‫بسم هللا الرحمن الرحيم‬
Interpretation
of urine
cytology
Nashwa Emara M.D.,phd
ASS. Prof. Pathology
Function
• Majority of UT malignancies
are urothelial CA.
• The main function of urine
cytology is diagnosis of UC.
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).
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
Ileal conduit urine
Deep Vs Superficial Cells
Columnar and Squamous Cells
Normal Urine Cytology
Washing, Instrumentation,
Lithiasis
Diagnostic Accuracy
Number of Specimens:
-Voided urine on 3 consecutive days.
+ 50% accuracy (1 specimen)
+ 75-90% accuracy (3 specimens)
Patient Population:
High risk and history of CA
Tumor Grade:
• HG UC: 78 - 98%
• LG UC: 0 - 70%
Grading Systems for Papillary UC
1973 WHO
1998 WHO/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
WHO Grading
of 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
PUNLMP
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
Low-grade Urothelial
Carcinoma vs Reactive
Low-grade Urothelial
Carcinoma
Diff. Diag. of LGUC
Reactive/reparative changes
Instrumentation effect
Lithiasis
Upper urinary tract sampling
Low-grade UC Vs Benign
LGUC Vs Instrumentation
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.
Lithiasis
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
Renal Pelvis & Ureter Brushings
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 %.
- Specificity > 95%.
HGUC
Diff. Diag. of HGUC
Viral infection
Therapy effect
Degenerative and reactive
changes
Upper urinary tract specimens
Stones
Polyoma Virus (Decoy Cells)
Therapy Effect
Degenerative Changes
Diagnostic
categories
Negative
Atypical, rule out LGUC
/PUNLMP
Suspicious for HG UC/
malignancy
HG UC/ other
malignancies(Murphy)
Summary
Urothelial neoplasms can be separated into
2 main categories:
–Low grade neoplasia (PUNLMP and LG UC).
–High grade UC.
Urine cytology best applied to HG UC.
Cytology less helpful for detecting and
monitoring LG neoplasms.
–Not major limitation.
–LG neoplasms rarely aggressive and can be
readily detected by cystoscopy.
N.B.: Ancillary techniques are highly sensitive
GOOD LUCK…..