What is the significance of non-squamous epithelial cells on a Urinalysis (UA)?

Significance of Non-Squamous Epithelial Cells on Urinalysis

The presence of non-squamous epithelial cells on urinalysis is clinically significant as they may indicate renal tubular injury, urothelial damage, or potentially malignancy, warranting further evaluation based on clinical context and risk factors.

Types of Epithelial Cells in Urine

• Squamous epithelial cells: Generally considered contaminants from the distal urethra or external genitalia
• Non-squamous epithelial cells: Include two important subtypes:
  • Renal tubular epithelial (RTE) cells: Indicate renal tubular injury
  • Transitional (urothelial) cells: Originate from the lining of the urinary tract (renal pelvis, ureters, bladder, and proximal urethra)

Clinical Significance

Renal Tubular Epithelial Cells

• Indicate active renal parenchymal damage
• May be present in:
  • Acute tubular necrosis (ATN)
  • Acute interstitial nephritis
  • Glomerulonephritis
  • Drug-induced nephrotoxicity
  • Pyelonephritis

Transitional (Urothelial) Cells

• May indicate:
  • Normal exfoliation (small numbers)
  • Inflammation of the urinary tract
  • Urothelial injury
  • Potential urothelial malignancy when atypical 1

Diagnostic Considerations

Laboratory Interpretation Challenges

• Studies show significant discrepancies between laboratory and nephrologist identification of epithelial cell types 2
• Laboratories frequently misidentify renal tubular epithelial cells as squamous cells 2
• Many laboratories (82.6% in one survey) do not differentiate between epithelial cell subtypes despite clinical relevance 3

Evaluation Algorithm

1. Quantify and identify cell type:

   • RTE cells: Smaller than squamous cells, round to cuboidal with central nucleus
   • Transitional cells: Pear-shaped or round with eccentric nucleus
   • Presence of >8 non-squamous epithelial cells/lpf warrants attention 4

2. Consider clinical context:

   • Patient symptoms (hematuria, dysuria, flank pain)
   • Medication history (nephrotoxic drugs)
   • Underlying conditions (hypertension, diabetes)

3. Additional urinalysis findings:

   • Presence of casts (particularly RTE casts)
   • Proteinuria
   • Hematuria
   • Pyuria

4. Further evaluation based on risk stratification:

   • If hematuria present: Follow hematuria evaluation guidelines 1
   • If suspicion for renal disease: Consider nephrology consultation
   • If suspicion for urothelial pathology: Consider urology consultation

Special Considerations

Malignancy Risk Assessment

• Atypical non-squamous epithelial cells may indicate urothelial carcinoma 1
• Urothelial cancers account for >90% of urinary tract malignancies 1, 5
• Risk factors include:
  • Smoking history
  • Occupational exposures
  • Chronic inflammation
  • Indwelling catheters (in neurogenic bladder) 5

Neurogenic Bladder Patients

• Higher risk of squamous cell carcinoma (25-81% of bladder cancers in this population) 1, 5
• Surveillance cystoscopy and cytology are poor screening tests in this population 1
• Changes in urinary symptoms warrant urodynamic studies 1

Rare Findings

• Atypical squamous cells in urine may occasionally indicate non-urological malignancies such as endometrial carcinoma with squamous differentiation 6

Pitfalls to Avoid

1. Misidentification: Non-squamous epithelial cells are frequently misidentified as squamous cells by laboratory technicians 2

2. Overlooking significance: Non-squamous epithelial cells should not be dismissed as contamination 4

3. Inadequate follow-up: Persistent presence of non-squamous epithelial cells warrants investigation, particularly when accompanied by hematuria or other concerning symptoms

4. Missing malignancy: Atypical non-squamous cells may be the first indication of urothelial carcinoma and should prompt appropriate evaluation 1, 5