title: Upper and Lower Gastrointestinal Findings in PTEN Mutation-Positive Cowden Syndrome Patients Participating in an Active Surveillance Program.
abstract: OBJECTIVE
  Cowden syndrome (CS), associated with germline PTEN mutations, is an autosomal-dominant disorder with increased frequencies of thyroid and breast cancers. Recent reports document the occurrence of gastrointestinal (GI) polyps and increased risk of colon cancer in PTEN mutation carriers. Studies to date, however, have not been based on mutation carriers undergoing active, systematic, routine-interval GI surveillance. Our objective is to document the upper and lower GI findings in CS patients undergoing such an active GI surveillance program.
  
  
  METHODS
  In a 5-year period, 3,000 consecutive patients were referred to our high-risk GI cancer clinic for various reasons. Of these 3,000, 10 met full-blown clinical criteria for the diagnosis of CS. Individuals with identified PTEN mutations underwent annual upper and lower endoscopy surveillance programs using dual white light and narrow-band imaging. All biopsies including archived materials were reviewed by a single dedicated GI pathologist.
  
  
  RESULTS
  Ten PTEN mutation carriers from different ethnic backgrounds were invited and all participated in the active GI surveillance program. Eight patients had colonic polyps, mostly hyperplastic (eight patients) and hamartomatous (five patients), but also adenomatous (three patients), ganglioneuromatous (three patients), and juvenile polyps (two patients). One patient (10%) had an early-onset rectal cancer (aged 44 years), which was null for PTEN expression on immunohistochemistry. All patients had gastric polyps and nine (90%) had duodenal polyps, mostly hyperplastic and hamartomatous. Additional three patients (30%) had adenomatous duodenal polyps.
  
  
  CONCLUSIONS
  PTEN mutation-positive CS patients have a higher frequency of upper GI polyps than previously believed. They appear prone to develop adenomatous upper and lower tract dysplastic polyps and cancer. Thus, the polyps encountered during upper or lower endoscopy in these patients should not be automatically considered innocent hamartomas without malignant potential. Active surveillance programs in specialized centers should be considered in these patients.
authors.affiliation: Gastroenterology Department, Rabin Medical Center, Petach Tikva, Israel.
authors.forename: Zohar
authors.initials: Z
authors.lastname: Levi
authors.forename: Hagit N
authors.initials: HN
authors.lastname: Baris
authors.forename: Inbal
authors.initials: I
authors.lastname: Kedar
authors.forename: Yaron
authors.initials: Y
authors.lastname: Niv
authors.forename: Alex
authors.initials: A
authors.lastname: Geller
authors.forename: Eyal
authors.initials: E
authors.lastname: Gal
authors.forename: Rachel
authors.initials: R
authors.lastname: Gingold
authors.forename: Sara
authors.initials: S
authors.lastname: Morgenstern
authors.forename: Yacov
authors.initials: Y
authors.lastname: Baruch
authors.forename: Brandie Heald
authors.initials: BH
authors.lastname: Leach
authors.forename: Mary P
authors.initials: MP
authors.lastname: Bronner
authors.forename: Charis
authors.initials: C
authors.lastname: Eng