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Management of AGC in a 45 Year-Old

Jan 2013 – by A. Menzin, MD

An asymptomatic 45 year-old woman has atypical glandular cells, not otherwise specified, on a routine cervical cytology screening test. Colposcopic assessment is negative. How should this woman be managed?

Atypical glandular cells (AGC) are an uncommon (approximately 3:1000 specimens), but significant cervical cytology finding. Several retrospective studies have reported that the prevalence of invasive malignancy in women with AGC is 2-5%. A colposcopic evaluation is advised for all women with an AGC report, and should include endocervical sampling, with the addition of endometrial sampling in women over age 35, or younger women at high risk for endometrial neolasia. (Reflex HPV testing is not a sufficient response to an AGC report.) Unfortunately, colposcopic evaluation is often negative even when disease is present. There are no characteristic colposcopic features of cervical adenocarcinoma-in-situ (AIS), and lesions may be within the endocervical canal or glandular crypts beyond the limits of colposcopic visualization.

For women with AGC, not otherwise specified (NOS), if the initial evaluation is negative, repeat co-testing with cervical cytology and HPV in 12 months is indicated. Those with no further evidence of a cytologic abnormality or HPV should be followed with routine screening; the subsequent finding of a cytologic abnormality or HPV should be followed by repeat colposcopic evaluation.

Women with a report of AGC, favor neoplasia, in whom invasive disease is not identified at colposcopy, should undergo conization, with consideration given to endometrial sampling. When AIS is detected at the time of colposcopy, a cone biopsy should be performed to exclude concurrent invasive disease.

The excisional procedure should remove the entire transformation zone and have interpretable margins (avoiding tissue disruption or cautery artifact), with some preferring cold knife conization to laser excision or LEEP. Sampling of the endocervical canal above the cone specimen is advised at the time of the excisional procedure.

Adenocarcinoma-in-situ (AIS) is a common finding when AGC is reported. Unlike squamous lesions, AIS may be multifocal. If an excisional procedure is performed, the margin status is an important predictor of residual disease in the cervix, with persistent AIS occurring in more than 50% of woman with positive margins. Even with negative margins, there may be residual or recurrent AIS or even adenocarcinoma, so close surveillance is required. Co-testing with cervical cytology and HPV at 12 months is appropriate. Any further evidence of glandular disease will require repeat conization.

When the conization margins are positive for AIS, additional treatment is required. If the woman is postmenopausal or has completed her family, a simple hysterectomy is appropriate. If fertility preservation is important, a repeat conization is required, followed by close surveillance. The consequences of conization on the successful completion of future pregnancies should be discussed.

AIS and cervical adenocarcinoma are the most common glandular neoplasias associated with an AGC cytology result. However, many other cancers may be the cause of abnormal glandular cells on a pap test. Endometrial lesions are the most common of these. Cancers of the fallopian tubes and ovaries, and rarely intra-abdominal cancers have also been reported.

References

1. Salani R, Puri I, Bristow RE. Adenocarcinoma in situ of the cervix: a meta-analysis of 1278 patients evaluating the predicting value of conization margin status. Am J Obstet Gynecol 2009;200:182.e1-5.
2. Massad LS, Einstein MH, Huh WK, et al. 2012 Updated Consensus Guidelines for the Management of Abnormal Cervical Cancer Screening Tests and Cancer Precursors. Obstet Gynecol 2013;121:829-46.