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Abnormal Pap Smear

Epithelial Cell Abnormalities: Squamous Cell

Atypical Squamous Cells of Undetermined Significance. The atypical squamous cells of undetermined significance (ASCUS) category is restricted to those slides in which the cellular changes exceed those that can be attributed to reactive or reparative processes, but that fall short of a definitive diagnosis of a squamous intraepithelial lesion. The report should be further qualified, if possible, to indicate whether a reactive process or a squamous intraepithelial lesion is favored. Hyperkeratosis, parakeratosis, and dys-keratosis are descriptors that are not included abnormal pap smear.

The ASCUS category remains controversial. In August 1992, the National Cancer Institute Early Detection Branch invited clinical experts to participate in a workshop to develop interim guidelines for the management of women with abnormal cervical cytology. This workshop concluded that an ASCUS report should be expected.

Low-Grade Squamous Intraepithelial Lesion. The category of low-grade squamous intraepithelial lesion encompasses human papillomavirus (HPV) and mild dysplasia/cervical intraepithelial neoplasia (CIN) I. The inclusion of the cellular changes supportive of HPV infection (previously termed koilocytosis, koilocytotic atypia, or condylomatous atypia) in the category of low-grade squamous intraepithelial lesion requires that the diagnosis be based on specific cellular criteria to avoid overinterpretation of non-specific artifactual changes mimicking koilocytosis. A cytoplasmic halo without the typical "raisinoid" eccentric nucleus should not be interpreted as koilocytosis.

Cellular changes associated with HPV are included in the category of low-grade squamous intraepithelial lesion because the natural history and cytologic features of both HPV and CIN I (mild dysplasia) lesions are similar. Long-term follow-up studies have shown that 14% of lesions previously classified as koilocytosis.

High-Grade Intraepithelial Lesion. The category of high-grade intraepithelial lesion encompasses moderate and severe dysplasia, carcinoma in situ/CIN II, and CIN III. The rationale for combining CIN II and CIN 11I into the category of high-grade intraepithelial lesion is also based on biologic and virologic studies. The HPV mix of the two lesions is similar, and the separation of the two lesions has been irreproducible in inter- and intraobserver studies.

Glandular Cell Abnormalities

Endometrial Cells. The presence of endometrial cells, cytologically benign, in a postmenopausal woman not receiving exogenous hormones should be investigated even when the cells are normal in appearance. Such cells may be associated with inadvertent sampling of the lower uterine segment, endometrial polyps, endometrial hyperplasia.

Atypical Glandular Cells of Undetermined Significance. The term "atypical glandular cells of undetermined significance'' is used to report changes beyond those encountered in the benign reactive processes but insufficient for a diagnosis of adenocarcinoma. The report should indicate whether the cells are thought to be of endocervical or endometrial origin, when possible.

Adenocarcinoma. A report of adenocarcinoma indicates a probable invasive tumor. The report should specify whether an endometrial, endocervical, or extrauterine site is suspected.

Other Neoplasias. Other malignant neoplasms may be suspected on the basis of certain cytologic findings. These include small cell carcinoma, melanoma, lymphoma, and sarcoma.

Follow-up

Atypical Squamous Cells of Undetermined Significance

There are several management options for patients whose tests are classified as ASCUS. Some reports have indicated that there is a 10-40% rate of CIN found in patients with this report. Invasive cancer is very rare.

The 1991 Bethesda Conference recommended classifying ASCUS as "favor reactive" or "favor neoplasia." The validity of this subclassification in predicting CIN by biopsy was subsequently confirmed.

Atypical Glandular Cells of Undetermined Significance

A report of atypical glandular cells of undetermined significance should indicate, when possible, whether an endometrial or endocervical origin is favored. Atypical endometrial cells should be evaluated by endometrial biopsy. Atypical endocervical cells are further subclassified as favoring either a reactive or a neoplastic process. In a series of 63 patients, 2 women had invasive adenocarcinoma, 5 women had adenocarcinoma in situ, and 17 women.

Low-Grade Squamous

Intraepithelial Lesion

Analysis of the screening programs in British Columbia indicate that low-grade lesions in women younger than 34 years of age will regress spontaneously 84% of the time. For women older than 34 years, 40% of lesions will regress. Despite the fact that most low-grade lesions will regress spontaneously.

High-Grade Squamous

Intraepithelial Lesion

Any woman with a cytologic specimen suggesting the presence of a high-grade lesion should undergo colposcopy and directed biopsy. No other management approach is currently acceptable. After confirmation of a high-grade lesion, therapy aimed at destruction or removal of the entire transformation zone should be performed.

Treatment

The histologic diagnosis and the extent of the lesion always must be determined before treatment is performed. A variety of techniques have been used to treat CIN, including surgical excision, cryosurgery, laser vaporization, and loop electrosurgical excision. All of these modalities have a small (2-4%) risk of hemorrhage, later cervical stenosis, and infertility.

Ablative therapy such as cryosurgery or laser vaporization is appropriate when the following conditions exist:

Cryosurgery should be used only for small, low-grade lesions that can be easily covered by the cryoprobe. Several large series indicate a 93-96% cure rate for CIN I and II, but a 77-92% cure rate for CIN III.

Laser vaporization may be chosen for patients who have either large lesions on the exocervix that extend onto the vagina or an irregular "fishmouth" cervix with deep clefts. The major advantage of laser vaporization therapy is the ability to control the depth and width of destruction by direct vision through the colposcope.

Loop electrosurgical excision has largely replaced the ablative techniques for treatment of all grades of CIN. Its major advantage is that it produces a tissue specimen, which can be examined to ensure that invasive carcinoma is not present. Recent series have found unexpected microinvasive or invasive squamous lesions in 0.7%.