A diagnosis of Atypical Glandular Cells (AGC) is a finding from a Pap test that screens for abnormal cells on the cervix. This result indicates that glandular cells show changes more pronounced than typical reactive or inflammatory processes, yet these changes are not severe enough to be definitively classified as cancer. AGC is not a cancer diagnosis itself, but it signals an abnormality carrying a higher risk of underlying pre-cancer or cancer compared to common abnormal findings involving squamous cells. An AGC result requires immediate and comprehensive follow-up because it can indicate a potentially serious condition.
The Spectrum of Risk: AGC and Malignancy
The presence of atypical glandular cells suggests a spectrum of potential diagnoses, ranging from benign conditions to invasive cancers. Although many AGC cases relate to inflammation, polyps, or other non-cancerous changes, the finding is associated with a significant risk of pre-cancerous or cancerous lesions. Studies show that between 9% and 38% of women with an AGC result have an underlying high-grade pre-cancer or cancer, necessitating diligent follow-up.
The risk of finding an invasive cancer is generally cited to be in the range of 3% to 17% of all AGC cases. This rate is higher than the risk associated with many squamous cell abnormalities. The cancers most commonly detected following an AGC result are glandular cancers, such as endocervical adenocarcinoma or endometrial adenocarcinoma.
Glandular cell abnormalities present a greater challenge for screening and early detection compared to squamous cell abnormalities. Glandular cells line the inner cervical canal, which is often harder to visualize and sample effectively during a standard Pap test. The abnormality may also originate from the uterine lining (endometrium) or even fallopian tubes and ovaries, broadening the scope of investigation required. This complexity necessitates ongoing surveillance.
Understanding Atypical Glandular Cells
The cells sampled during a Pap test are categorized based on the Bethesda System, which provides a standardized way to report cervical cytology findings. Glandular cells are specialized cells that line the inner part of the cervix (endocervical canal) and the lining of the uterus (endometrium). These are distinct from the squamous cells that line the outer cervix and vagina.
When glandular cells are deemed atypical, a pathologist observes specific cellular changes, such as enlarged nuclei, alterations in cell shape, or nuclear crowding. These changes do not fully meet the definitive criteria for a diagnosis of adenocarcinoma in situ or invasive cancer. The pathology report further classifies the finding to guide management.
AGC Classifications
The two main classifications for AGC are Atypical Glandular Cells Not Otherwise Specified (AGC-NOS) and Atypical Glandular Cells Favor Neoplastic (AGC-FN).
AGC-NOS is used when cellular changes are apparent but lack specific features that strongly suggest a pre-cancerous or cancerous process. AGC-FN carries a higher suspicion of true neoplasia because the cells exhibit more worrisome features, such as pronounced nuclear irregularities or the formation of structures like rosettes.
Pathologists attempt to specify the origin of the atypical cells, classifying them as endocervical (inner cervix) or endometrial (uterine lining) when possible. This distinction is important because the underlying pathology for each location differs. Endocervical adenocarcinoma is often associated with high-risk Human Papillomavirus (HPV), while endometrial cancer is commonly linked to hormonal factors like unopposed estrogen exposure.
Navigating the Follow-Up Diagnostic Steps
Following an AGC diagnosis, a thorough diagnostic work-up is immediately required to determine the cause of the cellular changes. The standard first step involves colposcopy, which uses a magnifying instrument to visually examine the cervix and take directed biopsies of any suspicious areas.
Sampling of the endocervical canal is mandatory for all patients with an AGC finding. This involves endocervical curettage (ECC) to collect cells from the upper portion of the cervical canal not visible with the colposcope. Endometrial sampling (a biopsy of the uterine lining) is also required for women over 35, or for younger women with risk factors for endometrial cancer, such as unexplained uterine bleeding.
High-risk Human Papillomavirus (HPV) testing is often included in the initial evaluation, particularly for AGC of endocervical origin. If the initial work-up, including colposcopy and sampling, is negative, the follow-up protocol is tailored based on the initial AGC classification.
For an AGC-NOS finding with negative results, a patient typically enters a surveillance period involving repeat co-testing with cytology and HPV testing at 12 and 24 months. A diagnosis of AGC-FN warrants a more aggressive approach due to the higher risk of underlying disease. If initial testing is negative, a cone biopsy or excisional procedure may still be recommended to remove a larger, intact sample for a more definitive diagnosis.