What are the next steps in evaluating a patient with hematuria (presence of red blood cells (RBC) in urine) and squamous cells in a clean catch urine sample?

Squamous Cells in Clean Catch Urine: Clinical Significance and Next Steps

Squamous cells in a clean catch urine specimen do not indicate contamination and should not delay or prevent appropriate evaluation of hematuria. The presence of RBCs requires confirmation with microscopic urinalysis and subsequent risk-stratified workup regardless of squamous cell presence.

Understanding Squamous Cells in Urine

• Squamous cells are present in 94-96% of both catheterized and clean catch urine samples from women and do not predict bacterial contamination 1
• The overall predictive value of squamous cells for bacterial contamination is only 21% in midstream clean catch samples 1
• Squamous cells are normally shed from the urethra, trigone area of the bladder, or cervicovaginal region in women 2
• Laboratory personnel may incorrectly report renal tubular epithelial cells as squamous cells, which can lead to misinterpretation 3

Confirming True Hematuria

Before initiating any workup, confirm true microscopic hematuria with ≥3 RBCs per high-power field on microscopic examination of at least two of three properly collected clean-catch midstream urine specimens 4, 5. This is critical because:

• Dipstick testing has limited specificity (65-99%) and requires microscopic confirmation 4, 5
• The presence of both RBCs and blood on dipstick suggests true hematuria, not a false-positive result 6
• Do not proceed with extensive urologic workup based solely on dipstick results 5

Risk Stratification for Confirmed Hematuria

Once microscopic hematuria is confirmed (≥3 RBCs/HPF on 2 of 3 specimens), stratify patients into risk categories 5:

High-Risk Features (Require Full Urologic Evaluation)

• Age ≥60 years (men) or ≥60 years (women) 5
• Smoking history >30 pack-years 5, 7

• 25 RBCs per high-power field 5

• Any history of gross hematuria 5, 7
• Occupational exposure to chemicals/dyes (benzenes, aromatic amines) 4, 7
• Irritative voiding symptoms without infection 5, 7

Intermediate-Risk Features

• Women age 50-59 years or men age 40-59 years 5
• Smoking history 10-30 pack-years 5
• 11-25 RBCs per high-power field 5

Low-Risk Features

• Women age <50 years or men age <40 years 5
• Never smoker or <10 pack-years 5
• 3-10 RBCs per high-power field 5

Distinguishing Glomerular from Non-Glomerular Sources

Examine urinary sediment for features suggesting glomerular disease 5, 7:

Glomerular Indicators (Require Nephrology Referral)

• 80% dysmorphic RBCs 5, 6

• Red blood cell casts (pathognomonic for glomerular disease) 5, 6
• Significant proteinuria (>500 mg/24 hours or protein-to-creatinine ratio >0.5) 5, 6
• Tea-colored or cola-colored urine 5
• Elevated serum creatinine or declining renal function 5, 6

Non-Glomerular Indicators (Proceed with Urologic Evaluation)

• <20% dysmorphic RBCs 6
• Absence of red cell casts 6
• Minimal or no proteinuria 6
• Bright red blood 6

Complete Urologic Evaluation for Non-Glomerular Hematuria

Upper Tract Imaging

Multiphasic CT urography is the preferred imaging modality 5, 7, 6, including:

• Unenhanced phase (to detect stones) 6
• Nephrographic phase (to detect renal masses) 6
• Excretory phase (to evaluate collecting systems, ureters, bladder) 6

Lower Tract Evaluation

Cystoscopy is mandatory for 5, 6:

• All patients ≥40 years old with confirmed microscopic hematuria 6
• Younger patients with risk factors (smoking, occupational exposure, irritative symptoms, history of gross hematuria) 6
• Flexible cystoscopy is preferred over rigid cystoscopy as it causes less pain with equivalent or superior diagnostic accuracy 5

Laboratory Testing

• Serum creatinine to assess renal function 5, 7
• Complete urinalysis with microscopy 5
• Urine culture if infection suspected (preferably before antibiotics) 5, 7
• Voided urine cytology in high-risk patients 5, 7

Special Considerations

If Urinary Tract Infection is Suspected

• Obtain urine culture before initiating antibiotics 7
• Treat appropriately and repeat urinalysis 6 weeks after treatment completion to confirm resolution of hematuria 7
• If hematuria persists after documented UTI treatment, proceed with risk-stratified evaluation 7

If Glomerular Disease is Suspected

Refer to nephrology in addition to completing urologic evaluation 5, 6 if:

• Dysmorphic RBCs >80% with or without red cell casts 6
• Proteinuria >500 mg/24 hours 6
• Elevated serum creatinine or declining renal function 6
• Hypertension accompanying hematuria and proteinuria 6

Follow-Up Protocol for Negative Initial Evaluation

If complete urologic workup is negative but hematuria persists 5, 6:

• Repeat urinalysis at 6,12,24, and 36 months 5, 6
• Monitor blood pressure at each visit 5, 6
• Consider repeat complete evaluation within 3-5 years for persistent hematuria in high-risk patients 6

Immediate Re-Evaluation is Warranted If:

• Gross hematuria develops 5, 6
• Significant increase in degree of microscopic hematuria 5, 6
• New urologic symptoms appear 5, 6
• Development of hypertension, proteinuria, or evidence of glomerular bleeding 5, 6

Critical Pitfalls to Avoid

• Never dismiss hematuria because squamous cells are present—squamous cells do not indicate contamination 1
• Never defer evaluation due to anticoagulation or antiplatelet therapy—these medications may unmask underlying pathology but do not cause hematuria 5, 6
• Never ignore gross hematuria, even if self-limited—it carries a 30-40% malignancy risk and mandates urgent urologic referral 5, 6
• Never rely solely on dipstick testing—confirm with microscopic urinalysis showing ≥3 RBCs/HPF before initiating workup 4, 5
• Never attribute hematuria to a "convenient explanation" like crystals or medication without completing appropriate evaluation 6