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Examining the Evidence

Q Do atypical glandular cells on Pap test require aggressive follow-up?

June 2006 · Vol. 18, No. 6

<huc>A</huc> Yes. Perform colposcopy and directed biopsy, endocervical evaluation, and a pelvic examination in all women with atypical glandular cells on Pap test, and perform an endometrial biopsy in women with risk factors for endometrial cancer.

This analysis found that roughly 29% of women with atypical glandular cells had conditions that required follow-up or treatment, and 5.2% had a malignancy. Therefore, methodical follow-up is not only warranted, but necessary.

Details of the study

Schnatz and colleagues reviewed 3,890 Pap tests that had a finding of atypical glandular cells of undetermined significance (AGUS), for which follow-up details were available.

They found these rates of pathology:

  • 8.5% low-grade squamous intraepithelial lesions (LSIL)
  • 11.1% high-grade squamous intraepithelial lesions (HSIL)
  • 2.9% adenocarcinoma in situ
  • 1.4% endometrial hyperplasia
  • 5.2% malignancy, The distribution of cancers was:
  • 57.6% endometrial adenocarcinoma
  • 23.6% cervical adenocarcinoma
  • 6.4% ovarian and fallopian tube carcinoma
  • 5.4% squamous cell carcinoma of the cervix
  • 6.9% other cancers

Expert commentary

Several years ago I gave a talk entitled, “AGUS scares me.” It still does.

For almost 2 decades I have been preaching that, except for a finding of invasive squamous cancer, the single most important cervical cytology report is one that confirms atypical glandular cells (now abbreviated as AGC under the Bethesda System). Virtually every paper written on the subject has shown that AGC are markers for cancer in a high proportion of cases, yet I continue to see clinicians react merely by repeating the sample, or quitting after a negative colposcopy.

Schnatz and colleagues confirmed that such action is insufficient. In their compilation of published research on the subject, 5.2% of all women with AGC and followup had invasive cancer, usually in the pelvis. That rate is many times higher than the cancer risk of HSIL, yet AGC often elicits a far less aggressive evaluation.

Does age matter?

I do wish the authors had done more to explore age as a variable. Most individual series are too small to establish guidelines based on age, but this review of the literature was an opportunity for meaningful observations.

Most of us are not as worried about a report of AGC in a young woman, particularly if she is pregnant. However, that clinical impression is based on very scant data. This study would have been a good place to investigate whether we should pursue AGC differently in young women, and perhaps at what age we should begin to consider endometrial biopsy.

1 in 15 cancers nonpelvic

Of the 203 invasive cancers associated with atypical glandular cells, most originated in the pelvic organs. The authors present a reasonable sequence of evaluation, starting with colposcopy, endocervical evaluation,endometrial biopsy, conization, and pelvic ultrasound—more or less in that order. However, 14 (6.9%), or 1 in 15, of the cancers were located outside the reproductive organs. The authors did not emphasize this finding as much as I would have liked.

Consider colonoscopy, ultrasound, CT

If no source of the AGC is identified in the pelvis, particularly if the patient is older than 50, consider further tests (eg, colonoscopy, abdominal ultrasound, computed tomography). Although nonpelvic malignancies responsible for AGC are often already metastasized, a few cures have been achieved with careful, thorough investigation.

The author reports no financial relationships relevant to this article.