What is the significance of finding endometrial cells on a Pap (Papanicolaou) smear?

Management of Endometrial Cells on Pap Smear

The significance of endometrial cells on Pap smear depends primarily on menopausal status, with postmenopausal women requiring endometrial assessment regardless of symptoms, while premenopausal women generally need no further evaluation unless symptomatic.

Clinical Significance Based on Menopausal Status

Premenopausal Women

• For asymptomatic premenopausal women with benign endometrial cells, endometrial stromal cells, or histiocytes on Pap smear, no further evaluation is recommended as these findings are rarely associated with significant pathology 1
• Benign endometrial cells are a normal finding during the proliferative phase of the menstrual cycle in premenopausal women 1

Postmenopausal Women

• Approximately 0.5-1.8% of cervical cytology specimens from women 40 years and older will contain endometrial cells 1, 2
• Benign-appearing endometrial cells in postmenopausal women are associated with significant endometrial pathology in approximately 7% of cases 1, 2
• Studies have found endometrial pathology in 30% of postmenopausal women with benign endometrial cells on Pap smear, including:
  • Endometrial polyps (20%)
  • Endometrial hyperplasia (6%)
  • Endometrial adenocarcinoma (4%) 3
• The risk is higher in women over 50 years compared to those aged 40-50 years 4

Management Recommendations

For Premenopausal Women

• No further evaluation is recommended for asymptomatic premenopausal women with benign endometrial cells on Pap smear 1
• Consider endometrial assessment in premenopausal women with:
  • Unexplained vaginal bleeding
  • Conditions suggesting chronic anovulation 1

For Postmenopausal Women

• Endometrial assessment is recommended for all postmenopausal women with benign endometrial cells on Pap smear, regardless of symptoms 1, 2
• The recommended diagnostic pathway includes:
  1. Transvaginal ultrasound to measure endometrial thickness
     • A thickness ≤4 mm has a high negative predictive value for endometrial cancer 2, 5
     • If endometrial thickness is ≥5 mm, proceed to tissue sampling 2, 5
  2. Endometrial tissue sampling using Pipelle or Vabra devices (sensitivity 99.6% and 97.1% respectively) 1, 2
  3. If initial sampling is inadequate or inconclusive, consider hysteroscopy with directed biopsies 1, 5

Types of Endometrial Cells and Their Significance

• Glandular cells carry greater risk than stromal cells/histiocytes 6
• The presence of endometrial glandular cells in Pap smears was associated with five times the likelihood of significant endometrial disease compared to women with normal Pap smears 6
• Degenerative endometrial debris accompanied by benign-looking endometrial cells may be particularly concerning, with one study finding malignancy in 41% of such cases regardless of menopausal status 7

Special Considerations

• Hormone replacement therapy (HRT) increases the rate of shedding of benign-appearing endometrial cells but does not eliminate the elevated risk of pathology 1
• Benign-appearing glandular cells after hysterectomy (derived from small accessory ducts, foci of benign adenosis, or prolapse of the fallopian tube) have no clinical significance 1

Potential Pitfalls

• Do not dismiss the finding of normal endometrial cells in postmenopausal women as insignificant, even in asymptomatic patients 2
• The false-negative rate of office endometrial biopsy is approximately 10%, requiring follow-up if clinical suspicion remains high 2, 5
• Do not rely solely on Pap smears for evaluation of endometrial pathology, as they are designed primarily for cervical cancer screening 2