Thyroid nodule shape and prediction of malignancy

Background: Thyroid nodules are common; the vast majority benign. Preoperative determination of malignancy remains imprecise, despite fine-needle aspiration (FNA). Numerous risk factors have been proposed for predicting malignancy, though few have been found useful. Oxygen delivery is a crucial component for tumor cell growth. It has been hypothesized that malignant tumors may configure their shape to maximize access to local nutrient delivery. Mathematically, surface area to volume is maximized by a spherical shape. We sought to determine if spherical shape is a predictor of malignancy. Methods: Seven hundred forty-seven consecutive patients underwent ultrasound evaluation and FNA of 993 solid thyroid nodules (< 25% cystic) between 1995 and 2000 and were retrospectively analyzed. Nodules were classified as benign or malignant based on FNA and/or surgical pathology. Spherical shape was estimated by calculating a ratio of the longest to shortest dimensions, and rate of malignancy correlated. Results: Spherical shape was independently correlated with risk of malignancy (p < 0.001). Thyroid cancer was detected in 11% of all nodules, but ranged from 18% in spherical nodules to 5% in those least spherical. Nodules found to have suspicious or intermediate cytology showed similar variation in malignant risk. A long to short axis ratio greater than 2.5 was 100% predictive of a benign process, although present in only 4% of our cohort. A prospective validation was performed and confirmed consistent results (p < 0.01). Conclusion: Spherical shape is associated with an increased rate of malignancy in solid thyroid nodules. Determination of shape may assist in clinical risk assessment of thyroid cancer.