What does the presence of squamous cells in urine indicate and how is it treated?

Squamous Cells in Urine: Clinical Significance and Management

The presence of squamous cells in urine typically indicates specimen contamination from the distal urethra or perineal/vaginal area, but when present in significant numbers alongside white blood cells or when atypical, they warrant careful evaluation and potentially specimen recollection using a more reliable method. 1

Normal Anatomic Origin

Squamous epithelial cells normally line specific anatomic regions:

• The distal third of the urethra is dominated by squamous epithelium 2
• The trigone area of the bladder contains squamous epithelium 1
• In women, the cervicovaginal region contributes squamous cells 1

Clinical Interpretation Based on Quantity and Context

Benign Squamous Cells (Most Common Scenario)

When numerous squamous cells appear alongside >10 WBCs and mixed bacterial flora, this strongly suggests specimen contamination rather than true infection. 1

• Clean-catch specimens have a 27% contamination rate 1
• Bag specimens have a 65-68% contamination rate 1
• Catheterized specimens have only a 4.7% contamination rate with 95% sensitivity and 99% specificity 1

Proper perineal cleansing before collection reduces contamination rates from 23.9% to 7.8%. 1

Impact on Urinalysis Performance

Squamous cells significantly impair the predictive value of urinalysis for bacteriuria:

• Samples with <8 SECs/low-powered field predict bacteriuria with 75% sensitivity and 84% specificity 3
• Samples with >8 SECs/low-powered field show reduced performance: 86% sensitivity but only 70% specificity 3
• The positive likelihood ratio drops from 4.98 to 2.35 when >8 SECs/lpf are present 3

Importantly, squamous cell count is a poor predictor of urine culture contamination itself (area under ROC curve = 0.680), meaning their presence should not be used to dismiss abnormal culture results. 3

Atypical Squamous Cells: High-Risk Finding

When atypical squamous cells (ASC) are identified—characterized by keratinizing cells with large hyperchromatic nuclei, high nuclear-to-cytoplasmic ratio, and densely orangeophilic cytoplasm—this represents a significant finding with substantial malignancy risk. 4, 5

Risk Stratification for Atypical Squamous Cells

The risk of high-grade malignancy varies by atypia grade and accompanying findings:

• Low-grade squamous atypia alone: 70% risk of high-grade malignancy 5
• High-grade squamous atypia alone: 92% risk of high-grade malignancy 5
• Any ASC with accompanying urothelial cell abnormality: 94% risk of high-grade malignancy 5
• ASC without urothelial abnormality: 37% risk of high-grade malignancy 5

Malignancies Associated with Atypical Squamous Cells

When malignancy is diagnosed following ASC detection, the following are found:

• Squamous cell carcinoma of the bladder (most common) 4
• Urothelial carcinoma with squamous differentiation 4, 5
• High-grade cervical squamous cell carcinoma (6% of cases in women) 4
• Rarely, endometrioid adenocarcinoma of the endometrium with squamous differentiation 6

Notably, 51% of malignancies show only rare atypical squamous cells in urine, so even small numbers warrant attention. 5

Management Algorithm

For Benign-Appearing Squamous Cells

1. If clinical suspicion for UTI remains high despite numerous squamous cells:

   • Recollect specimen using catheterization for optimal accuracy 1
   • Ensure proper perineal cleansing if repeat clean-catch is attempted 1

2. If squamous cells are present with negative urinalysis:

   • No specific treatment required 1
   • Consider contamination as the source 1

For Atypical Squamous Cells

Any report of atypical squamous cells requires immediate urologic evaluation regardless of quantity. 5

1. Cystoscopy with biopsy to evaluate for:

   • Bladder squamous cell carcinoma 4
   • Urothelial carcinoma with squamous differentiation 4
   • Squamous metaplasia 4

2. In women, pelvic examination with cervical cytology to exclude:

   • Cervical squamous intraepithelial lesion 4
   • Cervical squamous cell carcinoma 4

3. Upper tract imaging if no bladder or cervical source identified 1

4. The Bethesda System should be used for reporting urine cytology results with appropriate follow-up for epithelial cell abnormalities. 1

Common Pitfalls to Avoid

• Do not dismiss abnormal urine cultures solely based on squamous cell presence, as squamous cells poorly predict culture contamination 3
• Do not assume all squamous cells represent contamination—atypical squamous cells occur in only 0.15-0.3% of specimens but carry high malignancy risk 4, 5
• Do not overlook rare atypical squamous cells, as half of associated malignancies present with only rare cells 5
• In women with ASC, do not skip pelvic examination, as 6% have cervical malignancy 4