Urine cytopathology

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Urine cytopathology is a large part of cytopathology.

Urine cytology - squamous cells and urothelial cells. (WC)
Urine cytology. (WC)
Urine cytology. (WC)

This article deals only with urine cytopathology. An introduction to cytopathology is in the cytopathology article.

DDx

Common

  • Negative for malignancy.
  • Urothelial carcinoma.
    • AKA urothelial cell carcinoma, abbreviated UCC.
  • Urothelial carcinoma with squamous features.
  • Polyomavirus infection.
  • Acute inflammation.
  • Chronic inflammation.

Rare

  • Schistosoma.
  • Malignancies other than urothelial carcinoma (UC):

Usually not reported

  • Candida.
    • Quite common.
  • Large (benign) squamous component.
    • Usually contamination from gential tract (in females).

Paris system for urinary cytology

This is a reporting standard with the following categories:[1]

  1. Nondiagnostic/unsatisfactory
  2. Negative for high-grade urothelial carcinoma
  3. Atypical urothelial cells
  4. Suspicious for high-grade urothelial carcinoma
  5. High-grade urothelial carcinoma
  6. Low-grade urothelial neoplasm
  7. Other malignancy (includes both primary and secondary) and miscellaneous lesions

Normal

General

  • Benign cells are often in small clumps.

Major cell types

Practical cell typing:[2]

Nucleus Cell border
Urothelium Larger Smooth/elliptical
Squamous epithelium Smaller Irregular/jagged

Images

Case 1

  • Benign - c/w renal tubular cells - very high mag. (WC)

  • Benign - c/w renal tubular cells - very high mag. (WC)

Case 2

  • BUC - very high mag. (WC)

  • BUC - very high mag. (WC)

  • BUC - very high mag. (WC)

Case 3

  • BUC - high mag. (WC)

  • BUC - very high mag. (WC)

  • BUC - very high mag. (WC)

Case 4

  • BUC - high mag.

  • BUC - very high mag.

  • BUC - very high mag.

  • BUC - very high mag.

Degenerative cells

Features:

  • Nucleus protrudes through cell membrane.
  • Chromatin degeration:
    • "Cobweb" appearance - white holes/pale staining.
    • White holes/frayed appearance.
    • Small clumps of chromatin at the edge of nuclear membrane.
  • Frayed cell membrane/irregular cell membrane.
  • Vacuolated cytoplasm - "moth-eaten" appearance.
    • Normal urothelial cytoplasm is dense and has no vacuoles.

Urine crystals

Main article: Urine crystals

Tabular DDx

Urothelial carcinoma versus benign urothelium

Urothelial carcinoma Benign urothelium Use of feature Utility
Nuclear hyperchromasia Present Absent r/i & r/o UC Strong
Nuclear-to-cytoplasmic (NC) ratio ~1:1.2 ~1:2 r/i & r/o UC; 1:>=2 suggests benign Strong
Nuclear membrane irregularity (NMI) +/- Absent r/i UC; presence strong predictor of malignancy (absence of NMI of little value) Moderate
Cytoplasm Green/grey Green or grey & granular r/o UC; granular (suggests degeneration) Moderate
Coarse chromatin (CC) Present +/- r/o UC; absence of CC suggest benign Moderate
Nucleoli In scattered cells +/- in reactive Not useful Nil for diagnosing UC
Nuclear size >2.5X normal Usu. <=2X normal Alone not much value, many large cells benign, many small cells malignant Limited value, NC ratio much better measure

Degeneration versus UC[3]

Urothelial carcinoma Degeneration
Architecture Usually single cells Often small clusters
Cell borders Sharp Fuzzy/frayed
Cytoplasm Green, solid Grey, lacy/moth eaten
Nuclear membrane Irregular Usually regular
Chromatin Granular/coarse Granular/coarse

Polyomavirus versus urothelial carcinoma

Urothelial carcinoma Polyoma virus
Architecture Often single cells Single cells
Nucleus size Often 3-4X normal urothelial cell 2X normal urothelial cell nucleus (should not be larger)
Chromatin Clumped or "dancing" Ground glass inclusions/smudged
Nuclear membrane Usually irregular Regular

Urothelial carcinoma vs adenocarcinoma

The default diagnosis is urothelial carcinoma as this is the most likely if there is no prior history of malignancy.

Urothelial carcinoma Adenocarcinoma
Vacuoles None Present - mucin filled
Cytoplasm Dense appearing Fluffy
Chromatin Coarse - clumped or "dancing" Fine
History None History of adenocarcinoma
Nucleoli Often present, multiple Usually only one - every tumour cell

Notes:

  • Both have eccentric nuclei.

Human polyomavirus infection

Main article: Polyomavirus nephropathy

General

  • Caused by Human polyomavirus, AKA BK virus.[4]
  • Associated with immunosuppression/immunodeficiency.
  • BK virus related to JC virus.
  • BK virus associated with urothelial carcinoma.[5][6]

DDx:

  • Urothelial carcinoma.
    • May exist together with urothelial carcinoma ~ nuclei 2-4x the size of not infected malignant cells.[7]

Cytology

Features:[8][9]

  • "Decoy cells":
    • Usually 2x the size of a normal urothelial cell nucleus.
    • Single cells - important feature.
    • Scant "degenerative-appearing" cytoplasm.
    • High NC ratio.
    • Intranuclear inclusions - key feature.
      • Central smudging (or "wash-out") of the chromatin/"Ground glass" chromatin.
      • Surrounded by clear halo just deep to the nuclear membrane.
    • Nuclear membrane clumping.

Notes:

  • Normal urothelial cell nucleus ~ 1.5X the size of a lymphocyte.

Image

  • Polyomavirus. (WC)

IHC

"Inflammation" in urine specimens

  • One should resist the temptation to call "inflammation" in urine specimens, as processing concentrates the WBCs.
    • If the quantity of WBCs is truly "excessive"... then it ought to be called.

Urothelial cell carcinoma

Main article: Urothelial cell carcinoma
  • Abbreviated UCC.

General

  • Very hard/impossible to diagnose low-grade UCC on cytology.
    • The diagnosis of low-grade UCC is based on architecture (papillae).

Cytology

Features:[11]

  1. Hyperchromasia - low power feature.
  2. Irregular nuclear membrane - key feature.
  3. Increased NC ratio.
    • Often uniform - when comparing malignant cells.
  4. "Large nuclei" (3-4X the size of a normal urothelial cell) - low power feature.
    • These are not required for the diagnosis.[12]
    • Large nuclei may be seen in benign umbrella cell, where the NC ratio is normal.
  5. Nuclear size variation, >=2X other malign. looking cells - very useful.
  6. +/-Large irregular nucleoli - common.

Minimal criteria:

  • Criteria #1-3. †

Notes:

  • Coarse chromatin may be benign.
    • Fine/non-granular chromatin suggests benign.
  • One does not usually call squamous cell carcinoma on cytology.
    • If features of squamous differentiation are present one calls urothelial carcinoma with squamous features.

DDx:

  • Degeneration.
  • Polyomavirus.

† Willner et al. require all of the following:[13]

  1. Nucleus-to-cytoplasm ratio >0.7.
  2. Hyperchromasia (moderate or severe).
  3. Irregular nuclear membranes, marked.
  4. Coarse chromatin.

Willner's criteria can be remember by CHIN = coarse chromatin, hyperchromasia, irregular nuclear membrane, NC ratio increased.

Schistosoma

  • Associated with squamous cell carcinoma of the bladder.

Histology

Features of ova:

  • Elliptical ~80 micrometres max dimension.
  • S. haematobium has a "spike" approx. the size of a PMN.

Image

  • Schistosoma haematobium. (WC)

Trichomonas

Main article: Gynecologic_cytopathology#Trichomoniasis
  • Trichomonas is found in approximately 0.1% of urine cytology specimens.[14]

Atypical squamous cells in urine

  • Atypical squamous cells in urine cytology specimens are rare ~ 0.3%.[15]
  • An older series describes an association with SCC/UCC of the bladder and SCC of the cervix.[16]
Atypical squamous cells present, see comment.
Benign urothelial cells present in background.
Negative for High-Grade Urothelial Carcinoma.
 
Comment:
Due to the atypical squamous cells, consideration of further work-up is suggested within the clinical context, based on reported associations.[1]

1. Diagn Cytopathol. 2005 Dec;33(6):394-8. doi: 10.1002/dc.20344 - https://pubmed.ncbi.nlm.nih.gov/16299739/

See also

References

  1. ↑ Barkan, GA.; Wojcik, EM.; Nayar, R.; Savic-Prince, S.; Quek, ML.; Kurtycz, DF.; Rosenthal, DL. (2016). "The Paris System for Reporting Urinary Cytology: The Quest to Develop a Standardized Terminology.". Acta Cytol 60 (3): 185-97. doi:10.1159/000446270. PMID 27318895.
  2. ↑ SM. 7 January 2010.
  3. ↑ Adapted from GS. 2 February 2010.
  4. ↑ Lefkowitch, Jay H. (2006). Anatomic Pathology Board Review (1st ed.). Saunders. pp. 681 (Q26). ISBN 978-1416025887.
  5. ↑ Tsai, HL.; Chang, JW.; Wu, TH.; King, KL.; Yang, LY.; Chan, YJ.; Yang, AH.; Chang, FP. et al. (Jul 2014). "Outcomes of kidney transplant tourism and risk factors for de novo urothelial carcinoma.". Transplantation 98 (1): 79-87. doi:10.1097/TP.0000000000000023. PMID 24879380.
  6. ↑ Li, JY.; Fang, D.; Yong, TY.; Klebe, S.; Juneja, R.; Gleadle, JM. (Dec 2013). "Transitional cell carcinoma in a renal allograft with BK nephropathy.". Transpl Infect Dis 15 (6): E270-2. doi:10.1111/tid.12142. PMID 24103071.
  7. ↑ Loghavi, S.; Bose, S. (Jul 2011). "Polyomavirus infection and urothelial carcinoma.". Diagn Cytopathol 39 (7): 531-5. doi:10.1002/dc.21490. PMID 20891007.
  8. ↑ Lefkowitch, Jay H. (2006). Anatomic Pathology Board Review (1st ed.). Saunders. pp. 681-2 (Q26). ISBN 978-1416025887.
  9. ↑ SB. 27 January 2010.
  10. ↑ http://www.acta-cytol.com/toc/auto_abstract.php?id=22895
  11. ↑ Lefkowitch, Jay H. (2006). Anatomic Pathology Board Review (1st ed.). Saunders. pp. 682. ISBN 978-1416025887.
  12. ↑ SM. 12 January 2010.
  13. ↑ Willner J, Matloob A, Colanta A, Khader SN (2020). "Educational Case: Urothelial Carcinoma: An Overview of Pathologic Diagnosis". Acad Pathol 7: 2374289520958172. doi:10.1177/2374289520958172. PMID 33088909.
  14. ↑ Doxtader EE, Elsheikh TM (January 2017). "Diagnosis of trichomoniasis in men by urine cytology". Cancer Cytopathol 125 (1): 55–59. doi:10.1002/cncy.21778. PMID 27636204.
  15. ↑ Velez Torres JM, Zhao J, Epstein JI, Kryvenko ON (December 2022). "Condyloma acuminatum of the urinary tract demonstrates atypical squamous cells in urine cytology". Hum Pathol 130: 110–116. doi:10.1016/j.humpath.2022.10.006. PMID 36244465.
  16. ↑ Owens CL, Ali SZ (December 2005). "Atypical squamous cells in exfoliative urinary cytology: clinicopathologic correlates". Diagn Cytopathol 33 (6): 394–8. doi:10.1002/dc.20344. PMID 16299739.

External links

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