Molecular classification of patients with unexplained hamartomatous and hyperplastic polyposis.

CONTEXT: Significant proportions of patients with hamartomatous polyposis or with hyperplastic/mixed polyposis remain without specific clinical and molecular diagnosis or present atypically. Assigning a syndromic diagnosis is important because it guides management, especially surveillance and prophylactic surgery. OBJECTIVE: To systematically classify patients with unexplained hamartomatous or hyperplastic/mixed polyposis by extensive molecular analysis in the context of central rereview of histopathology results. DESIGN, SETTING, AND PATIENTS: Prospective, referral-based study of 49 unrelated patients from outside institutions (n = 28) and at a comprehensive cancer center (n = 21), conducted from May 2, 2002, until December 15, 2004. Germline analysis of PTEN, BMPR1A, STK11 (sequence, deletion), SMAD4, and ENG (sequence), specific exon screening of BRAF, MYH, and BHD, and rereview of polyp histology results were performed. MAIN OUTCOME MEASURES: Molecular, clinical, and histopathological findings in patients with unexplained polyposis. RESULTS: Of the 49 patients, 11 (22%) had germline mutations. Of 14 patients with juvenile polyposis, 2 with early-onset disease had mutations in ENG, encoding endoglin, previously only associated with hereditary hemorrhagic telangiectasia; 1 had hemizygous deletion encompassing PTEN and BMPR1A; and 1 had an SMAD4 mutation. One individual previously classified with Peutz-Jeghers syndrome had a PTEN deletion. Among 9 individuals with an unknown hamartomatous polyposis, 4 had mutations in STK11 (1), BMPR1A (2), and SMAD4 (1). Of the 23 patients with hyperplastic/mixed polyposis, 2 had PTEN mutations. Substantial discrepancies in histopathology results were seen. CONCLUSIONS: Systematic molecular classification of 49 patients with unexplained hamartomatous or hyperplastic polyposis uncovered a potential novel susceptibility gene, ENG, for juvenile polyposis. Importantly, given the substantial proportion of patients found to have germline mutations, more extensive analysis of the known susceptibility genes is indicated. Rereview of histology results by a dedicated gastrointestinal pathologist should be considered routinely, as organ-specific surveillance rests on defining syndromic diagnosis.

Familial polyposis in two Ethiopians.

Cases of familial polyposis coli and Peutz-Jeghers syndrome are reported for the first time in Ethiopia. One case seemed to have the defect as a new mutation in his gene while the other possibly inherited from his father. The one with polyposis coli had transmitted the disease to his offspring. This patient had total colectomy for prophylaxis against a potential carcinoma of the colon.

[Treatment of tumors of the small intestine in Peutz-Jeghers' syndrome. Value of a combined endoscopic and surgical approach. Apropos of 2 familial cases, one of which with a 15-year follow-up]. / Traitement des tumeurs du grêle du syndrome de Peutz-Jeghers. Intérêt d'une approche combinée, endoscopique et chirurgicale. A propos de 2 cas familiaux, dont l'un suivi 15 ans.

We report two cases of Peutz-Jeghers syndrome who underwent intraoperative enteroscopy. In the first case, the fiberscope was sterilized with ethylene oxide, while in the second, an electronic colonoscope was decontaminated with glutaraldehyde plus phenate. The endoscope was introduced through an enterotomy. This led to the discovery of several hamartoma greater than 10 mm which had gone undetected by the surgeon and guided the surgical procedure. In a case with approximately 30 hamartoma, associated endoscopic polypectomy and surgical removal of polyps by eversing the mucosa through enterotomies allowed the medicosurgical team to obtain a "clean small bowel" without resection.