Management of Atypical Glandular Cells
Though atypical glandular cells (AGC) are uncommon, occurring in approximately 3 per 1000 specimens, the associated risk of invasive malignancy is as high as 2-5%. All patients with AGC therefore require colposcopic evaluation and endocervical sampling (except in the setting of pregnancy when endocervical sampling should be avoided). Endometrial sampling should also be performed in patients over the age of 35, or in younger patients with risk factors for endometrial neoplasia, including abnormal uterine bleeding, obesity or conditions suggesting chronic anovulation. Reflex HPV testing is an insufficient evaluation for AGC. Colposcopic evaluation may be 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 patients 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.
Patients 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 provide an intact specimen with 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 excision bed is advised at the time of the procedure.
Unlike squamous lesions, AIS may be multifocal. If an excisional procedure is performed, the margin status is an important predictor of residual cervical disease, with persistent AIS occurring in more than 50% of cases with positive margins. Even with negative margins, there may be residual or recurrent AIS or even adenocarcinoma. Close surveillance is required. Co-testing with cervical cytology and HPV at 12 and 24 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 patient has completed child bearing, a simple hysterectomy is appropriate. If fertility preservation is important, a repeat conization is indicated, followed by close surveillance. The consequences of conization on future pregnancies should be discussed.
AIS and cervical adenocarcinoma are the most common glandular neoplasias associated with AGC cytology. However, atypical glandular cells can also be associated with polyps and metaplasia, as well as cancers of the endometrium, fallopian tubes, ovaries, and rarely, with intra-abdominal cancers, especially in older patients with negative HPV testing
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. PMID: 19019325.
Perkins RB, Guido RS, Castle PE, Chelmow D, et. al; 2019 ASCCP Risk-Based Management Consensus Guidelines Committee. 2019 ASCCP Risk-Based Management Consensus Guidelines for Abnormal Cervical Cancer Screening Tests and Cancer Precursors. J Low Genit Tract Dis. 2020 Apr;24(2):102-131. doi: 10.1097/LGT.0000000000000525. Erratum in: J Low Genit Tract Dis. 2020 Oct;24(4):427. PMID: 32243307; PMCID: PMC7147428.
Initial Approval: January 2013; Revised March 2017; Reaffirmed September 2018 and March 2020; Revised November 2021
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