What is the diagnostic approach for hematuria (presence of blood in urine), including the role of urine cytology?

Diagnostic Approach for Hematuria: The Role of Urine Cytology

Urine cytology should only be performed in patients with risk factors for transitional cell carcinoma, not as a routine test in the initial evaluation of hematuria. 1

Risk Stratification for Hematuria Evaluation

The American Urological Association (AUA) recommends classifying patients with microhematuria into risk categories:

• Low risk (0-0.4% cancer risk): 3-10 RBC/HPF + Age <60 years (women) or <40 years (men) + Non-smoker or <10 pack-years
• Intermediate risk (0.2-3.1% cancer risk): 11-25 RBC/HPF or Age 60+ (women)/40-59 (men) or 10-30 pack-years smoking
• High risk (1.3-6.3% cancer risk): >25 RBC/HPF or Age 60+ (men) or >30 pack-years smoking 1

Initial Diagnostic Approach

1. Confirm hematuria microscopically

   • Microscopic hematuria is defined as ≥3 RBC/HPF in a properly collected urine sample 1
   • Dipstick positivity alone is not reliable and requires microscopic confirmation

2. Basic laboratory evaluation

   • Complete blood count
   • Serum creatinine and BUN
   • Urinalysis with microscopic examination of urinary sediment
   • Urine culture to rule out infection 1

3. Imaging

   • CT Urography is the preferred imaging modality (sensitivity 92%, specificity 93%) 1
   • Alternative imaging options:
     • MR Urography for patients with contrast allergy or renal insufficiency
     • Renal ultrasound as an alternative or in young patients (sensitivity 50%, specificity 95%) 1

4. Cystoscopy

   • Recommended for all patients ≥35 years with microscopic hematuria
   • Particularly important for high-risk patients 1

Role of Urine Cytology

Urine cytology has a specific and limited role in hematuria evaluation:

• Not recommended for initial evaluation of all patients with hematuria 1

• Indicated only in patients with risk factors for transitional cell carcinoma 2, including:

  • History of smoking
  • Occupational exposure to chemicals or dyes
  • History of gross hematuria
  • Age >40 years
  • History of irritative voiding symptoms
  • History of urologic disorder or disease
  • History of pelvic irradiation
  • History of cyclophosphamide use
  • History of analgesic abuse

• If cytology is performed and shows malignant or atypical/suspicious cells, cystoscopy is required 2

Common Pitfalls to Avoid

1. Assuming UTI is the cause without proper evaluation

   • Urologic malignancy may be present even with a positive urine culture 1
   • Patients with UTI should be treated and urinalysis repeated after 6 weeks; if hematuria resolves, no additional evaluation is necessary 2

2. Attributing hematuria to anticoagulant/antiplatelet therapy

   • Anticoagulant/antiplatelet therapy should not be assumed as the cause of hematuria
   • Complete evaluation should still proceed 1

3. Overreliance on urine cytology

   • Urine cytology should not replace cystoscopy or imaging
   • Newer urinary markers lack sufficient data for routine use 2

4. Neglecting nephrology evaluation

   • Consider nephrology referral if there are signs of glomerular disease:
     • Significant proteinuria (>1,000 mg/24 hours)
     • Red cell casts
     • Dysmorphic RBCs 1

Follow-up for Negative Initial Evaluations

For patients with persistent asymptomatic microscopic hematuria after negative initial evaluation:

• Low-risk patients: Annual urinalysis
• Intermediate/high-risk patients: Consider urine cytology and repeat urinalysis at 6,12,24, and 36 months 1

Persistent microscopic hematuria indicates the presence of a renal disease that warrants close monitoring and evaluation 3.