Bic N. Cung, MD
Jack H. Mydlo, MD
BASICS
DESCRIPTION
• Urethral masses may be palpable; they are often visualized on cystoscopy or other imaging modalities.
• In females the most common differential includes: urethral caruncle, periurethral/Skene duct cyst, urethral prolapse, ectopic ureterocele, urethral diverticulum, vaginal wall cyst (Müllerian and Gartner duct), and urethral and vaginal malignancy.
• In men inflammatory lesions such as Lichens Sclerosis (LS) or Balanitis Xerotica Obliterans (BXO), periurethral abscess and malignancy can be commonly seen.
EPIDEMIOLOGY
Incidence
• Incidence of urethral mass unknown
• With respect to urethral malignancy:
– African Americans twice as likely of developing primary urethral cancer as whites
– Primary urethral cancer at least twice as common in males as in females (1).
– Most common from 5th to 7th decades of life.
Prevalence
N/A
RISK FACTORS
• Malignancy:
– Chronic inflammation may increase risk of malignancy.
– History of bladder cancer may suggest urethral recurrence.
– HPV-16 infection has been linked to urethral carcinoma in males (2).
• Benign mass
– Chronic UTIs may suggest anatomic problem such as diverticuli.
Genetics
None
PATHOPHYSIOLOGY
• Anatomic considerations: The male urethra (averages about 20 cm in length), is divided into distal and proximal portions. The distal urethra, which extends distally to proximally from the tip of the penis to just before the prostate, includes the meatus, the fossa navicularis, the penile or pendulous urethra, and the bulbar urethra. The proximal urethra, which extends from the bulbar urethra to the bladder neck, includes distally to proximally the membranous urethra and the prostatic urethra
– Lymphatic drainage varies according to region:
Distal urethra drains to superficial and deep inguinal lymph node (LN).
Proximal urethra drains to external iliac, obturator, and internal iliac LNs in pelvis.
– Sex accessory glands. These can be the source of infection due to obstruction of their secretory ducts.
Prostate
Glans Littre
Cowper gland
• Anatomicconsiderations: The female urethra is In adults, it is about 4 cm in length and is mostly contained within the anterior vaginal wall.
– Lymphatic drainage varies according to region:
Distal 1/3 urethra drains to superficial or deep inguinal LN.
Proximal 2/3 urethra drains to external iliac, internal iliac, and obturator (deep pelvic LN).
– Mucus glands
Skene gland: Mucus-producing gland that opens into distal urethra; homologous to the prostate glands in males. It can be the site of infection, cysts, or diverticuli.
ASSOCIATED CONDITIONS
None
GENERAL PREVENTION
Safe sexual practices can prevent STDs and decrease risk of inflammatory/infectious conditions.
DIAGNOSIS
HISTORY
• Age and sex of patient
– Malignancy more common >50
• Prior history of bladder cancer may suggest urethral recurrence, particularly in men
• Sexual history:
– Genital warts, gonorrhea may predispose to malignancy.
• Lower urinary tract symptoms:
– Frequency, urgency, hematuria, or dysuria may be associated with stricture or malignancy.
– Obstructive voiding symptoms such as weak stream, straining, and dribbling
• History of UTIs:
– May be associated with urethral diverticulum
PHYSICAL EXAM
• General exam: Assess for lower extremity edema.
• Lymph node assessment:
– Metastatic disease from the distal urethra can involve the superficial inguinal LN.
• External genitalia: Examine for lesions for condyloma acuminatum.
• Urethral exam:
– Carefully palpate full length of lesion.
Palpate for abscess or areas of tissue necrosis
– Note location, number, consistency, degree of fixation.
– Careful bimanual exam to assess for extent of local invasion and involvement of bladder if malignancy is suspected.
– Inspect meatus for discharge, mass, or stricture.
– Compression or stripping of a diverticulum in females may express purulent discharge.
• Inspect perineum for fistulous tracts.
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Urine analysis
• Urine culture
• Urine cytology
• Urethral swab: Culture for gonorrhea, Chlamydia, and TB
Imaging
• Ultrasound to evaluate urethral stricture, diverticulum, and foreign body.
• VCUG can help diagnose urethral diverticulum.
• Retrograde urethrogram (RUG) to assess for location and length of urethral stricture.
• Pelvic MRI or CT to assess for urethral diverticulum, metastasis to the pelvic and inguinal LN, evidence of corporal invasion by carcinoma.
– Pelvic MRI often considered imaging study of choice for urethral neoplasms.
Diagnostic Procedures/Surgery
• Cystoscopy allows direct visualization of the mass and allows for biopsy.
• Percutaneous aspiration of fluctuant mass may provide fluid for cytology and culture.
• Needle biopsy may provide tissue for diagnosis for deep lesions.
• Open surgical biopsy for diagnosis.
Pathologic Findings
Based on specific diagnosis
DIFFERENTIAL DIAGNOSIS
• Depends on clinical presentation and age of patient:
– Children are more likely to have congenital disease
– Young adults are more likely due to trauma or STI/STDs
– Older adults are at greater risk for primary or metastatic malignancy.
• Congenital conditions:
– Benign fibroepithelial polyp
– Retention cysts of Cowper gland ducts
– Ectopic ureterocele
– Urethral diverticulum
The 3 Ds: dysuria, dyspareunia, dribbling
• Inflammatory:
– Stricture disease secondary to gonococcal urethritis
– Periurethral abscess
– Accessory gland cysts/abscesses
– condylomata acuminata
– TB
– Lichens Sclerosis (LS) or Balanitis Xerotica Obliterans (BXO)
Most common cause of meatal stenosis in adults
• Traumatic:
– Stricture disease secondary to injury; hematoma, foreign body
• Benign neoplasms:
– Hemangioma
– Adenomatous polyps
– Squamous papilloma
– Transitional cell papilloma
– Leiomyomas:
Increased prevalence in females aged 30–50 yr.
– Inverted papilloma
Type I benign, type 2 higher malignant potential and requires follow-up.
– Polypoid urethritis
Most commonly seen in patients with chronic catheter use.
– Nephrogenic adenoma
– Amyloidosis
– Skene (paraurethral) gland, inflammation/adenoma/abscess
– Urethral caruncle:
More common in postmenopausal women
• Malignant neoplasms:
– Primary urethral carcinoma, more common in females.
Squamous cell (80%)
Transitional cell (15%)
Adenocarcinoma (4%)
Melanoma (1%)
Clear cell adenocarcinoma has been associated with urethral diverticulum.
Skene (paraurethral) gland adenocarcinoma
Metastatic disease
• Miscellaneous conditions
– Urethral prolapsed:
Interlabial, well-circumscribed mass most common in African American females aged 5–7 yr, postmenopausal women is the 2nd most common group.
Stone impacted in urethra or dierticulum
Foreign body
• Mass in corporal body in male:
– Metastatic deposit
– Fibrosis of corporal body from priapism or trauma
– Peyronie disease plaque
– Penile prosthesis
• Vaginal wall mass:
– Leiomyoma
– Vaginal wall cyst:
Gartner duct cysts
TREATMENT
GENERAL MEASURES
• Management is directed by the pathologic findings.
– Cystoscopic exam with biopsy will usually provide the diagnosis.
– Imaging and bimanual exam will provide staging information in the case of malignancy.
• In cases with locally advanced disease, multimodality therapy using chemotherapy with radiation is sometimes used.
• Condyloma of the urethra: Intraurethral 5-FU cream, biopsy with fulguration/laser ablation.
• Urethral mucosal prolapsed: Estrogen and anti-inflammatory cream.
• Infectious etiologies: Antibiotic specific to offending organism
MEDICATION
First Line
N/A
Second Line
N/A
SURGERY/OTHER PROCEDURES
• Urethral stricture:
– Dilation
– Internal urethrotomy
– Urethroplasty
• Urethral prolapsed:
– Excision
• Urethral diverticulum:
– Excision
• Benign neoplasm:
– Biopsy for diagnosis
– Excision, fulguration, laser ablation.
• Malignant neoplasms:
– Male urethra: Partial or total urethrectomy, possible penectomy with perineal urethrostomy.
– Female urethra: Total urethrectomy.
– Cystectomy necessary for high-grade lesions near bladder neck for both males and females.
– In females, this includes an anterior exenteration (urethrectomy, cystectomy with pelvic lymphadenectomy, hysterectomy with salpingectomy, and anterior vaginal wall).
– Inguinal and pelvic LN dissections are based on location of lesions.
ADDITIONAL TREATMENT
Radiation Therapy
• May be indicated in some cases of urethral cancer to decrease local recurrence.
• In women, radiation therapy using brachytherapy and external beam radiation combination is a suitable alternative.
Additional Therapies
Cisplatin-based chemo therapy has a role in the adjuvant and neo-adjuvant setting for advance disease (3).
Complementary & Alternative Therapies
Combination of chemotherapy, radiation therapy, and surgery is recommended for advanced female urethral cancer.
ONGOING CARE
PROGNOSIS
• Depends on etiology of mass
• Neoplasms:
– Males
Survival dependent on grade and stage of tumor.
Anterior urethral carcinoma of lower grade has best survival and posterior urethral carcinoma of higher grade has worst survival.
– Distal urethral carcinoma in females of low stage has 70–90% cure rates with surgery.
– Proximal urethral carcinoma in females are more likely of high stage and has poor prognosis, <20% 5-yr survival.
COMPLICATIONS
• Dependent on pathology and treatment
• Urethral stricture: Complications secondary to instrumentation and treatment of urethral mass.
FOLLOW-UP
Patient Monitoring
• Cystourethroscopy and urine cytology every 6 mo for urethral carcinoma.
• Urethral condyloma require urethroscopy and retreatment for disease eradication.
Patient Resources
• Urology Care Foundation: Urethral cancer. http://www.urologyhealth.org/urology/index.cfm?article=65
• Urology Care Foundation: Benign urethral lesions. http://www.urologyhealth.org/urology/index.cfm?article=110
REFERENCES
1. Swartz MA, Porter MP, Lin DW, et al. Incidence of primary urethral carcinoma in the United States. Urology. 2006;68:1164–1168.
2. Wiener JS, Liu ET, Walther PJ. Oncogenic human papillomavirus type 16 is associated with squamous cell cancer of the male urethra. Cancer Res. 1992;52:5018–5023.
3. Dayyani F, Pettaway CA, Kamat AM, et al. Retrospective analysis of survival outcomes and the role of cisplatin-based chemotherapy in patients with urethral carcinomas referred to medical oncologists. Urol Oncol. 2013;31(7):1171–1177.
ADDITIONAL READING
Gakis G, Witjes JA, Compérat E, et al. EAU guidelines on primary urethral carcinoma. Eur Urol. 2013;64(5):823–830.
See Also (Topic, Algorithm, Media)
• Ureterocele
• Urethra, Carcinoma, General Considerations
• Urethra, Caruncle
• Urethra, Diverticulum, Female
• Urethra, Squamous Cell Carcinoma
CODES
ICD9
• 189.3 Malignant neoplasm of urethra
• 223.81 Benign neoplasm of urethra
• 599.84 Other specified disorders of urethra
ICD10
• C68.0 Malignant neoplasm of urethra
• D30.4 Benign neoplasm of urethra
• N36.8 Other specified disorders of urethra
CLINICAL/SURGICAL PEARLS
• Many benign and malignant urethral masses can present with similar constellation of symptoms.
– Cystoscopic examination and biopsy are often necessary to confirm diagnosis.
• Draining fistulas of the penis and perineum should alert suspicion of malignancy.