Thyroid Nodule Size and Prediction of Cancer

Context: Thyroid nodule size is routinely measured, although its impact on thyroid cancer risk is unclear. Objective: Our objective was to evaluate the association of nodule size upon cancer risk. Design, Setting, and Patients: We conducted a retrospective cohort analysis at an academic hospital with 4955 consecutive patients evaluated between 1995 and 2009. Intervention: Ultrasound and ultrasound-guided fine-needle aspiration of nodules >1 cm was done. Indeterminate and malignant nodules were referred for surgery, and histopathology was reviewed. Main Outcome Measure: The presence and histological subtype of cancer was evaluated. Results: Of 7348 evaluated nodules, 927 (13%) were cancerous. Of those 1.0 to 1.9 cm in diameter, 10.5% were cancerous. In contrast, of those >2.0 cm, 15% were cancerous (P < .01). However, nodules 2.0 to 2.9, 3.0 to 3.9, and >4 cm were cancerous in 14%, 16%, and 15% of cases (P = .14), respectively, demonstrating no graded increase in risk beyond the 2-cm threshold. When malignant, the proportion of papillary carcinoma decreased (nodules 1.0-1.9 cm, 92% of cases; 2.0-2.9 cm, 88%; 3.0-3.9 cm, 83%; >4 cm, 74% [P < .01]), while follicular carcinoma increased (1.0-1.9 cm, 6%; 2.0-2.9 cm, 7%; 3.0-3.9 cm, 12%; >4 cm, 16% [P < .01]) as nodules enlarged. Nodules size did not influence cytology distribution or risk of false-negative aspirates. Conclusions: Increasing thyroid nodule size impacts cancer risk in a nonlinear fashion. A threshold is detected at 2.0 cm, beyond which cancer risk is unchanged. However, the risk of follicular carcinomas and other rare thyroid malignancies increases as nodules enlarge. (J Clin Endocrinol Metab 98: 564-570, 2013)