What is the significance of occasional squamous cells in a patient's urine and how should it be evaluated and managed?

Occasional Squamous Cells in Urine: Clinical Significance and Management

Occasional squamous cells in urine are typically benign and represent normal shedding from the distal urethra or, in women, contamination from the cervicovaginal region—no specific intervention is required unless accompanied by other concerning findings.

Origin and Normal Presence

Squamous epithelial cells are normal anatomic components of the urinary tract:

• The distal third of the urethra is naturally lined with squamous epithelium, while the proximal two-thirds contains transitional epithelium 1, 2
• In women, squamous cells commonly originate from the bladder trigone, distal urethra, or cervicovaginal region 2, 3
• These cells are found in 94-96% of urine samples from women, regardless of collection method 4

Clinical Interpretation of "Occasional" Squamous Cells

The presence of occasional squamous cells alone does not indicate pathology and requires no further workup. 2, 4

Key interpretation principles:

• Squamous cells do NOT reliably predict bacterial contamination—they were present in 94% of catheterized samples (which had 0% contamination) and 96% of clean-catch samples (only 21% contaminated) 4
• A significant number of squamous cells alongside >10 WBCs suggests potential sample contamination rather than true infection 2
• Squamous cells may reduce the predictive performance of urinalysis for bacteriuria when present in high numbers (>8 cells/low-powered field), but occasional cells do not affect interpretation 5

When Squamous Cells Warrant Further Evaluation

Atypical squamous cells (ASC) are distinctly different from benign squamous cells and require investigation. ASC are characterized by:

• Keratinizing cells with large, hyperchromatic smudgy nuclei 6
• High nuclear-to-cytoplasmic ratio 6
• Abnormal nuclear or cytoplasmic shapes 6
• Densely orangeophilic cytoplasm 6

Risk Stratification for Atypical Squamous Cells

If ASC are identified (not "occasional" benign squamous cells), the risk of malignancy is substantial:

• Low-grade squamous atypia without accompanying urothelial cell abnormality: 70% risk of high-grade malignancy 7
• High-grade squamous atypia without accompanying urothelial cell abnormality: 92% risk of high-grade malignancy 7
• Any grade squamous atypia WITH accompanying urothelial cell abnormality: >90% risk of high-grade malignancy 7
• Overall, 31% of patients with ASC in urine were subsequently diagnosed with squamous cell carcinoma 6

Malignancies Associated with Atypical Squamous Cells

When malignancy is found, it typically represents:

• Squamous cell carcinoma of the bladder (25% of cases with adequate follow-up) 6
• Urothelial carcinoma with squamous differentiation 6, 7
• High-grade cervical squamous cell carcinoma (6% of cases) 6
• Endometrioid adenocarcinoma of the endometrium with squamous differentiation (rare) 3

Management Algorithm

For Occasional Benign Squamous Cells:

• No further workup required 2, 4
• If accompanied by pyuria and mixed bacterial flora suggesting contamination, consider recollection using proper technique if clinical suspicion for UTI remains high 2

For Atypical Squamous Cells:

1. Immediate cystoscopy with biopsy of any visible lesions 1
2. Pelvic examination in women to exclude cervical or endometrial malignancy 6, 3
3. Upper tract imaging (CT urography preferred) to evaluate for synchronous lesions 1
4. Urine cytology if not already performed 1

Collection Technique to Minimize Contamination

When recollection is needed:

• Catheterization provides the most reliable specimens (4.7% contamination rate vs. 27% for clean-catch) with 95% sensitivity and 99% specificity 2
• Proper perineal cleansing before clean-catch collection reduces contamination from 23.9% to 7.8% 2
• Bag specimens have the highest contamination rate (65-68%) and should be avoided when possible 2

Critical Pitfalls to Avoid

• Do not assume squamous cells indicate contamination—this is not supported by evidence and may lead to dismissing legitimate specimens 4, 5
• Do not confuse benign squamous cells with atypical squamous cells—the latter require immediate investigation due to high malignancy risk 6, 7
• Do not overlook the need for pelvic examination in women with ASC—cervical and endometrial malignancies can present with urinary ASC 6, 3
• In immunosuppressed patients (including HIV), maintain heightened vigilance—squamous cell carcinomas occur more frequently and may arise in or resemble benign lesions 1