Bnef reports population, the rate of ASCUS is two to three times the rate of SIL.3 A greater frequency of ASCUS smears may indi­ cate overuse of the diagnosis; however, high-risk populations may have a high­ Management of patients with er incidence. Recent data from several atypical squamous cells of cytopathology laboratories demonstrat­ ed the prevalence of ASCUS to have a undetermined significance (ASCUS) general range of 1.6% to 9.2%; and fol­ low-up of patients with ASCUS smears on Papanicolaou smears showed 10% to 45% with LSIL, less than 7% with HSIL, and less than 1 % RICHARD R. TERRY, DO with cervical cancer.2 Management of patients whose Papanicolaou smears show atypical squamous cells Cytopathologic diagnosis · of undetermined significance (ASCUS) is a complex challenge for the family The term ASCUS is an attempt to classify physician. It is critical that patients with the ASCUS smear be properly evaluat­ cellular changes that are considered nei­ ed and triaged, as the ASCUS smear may be a manifestation of high-grade disease ther reactive nor reparative),? ASCUS in 20% or more of cases. Several options for triage exist. Colposcopy is consid­ encompasses cellular nuclear abnormal­ ered by many the option of choice. However, alternative options include cer­ ities that are not clearly SIL or that owe vicography, speculoscopy, and human papillomavirus subtyping. For proper man­ their existence to inflammatory changes. agement of the patient with the ASCUS smear, the clinician must consider the The precise etiology of the cellular ab­ patient's Pap test history, risk factors for cervical cancer, and the cytopathologist's normalities found in the ASCUS cate­ interpretation/recommendation. gory is not known. Pronounced epithe­ (Key words: Colposcopy, Papanicolaou test, ASCUS [atypical squamous cells lial changes secondary to repair and of undetermined significance], low-grade squamous lesion, high-grade squamous inflammation or nuclear changes associ­ lesion, human papilloma virus subtyping) ated with but not diagnostic of SIL often are classified as ASCUS) In addition, poor sampling or preparation of the Pap he worldwide incidence of cervical on the reporting of minimally abnor­ smear slide may result in an artifact and Tcancer and premalignant cervical mal smears. be misinterpreted as ASCUS. lesions has dramatically increased dur­ The Bethesda System (TBS) of The cytopathologic diagnosis of ing the past quarter century.1 Papani­ cytopathologic reporting developed in ASCUS is based on the following crite­ colaou's (Pap) test has been proved high­ 1988 provided a more concise report ria2,3 (Figures 1 and 2): ly effective as a screening tool for to the clinician than previous classifi­ o nuclear enlargement that is two to prevention of cervical cancer. Histori­ cation systems.2,3 The Bethesda System three times that of a normal squamous cally, several reporting systems have introduced the concept of squamous cell nucleus; been used to describe abnormal cervical intra epithelial lesions (SIL). The previ­ o variation in size and shape; cytology. This multiplicity of reporting ous systems lacked reproducibility; thus, o the possible presence of mild hyper­ systems has led to much confusion a squamous cell lesion under TBS could chromasia; and about management of abnormal Pap be classified as either high-grade (HSIL), o generally smooth nuclear outlines. smears. Previous cytologic systems were low-grade (LSIL), or atypical cells of ASCUS is not synonymous with the clear on the classification of profound­ undetermined significance (ASCUS) previously used terms squamous atypia, ly abnormal Pap smears, but ambiguous under the general category of epithelial inflammatory atypia, or atypical meta­ cell abnormality.4,s plasia. 2 Lesions with abnormalities that Dr Terry is Director, Wilson Osteopathic Family Prac­ do not correspond to the criteria for tice Residency, and Director, Family Practice Obstet­ Prevalence of ASCUS smears ASCUS are considered atypia. In a study rics and Gynecology, Wilson Memorial Hospital, John­ son City, NY. He is also an assistant professor of Some 3% to 10% of women who under­ correlating cytologic criteria and biopsy family medicine, State University of New York Upstate go cervical cytology grading in the Unit­ results, Sidawy and Tabbara8 report that Medical Center, Binghamton , NY; a clinical assistant professor, New York College of Osteopathic Medicine ed States have a cytologic diagnosis of smears designated as "inflammatory of New York Instrtute of Technology, Old Westbury, NY; ASCUS. This prevalence translates into atypia" may be reclassified as either and a clinical assistant professor, Lake Erie College of Osteopathic Medicine, Erie, Pa. approximately 1.5 to 5 million women ASCUS or reparative changes. Their data Correspondence to Richard R. Terry, DO, Direc­ each year. The diagnosis of ASCUS smear suggest that women with Pap smears tor, Wilson Osteopathic Family Practice Residency, Johnson City Family Care Center, 40 Arch St, Johnson in the community should not exceed 5% showing atypia with reparative changes City, NY 13790. of the Pap smear findings.6 In a screened have a high spontaneous regression rate Terry • Brief report JAOA • Vol 96 • No 8 • August 1996 • 465 and may be managed conservatively. Conversely, Pap smears that meet the ASCUS criteria indicate the need for more aggressive treatment. The distinction between the ASCUS smear and a smear showing reactive change and low-grade SIL is a problem. In fact, one study com­ paring interpretations by two sets of pathologists showed significant intraob­ server variability between the diagnosis of ASCUS versus HSIL and LSIL. It is appropriate that whenever an ASCUS smear is obtained there be some qualifi­ cations of the diagnosis.3.6 Management of the patient with an ASCUS smear is a dilemma for the clin­ ician. Proper triage is essential, as 20% or more ASCUS smears may represent SILJ.9. It is imperative that in patients in whom ASCUS represents a more advanced disease (that is, HSIL or inva­ sive cancer), the disease be identified and treated promptly.10 Colposcopy For further evaluation of advanced squa­ mous intraepitheliallesions, colposcopy is recommended. Yet, optimal manage­ ment of the patient with the ASCUS smear has yet to be defined. Some clini­ cians advocate colposcopy for all women with the ASCUS smear, whereas others recommend a "wait-and-see" approach and follow-up with repeated Pap tests. Several treatment options are available for Figure 2. Papanicolaou's test showing dysplasia. management of patients with the ASCUS smear. Careful review of all the clinical data pertinent to each case, taking into an unqualified diagnosis of ASCUS smear high fa lse-negative rate at the time of consideration previous Pap smear find­ or, if the cytopathologist favors a reactive colposcopy.8.10.12 A 1995 study of ings and any qualifications that the process, the Pap test may be repeated in patients with LSIL who were followed up pathologist may have provided regarding 4 to 6 months. If the smear shows nor­ conservatively with repeated Pap smears the diagnosis of the ASCUS smear, and mal cell s, the Pap test should be repeat­ demonstrated an unacceptably low sen­ evaluation of the patient's risk factors ed every 4 to 6 months until three con­ sitivity of the Pap smear. 13 Whether this for cervical neoplasia must be completed secutive negative smears appear.6 The information can be applied to conserva­ before triage. patient then can be followed up annual­ tive management of the patient with the One approach would be simply to ly. A second ASCUS smear mandates a ASCUS smear has yet to be determined. repeat the Pap test. At least half of colposcopic evaluation. This strategy can The Pap smear is of va lue as a screening ASCUS smears will regress over time. be safely applied to patients at low risk test, but it should not be considered a Montz and colleaguesll have reported a for cervical cancer. Patients with a history reliable diagnostic tool once an abnor­ 54% regression rate of ASCUS smears. In of Pap tests showing abnormality or mality has been identified. their study, 46% of patients continued to patients who have other risk factors may A patient with an ASCUS smear asso­ show ASCUS abnormalities but none require colposcopy after the first ASCUS ciated with inflammation should be progressed after 9 months of follow-up. smear. reevaluated in 2 to 3 months. If a specific Average regression time was 3.5 months. Critics of this conservative approach infection is identified, the patient should This approach is indicated in the case of point out that repeated Pap tests have a be treated and have another Pap test in 466 • ]AOA • Vol 96 • No 8 • August 1996 Terry · Brief report and 93 % in predicting HSIL. HPV-DNA Papanicolaou smear su btyping favorably compared with fol­ shows atypical squamous cells of undetermined low-up Pap smears, which showed sen­ significance (ASCUS) sitivities of only 60% and 73%, respec­ tively.l5 Cox and coworkers conclude I that high viral levels of HPV types asso­ ciated with cervical cancer are predictive I I I of high-grade lesions and that patients with ASCUS smears can be triaged based Smear with Epithelial Patient is ASCUS unqualified changes are post- represents on HPV testing results. Omer data are reparative secondary to menopausal premalignant less conclusive about me role of HPV­ cellular inflammation changes/ DNA subtyping.16,1? !t is estimated that neoplasia changes 11 % to 18 % of normal cervices contain HPV DNA.I? This presence of HPV DNA may represent dormant HPV infec­ J + tion that will eventually manifest as SIL, • Treat infec- • Institute trial • Repeat • • Do colpos- but this possibility has not been proved. Pap tion if noted of estrogen copy smear in • Repeat therapy In addition, it has been demonstrated in 4 to 6 Pap smear • Repeat other studies that the hybrid-capture months in 3 months Pap smear in DNA test was insufficiently sensitive in 4 to 6 months identifying high-grade lesions and overt cervical carcinoma.16 Figure 3.
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