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Special Feature
March 1, 2008

Image of the Month—Diagnosis

Arch Surg. 2008;143(3):312. doi:10.1001/archsurg.2007.62-b

Answer: Gastric Juvenile Polyposis (GJP) in Germline SMAD4Mutation Accompanied by Gastric Cancer

Upper gastrointestinal tract endoscopy on admission of the patient revealed a profuse polyposis of the stomach. Histopathologic examination of one of the polyps showed a tubular adenocarcinoma of the stomach, whereas dysplasia was seen in other lesions. Staging was without evidence of lymphogenic or hematogenic metastases. On colonoscopy, no additional polyps were detected, and the areas of prior polypectomy were inconspicuous. The patient underwent DNA analysis, and a germline SMAD4mutation was found. We subsequently performed a total gastrectomy with D2 lymphadenectomy and Roux-en-Y reconstruction. The postoperative course was uneventful. Histopathologically, multiple juvenile polyps with superficial erosions were found. Intraepithelial neoplasia was observed in some polyps. Moreover, the intraepithelial neoplasia focally invaded a microinvasive well-differentiated adenocarcinoma (intramucosal adenocarcinoma). Resection margins were tumor free, and 15 regional lymph nodes showed no evidence of carcinoma metastasis. At the first follow-up 3 months after surgery, the anemia and hypoproteinemia had resolved and the patient had no gastrointestinal problems.

Juvenile polyposis (JP) is a disorder characterized by multiple polyps in the gastrointestinal tract at a young age with an increased risk of developing cancer.1Recently, germline mutations in the MADH4gene (SMAD4) have been identified as the pathogenic cause in a subset of patients.2Cases with juvenile polyps restricted to the stomach (GJP)—hereditary or nonhereditary—have been reported in the literature.3However, it remains debatable whether GJP is a subtype of JP or a separate entity. The clinical manifestations in our patient (anemia and hypoproteinemia) are presumed to be the result of long-term blood and protein loss from gastric polyps. Such JP-related extraintestinal disorders as pulmonary arteriovenous malformations and hypertrophic osteoarthropathy were not evident in our patient. Seven additional members of the SMADgroup have been detected in humans, and they exhibit different functions in the signal transduction of transforming growth factor β. Approximately 20% of patients' families have been identified as SMAD4carriers, and 17% to 55% of patients with JP have gastrointestinal tract malignant neoplasms. However, the contribution of the SMAD4mutation to the histopathogenesis of JP and the exact mechanism of carcinogenesis remain to be elucidated with the help of additional molecular studies of the gene involved.4,5Massive gastric involvement, as seen in our patient, always necessitates total gastrectomy.

Correspondence:Ines Gockel, MD, Department of General and Abdominal Surgery, Johannes Gutenberg University, Langenbeckstr 1, 55131 Mainz, Germany (gockel@ach.klinik.uni-mainz.de).

Accepted for Publication:July 6, 2007.

Financial Disclosure:None reported.

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