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Arch Surg. 2008;143(3):312.

Answer: Gastric Juvenile Polyposis (GJP) in Germline SMAD4 Mutation 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 SMAD4 mutation 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.¹ Recently, germline mutations in the MADH4 gene (SMAD4) have been identified as the pathogenic cause in a subset of patients.² Cases with juvenile polyps restricted to the stomach (GJP)—hereditary or nonhereditary—have been reported in the literature.³ However, 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 SMAD group 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 SMAD4 carriers, and 17% to 55% of patients with JP have gastrointestinal tract malignant neoplasms. However, the contribution of the SMAD4 mutation 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.^4-5 Massive gastric involvement, as seen in our patient, always necessitates total gastrectomy.

AUTHOR INFORMATION

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

Accepted for Publication: July 6, 2007.

Financial Disclosure: None reported.

REFERENCES

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1. Jass JR, Williams CB, Bussey HJ, Morson BC. Juvenile polyposis: a precancerous condition. Histopathology. 1988;13(6):619-630. ISI | PUBMED 2. Howe JR, Roth S, Ringold JC; et al. Mutations in the SMAD4/DPC4 gene in juvenile polyposis. Science. 1998;280(5366):1086-1088. FREE FULL TEXT 3. Watanabe A, Nagashima H, Motoi M, Ogawa K. Familial juvenile polyposis of the stomach. Gastroenterology. 1979;77(1):148-151. ISI | PUBMED 4. Woodford-Richens K, Williamson J, Bevan S; et al. Allelic loss at SMAD4 in polyps from juvenile polyposis patients and use of fluorescence in situ hybridization to demonstrate clonal origin of the epithelium. Cancer Res. 2000;60(9):2477-2482. FREE FULL TEXT 5. Takaku K, Oshima M, Miyoshi H, Matsui M, Seldin MF, Taketo MM. Intestinal tumorigenesis in compound mutant mice of both Dpc4 (Smad4) and Apc genes. Cell. 1998;92(5):645-656. FULL TEXT | ISI | PUBMED

SECTION EDITOR: GRACE S. ROZYCKI, MD, MBA

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