DNA cytometry confirms the utility of the Bethesda System for the classification of Papanicolaou smears

BACKGROUND. Developed in 1989, the Bethesda System has largely replaced previous classifications of Papanicolaou (Pap) smears front the uterine cervix. The system is binary, dividing smears into two groups - low-grade, squamous, epithelial lesions (LSIL) or high-grade, squamous, epithelial lesions (HSIL). A third category, atypical squamous cells of undetermined significance (ASCUS), is used to classify minimal cellular changes that do not satisfy the criteria for the low- or high-grade categories. This study was designed to confirm the utility of this binary division and to compare the results with another classification system (the Munich II Nomenclature) that is not binary but contains three divisions or grades for dysplasia - low, intermediate, and high. METHODS, Pap smears were obtained from 593 women with a cytologic diagnosis of dysplasia based on the Munich System. Smears were then classified by the Bethesda System into LSIL or HSIL. Patients were followed for 2 years either with biopsy or repeat cytology. The initial smears were restained by the Feulgen method, and ploidy was evaluated by interactive DNA cytometry. RESULTS. Of 241 cases of LSIL, 39% were diploid, 57% polyploid, and 4% aneuploid, Of 352 cases classified HSIL, 4% were diploid, 17% polyploid, and 79% aneuploid. After 2 years of follow-up, 2 of 108 patients who were biopsied and who were originally classified as diploid progressed to cervical intraepithelial neoplasia/ carcinoma in situ (CIN/CIS) whereas 109 of 217 patients who were aneuploid and biopsied were found to have CINIII/CIS. CONCLUSIONS, The two divisions of the Bethesda System, LSIL and HSIL, correlated with ploidy as evaluated by cytometry. Aneuploidy was found to be useful to separate cases of HSIL from those of LSIL as defined in the Bethesda System. Because of the binary division, use of a system with three divisions for dysplasia, such as the Munich II Nomenclature, creates a therapeutic dilemma because a single diagnostic category (usually the intermediate grade) may contain both self-limiting and progressive lesions. DNA cytometry of Pap smears was found to be useful as a routine procedure. Cancer (Cancer Cytopathol) 2001;93:222-228. (C) 2001 American Cancer Society.