Female urethral diverticulum (UD) was originally described more than 200 years ago by Hey.¹ It is a relatively uncommon condition with an estimated incidence of between 0.02% and 4.7%²,³ and is thought to account for up to 1.4% of women presenting to urology services with incontinence.² This figure could be an underestimate due to the nonspecific plethora of symptoms that this condition may present with, the difficulties and delays in making a diagnosis due to a lack of awareness of the condition, and the potential for the condition to remain asymptomatic. A prevalence rate of 3% in an asymptomatic population was reported based on positive pressure urethrography in women being investigated for cervical cancer.⁴ The median age at time of diagnosis or treatment is between 36 and 46 years.⁵,⁶,⁷,⁸,⁹ A trend has been noted toward an increased rate of diagnosis over the last few decades,³ presumably due to increased awareness and diagnosis of this condition rather than an increasing prevalence.

The female urethra is a 4-cm-long tubular structure originating at the bladder neck and extending to the external urethral meatus. There are three distinct layers: the mucosal epithelium, the submucosal layer of elastic tissue which includes an extensive vascular network, and an outer muscular layer. The proximal third is lined by transitional epithelium and the distal two-thirds by stratified squamous epithelium (Fig. 36.1).¹⁰,¹¹ The anatomy of the paraurethral ducts has been described by Huffman¹² in detail, with variable numbers of paraurethral ducts terminating in tubular glands (Fig. 36.2), which exist over the entire length of the urethra posterolaterally and secrete mucous material that provide urethral lubrication. They are most prominent over the distal two-thirds, with the majority of the glands draining into the distal third of the urethra.¹³

A UD is commonly described as a benign, sac-like protrusion from the urethra with a surface lining that is continuous with the epithelial lumen of the urethra.¹⁴,¹⁵ However, there has been considerable variability of definitions used in the literature given the pathologic terms “diverticulum,” which implies the presence of all layers of the urethra including muscle, and “pseudodiverticulum,” which denotes the absence of at least one layer.¹⁶ This latter term more closely approximates the true histology of UD, with muscle tissue not being identified as a component of the diverticular wall on histopathology.¹⁶ Histologic examination of the epithelium of UD has identified the same findings as those seen in paraurethral cysts, with predominant cell types of squamous (42%), columnar (32%), combined squamous and columnar, and cuboidal.¹⁶

Given the indistinguishable histology of UD and paraurethral cysts,¹⁶ and with the dorsolateral anatomical position of the paraurethral glands in relation to the urethra also correlating with the location of twothirds of UD,¹⁷ a common origin is implicated and is in keeping with the most widely accepted hypothesis for UD development which is that of an acquired condition. The most common cause for UD is thought to be from infection of the periurethral glands, which can lead to obstruction and subsequent abscess formation as first described by Routh¹⁸ in 1890. When the abscess ruptures into the urethral lumen, it creates a fistulous connection with subsequent epithelialization of the tract. However, the causation of UD can be multifactorial with the final position and appearance of the diverticulum varying with its etiology. The urethral orifice may be midline or mediolateral and vary in size and position (Fig. 36.3), entering the proximal, mid, or distal urethra which can influence symptoms. Purulent material may be expressed on urethral compression (Fig. 36.4).

Alongside infection, other causes of acquired UD have been described, including trauma due to urethral surgery such as urethrovaginal fistula repair (Fig. 36.5), these UD are usually open and shallow as a result of a muscular defect in the posterior urethral wall. Other causes such as vaginal birth, urethral catheterization, urethral dilatation, and urethrotomy¹⁴,¹⁹ have also been reported. Previous synthetic midurethral sling has also been described as a possible aetiologic factor.¹⁹,²⁰ More recently, another etiology has been proposed for
development of proximal to midurethral UD, that of high pressure within the proximal urethra during voiding due to a high-tone nonrelaxing sphincter.²¹

Congenital UD has been described but is rare²²; however, it is important as can often be associated with other congenital urogenital abnormalities including persistence of Gartner duct with ectopic ureters (Figs. 36.6, 36.7 and 36.8).²³ Possible etiologies proposed are congenital dilatations of the paraurethral cysts or glands, faulty union of urogenital sinus folds, cloacogenic rests during development, or Mullerian duct cysts.¹⁴,¹⁷

A cyst or abscess of Skene gland and duct will also present as a paraurethral mass of the distal urethra with discharge and can be easily confused with UD. Although initially described by Skene²⁴ in 1880, their function is still not well understood. Wernert et al.²⁵ described the Skene gland as a group of glands arranged in long distal structures situated in the caudal two-thirds of the urethra, mainly in the dorsal and lateral mucosal stroma but extending in some cases to the smooth musculature of the septum urethrovaginale. They are tubuloalveolar formations on long ductal structures and resemble male prostate glands prior to puberty and androgenic stimulation and contain prostate-specific antigen and prostatic acid phosphatase on immunostaining. Controversy exists regarding the function of these glands: whether simply an embryologic remnant in the female or whether they have a role in sexual arousal and the ejaculation of lubricating fluid with orgasm²⁶ similar to the male prostate gland. Moalem and Reidenberg²⁷ have suggested that gland secretions may have antimicrobial qualities and protect from urinary tract infections.

Skene cysts of the gland or duct are found lateral to the distal urethra and external urethral meatus and when infection occurs can cause pain, dysuria, vaginal discharge, and dyspareunia. On examination, a palpable painful mass is present and purulent material can be expressed from the ductal orifice (Figs. 36.9 and 36.10A,B). The difference between a UD and a Skene cyst is the duct of the Skene cyst exits laterally and inferiorly
to the external urethral meatus and does not communicate with the urethra. When symptomatic, treatment is surgical drainage and complete cyst excision, as recurrent cyst and abscess formation is not uncommon (Fig. 36.10C,D). Histopathology of the cyst wall is always appropriate. As there is no communication with the urethra, the risk of fistula formation is less, although urethral injury is possible.

Although UD is commonly seen as a benign condition, stones or malignancy may develop within the diverticulum which can be easily missed, as seen on a magnetic resonance imaging (MRI) showing an intradiverticular filling defect which was a urethral adenocarcinoma (Fig. 36.11). This was missed by the other imaging modalities of ultrasound (USS) and computed tomography (CT) scanning.²⁸ Leiomyomas within UD have also been reported.²⁹ Stones are diagnosed with urethroscopy (Fig. 36.12) or radiology imaging and arise due to urinary stasis and cellular debris within the UD (Fig. 36.13). Malignancy has been reported in up to 6% of cases when examined histologically, with up to 10% of histology overall showing atypical glandular findings.⁶ Two-thirds of malignancies arising within UD are adenocarcinomas,³⁰ with transitional cell carcinomas exceedingly rare.³¹ Squamous cell cancer can also occur as in this woman who presented with a painless urethral mass (Fig. 36.14). Another study found the risk of unexpected tumors at surgery to be 2%³²; however, a high index of suspicion is needed for cancer with histologic review of all diverticulum pathology is essential. If the UD is small and asymptomatic, a conservative approach with regular imaging seems appropriate.

UD are commonly described as simple (20% to 40%), horseshoe or U-shaped (24% to 57%), or circumferential (23% to 37%) based on MRI findings.¹⁹,³³,³⁴ In 1993, Leach et al.³⁵ outlined a classification system for UD, called L/N/S/C3, with L relating to location within the urethra; N, number; S, size expressed in centimeters; and C3 standing for configuration, communication, and continence configuration. C1 identifies whether the UD is single, multiloculated, or saddle shaped; C2 identifies the site of communication with the urethral lumen, that is, whether it is distal, mid, or proximal; and C3 indicates the presence of stress urinary incontinence (SUI).³⁵ This classification does not appear to have been widely adopted, with only 10% of studies published after the classification was created using this system when analyzed in a 2016 systematic review.³⁶

There is significant discrepancy in the reported symptoms of UD due to the challenges in awareness and hence delay or difficulties in diagnosing this condition. Given the heterogeneity of symptoms that women can present with, often the diagnosis of UD can be significantly delayed and misdiagnosis is common. Historically, the presentation of UD has been described as the “three D’s”: dysuria, dyspareunia, and postmicturition dribbling, although with larger case series of women, it has become apparent that using this triad of symptoms for diagnosis would only identify 5% to 20% of cases¹⁵,³⁷ with up to 27% of women having none of these symptoms.³⁷ UD have been found in up to 3% of asymptomatic women.⁴ In our own series, the most common presenting symptoms were urinary urgency and frequency (60%), and dyspareunia (56%) with 88% having a tender anterior vaginal wall mass and 40% a urethral discharge.³⁸

Commonly, women may present with nonspecific irritative symptoms of the lower urinary tract such as urinary frequency and urgency, alongside SUI, recurrent urinary tract infections, and pain. The most common presenting symptoms are outlined in Table 36.1.⁵,⁹,¹³,¹⁹,³²,³³,³⁴,³⁷,³⁹,⁴⁰,⁴¹