Male Genital Tract

• Urothelium


  Composed of 5-6 layers of cells with oval nuclei, often with linear nuclear grooves and surface layer consists of flattened umbrella cells with abundant cytoplasm
• Urothelium


  • Rests on a well-developed basement membrane
  • Lamina propria beneath contains wisps of smooth muscle that form discontinuous muscularis mucosa
  • There is a deeper well-defined muscle bundles of the detrusor muscle (muscularis propria)
• Obstruction of urine outflow


  Increases intravesical pressure and musculature undergoes hypertrophy
• Ureters


  • Lie in a retroperitoneal position, as it enters the pelvis; pass anterior to either the common iliac or external iliac artery
  • In females, they lie close to uterine arteries
• Narrowings of the ureter

  • Ureteropelvic junction
  • Pelvic brim
  • Ureterovesical junction
• The narrowings are sites where stones can lodge
• Double and Bifid Ureters

  • Associated with double renal pelvises or with anomalous large kidney terminating in separate ureters
  • May pursue separate course in the bladder but commonly joined in the bladder and drain in a single orifice
  • Most are unilateral, no clinical significance
• Ureteropelvic Junction (UPJ) Obstruction

  • Most common cause of hydronephrosis in infants and children
  • Bilateral, associated with other anomalies, more common in male
  • In adults, more common in women and most often unilateral
  • Abnormal organization of smooth muscle bundles at the UPJ, to excess stromal deposition of collagen between smooth muscles
• Diverticula


  • Saccular outpouchings of the ureteral wall
  • Most are symptomatic, but urinary stasis may lead to infections
  • Dilation (hydroureter), elongation, and tortuosity of the ureters
• Ureteritis


  Typically NOT associated with infection
• Primary tumors of the ureter are rare
• Fibroepithelial Polyp


  • Tumor-like lesion presents as small mass projecting into the lumen, often in children, composed of loose, vascularized connective tissue overlaid by urothelium
• Primary malignant tumors of the ureter resemble those arising in the renal pelvis, calyces, and bladder
• Majority of ureteral tumors are urothelial carcinomas may cause obstruction
• Obstructive lesions


  Unilateral obstruction results to proximal causes, while bilateral obstruction arises from distal causes
• Sclerosing Retroperitoneal Fibrosis


  • Uncommon, fibrotic proliferative inflammatory process encasing the retroperitoneal structures and leading to hydronephrosis
  • Middle age to late age, more common in males
  • A subset is related to IgG4-related disease, with elevated serum IgG4 and fibroinflammatory lesions w/ IgG4 plasma cells
  • Often involves pancreas and salivary glands
  • Fibrous tissue containing a prominent infiltrate of lymphocytes with germinal centers, plasma cells (IgG4) and eosinophils
• Cystitis is common in young women of reproductive age
• Vesicoureteral Reflux


  • Most common and serious congenital anomaly
  • Major contributor to renal infection and scarring
• Congenital Diverticula


  • Focal failure of development of the normal musculature during fetal development
• Acquired Diverticula


  • Most often seen with prostatic enlargement, producing obstruction to urine outflow and marked thickening of the bladder wall, the increase in intravesical pressure causes outpouching of the wall
  • Frequently multiple and have narrow necks located between the interweaving hypertrophied muscle bundles
  • Urinary stasis may lead to infection or calculi formation
• Exstrophy of the Bladder


  • Developmental failure in the anterior wall of the abdomen and bladder, the bladder either communicates directly via a large defect or lies as an open sac
  • Exposed mucosa may undergo colonic glandular metaplasia and is subject to infections
  • Increased risk of adenocarcinoma
• Urachal anomalies


  • The urachus (canal that connects the fetal bladder with the allantois) is normally obliterated after birth
  • Sometimes remain in part or in whole
  • When totally patent, a fistulous urinary tract connects the bladder with the umbilicus
  • Sometimes, only the central region persists give rise to urachal cysts, lined by urothelium or metaplastic glandular epithelium
  • Carcinomas, mostly glandular tumors, may arise from such systs
• Common etiologic agents of cystitis

  • Coliforms: Escherichia coli
  • Proteus, Klebsiella, Enterobacter
  • Tuberculous cystitis
  • Candida albicans, cryptococcal
  • Schistosomiasis (S. haematobium)
  • Chlamydia, Mycoplasma
• Radiation cystitis may also happen due to irradiation
• Symptoms of cystitis


  • Frequency – urination every 15-20 minutes
  • Lower abdominal pain localized in suprapubic area
  • Dysuria – pain of burning sensation of urination
• Interstitial Cystitis (Chronic Pelvic Pain Syndrome)


  • Occurs most frequent in women characterized by intermittent, often severe suprapubic pain, frequency, urgency, hematuria, and dysuria and cystoscopic findings of fissures and hemorrhages
  • Etiology is unknown
  • Associated with chronic mucosal ulcers (Hunner ulcers), termed the late phase
  • Increase numbers of mucosal mast cells
  • Transmural fibrosis may appear late in the course
• Malakoplakia


  • Inflammatory reaction that appears to stem from defects in phagocyte function arises in the setting of bacterial infection, mostly in E. coli or Proteus species
  • Increased frequency in immunosuppressed patients
  • Soft, yellow, slightly raised mucosal plaques filled with large, foamy macrophages mixed with multinucleate giant cells
  • The macrophages have abundant granular cytoplasm
  • Laminated mineralized concretions due to deposition of calcium in enlarged lysosomes known as Michaelis-Gutmann bodies
• Polypoid Cystitis


  • Inflammatory lesions resulting from irritation of the mucosa
  • Indwelling catheters are the most common culprits
  • Urothelium is thrown into broad bulbous polypoid projections as a result of submucosal edema
• Cystitis Glandularis and Cystitis Cystica

  • Common lesions in which nests of urothelium (Brunn nests) grow downward to the lamina propria
  • Epithelial cells undergo metaplasia and take on a cuboidal or columnar appearance (cystitis glandularis) or retract to produce cystic spaces lined by flattened urothelium (cystitis cystica)
  • Since they coexist they are called cystitis cystica et glandularis
  • In a variant, goblet cells exist, resembling intestinal mucosa (intestinal or colonic metaplasia)
• Squamous Metaplasia


  Response to injury, urothelium is replaced by non-keratinizing squamouse epithelium
• Nephrogenic Adenoma


  • Results from implantation of shed renal tubular cells at sites of injured urothelium
  • The overlying urothelium may be focally replaced by cuboidal epithelium, which can assume papillary growth pattern
  • Tubular proliferation can infiltrate the underlying lamina propria and superficial detrusor muscle, mimicking malignant process
• Most epithelial tumors of the bladder are urothelial type, thus interchangeable called urothelial or transitional tumors
• 90% of all bladder tumors are urothelial tumors
• Urothelial tumors may be seen in any site where there is urothelium such as in renal pelvis and the distal urethra
• Two distinct precursor lesions to invasive urothelial carcinoma

  • Non-invasive papillary tumors – most common
  • Flat non-invasive urothelial carcinoma – carcinoma in situ
• Most common urothelial tumors originate from papillary urothelial hyperplasia
• Grading system for urothelial tumors

  • Low-grade
  • High-grade
• Once muscularis propria is invaded, there is 30% 5-year survival for urothelial carcinoma
• Epidemiology and Pathogenesis of urothelial tumors

  • Higher in men, 3:1, in developed countries, 50-80 y/o
  • Factors: Cigarette smoking – most important, 5-7-fold increase; Industrial exposure to aryl amines - 2-naphthylamine; Schistosoma haematobium; Long-term analgesic use; Long-term exposure to cyclophosphamide; Irradiation
  • Several acquired genetic mutations, strongly associated with gain-of-function mutation in FGFR3 found in non-invasive low-grade papillary carcinomas as its result in receptor tyrosine kinase
  • Loss-of-function mutations in TP53 and RB are seen in high-grade and often invasive tumors
  • Common are losses on chromosome 9 (deletions, monosomy)
  • 9p deletions (9p20) span region includes CDKN2A
• Papillomas


  • 1% or less, seen in younger patients, arise singly as small, delicate structures, superficially attached to mucosa by a stalk, referred as exophytic papillomas
  • The finger-like papilla have central core of loose fibrovascular tissue covered by epithelium identical to the urothelium
  • Inverted papillomas are completely benign consisting of inter-anastomosing cords of bland urothelium extending down the lamina propria