THE PARIS SYSTEM

FOR REPORTING
URINARY CYTOLOGY
Rawa Muhsin
 History
◦ Bethesda system for cervical cytology since 1988
◦ Paris system for urinary cytology conceived in Paris during the IACC in 2013
◦ Led by Rosenthal and Wojcik
 What matters in urine cytology?
◦ Is there high-grade urothelial carcinoma or not?
◦ Only HGUC can invade muscle
◦ Progression of LGUC to HGUC is uncertain, with more recent studies reporting a lower rate (1-5%)
◦ RAS mutations mutually exclusive with FGFR3 mutation, so may be totally separate pathways
 Categories in the Paris system
◦ Negative for high-grade urothelial carcinoma
◦ Positive for high-grade urothelial carcinoma
◦ Not quite enough
◦ Atypical urothelial cells (AUC) and suspicious for high-grade urothelial carcinoma (SHGUC)
◦ Difference is quantitative
 Adequacy
◦ If there are atypical cells, adequacy does not matter
◦ If there are no atypical cells
◦ Lack of obscuring features
◦ Appropriate benign urothelial cellularity (20 cells per 10 hpf)
◦ Adequate volume (30 mL)

◦ Don’t discard the first drops of the urine stream; they are rich in cells
◦ Anything below these cut-offs is “less-than-optimal” for evaluation
 Negative for High-Grade Urothelial Carcinoma
◦ >70% of all urine cytologies
◦ All entities that pose no significant risk to the patient for developing HGUC based upon available studies
◦ Benign urothelial, glandular, and squamous cells
◦ Stone-related changes
◦ Viral cytopathic effect
◦ Post-therapy effect
 Urothelial cells
◦ Adequacy criteria (20 cells per 10 hpf)
◦ Umbrella cells
◦ May appear atypical, but do not justify a diagnosis of atypia
◦ May contain abnormal amounts of DNA and confound DNA ploidy studies
 Squamous cells
◦ Urethra, vagina, and bladder trigone
 Glandular cells
◦ Uterine cervix and corpus
◦ Alert in post-menopausal women

◦ Bladder dome and trigone

◦ Cystitis cystica/glandularis
◦ Endometriosis and Mullerian rests
◦ Renal tubular epithelial cells
◦ Usually degenerated and resemble histiocytes
 Stone-related changes
◦ Clinical history and imaging
◦ Urothelial tissue fragments
◦ Crystalline material
 Viral cytopathic effect
◦ Polyoma virus
◦ Nuclear enlargement
◦ Chromatin homogenization with spider web dissolution
◦ Very smooth nuclear outline; if irregular look for malignancy
 Post-therapy effect
◦ Radiation
◦ Cytomegaly with preserved N/C ratio, cytoplasmic vacuoles, polychromasia

◦ BCG immunotherapy
◦ Granulomas

◦ Chemotherapy
◦ Nuclear enlargement, multinucleation, hyperchromasia of superficial cells

◦ Bladder diversion
◦ Large red intracytoplasmic inclusions
 Low-grade urothelial neoplasia
◦ Used for the histologic entities of urothelial papilloma, PUNLMP, and low-grade urothelial carcinoma
◦ 3D cellular papillary clusters (with nuclear overlapping) with fibrovascular cores including capillaries
◦ Risk of progression to high-grade urothelial carcinoma is low (if it happens at all)
Who is this?
END OF PART 1
 High-grade urothelial carcinoma
◦ Urine cytology has high sensitivity (up to 85%) and specificity (up to 88%) for HGUC
◦ Lower sensitivity for LGUC (up to 43.6%)

◦ Positive urine cytology is significantly associated with

◦ Subsequent recurrence of upper urinary tract urothelial carcinoma
◦ Tumor progression in Ta urothelial carcinoma (20% vs 2% at 5 years)
 High-grade urothelial carcinoma
◦ Cannot distinguish invasive HGUC from noninvasive HGUC or CIS
◦ Background in latter is clean

◦ Features
◦ High N/C ratio >0.7 (use lymphocytes as control)
◦ Hyperchromasia (use normal cells as control) and coarse chromatin
◦ Irregular nuclear membrane
◦ Necrosis

◦ At least 5—10 abnormal cells should be present

◦ Prominent nucleoli can also be present in reactive urothelial cells
 High-grade urothelial carcinoma
◦ HGUC can show differentiation towards
◦ Squamous
◦ Keratinization and intercellular bridges
◦ Glandular
◦ Glandular formation, cytoplasmic vacuolization

◦ Diagnosis of SqCC and adenoCA requires extensive sampling of the excision sample
 High-grade urothelial carcinoma
◦ Rate of malignancy: 1.0-6.3%
◦ Risk of malignancy: >90%
◦ Anticipatory phenomenon
◦ Positive urine cytology with an initial period of clinically undetectable disease followed by discovery of occult
urothelial carcinoma
◦ Longer follow-up required to avoid mislabeling as false positive
 Suspicious for HGUC
◦ Difference is quantitative only
◦ Identical nuclear features
◦ Few (<5-10) cells

◦ Exclude superficial and degenerated cells from consideration

◦ In voided specimens and history of HGUC use lower (5 cells) cut-off, in instrumented samples use higher
(10 cells) cut-off
 Atypical urothelial cells
◦ Difference is qualitative
◦ Partial nuclear features of HGUC
◦ Degenerative features including incomplete cytoplasm, incomplete nuclear membranes, poor chromatin detail

◦ Exclude known causes of atypia such as infections, reactive changes, seminal vesicle cells (these belong
in negative for HGUC)
 Level of certainty

Atypical
Negative for Suspicious
urothelial HGUC
HGUC for HGUC
cells
Diagnostic categories
 Risk of malignancy
◦ Negative for HGUC: 15.5%
◦ Atypical urothelial cells: 8.3-37.5%
◦ Suspicious for HGUC: 80-95%
◦ HGUC: 78-100%
END OF PART 2