What is the management approach for a patient with atypical glandular cells (AGC) not otherwise specified (NOS) on a Pap smear?

Management of Atypical Glandular Cells (AGC) Not Otherwise Specified

All patients with AGC-NOS require immediate colposcopy with endocervical sampling and HPV DNA testing; additionally, women ≥35 years old or those with risk factors for endometrial cancer need endometrial sampling regardless of age. 1

Initial Workup Algorithm

The evaluation must be comprehensive and cannot rely on repeat cytology or HPV testing alone for initial triage:

Required Components for ALL Patients with AGC-NOS:

• Colposcopy with directed biopsies of any suspicious lesions after acetic acid application 1
• Endocervical sampling using either endocervical curettage or cytobrush 1
• HPV DNA testing if not already obtained at time of colposcopy 1

Age-Based Additional Requirements:

• Women ≥35 years: Add endometrial sampling (biopsy, D&C, or hysteroscopy) 1
• Women <35 years: Add endometrial sampling ONLY if risk factors present, including unexplained vaginal bleeding, chronic anovulation, obesity, unopposed estrogen therapy, polycystic ovarian syndrome, tamoxifen use, or HNPCC 1

Critical Pitfall to Avoid:

Do NOT use repeat cytology alone or HPV testing alone as initial triage—this is explicitly unacceptable management. 1 AGC carries a 31-48% risk of significant pathology including CIN, adenocarcinoma in situ, or invasive cancer. 1, 2, 3

Management Based on Initial Findings

If No CIN or Glandular Neoplasia Found:

For HPV-positive patients:

• Repeat cytology combined with HPV DNA testing at 6 months 1
• Refer back to colposcopy if subsequent HPV positive OR cytology shows ASC-US or greater 1
• If both tests negative, return to routine screening 1

For HPV-negative patients:

• Repeat cytology combined with HPV DNA testing at 12 months 1
• Same referral criteria as above 1

For HPV-unknown status:

• Repeat cytology at 6-month intervals 1
• After 4 consecutive negative results, return to routine screening 1

If CIN (Without Glandular Neoplasia) Found:

• Manage according to standard CIN guidelines based on grade 1
• Important exception: If original cytology was AGC-NOS but biopsy shows only CIN 1 with adequate colposcopy and negative endocervical curettage, conservative management with repeat cytology every 6 months OR HPV testing at 12 months is acceptable 1

If Glandular Neoplasia or AIS Found:

• Diagnostic excisional procedure is mandatory (preferably cold knife conization over LEEP) 1
• The specimen must provide intact margins for interpretation 1
• Concomitant endocervical sampling is preferred 1
• Strong consideration for referral to gynecologic oncologist 1, 4

Special Populations

Pregnant Women:

• Initial evaluation identical to non-pregnant women EXCEPT endocervical curettage and endometrial biopsy are contraindicated 1
• Colposcopy with directed biopsies and HPV testing still required 1

Clinical Context and Evidence Strength

The aggressive workup is justified by research showing:

• 19.5-48% of AGC cases harbor significant pathology 2, 5, 6
• 9.7-32.3% have malignant lesions including endometrial, cervical, or ovarian cancers 2, 3, 6
• HPV positivity predicts 20% risk of CIN 3 or cancer 1
• Even AGC "favor benign" carries 12.5% risk of neoplasia 7

The 2006 ASCCP Consensus Guidelines (updated 2009) provide the definitive management framework, with consistent recommendations across multiple guideline bodies including NCCN and ACOG. 1