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• Functions as the terminal duct for both the genital and urinary system
• Epithelium is derived from the urogenital sinus, which forms from the ventral portion of the endodermal cloaca after its division (Bostwick: Urologic Surgical Pathology, 3rd Edition, 2014)

• Measures 15 - 20 cm in length
• Urethral sphincter surrounds the urethra
  • Extends from the bladder neck to the inferior fascia of the urogenital diaphragm (Int Urol Nephrol 2014;46:1469)
  • Controls urination and discharge of semen into urethra
  • Composed of smooth and striated muscle
• Divided into prostatic, membranous and penile urethra (Ross: Histology - A Text and Atlas, 7th Edition, 2015, Gartner: Color Textbook of Histology, 3rd Edition, 2006)
  • Prostatic urethra
    • Extends from the bladder neck through the prostate gland (3 - 4 cm)
    • Lined by urothelium
    • Ejaculatory ducts enter at the posterior wall
    • Most prostatic ducts empty into the posterior and lateral walls (Bostwick: Urologic Surgical Pathology, 3rd Edition, 2014)
    • Verumontanum (Müllerian vestige) is posterior to the mid prostatic urethra into which the ejaculatory ducts empty and subsequently join with the prostatic urethra (Ross: Histology - A Text and Atlas, 7th Edition, 2015)
  • Membranous urethra
    • Extends from the apex of the prostate to the bulb of the penis (1 cm) (Ross: Histology - A Text and Atlas, 2015, 7th Edition, 2015, Bostwick: Urologic Surgical Pathology, 3rd Edition, 2014)
    • Lined by stratified / pseudostratified columnar epithelium (similar to urothelium but lacking umbrella cells)
    • Passes through the urogenital diaphragm as it enters the perineum
    • Surrounded by external voluntary sphincter formed by skeletal muscle of the urogenital diaphragm
  • Penile (spongy) urethra
    • Extends through the penis to the urethral meatus opening in the glans (15 cm) (Ross: Histology - A Text and Atlas, 7th Edition, 2015, Bostwick: Urologic Surgical Pathology, 3rd Edition, 2014)
    • Divided into 3 regions
      • Bulbar urethra: spans the bulb of the penis, lined by stratified / pseudostratified columnar epithelium
      • Pendulous urethra: spans the pendulous penis (shaft), lined by stratified / pseudostratified columnar epithelium
      • Fossa navicularis: dilated portion in the glans, lined by nonkeratinizing squamous epithelium
    • Surrounded by the corpus spongiosum
    • Bulbourethral (Cowper) glands, glands of Littré (mucous glands) and intraepithelial (juxtaepithelial) glands empty into the penile urethra

Contributed by Debra L. Zynger, M.D.

• Urothelium
  • Basal layers are composed of either low columnar or cuboidal cells, followed by several layers of polyhedral cells
  • Most superficially composed of round, dome shaped umbrella cells that are occasionally multinucleated and flattened according to amount of distention
• Stratified / pseudostratified columnar epithelium
  • Multiple cell layers of polyhedral cells; the most superficial are columnar
  • Stratified / pseudostratified; in the pseudostratified layer, all cells are in contact with the basal layer
• Nonkeratinizing squamous epithelium
  • Composed of multiple layers
  • Divided into zones according to cell shapes: cuboidal (deepest), polymorphous (middle), squamous / flattened (superficial)
• Urethral / periurethral glands
  • Bulbourethral (Cowper) glands: mucous - acinous glands in the bulbous and membranous urethra with uniform pale cytoplasm and basal, compressed nuclei
  • Littré glands: tubuloacinar mucinous glands with uniform, pale eosinophilic to clear cytoplasm and basally flattened nuclei in penile urethra (Mills: Histology for Pathologists, 4th Edition, 2012)
  • Intraepithelial (juxtaepithelial) glands: nests of cells with eosinophilic to flocculent cytoplasm with basally placed nucleus located at the junction of the epithelium and subepithelium

Contributed by Debra L. Zynger, M.D.

The image above shows a prostate needle core biopsy that also contained skeletal muscle (not shown). What is your diagnosis?

1. Bulbourethral (Cowper) glands
2. Fossa navicularis
3. Prostatic adenocarcinoma, atrophic type
4. Prostatic adenocarcinoma, foamy type

A. Bulbourethral (Cowper) glands. Bulbourethral (Cowper) glands are shown, which are near the prostatic apex and usually in close proximity to skeletal muscle. These are a mixture of mucinous glands with bland flattened nuclei and occasional nonmucinous glands / ducts in which the multilayered nature of the epithelium is easier to appreciate. Bulbourethral (Cowper) glands mimic prostatic adenocarcinoma. In particular, the mucinous glands overlap in morphology with foamy prostatic adenocarcinoma. In difficult cases, immunostains can be performed in which adenocarcinoma will lack basal cells and have expression of AMACR, while bulbourethral (Cowper) glands will have patchy basal cells and have weak to no AMACR staining.

Answer B is incorrect because fossa navicularis is a part of the penile urethra, lined by squamous epithelium. Answer C is incorrect because prostatic adenocarcinoma, atrophic type is a type of carcinoma that mimics atrophy. Answer D is incorrect because prostatic adenocarcinoma, foamy type is a type of carcinoma that mimics bulbourethral glands. Prostatic adenocarcinoma, foamy type will not have the bland duct structures mixed with mucinous glands and will not be exclusively found near skeletal muscle.

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Reference: Anatomy & histology-male urethra