Atrophic Pattern on Pap Smear
An atrophic pattern on a Pap smear indicates benign cellular changes related to estrogen deficiency in postmenopausal women, characterized by uniform nuclear enlargement in squamous cells that can mimic dysplasia but typically resolves with estrogen treatment. 1, 2
What Atrophic Changes Look Like
The atrophic cervical smear pattern shows specific cytologic features that distinguish it from true dysplasia:
- Uniform nuclear enlargement across the squamous cell population is the hallmark finding, which by nuclear size criteria alone could technically qualify as atypical squamous cells of undetermined significance (ASCUS) 2
- The nuclear enlargement is uniform and consistent throughout the cell population, rather than showing the variability seen in true dysplasia 2
- These changes occur due to physiologic estrogen decline in postmenopausal women 1
The Clinical Problem: False Positives
Atrophic changes create a significant diagnostic challenge because they can mimic high-grade cervical intraepithelial neoplasia (CIN2-3):
- Atrophic epithelium may be misclassified as ASCUS or even squamous intraepithelial lesion (SIL) based on nuclear enlargement alone 3, 2
- The ASCUS-to-SIL ratio is significantly elevated in postmenopausal women (4.1:1) compared to premenopausal women (1.9:1), indicating overcalling of abnormalities 4
- Only 12% of perimenopausal and 29.7% of postmenopausal women with ASCUS diagnoses actually have true SIL on follow-up 4
Key Distinguishing Features
Nuclear enlargement alone is NOT sufficient for diagnosing ASCUS or SIL in postmenopausal smears. 2 True dysplasia shows additional features:
- Nuclear hyperchromasia (darker staining nuclei) is the most reliable indicator of true SIL in atrophic smears 2
- Irregular nuclear contours (membrane irregularities) distinguish dysplasia from benign atrophy 2, 4
- Atrophic changes show uniform nuclear features that resolve with estrogen, while dysplastic changes persist 2
Recommended Management Approach
When an atrophic pattern with atypia is reported, the standard approach is estrogen treatment followed by repeat cytology:
- Treat with vaginal estrogen preparation and repeat the Pap smear after completion of therapy 1
- A five-night regimen of 25-mcg vaginal estradiol tablets (one tablet nightly) before repeat Pap testing reduces the odds of an atrophic smear by 99% (OR 0.01,95% CI 0.03-0.26) compared to no estrogen 5
- If cytologic appearance normalizes with estrogen therapy, the patient can return to routine follow-up 1
- If abnormalities persist after estrogen treatment, refer for colposcopy as this suggests true dysplasia rather than atrophy 1
Alternative Diagnostic Strategy: HPV Testing
For postmenopausal women with atrophic ASCUS, HPV testing offers an alternative management strategy:
- HR-HPV testing with colposcopy referral only if positive is appropriate given the lower HPV prevalence (31-50%) in menopausal women compared to younger women (65-71%) 1
- This approach avoids unnecessary colposcopy in HPV-negative women whose atypia is likely benign and atrophy-related 1
Advanced Diagnostic Tool (Not Routine Practice)
Research has identified a more definitive test, though not widely implemented:
- Ki-67 (MIB-1) immunostaining on the original Pap smear can distinguish atrophy from dysplasia with high accuracy 3, 6
- Negative Ki-67 expression reliably indicates normal atrophic pattern and can reduce false-positive diagnoses by 86% 6
- This method could substantially reduce unnecessary estrogen courses and repeat smears, though it requires specialized laboratory capabilities 3
Common Pitfalls to Avoid
- Do not diagnose ASCUS or SIL based solely on nuclear enlargement in postmenopausal women—this is an expected normal reactive change in atrophy 2
- Air-drying artifact can contribute to overcalling ASCUS in perimenopausal women and should be recognized 4
- Remember that atrophic changes are benign and reversible with estrogen, unlike true dysplasia 2