Transitional Epithelium (Urothelium)

At a glance

Stratified epithelium designed to stretch: umbrella cells on top, intermediate layers, and a basal layer on one basement membrane.
Thickness varies with distension (bladder full vs empty); apical plaques and tight junctions protect against urine.
CK7/GATA3/p63 positive; umbrella cells also CK20/uroplakin; basal cells p63+/CK5/6+.
Key mistakes to avoid: misreading relaxed “crowded” urothelium as dysplasia; remember muscularis propria orientation differs from GI.

1. Architecture

Stratified epithelium specialized to stretch (3–7 layers depending on distension)

Why: urinary tract volume changes a lot; more layers when relaxed, looks thinner when stretched.

Surface (apical) cells are large “umbrella” or “dome” cells (sometimes binucleated)

Why: these cells form the tight, urine-proof lid. Big surface lets them flatten when the bladder fills.

Intermediate layer of polygonal cells, several layers thick

Why: this is the buffer layer that allows the surface to move without tearing the basal part.

Basal layer of small cuboidal cells on a single basement membrane

Why: this is the germinative/anchoring layer, keeps the urothelium attached during stretching.

2. Cytologic Features

Umbrella cells with abundant eosinophilic cytoplasm and often 2 nuclei

Why: they need extra membrane machinery and metabolic capacity to maintain the barrier.

Apical “plaques” (urothelial plaques) ultrastructurally

Why: these give the surface its impermeability to urine.

Cells look taller and more crowded when bladder is empty; flatter and fewer apparent layers when full

Why: same epithelium, different mechanical state.

3. Polarity and Attachment

Apical pole faces urine

Why: all barrier specializations are here.

Lateral borders with strong junctional complexes

Why: urine must not leak between cells.

Basal cells attached to basement membrane

Why: provides the fixed reference while upper layers slide.

4. Junctional Complexes

Tight junctions at the apex of umbrella cells

Why: first line of defense against toxic, hyperosmolar urine.

Desmosomes between deeper cells

Why: bladder distends and recoils; desmosomes keep the stack as one sheet.

Specialized apical membrane with fusiform vesicles (on EM)

Why: membrane can be added/removed quickly to adjust to volume.

5. Basement Membrane

Single, continuous basement membrane

Why: even though the top moves, the bottom must stay fixed to allow regeneration.

6. Cytoskeleton

Well-developed actin cortex in umbrella cells

Why: supports the very wide apical surface during stretching.

Cytokeratins typical of urothelium (see below)

Why: gives the urothelial identity and mechanical strength.

7. Immunohistochemistry / Biomarkers

Positive (core urothelial panel):

CK7
CK20 (usually superficial cells)
Uroplakin II / III
GATA3
p63 (basal/suprabasal)
Why: together these confirm “this is urothelium,” especially in biopsies and in metastatic workups.

Pattern to remember:

Superficial umbrella cells: CK20+, uroplakin+, GATA3+
Basal/intermediate cells: p63+, CK7+, often CK5/6
Why: top cells show “urine-facing” differentiation, bottom cells show “stem/basal” program.

Negative / helpful to exclude:

CDX2, strong diffuse CK20 of colorectal-type
TTF1 pulmonary
Endothelial markers (CD31, ERG)
Why: helps when you have a small fragment in the bladder/ureter and need to prove it is urothelium.

8. Vascularity and Nutrition

Avascular epithelium, fed from lamina propria

Why: vessels in the urothelium would be exposed to urine and get damaged; better to keep them in the connective tissue.

9. Functional Correlation

Main job: urine barrier that can stretch

Why: urine is hypertonic and contains waste; if it leaks, you get chemical cystitis and fluid shifts.

Apical plaques + tight junctions = high resistance to water, ions, urea

Why: bladder may store urine for hours; barrier must not fatigue.

Stratification = protection from mechanical trauma during filling/voiding

Why: lumen diameter changes quickly.

10. Regeneration and Injury

Basal cells can proliferate to replace surface cells

Why: umbrella cells are exposed to toxic urine and can be lost.

Chronic irritation (stones, catheters, infection) → squamous or glandular metaplasia

Why: if the environment becomes too harsh or too inflammatory, urothelium switches to a phenotype better suited for that insult.

11. Typical Anatomic Correlates

Renal pelvis, calyces, ureter, urinary bladder, proximal urethra (female; prostatic part in male)

Why: every urinary segment that must both conduct and sometimes store urine uses urothelium.