AGUS Reports Scare Me
Special Feature
AGUS Reports Scare Me
By Kenneth Noller, MD
In general, clinicians are familiar with the Bethesda System (TBS) for Pap smear reports, since virtually all laboratories in the United States now use that terminology.1 While it was a nuisance to learn new words for the "same old diseases," most of us have adapted. In fact, now I actually prefer the new terminology. ASCUS reports remain a bother, but when disease is present, it is of the squamous type that is easy to handle.
However, reports of Pap smears showing the presence of "atypical glandular cells of undetermined significance" (AGUS) are different, are worrisome, and, quite frankly, scare me. The AGUS category was created for the same reason as the ASCUS category: To allow cytopathologists to indicate that they see glandular-type cells that are clearly not normal, but also are clearly not diagnostic of glandular neoplasia. For the first several years after TBS was introduced, I believed that most AGUS reports indicated infection of the endocervical epithelium with the human papillomavirus, most often Type 18. I expected that the virus would either become subclinical or develop into an intraepithelial lesion that would be detected on subsequent smears and could then be treated.
Several articles about AGUS have now been published, including one from my institution. These articles have shocked me out of my complacency, as it appears that an AGUS report is worrisome. The Table shows a summary of the final pathologic diagnosis among the 235 women in three of these reports.2-4 While it is not exactly correct to merely add up the numbers from each of these separate papers, there were enough similarities that I feel comfortable presenting the information in this manner.
| Table | |
| Summary of Pathology in 235 Women with AGUS Cytology* | |
| CIN I | 18 |
| CIN II-III | 26 |
| AIS, Cx | 6 |
| Inv CA Cx | 8 |
| Endometrial AC | 9 |
| Other cancer | 5§ |
| * Summary of three published studies | |
| § Ovary 3, Pancreas 1, Colon 1 | |
The most common diagnosis was a squamous intraepithelial lesion (dysplasia). However, much more concerning is the fact that fully 9.4% of these women were found to have some type of invasive cancer. Endometrial adenocarcinoma is the most common invasive lesion (9 cases), but eight women had invasive endocervical adenocarcinoma. For many years, it has been recognized that women with adenocarcinoma of the endometrium frequently shed endometrial cancer cells that are found on Pap smears, and these can be interpreted as showing endometrial cancer. However, those cases are not included in the AGUS category. Thus, even after all of the obvious endometrial cancers have been removed, this tumor still represents the most commonly found invasive lesion in women with AGUS reports. For women older than age 35 (some authors recommend an older age), an AGUS report should be an indication for an endometrial biopsy. Fortunately, the lesion has not yet been diagnosed in women younger than 35 years, and most cases have been found in menopausal or perimenopausal women.
Invasive endocervical adenocarcinoma is also found frequently in women with AGUS reports. Thus, a thorough investigation of the cervix and endocervix must be part of the evaluation of every woman with an AGUS smear. Colposcopy, biopsy, endocervical sampling, and, in many cases, cone biopsy (either with knife or loop electroexcision) are warranted in many cases. In general, if a woman has an AGUS smear, we must continue the work-up until some answer is found. If colposcopy and biopsy uncover a significant dysplastic lesion, it is probably safe to stop searching. However, if colposcopy, biopsy, and endocervical sampling are all negative, conization is probably a good idea. In the future, we may decide that it is safe to stop before conization in some cases, and to follow AGUS patients with frequent cytologic evaluation. However, based on the limited information we have at this time, conization is probably indicated if no disease has been found.
The several cases of ovarian cancer that are part of these series (as well as the other intra-abdominal cancers) suggest that close follow-up for all women with AGUS smears without cervical or endometrial pathology is warranted. Certainly, these conditions are rare enough that exploratory surgery or laparoscopy cannot be recommended, though non-invasive techniques such as serum tumor markers or, possibly, pelvic ultrasonography might be indicated in select cases.
One word of caution: The reports that are summarized in the Table came from top-notch cytology laboratories where AGUS smears represent less than one-half of 1% of all reports. Some hospital laboratories report AGUS rates as high as 3-4%. Obviously, at these hospitals, there is a much lower likelihood of finding a significant lesion in a woman with an AGUS Pap smear. The recommendations I have made would only apply to a laboratory with a low AGUS rate. Just as with ASCUS reports, it is important for each clinician to know the AGUS rate for the laboratories most commonly used.
References
1. Kurman RJ, Solomon D. The Bethesda System for Reporting Cervical/Vaginal Cytologic Diagnoses. New York, NY: Springer Verlag; 1994: 64-73.
2. Kennedy WA, et al. Gynecol Oncol 1996;63:14-18.
3. Zweizig S, et al. Gynecol Oncol 1997;65:314-318.
4. Duska LR, et al. Obstet Gynecol 1998;91:278-282.
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