Utilizing PTEN immunohistochemistry as a screening test for Cowden syndrome

Cowden syndrome (CS) is a multisystem disease with an elevated lifetime risk of internal malignancy. We aim to assess the role of PTEN immunostain as a screening test for CS in a variety of common CS-associated neoplasms, with a particular focus on cutaneous tumors.

We retrospectively searched for patients meeting criteria for CS and/or demonstrating germline PTEN mutation from 2008 to 2022. We then performed PTEN immunostains on tumors of these patients as well as control cases.

Our study included 30 patients with CS who had a total of 25 CS-associated malignancies (13 thyroid, 8 breast, and 4 endometrial carcinomas). Specifically, there were 11 patients with biopsy-confirmed CS-associated cutaneous neoplasms, including 1 patient with multiple trichilemmomas and 3 with multiple sclerotic fibromas. In total, 45 CS-associated tumors (6 trichilemmomas, 7 sclerotic fibromas, 5 thyroid carcinomas, 18 adenomatous thyroid nodules, 6 breast carcinomas, and 3 endometrial carcinomas) and 31 non-CS cases (9 trichilemmomas, 5 sclerotic fibromas, 8 adenomatous thyroid nodules, and 3 thyroid, 3 breast, and 3 endometrial carcinomas) were available for PTEN immunohistochemical staining. PTEN expression was lost in 43 (96%) of 45 CS-associated lesions and retained in 30 (97%) of 31 sporadic tumors. The overall sensitivity and specificity of PTEN loss of expression as a screening test for CS were 96% and 97%, respectively.

PTEN immunohistochemistry on CS-associated tumors, especially trichilemmomas, can serve as a readily accessible and cost-effective screening test for CS.