Indolent Behavior of Malignant Bethesda III Nodules Compared to Bethesda V/VI Nodules

Background: The Bethesda system classifies all fine-needle aspiration specimens into 1 of 6 categories. We speculated that cancers within each Bethesda category would have distinct clinical behavior. Methods: This is a retrospective analysis of patients from a single academic medical center with a histologic diagnosis of thyroid cancer who had an initial diagnosis of Bethesda III, IV, V, or VI cytology. Results: A total of 556 cases were included, with 87 cases of Bethesda III, 109 cases of IV, 120 cases of V, and 240 cases of VI. Bethesda III showed similarities with V/VI compared to IV with a predominance of papillary thyroid cancer. The interval from diagnosis to surgery was longer in Bethesda III compared to Bethesda V/VI (median 78 vs 41 days, P < .001) (Fig. 1). Yet, patients with Bethesda III had a higher probability of achieving remission (62% vs 46%, P < .03), a lower possibility of recurrence (8% vs 24%, P < .001), and a shorter interval to achieve remission (median 1218 vs 1682 days, P = .02) compared to Bethesda V/VI, which did not change after adjusting for age, sex, radioactive iodine therapy, mode of surgery, and tumor size. More than 70% of Bethesda III that later presented with recurrence had T3/T4 disease or distant metastasis. Conclusion: Cancers with Bethesda III cytology had a less aggressive clinical phenotype with better prognosis compared to V/VI despite histological similarities. The time to remission was shorter in Bethesda III despite a longer interval between diagnosis and surgery. The initial cytological diagnosis may guide management.