Module 11 Part 1 - Urinary Cytopathology

Question 1

Aetiology of Bladder Cancer

Answer 1

Smoking
Workplace exposure to chemicals 
Chemotherapy
Diabetes
Cyclophosphamide (chemo drug)
Family history
Chronic inflammation of the bladder

Question 2

Diagnostic Categories for TPS

Answer 2

Negative for HGUC
Atypical urothelial cells
Suspicious for HGUC
High grade urothelial carcinoma
Low grade urothelial neoplasia
Other malignancies
- primary/secondary

Question 3

Voided Sample

Answer 3

Voided urine is the sample of choice as a screening tool for patients with urinary symptoms

• x3 voided urine samples recommended
• low cellularity in males
• in females usually see increased epithelial cells
• voided urines are often fresh specimens and need to be processed quickly

Question 4

Sample Collection - Others

Answer 4

Catheterised samples
- invasive procedure
- often highly cellular containing more cell clusters, mimics low grade papillary carcinoma
Ileal conduit
- total cystectomy; anastomosis of ureters to an ileal loop
- usually highly cellular specimens which demonstrate degeneration and contamination with intestinal cells
Bladder washings
- irrigating bladder with saline or an electrolytic solution
- provides better yield

Question 5

Urinary Tract Histology

Answer 5

Transitional epithelium
Demonstrates unique ultrastructural folds to provide additional bladder expansion and junctional complexes that provide a watertight seal
Transitional epithelium in the calices is 2-3 layers thick
In the ureters its 4-5 cell layers thick

Question 6

Benign Cytology

Answer 6

Transitional cells usually present in all urine samples
Voided urine they occur singly or form loosely cohesive clusters or sheets
Cytoplasm is opaque or granular
Usually stain basophilic with Pap stain
Renal tubular cells are rarely found in the voided urine usually seen in catheterised specimens

Question 7

Negative Criteria

Answer 7

Negative for HGUC
- for cases where LGUC can not be excluded
Negative/reactive:
Dx entities include:
- reactive changes due to stones
- clusters in instrumented urine
- polyomavirus
- superficial umbrella cells
- seminal vesicle cells
- ileal conduit

Question 8

Morphological Criteria - Negative for HGUC

Answer 8

N/C or < 0.5
Clusters of single cells
Maintained cell polarity
Nuclei:
- pale, uniform chromatin
- smooth membrane
- small nucleoli

Question 9

Sources of Glandular Cells in Urine Specimens

Answer 9

Normal lining - urothelial differentiates along several pathways 
Cystitis glandularis
Periurethral glands
Prostate
Kidney
Seminal vesicle
Epididymis
Vas deferens
Others

Question 10

Urine Specimen Adequacy

Answer 10

Adequate - at least 20 epithelial cells
Suboptimal - < 20 epithelial cells
Inadequate - no epithelial cells

Question 11

Features of Normal Voided Urine Cytology

Answer 11

Urothelial cells
- variable in size
- opaque granular or vacuolated cytoplasm
Squamous cells
Metaplastic cells
WBC's, RBC's
Spermatozoa

Question 12

Urinary Casts

Answer 12

May be present and may be non-specific or may signify renal manifestations
Hyaline casts and granular casts are physiologic and may be seen in large numbers particularly as a result of physical stress
RBC casts are a sign of glomerular disease
WBC casts are seen in tubulointerstitial disease associated with renal rejection
Epithelial casts can be seen in any disease including acute tubular necrosis
Fatty casts are present in patients with nephrotic syndrome

Question 13

Causes of Haemutria

Answer 13

Inflammation
- acute such as E.coli
- chronic such as TB
- specific organisms: trichomonads, candida albicans etc. 
- schistosoma haematobium
Glomerulonephritis 
Calculus - stones
Neoplasia
Non-infectious causes:
- radiotherapy changes
- chemicals
- irritation
- chemotherapy

Question 14

Cystitis - Cytological Features

Answer 14

Increase PMNs
Necrotic cell debris
Urothelial cells with degenerative changes
Reactive urothelial atypia

Question 15

Virus Infections of the Urinary Tract - CMV

Answer 15

Young children, immunosuppressed, cancer patients, transplants or AIDs patients all at risk
Renal tubular epithelium is frequently involved and the disease is often seen in kidney transplant patients
Affected cells are large, contain basophilic or eosinophilic single nuclear inclusions surrounded by clear halos
Inclusion sharply demarcated from nuclear membrane
Chromatin condensed peripherally

Question 16

Virus Infections of the Urinary Tract - Polyomaviruses

Answer 16

Important in urinary cytology becuase the active infection is often localised to the brain and urinary tract
Like CMV the virus infects or reactivates if the hosts immunity is imparied
The BKV genotype in urine and serum is related to a high frequncy and high number of virus infected cells known as decoy cells
Found in patients with other types of UTI’s, haematuria and prostatic hypertrophy

Question 17

Polyomavirus - Cytological Features

Answer 17

Usually occur singly with eccentric, enlarged nuclei
Nuclei appear homogenous and clear
Nuclear inclusions often fills entire nucleus
With only a small rim of often basophilic cytoplasm
Diagnostic pitfalls:
- mimics TCC

Question 18

Urinary Tract Calculi

Answer 18

Associated with changes and atypia within the urothelium that are the major causes of false positive cytology diagnosis
Cytology characterised by presence of clusters of epithelial cells with smooth borders
Clusters may be papillary in shape
Nuclei centrally located, normal in size and shape and surrounded by uniform rim of cytoplasm
Renal calculi formed when urine is saturated with salt and minerals such as oxalate crystals and uric acid

Question 19

Criteria for Atypical Urothelial Cells (AUC)

Answer 19

Definition:
- mild-moderate cytological atypia that falls short of the 'SHGUC' category
N/C ratio of 0.5/0.7
Nuclear hyperchromasia, mild-moderate
Irregular granular chromatin 
Irregular nuclear membrane
Degenerative cells of uncertain atypia
Parachromatin clearing
Multiple nucleoli
Loss of nuclear polarity