What is the clinical significance of finding squamous epithelial cells in urine?

Clinical Significance of Squamous Epithelial Cells in Urine

The presence of squamous epithelial cells in urine is primarily a marker of specimen contamination rather than a sign of pathology, but in rare cases (0.3-0.9% of specimens) atypical squamous cells may indicate underlying malignancy, warranting further investigation. 1, 2, 3

Normal Squamous Epithelial Cells

• Origin: Squamous epithelial cells in urine typically originate from:

  • In women: Vaginal contamination during collection
  • In men: Exfoliation from the distal urethra
  • In both sexes: The trigone area of the bladder

• Clinical Significance:

  • Poor predictor of urine culture contamination (area under ROC curve = 0.680) 1
  • May affect urinalysis performance in predicting bacteriuria:
    • Samples with <8 squamous cells/low-powered field: Better predictive value (sensitivity 75%, specificity 84%)
    • Samples with >8 squamous cells/low-powered field: Reduced specificity (sensitivity 86%, specificity 70%) 1

Atypical Squamous Cells (ASCs)

• Incidence: Rare finding in urine specimens (0.3-0.9%) 2, 3

• Characteristics of ASCs:

  • Keratinizing cells with large, hyperchromatic nuclei
  • High nuclear-to-cytoplasmic ratio
  • Abnormal nuclear or cytoplasmic shapes
  • Densely orangeophilic cytoplasm 2

• Clinical Significance:

  • High risk of malignancy: Recent studies show atypical squamous cells are associated with significant risk of high-grade malignancy 4
    • Low-grade squamous atypia: 70% risk of high-grade malignancy
    • High-grade squamous atypia: 92% risk of high-grade malignancy
    • When accompanied by urothelial cell abnormalities: 94% risk of high-grade malignancy 4

• Potential underlying conditions:

  1. Squamous cell carcinoma of the bladder (25-31% of cases with ASCs) 2
  2. Urothelial carcinoma with squamous differentiation 2
  3. Squamous cell carcinoma from non-urinary tract sources (6-38% of cases) 2, 3
  4. Cervical squamous cell carcinoma in women 2, 5
  5. Endometrial carcinoma with squamous differentiation 5

Evaluation Algorithm for Squamous Cells in Urine

1. For normal-appearing squamous epithelial cells:

   • Generally indicates specimen contamination
   • Consider repeat collection if high numbers present (>8/lpf)
   • Note that they may reduce the predictive value of other urinalysis parameters 1

2. For atypical squamous cells:

   • Immediate further investigation is warranted
   • Cystoscopy with potential biopsy of suspicious lesions 6
   • In women, pelvic examination to rule out gynecologic source 2
   • Upper tract imaging (CT urography) to evaluate for malignancy 6

Risk Factors to Consider When Finding ASCs

• History of chronic bladder inflammation
• Indwelling catheters
• Bladder stones
• Neurogenic bladder dysfunction
• History of schistosomiasis (especially with travel to endemic areas)
• Previous history of urothelial or squamous cell carcinoma 6

Common Pitfalls

• Dismissing all squamous cells as mere contamination without evaluating for atypia
• Failing to consider non-urinary tract sources of atypical squamous cells
• Not recognizing that even rare atypical squamous cells (found in 51% of malignancies) can indicate significant pathology 4
• Overlooking the need for gynecologic evaluation in women with unexplained ASCs in urine

Remember that while normal squamous epithelial cells are usually benign findings, atypical squamous cells require thorough investigation due to their strong association with malignancy.