Urine cytology is useful for diagnosing urothelial carcinoma (UC), especially high-grade UC. It has high sensitivity for detecting high-grade lesions but is less reliable for low-grade UC and papillary urothelial neoplasms of low malignant potential (PUNLMP) due to their more subtle cytological features and lower shed cell numbers. Cytology is best at detecting high-grade UC, which has a high mortality rate, but is less helpful for monitoring and detecting low-grade neoplasms, which are rarely aggressive. While this limits cytology for low-grade lesions, cystoscopy can readily identify them.

1. ‫بسم‬‫بسم‬‫ا‬‫ا‬‫الرحمن‬‫الرحمن‬
‫الرحيم‬‫الرحيم‬

2. InterpretatIo
n of urIne
cytology
nashwa emara m.D.,phD
ass. prof. pathology

3. functIon
• Majority of UT malignancies
are urothelial CA.
• The main function of urine
cytology is diagnosis of UC.

4. InDIcatIons
Diagnosis of symptomatic patientsDiagnosis of symptomatic patients
(hematuria).(hematuria).
Screen high risk patients (industrialScreen high risk patients (industrial
chemicals, metals, etc.)chemicals, metals, etc.)
Follow-up patients with UT neoplasia.Follow-up patients with UT neoplasia.
Complementary to cystoscopy and biopsy:Complementary to cystoscopy and biopsy:
detect small and hidden lesions (diverticuli,detect small and hidden lesions (diverticuli,
ureters, renal pelvis)..ureters, renal pelvis)..
Urine cytology is the most reliable methodUrine cytology is the most reliable method
for detecting urothelial CIS (>biopsies).for detecting urothelial CIS (>biopsies).

5. types of specImens
Voided urineVoided urine (avoid 1st morning(avoid 1st morning
specimens)specimens)
Catheterized urineCatheterized urine (in Females)(in Females)
Washings/BrushingsWashings/Brushings
Superior to voided urine butSuperior to voided urine but
localized, may not sample upperlocalized, may not sample upper
urinary tract and urethraurinary tract and urethra
Ileal conduit urineIleal conduit urine

6. Deep Vs Superficial CellsDeep Vs Superficial Cells

7. Columnar and Squamous CellsColumnar and Squamous Cells

8. Normal Urine CytologyNormal Urine Cytology

9. Washing, Instrumentation,Washing, Instrumentation,
LithiasisLithiasis

10. Diagnostic
accuracy
Number of Specimens:Number of Specimens:
-Voided urine on 3 consecutive days.-Voided urine on 3 consecutive days.
+ 50% accuracy (1 specimen)+ 50% accuracy (1 specimen)
+ 75-90% accuracy (3 specimens)+ 75-90% accuracy (3 specimens)
Patient Population:Patient Population:
High risk and history of CAHigh risk and history of CA
Tumor Grade:Tumor Grade:
•• HG UC: 78 - 98%HG UC: 78 - 98%
•• LG UC: 0 - 70%LG UC: 0 - 70%

11. Grading Systems for Papillary UCGrading Systems for Papillary UC
1973 WHO 1998WHO/ISUP Urinary Cytology
Papilloma Papilloma Low-grade Papillary
Urothelial Lesion*
Grade I
PUNLMP
Low-grade Papillary
Urothelial Lesion
Grade II Low-Grade Low-grade
Urothelial
Carcinoma
Grade III High-Grade High-grade
Urothelial
Carcinoma

12. WHO GradingWHO Grading
of Papillary Urothelial Malignanciesof Papillary Urothelial Malignancies
Features PUNLMP Low-grade UC High-grade UC
Polarity Normal Minimal loss Disordered
Superficial cells Usually present May be present Absent
Papillary architecture Delicate Fused+ Delicate Fused
Nuclear size Increased Increased Greatly increased
Pleomorphism Slight Moderate Marked
Nuclear polarization Slight abnormal Abnormal Absent
Hyperchromasia Slight Moderate Marked
Mitoses None or Rare Present Prominent
Nuclear grooves Present Present Absent
Chromatin Fine, uniform Mild variation Marked variation

13. PUNLMPPUNLMP

14. Low-graDe
urotheLiaL
carcinomaCytologic diagnosis of LG PUC isCytologic diagnosis of LG PUC is
problematicproblematic
Minimal shedding of neoplastic cellsMinimal shedding of neoplastic cells
Subtle cytologic alterationsSubtle cytologic alterations
Difficult to distinguish from reactiveDifficult to distinguish from reactive
changes, i.e. stones, instrumentationchanges, i.e. stones, instrumentation
Cytologic overlap between PUNLMPCytologic overlap between PUNLMP
and LG UC, some casesand LG UC, some cases
indistinguishableindistinguishable

15. Low-graDe urotheLiaL
carcinoma vs reactive

16. Low-graDe urotheLiaL
carcinoma

17. Diff. Diag. of LgUC
Reactive/reparative changesReactive/reparative changes
Instrumentation effectInstrumentation effect
LithiasisLithiasis
Upper urinary tract samplingUpper urinary tract sampling

18. Low-grade UC Vs BenignLow-grade UC Vs Benign

19. LGUC Vs InstrumentationLGUC Vs Instrumentation

20. instrUmentation
effeCt
Catheterized urine & bl. wash specimens.Catheterized urine & bl. wash specimens.
Large pseudopapillary groups and 3DLarge pseudopapillary groups and 3D
clusters.clusters.
Nuclear overlap and crowding.Nuclear overlap and crowding.
Low N/C ratio.Low N/C ratio.
Finely granular chromatin with evenFinely granular chromatin with even
distribution.distribution.
Well defined cytoplasmic borders.Well defined cytoplasmic borders.
Nuclear palisading at periphery of clustersNuclear palisading at periphery of clusters
with abundant cytoplasm.with abundant cytoplasm.

21. LithiasisLithiasis

22. CytoLogy of Upper Urinary
traCt speCimens
Direct sampling of upper UT is effective inDirect sampling of upper UT is effective in
detecting HG UC, but poor for low gradedetecting HG UC, but poor for low grade
lesionslesions
Normal upper UT epithelium shows moreNormal upper UT epithelium shows more
atypia than lower UT and occasionally moreatypia than lower UT and occasionally more
than LG UCthan LG UC
High N/C ratio, enlarged nuclei, nuclearHigh N/C ratio, enlarged nuclei, nuclear
membrane irregularitiesmembrane irregularities
Often present in papillary clustersOften present in papillary clusters
Almost impossible to distinguish low gradeAlmost impossible to distinguish low grade
UC from upper tract benign changesUC from upper tract benign changes

23. Renal Pelvis & Ureter BrushingsRenal Pelvis & Ureter Brushings

24. HigH-graDe
UrotHeLiaL
CarCinoma
Often invasive, 70 mortality.Often invasive, 70 mortality.
Can not reliably separate CIS fromCan not reliably separate CIS from
invasive high-grade UC.invasive high-grade UC.
High diagnostic accuracy of cytology:High diagnostic accuracy of cytology:
- Sensitivity 80 %.- Sensitivity 80 %.
- Specificity > 95%.- Specificity > 95%.

25. HGUCHGUC

26. Diff. Diag. of HgUC
Viral infectionViral infection
Therapy effectTherapy effect
Degenerative and reactiveDegenerative and reactive
changeschanges
Upper urinary tract specimensUpper urinary tract specimens
StonesStones

27. Polyoma Virus (Decoy CellsPolyoma Virus (Decoy Cells((

28. Therapy EffectTherapy Effect

29. Degenerative ChangesDegenerative Changes

30. DiagnostiC
Categories
NegativeNegative
Atypical, rule out LGUCAtypical, rule out LGUC
/PUNLMP/PUNLMP
Suspicious for HG UC/Suspicious for HG UC/
malignancymalignancy
HG UC/ otherHG UC/ other
malignanciesmalignancies(Murphy)(Murphy)

31. sUmmary
Urothelial neoplasms can be separated intoUrothelial neoplasms can be separated into
2 main categories:2 main categories:
––Low grade neoplasia (PUNLMP and LG UC(.Low grade neoplasia (PUNLMP and LG UC(.
––High grade UC.High grade UC.
Urine cytology best applied to HG UC.Urine cytology best applied to HG UC.
Cytology less helpful for detecting andCytology less helpful for detecting and
monitoring LG neoplasms.monitoring LG neoplasms.
––Not major limitation.Not major limitation.
––LG neoplasms rarely aggressive and can beLG neoplasms rarely aggressive and can be
readily detected by cystoscopy.readily detected by cystoscopy.

32. gooD LUCKgooD LUCK…..…..