Spectrum of colon polyposis and colonic neoplasia in the PTEN hamartoma tumor syndrome (PHTS).

Abstract

3627 Background: PHTS consists of a group of familial disorders associated with germline mutations of the PTEN gene. Cowden syndrome is the most common phenotype. Affected patients develop a variety of tumors, including polyposis of the gastrointestinal tract. Based on current literature, PHTS is not associated with an increased risk of colon cancer; therefore, the risk of neoplastic transformation and appropriate screening intervals for PHTS-associated colon polyposis is not well characterized. This study was performed to better define the incidence and outcomes of colon polyposis in PHTS. Methods: Patients with a clinical diagnosis of PHTS at the Mayo Clinic were identified from 1980 to 2009. Only patients that met the NCCN consortium criteria for diagnosis were included. The relevant clinical information, onco-pathology data and molecular studies were retrospectively reviewed. Results: 47 patients with PHTS were identified, of which 17 (36%) had colon studies at our institution. All met criteria for Cowden disease. Of the 14 that underwent a colonoscopy, 13 (93%) were noted to have diffuse polyposis, with 9 (64%) estimated to have > 50 polyps. 15 patients had colon biopsies reviewed (median age 47 at first biopsy). The spectrum of tumors included hamartomas (n = 12), ganglioneuromas (n = 6) and tubular adenomas (n = 6). 7 (47%) patients had low-grade dysplasia (median age 50 at first detection), including 1 patient with dysplasia within hamartomatous polyps. 2 (12%) patients, age 56 and 62, had early-stage (T1N0M0, grade II and T2N0M0, grade III) left-sided colonic adenocarcinomas. Neither showed evidence of microsatellite instability. 7 (41%) patients underwent colectomy (median age 45), of which 4 had colonic dysplasia/neoplasia and 3 had symptomatic polyposis. Conclusions: This is the largest series from a single institution to examine the colonic manifestations of PHTS. Our findings suggest that germline mutations in the PTEN gene are associated with a spectrum of colonic tumors, including hamartomas, ganglioneuromas, tubular adenomas and colon cancer. Colonic dysplasia and neoplasia were more common then expected. If confirmed, colon cancer screening recommendations should be developed for patients with PHTS. No significant financial relationships to disclose.