Differentiated cervical intraepithelial neoplasia-associated invasive cervical squamous cell carcinoma as a source of major cytopathological and surgical pathological discrepancy in Papanicolaou smear screening tests.

INTRODUCTION: Differentiated cervical intraepithelial neoplasia (dCIN) analogous to differentiated squamous intraepithelial neoplasia of the vulva is characterised by the proliferation of atypical cells limited to the basal/parabasal layers. Exfoliative cytology of dCIN has not been investigated.

METHODS AND RESULTS: A 46-year-old woman, with a history of normal Papanicolaou (Pap) smear up to 2 years prior to the occurrence of postcoital vaginal bleeding had two consecutive Pap smears, which only revealed atypical squamous cells of unknown significance (ASCUS). The subsequent cervical biopsy revealed dCIN. The cone biopsy showed the invasive cervical squamous cell carcinoma (ICC) that developed from the overlying dCIN. Review of 32 consecutive cases of ICC revealed a second case of dCIN-associated ICC (Group 1) preceded by ASCUS suspicious for high-grade neoplastic cells. In both cases, the ASCUS were keratinised atypical cells without koilocytosis. In addition, there were another seven cases showing focal dCIN associated with extensive usual CIN (Group 2). In comparison with the remaining 24 cases with usual CIN (Group 3), Group 2 lesions occurred in younger patients (mean ages of 36 ± 3 vs 47 ± 9 years) and were associated with shorter intervals after the last normal Pap smears. Pap smears in Group 2 occasionally consisted only of ASCUS cells.

CONCLUSIONS: dCIN may occur in the cervix and accounts for a short interval of normal Pap smears and false negative or low-grade Pap smears in ICC.