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  1. 1. ‫بسم‬‫بسم‬‫ا‬‫ا‬‫الرحمن‬‫الرحمن‬ ‫الرحيم‬‫الرحيم‬
  2. 2. InterpretatIo n of urIne cytology nashwa emara m.D.,phD ass. prof. pathology
  3. 3. functIon • Majority of UT malignancies are urothelial CA. • The main function of urine cytology is diagnosis of UC.
  4. 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. 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. 6. Deep Vs Superficial CellsDeep Vs Superficial Cells
  7. 7. Columnar and Squamous CellsColumnar and Squamous Cells
  8. 8. Normal Urine CytologyNormal Urine Cytology
  9. 9. Washing, Instrumentation,Washing, Instrumentation, LithiasisLithiasis
  10. 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. 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. 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
  14. 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. 15. Low-graDe urotheLiaL carcinoma vs reactive
  16. 16. Low-graDe urotheLiaL carcinoma
  17. 17. Diff. Diag. of LgUC Reactive/reparative changesReactive/reparative changes Instrumentation effectInstrumentation effect LithiasisLithiasis Upper urinary tract samplingUpper urinary tract sampling
  18. 18. Low-grade UC Vs BenignLow-grade UC Vs Benign
  19. 19. LGUC Vs InstrumentationLGUC Vs Instrumentation
  20. 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. 21. LithiasisLithiasis
  22. 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. 23. Renal Pelvis & Ureter BrushingsRenal Pelvis & Ureter Brushings
  24. 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. 25. HGUCHGUC
  26. 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. 27. Polyoma Virus (Decoy CellsPolyoma Virus (Decoy Cells((
  28. 28. Therapy EffectTherapy Effect
  29. 29. Degenerative ChangesDegenerative Changes
  30. 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. 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. 32. gooD LUCKgooD LUCK…..…..