Thyroid pathologic findings in patients with Cowden disease

We describe the histologic findings in thyroid glands from six female and five male patients with Cowden disease. The patients were aged 9 to 43 years (mean age, 26 years). The salient thyroid lesions in this syndrome were multicentric follicular adenomas and adenomatous (parenchymatous, hyperplastic) nodules showing a wide range of nonspecific cytoarchitectural patterns. Multiple tiny cellular foci, so-called microadenomas, were also a feature. Specific lesions composed of oxyphil or clear cells, a tumor with features of hyalinizing trabecular adenoma, and an adenolipoma also occurred. Two cases showed a follicular carcinoma in addition to multiple benign follicular cell proliferations. The follicular carcinomas occurred at an older age and were larger in size than the clinically significant benign nodular lesions, suggesting tumor progression. All tumors showed thyroglobulin immunoreactivity and were negative for calcitonin. The histologic findings of a multiple adenomatous goiter or multiple follicular adenomas, particularly in children and young adults, should alert the pathologist and physician to the possibility of an inherited trait, such as Cowden disease, with its implications for family screening. The tumors are usually benign and well demarcated, but, because of multicentricity and increased risk of recurrence or progression to carcinoma, total thyroidectomy should be advocated.