What does the presence of elevated squamous epithelial cells in a urine sample indicate?

Elevated Squamous Epithelial Cells in Urine: Clinical Significance and Interpretation

The presence of elevated squamous epithelial cells in a urine sample primarily indicates specimen contamination rather than pathology, and generally does not require clinical intervention or follow-up testing unless accompanied by other concerning findings.

Understanding Squamous Epithelial Cells in Urine

Squamous epithelial cells in urine samples typically originate from:

• The distal urethra
• The vaginal area in women
• The periurethral region

Clinical Significance

• Not indicative of infection: Research has demonstrated that squamous cells are poor predictors of bacterial contamination in urine samples, with a positive predictive value of only 21% 1.
• Poor marker for culture contamination: A large study of over 19,000 records showed that squamous epithelial cell count is a poor predictor of urine culture contamination (area under ROC curve = 0.680) 2.
• Impact on urinalysis interpretation: High squamous cell counts (>8 cells/low-powered field) may reduce the reliability of urinalysis in predicting bacteriuria 2.

When to Be Concerned

While most cases of elevated squamous cells represent normal contamination, certain scenarios warrant further investigation:

1. Atypical squamous cells: The presence of atypical squamous cells (keratinizing cells with large hyperchromatic nuclei, high N/C ratio, abnormal shapes) is rare (0.3% of samples) but clinically significant, with 31% of such cases later diagnosed with squamous cell carcinoma 3.

2. Squamous cells with intracellular bacteria: This may indicate an intracellular bacterial community, potentially related to urinary tract infections caused by organisms like E. coli 4.

3. Context of hematuria or other concerning symptoms: In patients with hematuria, even with equivocal cytology findings including squamous cells, management should proceed with a high suspicion for malignancy 5.

Differential Considerations When Squamous Cells Are Elevated

1. Normal contamination: Most common explanation, especially in clean-catch specimens

2. Potential pathological causes:

   • Squamous metaplasia of the urothelium
   • Urothelial carcinoma with squamous differentiation
   • Squamous cell carcinoma of the bladder (rare, accounting for only 3% of bladder cancers in the US) 6
   • Gynecological pathology in women (including cervical/endometrial lesions) 7

Recommendations for Interpretation

• For routine specimens: Elevated squamous cells alone without other abnormal findings generally do not require follow-up.

• For specimens with other abnormalities:

  • If nitrites, leukocyte esterase, or bacteria are present, consider UTI regardless of squamous cell count 6.
  • If hematuria is present with elevated squamous cells, further investigation may be warranted to rule out malignancy 5.

• For specimen collection:

  • Catheterization or suprapubic aspiration provides more reliable specimens when diagnosis is critical 6.
  • A negative clean-catch specimen can reliably rule out UTI, but positive results with high squamous cell counts should be interpreted cautiously 6.

Practical Approach to Elevated Squamous Cells

1. Assess specimen quality: A urine sample with >10 WBCs and significant epithelial cells should be considered contaminated 6.

2. Consider clinical context: In asymptomatic patients, elevated squamous cells alone rarely warrant further investigation.

3. Look for associated findings: The presence of pyuria, bacteriuria, or hematuria alongside squamous cells should guide further management.

4. Repeat collection if necessary: If clinical suspicion for infection or malignancy exists despite contaminated specimen, obtain a better-quality specimen through improved technique or catheterization.

In summary, while elevated squamous epithelial cells typically represent specimen contamination, their presence should be interpreted in the context of other clinical and laboratory findings to determine appropriate next steps.