Prevalence and aggressiveness of papillary thyroid carcinoma in surgically-treated graves' disease patients: a retrospective matched cohort study

Reported rates of thyroid cancer in Graves' disease (GD) vary widely. The aim of this study was to evaluate the prevalence of papillary thyroid carcinoma (PTC), including aggressive forms, in GD compared to matched controls undergoing thyroidectomy. Furthermore, it seeks to elucidate any patient- or tumour-associated factors predictive of malignancy or an aggressive course. We performed a matched cohort study of GD patients undergoing thyroidectomy at our institution between 2006 to 2018. Clinicodemographic factors, preoperative characteristics, surgical factors, final histopathology as well postoperative course were collected. Aggressive PTC was defined as evidence of lymph node metastasis, extrathyroidal extension, gross vascular invasion and/or aggressive histologic variants. Prevalence of PTC was compared with sex, age and nodule size-matched euthyroid patients that underwent thyroidectomy in the same time period. A total of 132 patients were included in the study with a mean age of 46 (±14) years. Malignancy was identified in 36/66 (55%) patients with GD; 20/66 (30%) were incidental carcinomas and 9/66 (14%) were associated with aggressive pathologic features. In the aggressive group, lymph node metastasis to the central compartment was present in 8 (12%) cases, extrathyroidal extension in 4 (6%) cases and one (1.5%) patient had a diffuse sclerosing tumor variant. No significant differences in outcome were found between the two groups. GD patients were more likely to have incidental carcinomas (p = 0.035). Adjusting for baseline patient characteristics, GD patients demonstrated an increased likelihood of harbouring a malignancy (odds ratio (OR) = 2.67; 95% confidence interval (CI) 1.00-7.18) compared to controls. More than half of patients with GD undergoing thyroidectomy had concurrent thyroid malignancy with aggressive features present in 14% of patients. GD may confer a heightened risk of thyroid cancer; thyroid nodules should therefore be carefully investigated.