Cytological Features That Improve the Diagnostic Accuracy of Human Papillomavirus-Associated Glandular Lesions in Uterine Cervical Cytology

INTRODUCTION: The World Health Organization (WHO) Classification of Female Genital Tumours, Fifth Edition (2020), proposed a classification of uterine cervical glandular lesions according to whether they are associated with human papillomavirus (HPV) or not. The WHO recommends HPV genetic screening as an initial test that should be followed by cytology as a triage test in HPV-positive patients. MATERIALS AND METHODS: We selected 40 cytological specimens of HPV-associated glandular lesions including atypical glandular cells, adenocarcinoma in situ (AIS), and adenocarcinoma. We confirmed their histological type using biopsy or excisional specimens. We examined the cytological features of the glandular lesions in detail. RESULTS: The majority of HPV-associated adenocarcinoma was usual-type adenocarcinoma with enlarged nuclei, increased nuclear density, and heterogeneous to pale nuclear chromatin, and most cases showed apoptosis or mitosis. AIS exhibited stacked clusters with intense nuclear chromatin, so-called hyperchromatic crowded groups. AIS showed less nuclear pleomorphism compared to invasive adenocarcinoma and no background tumor diathesis. Conversely, adenocarcinoma tended to have a tumor diathesis. Stratified mucin-producing carcinoma had a foamy to vacuolated cytoplasm and tended to form nested clusters without a palisade arrangement. Some atypical glandular cells were found to have glandular involvement of high-grade squamous intraepithelial lesions by histology. CONCLUSION: To contribute to the early detection of glandular lesions, it is important to recognize the fundamental cytological features, especially hyperchromatic crowded groups, background tumor diathesis, and nuclear findings.