Atypical squamous cells of undetermined significance--rule out high-grade squamous intraepithelial lesion: cytopathologic characteristics and clinical correlates

The significance and clinical management of atypical squamous cells of undetermined significance (ASCUS) on cervical cytologic smears has been an area of much controversy. This study compiled a list of criteria useful in identifying the subset of cases that would be categorized as atypical squamous cells of undetermined significance- rule out high-grade squamous intraepithelial lesion (ASC-H) in the new Bethesda System terminology, which eventuate in a diagnosis of cervical intraepithelial neoplasia (CIN). The cytopathology files at Johns Hopkins Hospital were searched for ASC-H cases from the 3-yr period 1996-1998, which had definitive clinicopathologic follow-up (colposcopy and cervical biopsies). The smears were reviewed, cytomorphologic features studied, and clinical correlations performed. ASC-H was diagnosed in 257 of 45,428 gynecologic smears (0.6%), 72 having had clinicopathologic follow-up. Of these 72 cases, 35 (49%) on follow-up had a negative/reactive diagnosis (NR), whereas 37 (51%) turned out to be CIN [CIN-I-18 (49%) and CIN II and III-19 (51%)]. The significant cytomorphologic differences in the ASC-H category with a CIN follow-up (compared with an NR follow-up) were fewer atypical cells, more often discohesive or seen singly, more monomorphic, a higher nuclear-to-cytoplasmic (N/C) ratio, greater nuclear hyperchromasia, more coarse, unevenly dispersed chromatin, more prominent nuclear membrane irregularities, lack of nucleoli, chromocenters or nuclear grooves, and lack of an inflammatory background. Careful attention to subtle cytomorphologic characteristics may be helpful for a more definitive subdivision of ASC-H terminology into a NR and a CIN diagnosis.