1. بسم الله الرحمن الرحيم

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

5. Types of Specimens Voided urine (avoid 1st morning specimens) Catheterized urine (in Females) Washings/Brushings Superior to voided urine but localized, may not sample upper urinary tract and urethra Superior to voided urine but localized, may not sample upper urinary tract and urethra Ileal conduit urine

6. Deep Vs Superficial Cells Deep Vs Superficial Cells

7. Columnar and Squamous Cells

8. Normal Urine Cytology

9. Washing, Instrumentation, Lithiasis

10. Diagnostic Accuracy 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: High risk and history of CA High risk and history of CA Tumor Grade: HG UC: 78 - 98% HG UC: 78 - 98% LG UC: 0 - 70% LG UC: 0 - 70%

11. Grading Systems for Papillary UC Urinary Cytology1998 WHO/ISUP1973 WHO Low-grade Papillary Urothelial Lesion* Papilloma Low-grade Papillary Urothelial LesionPUNLMP Grade I Low-grade Urothelial Carcinoma Low-GradeGrade II High-grade Urothelial Carcinoma High-GradeGrade III

12. WHO Grading of Papillary Urothelial Malignancies High-grade UCLow-grade UCPUNLMPFeatures DisorderedMinimal lossNormalPolarity AbsentMay be presentUsually presentSuperficial cells FusedFused+ DelicateDelicatePapillary architecture Greatly increasedIncreased Nuclear size MarkedModerateSlightPleomorphism AbsentAbnormalSlight abnormalNuclear polarization MarkedModerateSlightHyperchromasia ProminentPresentNone or RareMitoses AbsentPresent Nuclear grooves Marked variationMild variationFine, uniformChromatin

13. PUNLMP

14. Low-grade Urothelial Carcinoma Cytologic diagnosis of LG PUC is problematic Minimal shedding of neoplastic cells Subtle cytologic alterations Difficult to distinguish from reactive changes, i.e. stones, instrumentation Cytologic overlap between PUNLMP and LG UC, some cases indistinguishable

15. Low-grade Urothelial Carcinoma vs Reactive

16. Low-grade Urothelial Carcinoma

17. Diff. Diag. of LGUC Reactive/reparative changes Instrumentation effect Lithiasis Upper urinary tract sampling

18. Low-grade UC Vs Benign

19. LGUC Vs Instrumentation

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

21. Lithiasis

22. Cytology of Upper Urinary Tract specimens Direct sampling of upper UT is effective in detecting HG UC, but poor for low grade lesions Normal upper UT epithelium shows more atypia than lower UT and occasionally more than LG UC High N/C ratio, enlarged nuclei, nuclear membrane irregularities Often present in papillary clusters Almost impossible to distinguish low grade UC from upper tract benign changes

23. Renal Pelvis & Ureter Brushings

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

25. HGUC

26. Diff. Diag. of HGUC Viral infection Viral infection Therapy effect Therapy effect Degenerative and reactive changes Degenerative and reactive changes Upper urinary tract specimens Upper urinary tract specimens Stones Stones

27. Polyoma Virus (Decoy Cells)

28. Therapy Effect

29. Degenerative Changes

30. Diagnostic categories Negative Negative Atypical, rule out LGUC /PUNLMP Atypical, rule out LGUC /PUNLMP Suspicious for HG UC/ malignancy Suspicious for HG UC/ malignancy HG UC/ other malignancies(Murphy) HG UC/ other malignancies(Murphy)

31. Summary Urothelial neoplasms can be separated into 2 main categories: Urothelial neoplasms can be separated into 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. Cytology less helpful for detecting and monitoring LG neoplasms. –Not major limitation. –Not major limitation. –LG neoplasms rarely aggressive and can be readily detected by cystoscopy. –LG neoplasms rarely aggressive and can be readily detected by cystoscopy. N.B.: Ancillary techniques are highly sensitive poorly specific, not for routine use N.B.: Ancillary techniques are highly sensitive poorly specific, not for routine use

32. GOOD LUCK…..