Evaluation and Management of the AGUS Papanicolaou Smear
The Bethesda system classifies atypical glandular cells of undetermined significance (AGUS) as glandular cells that demonstrate nuclear atypia appearing to exceed reactive or reparative changes but lacking unequivocal features of adenocarcinoma.
AGUS occurs in approximately 0.18 to 0.74 percent of all cervical smears.
A significant percentage of women with AGUS will have serious lesions, such as high-grade preinvasive squamous disease, adenocarcinoma in situ, adenocarcinoma or invasive cancers from sites other than the cervix.
Colposcopic examination is recommended for all women with a cytologic diagnosis of AGUS.
If AGUS that is suspicious for adenocarcinoma women should undergo cervical conization, even in the absence of detectable abnormalities on colposcopic examination.
AGUS occurs in approximately 0.18 to 0.74 percent of cervical smears.
Of women with AGUS smears, 50 to 80 percent will have no histologic abnormality on further evaluation.
However, 20 to 50 percent are found to have significant histologic abnormalities, such as cervical intraepithelial neoplasia, adenocarcinoma in situ (AIS) or adenocarcinoma.
The incidence of cervical adenocarcinoma in situ and adenocarcinoma has been steadily increasing over the past 20 years.
Most of the increase in cervical cancer in women younger than 35 years is attributable to adenocarcinomas.
As with cervical intraepithelial neoplasia, infection with human papillomavirus is considered to be a risk factor for adenocarcinoma in situ and adenocarcinoma.
In a prospective study of 46,000 women, HPV DNA was detected in 28 percent of women with AGUS Pap smears.
The final diagnoses for Pap smears that were initially labeled AGUS, HPV DNA was detected in 92 percent of women with high-grade squamous intraepithelial lesions, 56 percent with low-grade squamous intraepithelial lesions and 100 percent with adenocarcinoma in situ (AIS).
HPV types 16 and 18 are most commonly associated with squamous cell carcinomas, and adenocarcinomas.
HPV type 18 is more commonly seen with adenocarcinomas than is type 16.
AGUS classification for cytologic abnormalities of glandular cells: glandular cells that show nuclear atypia exceeding reactive or reparative changes, but lack unequivocal features of adenocarcinoma.
AGUS glandular cells maybe endocervical or endometrial in origin.
A diagnosis of AGUS on a Pap smear maybe associated with a multitude of abnormalities: includes high and low-grade squamous lesions, adenocarcinoma in situ, and adenocarcinoma.
Other possible benign findings include: squamous or tubular metaplasia, or polyps.
Colposcopy is recommended for all patients with AGUS readings.
For subtypes that are not suspicious for neoplasia, negative results from colposcopy, biopsy and endocervical curettage are thought to be sufficiently reassuring to allow follow-up with cytology every four to six months.
A cone biopsy is required for AGUS smears that are suspicious for neoplasia, because the incidence of adenocarcinoma in situ and adenocarcinoma is about 10 percent and the incidence of other cancers is up to 10 percent.
Endocervical curettage negative results has a 50 percent false-negative rate compared with cone biopsy,
but can provide a definitive diagnosis for patients in whom it is positive or indicates neoplasia.
For AGUS Pap smears, HPV testing for the detection of any high-grade lesion had 95 percent sensitivity and more than 50 percent specificity.
Endometrial biopsy for women older than 35 years is recommended, especially those with any abnormal bleeding and those with symptoms suggestive of endometrial carcinoma.
Colposcopy is recommended for all women with AGUS cytology.
Glandular lesions are often difficult to detect by colposcopy, particularly when glandular lesions exist along with squamous lesions.
Glandular lesions tend to be more subtle, and often missed during colposcopy.
The colposcopic appearance of AIS, adenocarcinoma in situ, and adenocarcinoma is very different from that of squamous lesions.
Management of patients with nonneoplastic AGUS subclassifications and negative colposcopic findings and endocervical curettage involves repeating a Pap smear every four months.
For patients with a nonneoplastic AGUS smear and positive colposcopic findings, cone biopsy is recommended.
Conization is necessary whether squamous or glandular lesions are found on colposcopy.
Squamous and glandular lesions coexist in 5 to 40 percent of patients?
Glandular lesions are much harder to detect and may be obscured by a more obvious squamous lesion.
Management of patients with neoplastic subclassifications involves conization, regardless of colposcopic findings.
Conization should be deep, at least 2.5 cm.
Cold knife conization is preferred to loop electrosurgical excision, so that the thermal artifact does not affect the margins and thus the histopathologic interpretation of the specimen.
AIS is probably the most controversial diagnosis of the glandular lesions.
AGUS Pap smears with AIS and positive margins, require a simple hysterectomy.
Conization should be performed for any AGUS Pap smear suspicious for neoplasia.