Gray zone Bethesda category III - Atypia of undetermined significance lesions of the thyroid: Potential diagnostic issues and image morphometry as a useful adjunct to cytomorphology

Objective: Atypia of undetermined significance (AUS) is an indeterminate category which presents a significant challenge for pathologists and clinicians. The management options are dependent on the rate of malignancy for a given populace.

Material and methods: This is a retrospective analysis of 61 cases of the AUS Bethesda category III with grouping into neoplastic and non-neoplastic according to the histopathology data and clinical follow-up. Detailed cytomorphological features were analyzed and image morphometry was done using image J software. Student's t-test was used.

Results: Out of the total 61 cases, 35 were neoplastic cases of AUS (histopathology proven), and 26 were non-neoplastic (on follow-up) cases. The risk of neoplasia and risk of malignancy observed were 57.4% and 47.5%, respectively. Neoplastic cases displayed prominent intranuclear inclusions (54%) and pseudopapillary clusters (20%). Majority of non-neoplastic cases revealed fine chromatin (96%) and pale chromatin (4%) while among neoplastic cases, 14% showed pale chromatin. Neoplastic cases showed moderate to marked nuclear pleomorphism (20%) compared to non-neoplastic cases which were monomorphic to mildly pleomorphic. None of the non-neoplastic cases exhibited frequent nuclear overlapping, nuclear grooving, or nucleoli which emphasizes the need for scrutiny of smears for these features. On image morphometry, cases with malignant outcome had larger nuclear area, perimeter, diameter, and nuclear density which were statistically significant.

Conclusion: The study illustrates the importance of identifying subtle cytomorphological features and usefulness of image morphometry as an adjunctive objective tool in AUS cases. This helps in making an accurate cytological diagnosis which guides the treating clinician regarding surgical management or need for clinical follow-up.