Chapter 12 - Bladder Flashcards
What indications or presentations generate bladder biopsies?
Hematuria
Abnormal urine cytology
History of neoplasm
Lesion seen on cystoscopy
Describe the normal morphologic appearance of urothelium.
5-7 cell thick layer of uniform cells without significant surface maturation. Basal mitoses, surface umbrella cells (pillowy and atypical).
Describe the layers deep to the urothelium.
Lamina propria (with vessels, lymphatics, smooth muscle fibers and even fat)
Detrusor muscularis propria
Adventitia or serosa (depending on site)
Describe and distinguish between von brunn’s nests, c**ystitis cystica, and cystitis glandularis
Von brunn’s nests are downward invaginations of normal, bland urothelium.
Cystitis cystica is when these nests develop central lumina.
Cystitis glandularis features columnar cell metaplasia.
Where and in whom is squamous metaplasia a common normal variant?
In the trigone area of the female bladder
What is the most likely cause of granulomatous cystitis?
Does it merit AFB/GMS staining?
Intravesical BCG therapy
Not if the history of BCG treatment is documented
Describe the pathogenesis of schistosoma infection.
Parasitic worms extrude their eggs into the bladder wall, causing an intense foreign-body reaction.
What is polypoid cystitis?
What is interstitial cystitis?
Polypoid cystitis is similar to an inflammatory polyp and is related to any chronic injury (eg catheters, stones, fistulae)
Interstitial cystitis is a poorly understood disease and a diagnosis of exclusion.
What is the cause, gross and microscopic appearance of malakoplakia?
A defective macrophage response to infection, resulting in grossly yellow plaques comprised of sheets of epithelioid histiocytes with Michaelis-Guttman bodies (resembling archery targets).
What is the progression of flat urothelial neoplasia?
Of papillary urothelial neoplasia?
Flat: Benign > dysplasia (rarely diagnosed) > carcinoma in situ > invasive carcinoma
Papillary: Papilloma > PUNLMP > LGPUC > HGPUC
What molecular abnormalities underlie the flat and papillary urothelial carcinoma pathways?
Flat: p53 loss, 9-, RB loss, INK4a loss, 8p-
Papillary: FGFR3, 9-, INK4a loss
What are the features of urothelial carcinoma in situ?
Increased nuclear size (4-5x lymphocytes)
Hyperchromatic nuclei with irregular (“boulder”) outlines
Denuding with clinging cells
*does not need to be full thickness*
How is urothelial dysplasia described and called?
Atypia not quite enough to call CIS.
Rarely called, as low-grade is ignored while high-grade is essentially CIS.
Distinguish between the morphologic appearances of papilloma and PUNLMP.
Papilloma have normal urothelial lining and are small.
PUNLMPs are thickened with good organization. Exceeding rare mitoses in the basal layer only.
Describe the morphologic appearance of papillary hyperplasia.
Undulating wave-like urothelium without true fibrovascular cores.
Distinguish between the morphologic appearance of low and high-grade papillary urothelial carcinoma.
Low-grade: Still fairly organized with subtle nuclear atypia. Uncommon mitoses.
High-grade: Very disordered, pleomorphic, full thickness mitoses. Often invasive.
What forms of nonurothelial differentiation can be seen in HGPUC?
How much high-grade behavior is required to define the lesion as high-grade?
Squamous or glandular
As little as 5% can define the entire lesion as high-grade.
What features define urothelial carcinoma invasion?
Irregular tongues or cells or single cells pushing into the lamina propria
Desmoplasia (uncommon)
Retraction artifact (stroma away from tumor nests)
Paradoxical differentiation
What is paradoxical differentiation?
Deep invasive urothelial carcinoma cells can acquire increased pink cytoplasm, mimicking maturing surface cells.
What is the most important threshold of bladder invasion?
Invasion of the muscularis propria (detrusor muscle).
Biopsies must identify it and determine involvement.
How can invasive carcinoma be distinguished from involvement of Von Brunn’s nests?
In von Brunn’s nest involvement, the nests are round and even without ragged borders, and appear basophilic with crowding or palisading of the outermost layer of cells.
Name and describe 3 mimics of urothelial carcinoma.
Inverted papilloma (grows into the LP but the normal urothelium not cross basement membrane)
Reactive urothelial changes (chromatin is evenly blue grey and nuclear contour smooth & oval)
Nephrogenic adenoma (benign proliferation with many appearances…)
Describe the morphologic appearance of nephrogenic adenoma.
Possibilities include cuboidal cells lining papillae, hobnail cells lining vessel-like structures, small thyroid-like tubules, and tubules mimicking signet ring tumors.
Describe the morphologic appearance of nested urothelial cell carcinoma.
An invasive urothelial carcinoma made of small bland nests resembling von Brunn’s nests. Look for an infiltrative pattern and architecturally complex pattern of nests.
Describe the morphologic appearance of lymphoepithelial-like carcinoma.
Resembles normal bladder with raging inflammation and tissue destruction. Malignant cells are often obscured by lymphocytes. Tumor cells have indistinct cytoplasmic borders.
Normal urothelium
Arrow: Umbrella cells
Arrowhead: Lymphocyte, for size comparison (2-3x smaller)
Cystitis Glandularis
Arrow: von Brunn’s nest
Asterisk: Lumen with columnar cell metaplasia
Flat carcinoma in situ.
Arrow: Denuding of urothelium
Papilloma
Arrow: Umbrella cell
Asterisk: Fibrovascular core
PUNLMP
Note thickening without atypia
LGPUC
Arrow: Fibrovascular core
Circle: Disorganized, enlarged cells
HGPUC
Arrow: Large mitosis
Invasive urothelial carcinoma
Arrow: Basement membrane, with cells below featuring paradoxical differentiation
Invasive carcinoma in the detrusor muscle.
Arrow: Cancer
Arrowheads: Detrusor muscle
Reactive nuclei
Note enlargement and prominent nucleoli with smooth nuclear outline and even chromatin.
Nephrogenic adenoma, no urothelium
Arrowheads: Multiple tiny tubules in the lamina propria with dark nuclei.
Lymphoepithelial-like carcinoma.
Arrow: Background of lymphocytes
Arrowhead: Malignant cells
Circle: Atypical mitosis
