Occurrence and Natural History of Thyroid Cancer in Patients with Cowden Syndrome

Cowden syndrome patients are at an increased risk of developing differentiated thyroid carcinoma (DTC). There are limited studies of thyroid cancer biology within this population. We aimed to describe the frequency and progression of DTC in this population.

We reviewed all patients with clinically or genetically confirmed Cowden syndrome treated at our institution between 1979 and 2017. Presentation, operative details, pathology, and adjuvant treatment for all thyroid diseases were analyzed.

Forty-seven patients were identified. Thirty-seven received a clinical diagnosis while 10 tested positive on genetic testing for the PTEN gene. Average follow-up time was 10 years. Twenty-three patients underwent a total thyroidectomy. Nine patients were diagnosed with thyroid cancer, with a mean age of 28.5 years, 4 cases of the follicular variant of papillary thyroid cancer (PTC), 4 of PTC, and 1 of cystic PTC. One patient required an interval lateral neck dissection but no patients developed distant metastasis. Fourteen patients underwent thyroidectomy, 12 due to follicular adenoma, Hürthle cell adenoma, or multinodular goiter, 1 due to Graves' disease, and 1 who elected to undergo a prophylactic thyroidectomy. No mortality was associated with thyroid cancer in these patients.

Patients with Cowden syndrome are at a significantly increased risk of developing DTC and have a younger age of onset. In this study, 20% of the patients with Cowden syndrome were diagnosed with DTC, but distant metastasis and overall mortality were absent. Clinical features were similar to those of sporadic DTC, proving that, apart from screening, Cowden syndrome-related DTC can be treated in similar fashion.