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- Polyposis
- gastric cancer
- adenocarcinoma
- family cancer
- familial adenomatous polyposis
- Helicobacter pylori
- gastrointestinal lymphoma
- gastric lymphoma
- IBD
- gastrectomy
- gastric carcinoma
We read with interest the article by Worthley et al1 regarding a new autosomal dominant syndrome characterised by fundic gland polyposis (FGP) and gastric cancer, which was not associated with familial adenomatous polyposis (FAP). We have experienced two similar cases of gastric adenocarcinoma occurring in pedigrees with familial FGP without FAP.
Case 1
A 56-year-old woman was referred to our institution for further investigation of her multiple gastric polyps. On admission, serology and 13C urea breath test yielded negative results for Helicobacter pylori. Upper gastrointestinal endoscopy revealed numerous fundic gland polyps covering the gastric fundus and corpus (figure 1A). In the fundus, there was also a flat and discoloured area circumscribed by polyps (figure 1B). A biopsy from the area revealed well-differentiated adenocarcinoma. No other polyps or adenomas were found in the duodenum. The colonoscopy did not show any colorectal lesions and the CT scan of the chest and abdomen was normal. A total gastrectomy was performed. Macroscopically, there were numerous small polypoid lesions. There was also a discoloured area measuring 6×5.5 cm in the gastric fundus (figure 1C). Histologically, numerous small fundic gland polyps were diffusely distributed (figure 1D). The tumour was a well-differentiated adenocarcinoma focally invading the superficial portion of the submucosa (figure 1E). Since hereditary hamartomatous polyposis was suspected, we performed an upper endoscopy on seven other family members: two sisters, one brother, two daughters, one son and one nephew. As a result, five of the seven subjects had similar gastric FGP (figure 2). The colonoscopies did not detect colorectal lesions in any of the seven subjects. The patient was negative for the mutation of APC, the ß-catenin, MADH4 and BMPR1A. She was alive and well at the time of this writing.
Case 2
A 42-year-old woman, whose daughter had been diagnosed as having numerous gastric polyps in her stomach, was admitted for the evaluation of possible gastric lesions in 1981. The endoscopy identified numerous small polyps in the corpus. The biopsy revealed her numerous gastric polyps to be fundic gland polyps. Her brother also had FGP, and her niece had gastric cancer (figure 2). The patient and her daughter had no colorectal polyps, as confirmed by a colonoscopy. The patient was negative for the mutation of APC, the ß-catenin, MADH4 and BMPR1A. In December 2003, the patient underwent a follow-up endoscopy, which revealed an irregularly shaped mass with erosion surrounded by fundic gland polyps in the greater curvature of the corpus (figure 1F). A biopsy revealed well-differentiated adenocarcinoma. The patient died due to multiple organ metastases in April 2004.
FAP-associated FGP is linked with a second hit of APC alteration,2 whereas sporadic FGP arises through mutations in the ß-catenin gene.3 Although FGP in patients with FAP was not regarded as a precursor of cancer, there have been several reports describing gastric adenocarcinoma or high-grade dysplasia associated with fundic gland polyps.4 The majority of such carcinoma or high-grade dysplasia developed in patients with FAP with germline mutation of APC.4 On the other hand, high-grade dysplasia occurring in the FGP in patients with no FAP is rare. To date, there have been no reports of cases with familial gastric carcinoma developing from FGP without FAP, except for three families in a recent report by Worthley et al.1 As seen in their study, their patients (as well as ours) developed gastric adenocarcinoma associated with FGP and had a family history of FGP, but they were negative for the germline mutation of APC, the ß-catenin, MADH4 and BMPR1A. In addition, the families in their study and in ours also showed an autosomal dominant pattern of inheritance for FGP. We thus consider that familial FGP is a hereditary precancerous condition distinctive of other well-recognised hamartomatous polyposis.1
Footnotes
Competing interests None.
Patient consent Obtained.
Ethics approval This study was approved by the ethics committee at Kyushu University Hospital.
Provenance and peer review Not commissioned; internally peer reviewed.