Urine cytopathology

Urine cytopathology is a large part of cytopathology.

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):
  • Lymphoma.
  • Melanoma.
  • Adenocarcinoma.

Usually not reported

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

Normal

General

• Benign cells are often in small clumps.

Cell types

Practical cell typing:

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

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.

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

	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.
• Associated with immunosuppression/immunodeficiency.
• BK virus related to JC virus.

DDx:

• Urothelial carcinoma.

Cytology

Features:

• "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.

Images:

• Polyomavirus (jhu.edu).
• Polyomavirus - example 2 (WC).

IHC

• JC/BK virus.

"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:

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

Minimal criteria:

• Criteria #2-4.

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.

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).

See also

• Cytopathology.
• Basics.
• Malakoplakia.
• Urothelium.