Immunohistochemical staining of thyroidectomy specimens for PTEN can aid in the identification of patients with Cowden syndrome.

Cowden syndrome (CS) is an autosomal dominant disorder caused by a germline mutation in PTEN (phosphatase and tensin homolog, deleted on chromosome 10) and characterized by the development of multiple hamartomas and carcinomas of the thyroid, breast, and uterus. Recognition of CS is important so that cancer screening and genetic counseling can be initiated. Pathologic findings in thyroidectomy specimens suggestive of, but not specific for, CS include multiple adenomatous nodules, follicular adenomas, and nodular hyperplasia, with or without follicular carcinoma or papillary thyroid carcinoma. The aim of our study was to determine whether immunohistochemical staining for PTEN could aid in the identification of CS in patients with these pathologic findings. We studied 21 thyroidectomy specimens from patients with a known history of CS or with pathologic findings that raised the possibility of CS. Immunohistochemistry for PTEN was performed on all cases, and assessment of PTEN expression was performed by a pathologist blinded to the clinical history and recorded as follows: intact expression in all lesional nodules, complete loss of expression in all lesional nodules, or heterogeneous loss of expression, with some nodules showing intact expression and other nodules showing complete loss of expression. Nine cases showed loss of PTEN expression, and 12 cases showed intact expression. Of the 9 cases that showed loss of PTEN expression, 8 patients were CS patients (5 showed complete loss of staining in all nodules, and 3 showed heterogeneous loss of staining), and 1 patient was determined not to have CS (this patient had a history of radiation treatment). Of the 12 patients whose thyroidectomy specimens showed intact PTEN expression, none had CS by clinical history, family history, or genotyping. Thus, the sensitivity and specificity of PTEN staining for the detection of CS are 100% and 92.3%, respectively. In summary, loss of PTEN expression in adenomatous thyroid nodules, whether in all nodules or in a subset of nodules, appears to be both sensitive and specific for CS.