Non-human papilloma virus associated adenocarcinomas of the cervix uteri. Cytologic features and diagnostic agreement using whole slide digital cytology imaging

Background: Non-Human Papilloma Virus associated adenocarcinomas (NHPVAs) are uncommon tumors of the cervix uteri which often show a deceptive morphology. Therefore, their diagnostic assessment may be challenging. Slide digital cytology imaging may be an useful tool to improve cytological diagnostic accuracy. However, this novel technology has not been applied to NHPVAs associated cytologies yet. Methods: The study included 31 whole slide digital cytology cases from 10 women with a proven histological diagnosis of NHPVA. As a control group, three further digital slides, from two women with a histological diagnosis of squamous intraepithelial lesion (SIL), were included. The digitally scanned cytological slides were revised to assess the concordance rate among three observers and to find out the most relevant NHPVA cytological criteria. Results: Overall diagnostic agreement between observers was 67.60% (K = 0.50; P < 0.0001). At the consensus diagnosis 34 cases were re-classified as at least suspicious for glandular lesion (n = 24), SIL (n = 2) and negative (n = 8). The most relevant cytologic features for atypical glandular cells or adenocarcinoma at consensus were evident nucleoli, nuclear overlapping and atypical enlarged nuclei. Conclusions: The diagnosis of NHPVA in digital cytology is feasible using criteria which are also used in conventional microscopy. Our study shows a moderate agreement for the cytological diagnosis of NHPVAs using whole slide digital cytology approach. These results are discussed taking into account the most relevant differential diagnostic issues.