The Paris System provides a standardized approach for reporting urinary cytology results with the aim of improving reproducibility and communication. It defines categories for negative, atypical urothelial cells, suspicious for high-grade urothelial carcinoma, and high-grade urothelial carcinoma based on nuclear and cytoplasmic features. Low-grade urothelial neoplasia requires the presence of three-dimensional clusters with fibrovascular cores. The system also provides guidance on specimen adequacy and the assessment of other malignancies and clinical management. Validation studies are still needed but the goal is to reliably detect high-grade urothelial neoplasia.

1. PARIS SYSTEM OF REPORTING
URINARY CYTOLOGY
MODERATOR- DR. MOMOTA NAIDING
PROFESSOR, DEPTT. OF PATHOLOGY
PRESENTER- DR. SHATABDI DAS
PGT, DEPTT. OF PATHOLOGY

2. Introduction
• Urine Urine is a liquid by-product of the
metabolism in humans and in many animals.
• The average urothelial cell has an approximate
diameter of 20 μm or a two-dimensional
surface area of 314 μm2(314 × 10 −12 m2 ).
• The urothelium is about six-seven cells thick,
so the total number of urothelial cells lining
the bladder is on the order of 10 8 –10 9 cells.

3. Goal of urine cytology
• A guided system for work up of hematuria.
• In follow-up cases of patients with history of
bladder cancer.
• To monitor patients after therapy for bladder
cancer.

4. Need for standardization of urine cytology
• To minimize the interobserver variation in
reporting urine cytology.
• Reproducibility
• Improvement of communication
• Atypical cells-Wide intraobserver variability

5. Normal urinary elements
• Urothelial cells
-Intermediate and superficial (umbrella) cells (voided urine)
-Intermediate, superficial and basal cells (catheterized urine,
washing)
• Squamous cells
• Miscellaneous findings
-Prostate and seminal vesicle epithelial cells
-Renal tubular cells and casts
-Crystals
-Inflammatory cells
-Degenerated intestinal epithelial cells (ileal conduit)

6. PARIS SYSTEM OF REPORTING URINARY
CYTOLOGY
• The Paris System (TPS) is a standardised,
comprehensive system for reporting urinary
cytology.
• It was developed over several years and
published in 2016 by a team of
cytopathologists, surgical pathologists and
urologists.

7. • Aim of Paris system of reporting cytology -
Ability to reliably detect high grade urothelial
neoplasia.

8. Components of Paris system of reporting
1. Pathogenesis of Urothelial Carcinoma
2. Adequacy
3. Negative for High Grade Urothelial Carcinoma
4. Atypical Urothelial Cells
5. Suspicious for High Grade Urothelial Carcinoma
6. High Grade Urothelial Carcinoma
7. Low Grade Urothelial Neoplasm
8. Other malignancies, both primary and secondary
9. Ancillary Studies
10. Clinical management
11. Preparatory techniques relative to Urinary Tract samples

9. Pathogenesis of urothelial carcinoma
Two pathways
Hyperplasia
pathway
More
common(80%)
Urothelial
hyperplasiaDeletion of
CDKN2A and FGFR3
mutationLGUC
Genetically
Stable pathway
Dysplasia
pathway
Less
common(20%)
High grade
papillary
tumour/ca-insitu
Higher chance of
invasion and
metastasis
Inactivating
mutation of Tp53
Genetically
unstable pathway

11. Preparatory techniques
• Materials and methods-
Bladder washings- best
Catheterized urine- second best
Voided specimens- third
• Processing of the urine samples-
membrane filtration (e.g.,Millipore),
cytocentrifugation (i.e., Shandon Cytospin),(CS)
BD SurePath Prep (SP)
Hologic ThinPrep (TP)

12. Adequacy

13. • Adequacy- is determined by the interplay of four
specimen characteristics:
-collection type
-cellularity
-volume and
-cytomorphological findings.
• At least 30 mL are necessary to consider a urine specimen
fully adequate when processed with SurePath.
• 20 undistorted well visualised cells per 10 hpf in bladder
washings.

14. Negative for high grade urothelial
carcinoma(NHGUC)
NHGUC
Urine sample, either
voided/instrumente
considered NHGUC, if
any of the following
components are present
Benign
urothelial/glandular/squamous cells
Benign urothelial tissue
fragments/urothelial sheets or clusters
Changes associated with lithiasis/viral
cytopathic effect-polyoma virus(BK virus-
decoy cells)
Post therapy effect/epithelial cells from
urinary diversions

15. Frothy and abundant
cytoplasm, low N:C ratio,
multinucleation common,
Nuclei- pale fine
granulation, prominent
nucleoli
Superficial urothelial umbrella
cells(NHGUC)

16. Nucleus- slightly small,
dark , round and
smooth nuclear
membrane, uniform
architecture
Cytoplasm- scanty,
high N:C ratio
Image- clusters of benign
smaller cells in addition to
benign superficial cells

17. Their nuclear and cytoplasmic
character is the same as other
superficial cells, but additionally,
they possess a thickened
cytoplasmic edge that doesn’t go all
around the cell. This
constitutes the asymmetric unit
membrane, providing a barrier
between the toxic urine and the
blood
Image: These true tissue
fragments (TTF) clearly illustrate
the image of “umbrella” cells. By
definition, they are the most
superfi cial cells in the bladder,
creating an “Umbrella” over all
other urothelial cells.

18. Easily dissociated into single cells.
These often have cells with
cytoplasmic (cercariaform) tails
Image: Intermediate urothelial cells.
The intermediate layer of
urothelium, immediately
underneath
the umbrella cells.

19. Image: Reactive umbrella cells. Most inflamed epithelial cells
demonstrate changes, especially in the nuclei. Nucleoli may become
prominent, but nuclear chromatin will remain finely granular and shapes
will remain round. The cytoplasm retains its transparency. Neutrophils
will ordinarily be the inflammatory cells, but lymphocytes may be
present if a chronic process is ongoing.
Reactive umbrella cells(NHGUC)

20. Image: Benign squamous cells. Two benign squamous cells line up
below an umbrella cell with three nuclei.
Benign squamous cells(NHGUC)

21. Image : Benign glandular cells

22. Histiocytic type
Glandular
Cast
Renal tubular cells(NHGUC)

23. Nuclei- uniform, finely spaced,
finely granular chromatin
Benign urothelial tissue fragment(NHGUC)
Causes of BUTF in voided urines are multifold, and include:
prostate/rectal manipulation prior to collection of the sample,
jogging, abdominal palpation etc.

24. Urothelium with nephrolithiasis(NHGUC)
round nuclei which are
evenly spaced. Chromatin
is finely granular and
nucleoli are inconspicuous.
Calcific concretions in
voided urine may be
recovered in patients with
history of renal calculi

25. Infections(NHGUC)
enlargement of the nucleus and nuclear
chromatin homogenization, caused by the viral
infection nucleus is always round or oval with a
very smooth outline. Cytoplasm is almost gone.
If the focal plane is changed,
then a spider web of
degenerated chromatin
comes into view
Almost all the cells display glassy
nuclear inclusions
diagnostic of Polyoma virus

26. Intravesicle BCG immunotherapy(NHGUC)
Multinucleation in usual superficial cells is
common. In contrast, Langhans-type giant
cells resulting from fused macrophages
are multinucleated but have their smaller
and slightly hyperchromatic nuclei
clustered at one pole of the cytoplasm.

27. Atypical urothelial cells
• The general diagnostic category AUC is
reserved for specimens that contain urothelial
cells with mild to moderate cytologic (not
architectural) atypia.

28. Criteria for AUS
• One major and one minor criteria out of the following-
Major criteria-
Non-superficial and non-degenerated urothelial cells
with an increased nuclear cytoplasmic (N/C) ratio
(>0.5)
Minor criteria-(any 1)
-Nuclear hyperchromasia
-Irregular nuclear membranes (chromatinic rim or
nuclear contour)
-Irregular, coarse, clumped chromatin

29. Normal cluster
High N/C ratio, and nuclear
contour
irregularity. Due to the
cytologic atypia seen in the
group on the bottom this case
should be categorized as AUC
AUC
High N/C ratios and
nuclear contour irregularity
Atypical urothelial cells

30. Suspicious for High-Grade Urothelial
Carcinoma (Suspicious)
• Used in cases with abnormal urothelial cells that
quantitatively fall short of a definitive diagnosis of
HGUC.
• A diagnosis of “SHGUC” is defined as non-superficial
and non-degenerated urothelial cells showing:
-Increased nuclear to cytoplasmic (N/C) ratio, at least
0.5–0.7
-Moderate to severe hyperchromasia
• At least one of the two following features:
-Irregular clumpy chromatin
-Marked irregular nuclear membranes

31. Well preserved Intermediate urothelial cells
showing increased N/C ratios,
hyperchromasia, and irregular nuclear
membranes, clumped chromatin

32. High grade urothelial carcinoma
• Cellularity: At least 5–10 abnormal cells
(>10cells)
• N/C ratio: 0.7 or greater
• Nucleus: Moderate to severe hyperchromasia
• Nuclear membrane: Markedly irregular
• Chromatin: Coarse/clumped

33. High n:c ratio(>0.7)
Nuclear hyperchromasia with
presence of necrosis

34. nuclear membrane irregularity with
focal thickness of nuclear membranes.
Nuclear shapes and sizes vary.
coarse and clumped nuclear
chromatin

35. cytoplasmic vacuolization reflects glandular
differentiation. Nuclear membrane
irregularity, hyperchromasia, and coarse
chromatin typify HGUC
A few cells exhibit classic features of high-
grade urothelial carcinoma (HGUC) adjacent
to cells of squamous differentiation

36. Other notable features
• Cellular pleomorphism
• Marked variation in cellular size and shapes, i.e.,
oval, rounded, elongated, or plasmacytoid
(Comet cells)
• Scant, pale, or dense cytoplasm
• Prominent nucleoli
• Mitoses
• Necrotic debris
• Inflammation

37. Low grade urothelial neoplasia
• Three -dimensional cellular papillary clusters
(defined as clusters of cells with nuclear
overlapping, forming “papillae”) with
fibrovascular cores including capillaries
• Only in the presence of this feature is the
definitive cytologic diagnosis of LGUN
possible.

39. Three-dimensional papillary structures have
central cores. Mild cytologic atypia and
disorganization of cells forming papillae
Three-dimensional cluster of cells with
nuclear overlapping, forming papillae.
There is a thin capillary vessel running
through the center of the cluster

40. Other Malignancies

41. Squamous cell carcinoma
• Malignant neoplasm that shows
exclusively squamous
differentiation, without
associated urothelial or
glandular elements.
• 5% of bladder cancers
• Pure squamous cell carcinoma is
rare
• associated with calculi,
diverticuli, schistosomiasis
• Squamous differentiation in UC
• Cytoplasmic keratinization
• Hyperchromatic angulated nuclei

42. Adenocarcinoma
• Rare, 0.5-2.5% of
bladder cancer
Enteric (colonic-type) AdCa
large nuclei, columnar to round, irregular,
hyperchromatic with thick nuclear membranes,
prominent nucleoli. cytoplasm-scant and
vacuolated
Signet ring cell carcinoma
a cluster of cells with one cell showing a
crescent-shaped hyperchromatic nucleus
pushed to the periphery of the cell by a
large cytoplasmic mucin-containing
vacuole
Clear cell AdCa
a cluster of cells with projecting
cytoplasm in a “hobnail
configuration” with abundant
vacuolated cytoplasm and
centrally located nuclei with
prominent nucleoli

43. Approach to diagnosis in urinary tract

44. Ancillary studies in urine cytology
• Urovysion FISH
• ImmunoCyt/uCyt+ test
• ProEX C
• Bladder Tumor Antigen test(BTA)
• Nuclear Matrix Protein test(NMP22)

45. • >=4 cells showing
gain of atleast 2 of
chromosome 3,
chromosome7,
chromosome 17
• >= 12 cells showing
deletion of p16
signals.

46. Clinical management

47. (0.5-0.7)

49. Summary
• HGUC – this is the one that matters –Negative for
HGUC
• The diagnosis “atypia” should not be used as a waste
basket and dx should be based on criteria
• LGUN – new diagnostic category, based on presence
of fibrovascular cores
• Not all malignant cells in urines are urothelial
carcinoma
• Future studies are needed for validation of TPS.

50. REFERENCE
• The Paris System for Reporting Urinary
Cytology- Dorothy L. Rosenthal, Eva M. Wojcik,
Daniel F. I. Kurtycz

51. Thank You