Peter A. Humphrey
I. NORMAL ANATOMY. The male urethra is divided into three anatomic regions: prostatic (bladder neck to apex of the prostate), bulbomembranous (apex of the prostate to inferior surface of urogenital diaphragm), and penile (inferior surface of urogenital diaphragm to the urethral meatus). The prostatic portion is lined by urothelium, the bulbomembranous portion is lined by pseudostratified or stratified columnar epithelium, and the penile portion shows a transition from the stratified columnar epithelium at its origin to squamous epithelium at the meatus.
The female urethra is lined by urothelium in the proximal one-third and squamous epithelium in the distal two-thirds. The urethra has associated periurethral glands. Skene glands are present in females and are concentrated distally. Bulbourethral (Cowper glands) and glands of Littre, located in the bulbomembranous portion and along the penile urethra, respectively, are present in males.
II. GROSS EXAMINATION AND TISSUE SAMPLING
A. Urethroscopic biopsy tissue samples should be entirely submitted for histologic examination, and three levels should be examined.
B. Surgical excision of urethral carcinoma. For men, the type of surgery is dependent on tumor location and extent and includes transurethral resection (TUR), local segmental excision, partial or radical penectomy, and cystoprostatectomy. TUR chips should be submitted in their entirety. Segmental excision specimens should be sampled to include sections of the proximal and distal margins and area of deepest growth. Urethrectomy (primary or secondary) involves stripping of all or part of the urethra with preservation of the penis and is performed for patients with primary urethral carcinoma or secondary involvement by bladder carcinoma; sampling should include sections of the proximal and distal margins and area of deepest growth. Gross processing of penectomy and cystoprostatectomy specimens is covered in Chapters 30 and 29, respectively.
For women, local excision of the distal urethra and adjacent vaginal wall is often sufficient surgical therapy for carcinoma of the urethra; sections of the mass, and urothelial, radial soft tissue, and vaginal mucosal margins should be submitted. For proximal urethral cancer in women, cystourethrectomy (anterior exenteration, with excision of part or all of the vagina) is often necessary; sections of the mass demonstrating relationships with adjacent structures and depth of invasion, grossly uninvolved urethra and urinary bladder, and ureteral and radial soft tissue margins should be submitted.
III. DIAGNOSTIC FEATURES OF BENIGN DISEASES
A. Congenital anomalies
1. Urethral valves are mucosal folds lined by normal urothelium that project into the urethral lumen causing obstruction, hematuria, or inflammation. Posterior urethral valves are usually seen in men and are associated with bladder neck hypertrophy.
2. Diverticula are invaginations of urethral mucosa usually seen in women as a result of infection, trauma, or obstruction. They are lined by urothelium that may undergo squamous or glandular metaplasia (e-Fig. 23.1).*
3. Fibroepithelial polyp is a congenital anomaly usually involving the posterior urethra of male infants and young boys. It consists of a fibrous connective tissue stalk lined by urothelium.
B. Inflammation and infection
1. Urethritis is an inflammatory response in the urethra that is usually secondary to sexually transmitted diseases. Diagnosis is made by examination of a urethral smear that shows neutrophils. Polypoid urethritis is usually seen in the prostatic urethra near the verumontanum and is the result of inflammation that induces multiple polypoid lesions with edematous stroma, distended blood vessels, and chronic inflammation (e-Fig. 23.2).
2. Caruncle is a pedunculated or sessile polypoid inflammatory mass in the distal urethra in postmenopausal women showing a mixed inflammatory infiltrate with rich vascularity (e-Fig. 23.3A and B).
3. Malakoplakia is a rare urethral granulomatous inflammatory process, showing histiocytes containing characteristic Michaelis-Gutmann bodies, more commonly seen in women.
4. Condyloma acuminatum of the urethra is caused by human papilloma virus (HPV), usually serotypes 6, 11, 16, and 18. It can primarily involve the urethra but more commonly arises by direct extension from similar lesions in adjacent sites including the external genitalia, perineum, and anus. Histologically, there is a flat or polypoid proliferation of squamous epithelium (e-Fig. 23.4) with koilocytic atypia. Multiplicity and recurrence are common.
1. Squamous metaplasia can occur as a response to chronic inflammatory insults secondary to infection, diverticula, calculi, or instrumentation.
2. Urethritis cystica and glandularis are small cysts lined by urothelial and glandular cells, respectively.
3. Nephrogenic adenoma (metaplasia) is rare in the urethra. It occurs at the site of previous damage, often related to a previous surgical procedure. Microscopically, there is a proliferation of tubular and papillary structures, sometimes with cystic change, lined by flattened to cuboidal to hobnail cells with bland nuclear features. Some cases may be due to implantation and growth of tubular epithelial cells shed from the kidney.
1. Urothelial hyperplasia is a reactive thickening of cytologically bland urothelium and can be flat or papillary. In the papillary form the mucosa can be undulating but still lacks a well-developed fibrovascular core.
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