Analysis of the loss of phosphatase and tensin homolog expression in thyroid tissue for the diagnosis of Cowden syndrome

• Published in: Surgery Vol. 176; no. 3; pp. 708 - 712
• Main Authors: Febrero Sánchez, Beatriz, Iborra, Emma, Sánchez-Pedreño, Paloma, Ros-Madrid, Inmaculada, Rodríguez, José M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2024
• Subjects: Adult; Aged; Female; Hamartoma Syndrome, Multiple - diagnosis; Hamartoma Syndrome, Multiple - genetics; Humans; Male; Middle Aged; PTEN Phosphohydrolase - genetics; PTEN Phosphohydrolase - metabolism; Retrospective Studies; Thyroid Gland - metabolism; Thyroid Gland - pathology; Thyroid Neoplasms - diagnosis; Thyroid Neoplasms - genetics; Thyroid Neoplasms - pathology; Thyroidectomy; Young Adult
• ISSN: 0039-6060; 1532-7361; 1532-7361
• DOI: 10.1016/j.surg.2024.06.005

Cowden syndrome is an autosomal-dominant disorder caused by a germline phosphatase and tensin homolog mutation, giving rise to several tumors with an aggressive clinical course. In the thyroid, there are certain histologic criteria that could be related to this syndrome that could be useful for its early detection. We sought to analyze the loss of phosphatase and tensin homolog in thyroid histologic pieces with certain histologic criteria and to determine the percentage of patients diagnosed with Cowden syndrome with this methodology. Five hundred thirty-five thyroid specimens collected were retrospectively analyzed (2017–2020). Those samples that presented certain histologic criteria were studied for loss of phosphatase and tensin homolog expression. Patients with loss of expression underwent a clinical study to rule out dermatologic or other lesions compatible with Cowden syndrome. Patients with positive clinical study were referred for genetic study. The phosphatase and tensin homolog study was performed in 6.7% (n = 36) of the thyroidectomy samples, showing loss of expression in 22% (n = 8); the most frequent histologic finding was the presence of multiple monomorphous adenomatous nodules. The samples with loss of expression showed more diffuse oncocytic changes. Of the 8 patients with loss of expression, 5 showed dermatologic lesions that could be associated with Cowden syndrome and 1 had a history of macrocephaly. These patients were referred for genetic study, being positive for Cowden syndromein in one quarter of the cases (n = 2). The immunohistochemical study of phosphatase and tensin homolog in pieces of thyroidectomies with histologic criteria suggestive of Cowden syndrome can help in its early diagnosis.