Urine and Bladder Washing Cytology - Cibas Flashcards
Most significant risk factors for bladder cancer
Aniline dyes
Cyclophosphamide
Smoking
Schistosomiasis
Voided Urine collection
Should be taken 3-4 hours after the patient last urinated, and morning voided urine should be avoided.
Features of morning voided urine
Low pH
Hypertonic
These can make any cells in morning voided urine degenerate faster.
Catheterized Urine collection
Generally less advantageous specimen.
Often urine collected from an indwelling catheter is a pooled specimen that has been at room temperature for many hours and is degraded. The tip of the catheter often scrapes off benign cell clusters, which can mimic the appearance of a low-grade papillary neoplasm.
Bladder Washing collection
Obtained through a catheter by irrigating the bladder with 5-10 pulses of 50 mL of saline, producing a cellular suspension of freshly exfoilated epithelial cells.
Provides better cellular preservation, greater cellularity, and a smaller chance of contamination by background beris.
Cytologic patterns of inadequate urine specimens
Absent or scant urothelial cells
Obscuring inflammation, blood, or lubricant
Marked degenerative changes
“Limited specimen”
An evidence based cutoff of less than 10-20 urothelial cells/10 hpf has been used for this descriptor, indicating lower sensitivity.
Paris System Reporting Terminology
“Negative for high-grade urothelial carcinoma”
“Atypical urothelial cells”
“Suspicious for high-grade urothelial carcinoma”
“High-grade urothelial carcinoma”
“Low grade urothelial neoplasia”
What you need to see to call “low grade urothelial carcinoma”
A fibrovascular core with capillaries
How clinicians tend to interpret reports
“Atypical” will be interpreted as negative in most clinical contexts.
“Suspicious” will be interpreted as warranting additional investigation.
Sensitivity of urine cytology for high grade urothelial carcinoma, including “suspicious” and “positive” categories.
~70%
Range of a normal urothelial cell
Intermediately sized with moderate finely granular or vacuolated cytoplas, a round nucleus, and a small nucleolus. Nuclei may be folded, triangular, or rhomboid. N:C ratio, however, should always be preserved.
May be squamoid, columnar, or spindled.
Umbrella cell atypia is not so uncommon, with multinucleation being a common feature.
Umbrella cell
Note the preserved N:C ratio and overall shape.
Squamous cells and basal urothelial cells
Basal urothelial cells are going to be rare in regular voided urine, but they will be fairly common in washing or brushing specimens.
Seminal vesicle cells
Note the lipofuscin pigment.
Degenerating intestinal epithelial cells and residual urothelial cells in an ileal loop specimen. May display Melamed-Wolinska bodies like urothelial cells.
Often mistaken for macrophages in a grungy background by novice cytologists.
What’s going on in the cytoplasm of this cell?
Melamed-Wolinska bodies
Pink-purple cytoplasmic inclusions found in urothelial, intestinal epithelial (ileal conduit), or prostatic epithelial cells (particularly when degenerating or neoplastic).
Malakoplakia (with Michaelis-Gutmann bodies)
An uncommon histiocytic inflammatory lesion of the bladder or upper respiratory tract resulting from infection.
Abundant granular cytoplasm filled with bacteria and bacterial fragments as well as basophilic, round, lamellated Michaelis-Gutmann bodies.
Single most common etiology of bladder infection
Candida species
Candida infection on urine cytology
Always look for dimorphism and pseudohyphae.
Herpes simplex virus cystitis
Multinucleation, ground glass chromatin texture, peripheral condensation of chromatin.
Cowdry A-type eosinophilic nuclear inclusions may be present. Nuclear molding may also be observed.
CMV most often affects renal tubular cells in immunocompromised patients.
Markedly enlarged cells with nuclear and cytoplasmic inclusions.
Nuclear inclusions are Cowdry B type, basophilic, solid, and solitary with a peripheral zone of chromatin clearing.
Trichomonas vaginalis
While principally a GYN pathogen, it can often be found in urine cytology specimens of affected individuals. Can also colonize and be found in the male genital/lower urinary tract, so do not rule this out if it is a male patient.
Pear-shaped with a small, oval, eccentrically placed nucleus and fine, red cytoplasmic granules.
BK virus infected cell, aka Decoy cell (so called because it can be confused with urothelial carcinoma)
A human polyomavirus acquired in childhood which remains latent in urothelial cells of the kidney and bladder.
Immunosuppression (classicaly for organ transplant) results in reactivation.
Cytologic featuers include glassy basophilic nuclear inclusion with coarse chromatin margination that sometimes forms cords or clumps, tear-drop or comet-shaped cells, and nuclear enlargement with preserved round nuclear contour.
Struvite crystals
Suggest infection by a urease-positive organism, most classically Proteus mirabilis
Ammonium biurate crystals
Sometimes called “thorny apples.” More commonly found in alkaline urine.
Calcium oxalate crystals
Bilirubin crystals
Cholesterol crystals
Cystine crystals
Types of urinary cast
Urinary cast differentials
Reactive urothelial cells
Note the prominent nucleoli and size variation with preserved N:C ratio and finely textured chromatin.
Often seen in the context of stones. Mitotic figures and dyscohesive clusters can also be seen in this setting.
Radiation or chemotherapy effect
Preserved N:C ratio with large cells and cytoplasmic vacuolation.
Nephrogenic adenoma
Cells are significantly smaller than intermediate cells, but with a similar sized nucleus. They form aggregates with honeycomb cell borders and have nice smooth nuclear contours with granular cytoplasm.
To confirm, make a cell block and stain for PAX2, PAX8, and AMACR.
Cells should be PAX2 +, PAX8 +, AMACR +, GATA3 neg.
Mullerianosis
Defined as “mullerian epithelium, stroma, or both in a site outside of the gynecologic tract.”
This includes endocervicosis, endosalpingosis, and endometriosis – all benign conditions.
High-grade urothelial carcinoma
Features: High N:C ratio, nuclear hyperchromasia, abnormal chromatin, irregular nuclear contour.
Some may contain Melamed-Wolinska bodies, but this is not specific.
C
Cytomorphologic features to call “suspicious” versus “positive” for high-grade urothelial carcinoma
“Suspicious for”
* Less than 10 abnormal cells
* N:C ratio of 0.5-0.7
* Moderate to severe nuclear hyperchromasia
* Clumpy chromatin or markedly irregular nuclear contour
“Positive for”
* At least 5-10 abnormal cells
* N:C ratio of at least 0.7
* Moderate to severe nuclear hyperchromasia
* Coarse/clumped chromatin
* Markedly irregular nuclear contour
Major cytomorphologic variants of urothelial carcinoma
- with jet-black chromatin
- with straight and curved nuclei
- with umbrella cell features
- with pale chromatin
- with smooth round nuclei and prominent nucleoli
- with smooth round nuclei and granular chromatin
It is often impossible to distinguish urothelial carcinoma from _____ by cytomorphology alone.
prostate
And really other carcinomas too, especially if there is no history. For this reason, it is often prudent to report malignant cells as “consistent with urothelial carcinoma.”
