What are the possible cervical and endometrial pathologies in a 50‑year‑old post‑menopausal woman with atypical glandular cells (AGC) and abnormal epithelial cells on Pap smear?

Differential Diagnosis in a 50-Year-Old Postmenopausal Woman with Atypical Glandular Cells and Abnormal Epithelial Cells

In a 50-year-old postmenopausal woman with atypical glandular cells (AGC) and abnormal epithelial cells on Pap smear, the most critical possibilities include endometrial adenocarcinoma (most common malignancy at 15% overall risk), cervical adenocarcinoma, cervical squamous cell carcinoma, high-grade squamous intraepithelial lesions (HSIL), and adenocarcinoma in situ (AIS), with approximately 32-57% of such patients harboring clinically significant preinvasive or invasive lesions. 1, 2, 3, 4

High-Risk Malignant Pathologies

Endometrial Pathology

• Endometrial adenocarcinoma is the single most common malignancy in postmenopausal women with AGC, accounting for 51.7% of all malignant lesions and occurring in 13-15% of all AGC cases in this age group. 1, 4
• Benign-appearing endometrial cells in postmenopausal women are associated with significant endometrial pathology in approximately 7% of cases, even when appearing benign on cytology. 5
• Endometrial hyperplasia represents a premalignant condition found in 7-11% of AGC cases in postmenopausal women. 2, 6

Cervical Glandular Pathology

• Cervical adenocarcinoma (invasive) occurs in 5-10% of postmenopausal women with AGC. 2, 3
• Adenocarcinoma in situ (AIS) of the cervix is found in 3-5% of cases and represents a high-grade precursor lesion requiring aggressive management. 2, 6
• Microinvasive adenocarcinoma accounts for approximately 3% of significant lesions. 6

Cervical Squamous Pathology

• High-grade squamous intraepithelial lesions (HSIL/CIN 2,3) represent 26-47% of significant lesions in postmenopausal women with AGC, making squamous lesions nearly as common as glandular pathology. 1, 2
• Invasive squamous cell carcinoma of the cervix occurs in 3-10% of AGC cases in this population. 2, 3
• Low-grade squamous intraepithelial lesions (LSIL) are found in 4-6% of cases. 1, 6

Other Malignancies

• Ovarian adenocarcinoma can present with AGC on Pap smear in approximately 2.5% of cases. 3
• Metastatic disease to the vagina or cervix from other primary sites occurs in approximately 2.5% of cases. 2, 3

Benign and Reactive Pathologies

Benign Cervical Lesions

• Microglandular hyperplasia of the cervix, atypical squamous metaplasia, cervical endometriosis, and tubal metaplasia collectively account for a minority of AGC findings. 6
• Cervical polyps and cervical myomas are common benign findings that can produce AGC cytology. 6
• Chronic cervicitis and inflammatory changes are the most common non-malignant findings but should not be assumed without tissue diagnosis. 4

Benign Uterine Lesions

• Endometrial polyps, uterine myomas, and adenomyosis can occasionally produce AGC on Pap smear. 6

Critical Clinical Context

Age-Specific Risk Stratification

• Postmenopausal women (≥50 years) with AGC have a 76.7% likelihood of having a malignant glandular lesion if significant pathology is present, compared to younger women who are more likely to have squamous lesions. 4
• Women over 40 years, particularly postmenopausal women, are significantly more likely to have clinically significant histological abnormalities (P < 0.001). 2, 3

Overall Risk Assessment

• The overall rate of clinically significant lesions (preinvasive or invasive, glandular or squamous) ranges from 25-57% in postmenopausal women with AGC. 1, 2, 6, 3
• The risk of invasive cancer specifically ranges from 3-26% depending on the study population. 7, 2, 3, 4
• AGC is associated with clinically significant lesions in approximately 45% of all patients across age groups. 7, 8

Symptom Correlation

• Abnormal vaginal bleeding is the most common presenting symptom (30.6%) and is significantly associated with pathological outcomes (P = 0.041). 2, 3
• Symptomatic patients at the time of AGC diagnosis have significantly higher rates of significant pathology compared to asymptomatic patients. 3

Important Clinical Pitfalls

• The presence of "benign-appearing" endometrial cells in a postmenopausal woman should never be dismissed, as significant endometrial pathology remains elevated even in this setting. 5
• AGC cytology can represent either squamous or glandular pathology—approximately 47-56% of significant lesions in postmenopausal women are squamous rather than glandular. 1, 4
• The incidence of AGC on Pap smears is low (0.08-0.8%), but the high rate of underlying significant pathology (25-57%) mandates aggressive workup in all cases. 2, 6, 3, 4
• Postmenopausal status, age >50 years, presence of symptoms, and AGC "favor neoplasia" designation are all independent predictors of significant pathological outcomes. 3