Gastrointestinal Manifestations of Cowden Syndrome

Abstract

Purpose: Cowden syndrome (CS) is an under diagnosed, under recognized, autosomal dominant inherited syndrome. CD is associated with germline mutations in the PTEN gene and exhibits an increase risk of breast, thyroid, and possibly other malignancies. Although various benign gastrointestinal lesions, including esophageal glycogenic acanthosis and hamartomatous polyps have been described, the colorectal cancer (CRC) risk remains poorly characterized. Methods: Nine patients (7 female, 2 males with a median age of 52.3) with a previous diagnosis of CS based on clinical criteria (International Cowden Consortium version 2000) and/or presence of a PTEN mutation were studied. All patients underwent colonoscopy, and four patients also underwent upper endoscopy. Results: One case was diagnosed with CRC at age 42. Four patients had a family history of CRC, three with affected first degree relatives (FDR). Two cases had a family history of colon polyps and CRC before age 45 years of age. One case had two FDR with CRC and a second degree relative with CRC at age 12. Two cases had FDR with CRC after age 45. Multiple colon polyps were observed in seven patients (78%). The polyps were mostly sessile, 1 to 4mm in size and universally distributed throughout the colon. Hamartomatous polyps were present in all cases with polyps. Three patients had adenomatous polyps. Inflammatory and hyperplastic polyps were also seen. Upper GI manifestations included esophageal acanthosis, and, multiple gastric and duodenal non-adenomatous polyps were seen. Conclusions: We found CRC in 1/9 (11%) patients with CS and three cases with first degree relatives with CRC. This study suggests further investigation of CS registries for prevalence of CRC and the potential contribution of CS to familial CRC. Endoscopic surveillance may be indicated in patients with CS.