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Management of Atypical Glandular Cells

Author: Andrew W. Menzin, MD

Editor: Paula J. Hillard, MD

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Atypical glandular cells (AGC) are uncommon, occurring in approximately 3 per 1000 specimens, but are a significant cervical cytology finding. Several retrospective studies have reported a 2-5% prevalence of invasive malignancy in women with AGC. A colposcopic evaluation is advised for all women with an AGC report, and should include endocervical sampling. Endometrial sampling should also be performed in women over age 35, or younger women at high risk for endometrial neoplasia, including those with PCOS or other conditions suggesting chronic anovulation or unexplained vaginal bleeding. Reflex HPV testing is not a sufficient evaluation for AGC. 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 (no CIN2+, AIS, or cancer), repeat co-testing with cervical cytology and HPV testing in 12 and 24 months is indicated. Those with no further evidence of a cytologic abnormality or HPV should be followed with co-testing in 3 years; the subsequent finding of any cytologic abnormality or HPV should be evaluated 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.

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.

Additional treatment is required when the conization margins are positive for AIS. If the woman is postmenopausal or has completed her family, a simple hysterectomy is appropriate. If fertility preservation is important, a repeat conization is indicated, 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, other cancers may be the cause of abnormal glandular cells on cervical cytology. Endometrial lesions are the most common. Cancers of the fallopian tubes, ovaries, and rarely intra-abdominal cancers have been reported.


Further Reading:

Salani R, Puri I, Bristow RE., Adenocarcinoma in situ of the uterine cervix: a metaanalysis of 1278 patients evaluating the predictive value of conization margin status. Am J Obstet Gynecol. 2009 Feb;200(2):182.e1-5. doi: 10.1016/j.ajog.2008.09.012. Epub 2008 Nov 18.

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 Apr;121(4):829-46. doi: 10.1097/AOG.0b013e3182883a34.

Initial Approval:  January 2013; Revised March 2017; Reaffirmed September 2018 and March 2020


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