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Acidic alterations: impact of glacial acetic acid treatment on interpretations of atypical endocervical and atypical glandular cells, not otherwise specified in Pap tests
Glacial acetic acid (GAA) is used in ThinPrep Pap tests to clear excess blood, but it may alter glandular cell appearance, particularly that of endocervical cells, potentially increasing false-positive interpretations. This may be countered by increased awareness of these cytologic alterations. We retrospectively analyzed all cervical and vaginal Pap tests from 2018 to 2022, comparing rates of "Atypical Endocervical Cells" (AEC) and "Atypical Glandular Cells, Not Otherwise Specified" (AGC) interpretations in GAA-treated and untreated Pap tests. Human papillomavirus status and histologic follow-up within 1 year were recorded for GAA-treated Pap tests. Histologic follow-up for a GAA-untreated control group was recorded. AGC and AEC interpretations were significantly more frequent in GAA-treated Pap tests compared to untreated tests (AGC, 39/7004 versus 85/258,185, respectively; AEC, 34/7004 GAA-treated Pap tests versus 417/258,185 untreated Pap tests; P < 0.0001 for both). For GAA-treated tests with AGC interpretations, age was significantly associated with a malignant histologic outcome (P < 0.001), while no such association was observed for those with AEC interpretations (P = 0.19). Malignant histologic follow-up was significantly lower in GAA-treated group with AEC interpretation compared to control group (P < 0.001), and no significant difference was seen in malignant histologic follow-up for GAA-treated and control group with AGC interpretation (P = 0.61). GAA-treated Pap tests showed significantly higher rates of AGC and AEC interpretations compared to untreated tests. Additional follow-up may be warranted for patients with GAA-treated Pap tests and AGC interpretations, particularly in older patients.