Glandular cell atypia on Papanicolaou smears: interobserver variability in the diagnosis and prediction of cell of origin

BACKGROUND: The 2001 Bethesda System recommended qualification of atypical glandular cells (AGC) to indicate the site of origin and separated endocervical adenocarcinoma in situ (AIS) from "AGC favor neoplastic" as a specific diagnostic category. To the authors' knowledge, the literature evaluating the reproducibility of Papanicolaou (Pap) smear diagnosis of glandular cell abnormalities with emphasis on the cell of origin is limited. The aim of the current study was to investigate whether a variety of benign to neoplastic glandular lesions can be reliably classified on Pap smear with regard to diagnosis and cell of origin. METHODS: Twenty-three conventional Pap smears (CPS) with glandular cellular changes varying from benign to adenocarcinoma (ACA) were reviewed by six observers. They were asked to categorize each smear according to cell of origin (endocervical vs. endometrial) and diagnosis (benign, AGC, or ACA). Kappa statistics were used to evaluate interobserver agreement and correlation of interobserver agreement with experience. RESULTS: There was no consensus among observers for both the origin of the cells and the diagnosis. Interobserver agreement for site was poor (kappa < 0.4) especially in the AGC category. Unanimous agreement for site was reached for 7 of 23 smears (30%). Two of five endocervical AIS were classified as endometrial and another two were classified as benign by four observers. Interobserver agreement was poor in all diagnostic categories (kappa < 0.4) and showed slight correlation with level of experience. Unanimous agreement for diagnosis was reached for only 2 smears (9%). Three of 11 (27%) smears demonstrating preneoplastic/neoplastic processes were diagnosed as benign by 3 observers. Three (25%) benign CPS were diagnosed as ACA by 2 observers. Accurate prediction of the final histologic diagnosis by observers varied from 30% to 87% and did not correlate closely with experience. CONCLUSIONS: Cytologic diagnosis of glandular lesions by CPS was problematic and suffered from significant interobserver subjectivity.