transitional epithelium

**Histology** - Stratified epithelium with 3 layers: basal cells, intermediate cells, and superficial "umbrella" (dome-shaped) cells. - Umbrella cells are large, sometimes binucleate, and have a scalloped luminal surface. When the organ stretches, the cells flatten and appear fewer layers thick. When it is empty, the cells look cuboidal and dome-shaped, with more layers. - Apical membrane has rigid plaques made of uroplakins (UPIA, UPIB, UPII, UPIII). These form the asymmetric unit membrane. Tight junctions between umbrella cells make the barrier (the "blood-urine barrier") nearly impermeable to water and urine solutes. Discoidal/fusiform vesicles in the cytoplasm fuse with the apical membrane to add surface area during filling. - Lies on a basement membrane over lamina propria (and then muscularis propria/detrusor in the bladder).

**Distribution** - Minor calyces, major calyces, renal pelvis, ureters, bladder, and the proximal (prostatic) urethra in males. Distal urethra changes to stratified columnar and then stratified squamous.

**Clinical significance** - **Urothelial (transitional cell) carcinoma:** The most common bladder cancer in the US. It can also arise in the renal pelvis, ureter, or urethra. Typically presents with painless hematuria. Risk factors include smoking (most important), aniline dyes/benzidine (azo dyes), occupational exposure (rubber, textile, leather), cyclophosphamide, phenacetin, and chronic analgesic use. It shows a "field defect," so tumors are often multifocal and recur. Papillary (often low grade) and flat carcinoma in situ (CIS) are the main patterns. The genetics involve FGFR3 and HRAS in low-grade papillary tumors, and TP53 and RB loss in CIS/invasive tumors. Treatment depends on muscle invasion: TURBT with intravesical BCG for non-muscle-invasive disease, and cystectomy ± chemotherapy for muscle-invasive disease. - **Squamous cell carcinoma of the bladder:** Arises from squamous metaplasia of urothelium after chronic irritation. Associated with Schistosoma haematobium (Egypt/Middle East), chronic catheterization, and recurrent stones/infections. - **Adenocarcinoma of the bladder:** Associated with urachal remnants (dome of the bladder) and cystitis glandularis/bladder exstrophy. - **Metaplasia:** Chronic irritation can cause squamous or glandular metaplasia of urothelium. - **Cytology:** Urine cytology detects exfoliated malignant urothelial cells, which is most sensitive for high-grade tumors. - **Embryology:** Bladder urothelium arises from endoderm of the urogenital sinus (the trigone is mesoderm-derived). The ureters, renal pelvis, and calyces arise from the ureteric bud (intermediate mesoderm).

**High-yield pearls** - Name "transitional" reflects the cells' changing shape with distension; "urothelium" is the preferred term. - Painless hematuria in an older smoker means bladder cancer until proven otherwise. - Schistosoma haematobium means squamous cell carcinoma, not urothelial carcinoma.