vagina (arrow). B, septate anterior vaginal wall cyst.
tract assessment (anatomical and functional). Other methods of vaginal evaluation include transvaginal ultrasound, vaginoscopy74 or contrast vaginography 75 to assist in anatomical delineation. However, these methods are not crucial to diagnosis or operative planning. When upper tract evaluation reveals absence of a renal moiety, the vaginal lesion may be simply excised. No recurrence and only l febrile complication were noted by Blackwell and McElin using only simple transvaginal excision in 22 cases. 71 Marsupialization of isolated duct remnants has also been described occasionally. 75 · 76 With poorly functional renal parenchyma and ureteral ectopia into a Gartner's duct cyst, nephroureterectomy is performed and the vaginal component is allowed to decompress spontaneously. Gotoh and Koyanagi reported no complications in 5 patients undergoing this form of therapy. 72 They also reviewed 16 previously reported patients, 9 of whom underwent nephrectomy with all patients undergoing resection or unroofing of the vaginal component. Leiomyoma: Smooth muscle tumors of the vagina can occur at any location in the vagina, although they most commonly occur on the anterior vaginal wall (fig. U). These tumors may be completely asymptomatic, or they may cause obstruction to either urinary or genital systems and result in dystocia. 77 Leiomyomas may also show hormonal responsiveness, with recurrence after prior complete resection during pregnancy. 78 Evaluation should verify the solid or solid with cystic components of the tumor and also exclude a coexisting large uterine fibroma. 79 More than 250 cases have been reported. These lesions are usually solitary, although 3 multicentric lesions have been described. 79 Therapy involves local resection or enucleation of the entire tumor, since recurrence is possible. A total of 60 patients underwent local excision, with 5 local recurrences and 1 malignancy discovered (leiomyosarcoma). 80 Miscellaneous: Reports of vaginal masses have included fibromas, 81 histiocytomas, neural tumors (5 neurofibromas in 12 years, Armed Forces Institute of Pathology) and vascular lesions. 82 Vaginal varices can be identified in this area of the vaginal wall. Management of these lesions is predicated
FIG. 11. Large anterior wall vaginal leiomyoma. (Allis clamp is on reflected vaginal wall.)
by adequate delineation of the extent of the mass and any possible relationship to the urinary tract. Endometrioma occasionally will implant on the anterior vaginal wall in the presence oflesions elsewhere in the pelvis. These lesions may grow to significant size. Infectious masses include viral (condylomas) and microbial (vaginitis emphysematosa or etiology due to Hemophilus vaginalis) types. 83 Table 2 represents a summary of the differential diagnoses of urethral and vaginal lesions. Figure 12 depicts common anterior vaginal wall tumors.
1950
BENIGN FEMALE PERIURETHRAL MASSES TABLE
Lesion
2. Differential diagnostic considerations for urethral and anterior vaginal wall lesions Location
Symptoms, Physical Findings
Cystoscopic and Radiographic Findings Orifice of diverticulum visible on urethral floor, voiding cystourethrography opacifies lesion None or extrinsic compression
May be multilocular
None or extrinsic compression, IVP may indicate ectopic ureteral drainage None or extrinsic compression
Rule out ureteral ectopia before excision
Urethral diverticulum
Anterior vaginal wall, midline
Vaginal wall cyst Gartner's duct cyst
Anterior vaginal wall, midline or eccentric Anterolat. vaginal wall
Urinary tract infection, dysuria, dyspareunia, post-void dribbling, cystic mass Cystic mass may be multiloculated Cystic mass
Leiomyoma, hamartoma
Vaginal wall
Solid mass
Urethral diverticulum "
.'-' inclusion cyst
Gartner's duct cyst
Fm. 12. Urethral and anterior vaginal wall lesions. A, urethral diverticulum. B, vaginal wall inclusion cyst. C, Gartner's duct cyst.
Evaluation and management of periurethral and anterior vaginal wall lesions involve a systematic approach using a careful physical examination supplemented by specific diagnostic tests. Management of these tumors relies on definition of any possible communication with the urethra and delineation of upper tract status. Individualized therapy based on the presumptive diagnosis can then be performed and a successful outcome achieved. Dr. F. Y. Miyazaki supplied figure 1. REFERENCES
1. Stephens, F. D.: Congenital Malformations of the Urinary Tract. New York: Praeger Publishers, 1983. 2. Hamilton, W. J. and Mossman, H. W.: The urogenital system. In: Human Embryology: Prenatal Development of Form and Function, 4th ed. Baltimore: Williams & Wilkins, p. 377, 1976. 3. Waterman, R. E.: Human embryo and fetus. In: Atlas of Human Reproduction by Scanning Electron Microscopy. Edited by E. S. E. Hafez and P. Kenemans. Hingham, Massachusetts: Kluwer Boston, Inc., 1982. 4. Tanagho, E. A.: Embryologic basis for lower ureteral anomalies: a hypothesis. Urology, 7: 451, 1976. 5. Mandell, J., Bauer, S. B., Colodny, A. H., Lebowitz, R. L. and Retik, A. B.: Ureteral ectopia in infants and children. J.-uroL, 126: 219, 1981. 6. Huisman, A. B.: Aspects on the anatomy of the female urethra with special relation to urinary continence. Contr. Gynec. Obst., 10: 1, 1983.
Comments
Rule out malignancy
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