UROTHELIAL CARCINOMA

· Affects the urinary bladder, renal pelvis, and ureter

· Sites: Lateral or posterior walls at the base of the urinary
bladder
· Causes: (Pee SAC)
® Phenacetin
® Smoking - 4x greater risk
® Workers in Aniline dye, rubber, paint, and leather industries
® Cyclophosphamide, arsenic exposure
® Nitrosamines
® Schistosoma haematobium infection (30%)
· Pathogenesis
® Genetic factors: p53 and RB supressor genes and HRAS
proto-oncogene, alterations in EGFR
® Environmental factors
® Gross findings
▪ Tumor in the pelvis
o A small non-invasive papillary urothelial carcinoma
involving the renal pelvis
o Patient will present with gross hematuria
o Smooth, pink-gray urothelial lining in the uninvolved
areas

Figure X. H&E slide of a NORMAL urothelium of the urinary bladder,

characterized with 6-7 layers of cells, with intact basement membrane, and good
basal nuclei polarity.

Table __. Classification of bladder tumors.

From the recording: No need to memorize the table, just be familiar that a
Figure X. Gross specimen of papillary urothelial carcinoma. A papillary tumor papilloma is benign, a PUNLMP has borderline potential, and that both low grade
extended at the calyces with cauliflower-like pattern, showing multifocal, and high grade papillary carcinomas are malignant
exophytic, pink-tan neoplasm arising in the calyces and pelvis.

· WHO Classification of Non-invasive and Invasive Urothelial

® Histopathology Neoplasia
▪ Both low grade and high grade wil present with increased ® Non-invasive Urothelial Neoplasia
layers in urothelium (> 7 layers)
▪ Hyperplasia (flat and paillary
▪ Low Grade- usually papillary and typically not invasive
▪ High Grade- papillary or flat and usually invasive ▪ Reactive atypia
▪ Atypia of unknown significance
▪ Urothelial dysplasia (low-grade intraurothelial neoplasia)
▪ Urothelial carcinoma in situ (high-grade intraurothelial
neoplasia)
▪ Urothelial papilloma
▪ Urothelial papilloma, inverted type
▪ Papillary urothelial neoplasm of low malignant potential
▪ Non-invasive low-grade papillary urothelial carcinoma
▪ Non-invasive high-grade papillary urothelial carcinoma
® Invasive Urothelial Neoplasia
▪ Lamina propria invasion
Figure X. Left: Low grade papillary urothelial carcinoma characterized with mild ▪ Muscularis propria (detrusor muscle) invasion
pleiomorphism, increased mitotic activity, and loss of nuclei polarity Right: High
grade papillary urothelial carcinoma characterized with more atypical cells · Prognosis:
® Five year survival rate for all stages combined is 80%
® Potential for recurrence is greatest with high grade, multifocal
disease and increasing size of the tumor
® Poor prognosis
▪ Infiltration of the wall of the pelvis and calyces
▪ Easily infiltrates the fatty tissue
· Clinical Features
 ® Hematuria- via fragmentation
® Palpable hydronephrosis and flank pain due to blockage of
urinary outflow
® In 50% of cases, there is a preexisting or concomitant
bladder urothelial tumor
· Tumors that can arise
® Transitional epithelial carcinoma
® Atypia, loss of polarity
® Squamous Cell Carcinoma
® Risk factors: renal stones and chronic infection