High grade squamous cervical lesions following negative Papanicolaou smears: false-negative cervical cytology or rapid progression

Abstract

The cervical cytologic finding of a high grade squamous intraepithelial lesion (HGSIL) or carcinoma shortly following a negative smear is unusual. To determine if such cases are due to screening errors, inadequate sampling, or rapidly progressive lesions, a review of negative smears (immediately preceding a diagnosis of HGSIL or carcinoma by at most 2 yr) was performed on 17 patients (all such patients in our 1990-92 files, representing 6% (17/290) of such diagnoses). The time between negative smear and positive result averaged 9.3 mo. Eighty-eight percent of these patients had prior histories of a cytologic abnormality. Upon review, 16 of 17 "negative" smears contained a cytologic abnormality. Atypical immature squamous metaplastic type cells (AISMTs) were found in 11 of 16 cases, atypical squamous cells or slight dysplasia were found in 5 of 16, HGSIL was found in 5 of 16, and atypical cells of undetermined type and origin were noted in 1 of 16. Combinations of the above diagnoses were present in 6 of 16 cases. The number of abnormal cells per slide was estimated, with < 10 cells in 1 case, < 50 in 4 cases, 50-100 in 7 cases, 100-200 in 3 cases, and > 200 in 1 case. In this study, screening and/or evaluation errors were the dominant cause of false-negative cytologic diagnoses, with AISMTs accounting for the most commonly missed or misinterpreted cells. These cells are small and have hyperchromatic nuclei with elevated nucleus to cytoplasmic ratio and nuclear irregularities.