n of urIne
nashwa emara m.D.,phD
ass. prof. pathology
• Majority of UT malignancies
are urothelial CA.
• The main function of urine
cytology is diagnosis of UC.
Diagnosis of symptomatic patientsDiagnosis of symptomatic patients
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).
types of specImens
Voided urineVoided urine (avoid 1st morning(avoid 1st morning
Catheterized urineCatheterized urine (in Females)(in Females)
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
Deep Vs Superficial CellsDeep Vs Superficial Cells
Columnar and Squamous CellsColumnar and Squamous Cells
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%
Grading Systems for Papillary UCGrading Systems for Papillary UC
1973 WHO 1998WHO/ISUP Urinary Cytology
Papilloma Papilloma Low-grade Papillary
Grade II Low-Grade Low-grade
Grade III High-Grade High-grade
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
carcinomaCytologic diagnosis of LG PUC isCytologic diagnosis of LG PUC is
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
LGUC Vs InstrumentationLGUC Vs Instrumentation
Catheterized urine & bl. wash specimens.Catheterized urine & bl. wash specimens.
Large pseudopapillary groups and 3DLarge pseudopapillary groups and 3D
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
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.
CytoLogy of Upper Urinary
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
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
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%.
Atypical, rule out LGUCAtypical, rule out LGUC
Suspicious for HG UC/Suspicious for HG UC/
HG UC/ otherHG UC/ other
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.