Oncophenotypic Review and Clinical Correlates of Phosphatase and Tensin Homolog on Chromosome 10 Hamartoma Tumor Syndrome

Abstract

TO THE EDITOR: PTEN (phosphatase and tensin homolog on chromosome 10) hamartoma tumor syndrome (PHTS) is a rare autosomal dominant disorder encompassing four clinically distinct syndromes caused by germline mutations of the PTEN gene. PTEN is a dual-specificity phosphatase that plays a role as a tumor suppressor by negatively regulating the cell-survival signaling pathway initiated by phosphatidylinositol 3-kinase and the mitogen-activated protein kinase pathways. 1 These syndromes: Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome, Proteus syndrome, and Proteus-Like syndrome, are characterized by unregulated cellular proliferation leading to formation of benignhamartomasandmalignancies.BecauseoftherarityofPHTS, data regarding cancer risks in PHTS are limited and mostly based on small series and reports. We performed a retrospective analysis of patients who met National Comprehensive Cancer Network criteria for PHTS 2 and who presented to the Mayo Clinic between 1980and2009.Oncopathology,moleculardata,andclinicalinformation for these patients were analyzed. Forty-six patients met the criteria for PHTS. Among these, 40 patients had CS (three with Lhermitte-Duclos disease), and six had Bannayan-Riley-Ruvalcaba syndrome. Thyroid diseases were most common; there were 27 patients (58%) with benign thyroid conditions including multinodular goiters, thyroid adenomas, and hamartomas.Sevenpatients(15%)hadthyroidneoplasms.Contrarytowhat would be expected on the basis of existing literature, papillary cancers of the thyroid (n 6) were seen more often than follicular cancers