A 38-year-old woman undergoes cervical cytology screening. The Pap test shows atypical glandular cells (AGC). Colposcopy with endocervical curettage reveals the lesion marked **A** in the diagram — atypical endocervical glandular cells with preserved glandular architecture and an intact basement membrane with no stromal invasion. HPV testing is positive for HPV 18. Based on this histopathologic finding, which of the following is the most appropriate next management step?

Explanation

## Why cold knife conization with negative margin assessment and surveillance is right Cervical adenocarcinoma in situ (AIS) — characterized by the atypical glandular cells marked **A** with preserved architecture and intact basement membrane — is a pre-invasive lesion with significant risk of progression and recurrence. The gold-standard management is conization (cold knife or LEEP) to achieve complete excision with negative margins, followed by long-term surveillance with cytology and HPV testing every 6 months for at least 3 years. This approach balances fertility preservation in younger women with adequate oncologic control. The strong association with HPV 18 and the multifocal nature of AIS lesions necessitate rigorous margin assessment and close follow-up, as recurrence rates after cone alone are 15–30% (Robbins 10e, Ch 22). ## Why each distractor is wrong - **Repeat Pap cytology in 6 months and observe for regression**: AIS is not a cytologic finding that regresses spontaneously. Observation without excision risks progression to invasive adenocarcinoma. AIS is a pre-invasive lesion requiring definitive surgical management, not conservative surveillance. - **Immediate hysterectomy to prevent progression to invasive adenocarcinoma**: While hysterectomy is reserved for women who have completed childbearing or have high recurrence risk, it is not the first-line management for a 38-year-old woman who may desire fertility. Conization with negative margins is the standard initial approach; hysterectomy is offered only if recurrence occurs or fertility is not desired. - **Topical 5-fluorouracil application to the cervix followed by repeat colposcopy in 3 months**: Topical chemotherapy is not an evidence-based treatment for AIS. AIS requires surgical excision to achieve negative margins and allow histopathologic assessment. Medical therapy alone is inadequate for a pre-invasive lesion with malignant potential. **High-Yield:** Atypical glandular cells (AGC) on Pap cytology mandate colposcopy + endocervical curettage; if AIS is confirmed, conization with negative margins + long-term surveillance (cytology + HPV testing every 6 months × 3 years) is standard; HPV 18 predominates in adenocarcinoma (vs HPV 16 in squamous lesions). [cite: Robbins and Cotran Pathologic Basis of Disease, 10th edition, Chapter 22 — Female Genital Tract]