Gastric neoplasms in patients with familial adenomatous polyposis: endoscopic and clinicopathologic features

      Background and Aims

      Gastric neoplasms in patients with familial adenomatous polyposis (FAP) occur at a high rate and can cause death. The endoscopic findings of gastric neoplasms in these patients are characteristic but not well recognized. To identify the relevant characteristics to enable early detection, we retrospectively investigated endoscopic findings of gastric neoplasms in patients with FAP and then compared the clinical, histopathologic, and genetic features among subgroups.


      Of 234 patients with 171 pedigrees at 2 institutes, 56 cases (24%, 133 gastric neoplasms) with 44 pedigrees were examined. Immunostaining was performed for histopathologic evaluation by 1 blinded pathologist. According to the endoscopic findings, gastric neoplasms were divided into 4 types based on location (L: antrum and pylorus, UM: the rest of the stomach) and color (W: white, T: translucent, R: reddish) and their clinicopathologic features examined.


      Of the cases, 93% could be classified into a single type. Among histologic phenotypes, high-grade dysplasia was present in 26% (type L), 41% (type UM-W), 0% (type UM-T), and 22% (type UM-R). The immunologic phenotype comprised the gastric type in 69% (93% in Type UM) and the intestinal phenotype, including the mixed type, in 31% (61% in type L). Moreover, 96% of patients had concurrent duodenal neoplasms. Adenomatous polyposis coli gene status was identified in 93% of patients; the pathogenic variant was detected in 98% but did not influence any endoscopic features.


      Gastric neoplasms in patients with FAP were stratified into 4 types according to their endoscopic findings. The endoscopic phenotype was related to the histopathologic phenotype but not to germline variants.

      Graphical abstract


      APC (adenomatous polyposis coli), FAP (familial adenomatous polyposis), FGP (fundic gland polyp), H pylori (Helicobacter pylori), HGD (high-grade dysplasia), LGD (low-grade dysplasia), WLI (white-light imaging)
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        • Iwama T.
        • Tamura K.
        • Morita T.
        • et al.
        A clinical overview of familial adenomatous polyposis derived from the database of the Polyposis Registry of Japan.
        Int J Clin Oncol. 2004; 9: 308-316
        • Bianchi L.K.
        • Burke C.A.
        • Bennett A.E.
        • et al.
        Fundic gland polyp dysplasia is common in familial adenomatous polyposis.
        Clin Gastroenterol Hepatol. 2008; 6: 180-185
        • de Campos F.G.
        • Perez R.O.
        • Imperiale A.R.
        • et al.
        Evaluating causes of death in familial adenomatous polyposis.
        J Gastrointest Surg. 2010; 14: 1943-1949
        • Wood L.D.
        • Salaria S.N.
        • Cruise M.W.
        • et al.
        Upper GI tract lesions in familial adenomatous polyposis (FAP): enrichment of pyloric gland adenomas and other gastric and duodenal neoplasms.
        Am J Surg Pathol. 2014; 38: 389-393
        • Ngamruengphong S.
        • Boardman L.A.
        • Heigh R.I.
        • et al.
        Gastric adenomas in familial adenomatous polyposis are common, but subtle, and have a benign course.
        Hered Cancer Clin Pract. 2014; 12: 4
        • Yamaguchi T.
        • Ishida H.
        • Ueno H.
        • et al.
        Upper gastrointestinal tumours in Japanese familial adenomatous polyposis patients.
        Jpn J Clin Oncol. 2016; 46: 310-315
        • Nakamura K.
        • Nonaka S.
        • Nakajima T.
        • et al.
        Clinical outcomes of gastric polyps and neoplasms in patients with familial adenomatous polyposis.
        Endosc Int Open. 2017; 5: E137-E145
        • Nakano K.
        • Kawachi H.
        • Chino A.
        • et al.
        Phenotypic variations of gastric neoplasms in familial adenomatous polyposis are associated with endoscopic status of atrophic gastritis.
        Dig Endosc. 2020; 32: 547-556
        • Mankaney G.
        • Leone P.
        • Cruise M.
        • et al.
        Gastric cancer in FAP: a concerning rise in incidence.
        Fam Cancer. 2017; 16: 371-376
        • Park J.G.
        • Park K.J.
        • Ahn Y.O.
        • et al.
        Risk of gastric cancer among Korean familial adenomatous polyposis patients. Report of three cases.
        Dis Colon Rectum. 1992; 35: 996-998
        • Iwama T.
        • Mishima Y.
        • Utsunomiya J.
        The impact of familial adenomatous polyposis on the tumorigenesis and mortality at the several organs. Its rational treatment.
        Ann Surg. 1993; 217: 101-108
        • Walton S.J.
        • Frayling I.M.
        • Clark S.K.
        • et al.
        Gastric tumours in FAP.
        Fam Cancer. 2017; 16: 363-369
      1. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology genetic/familial high-risk assessment: colorectal, version 3. 2017. Available at: Accessed July 7, 2021.

        • Ishida H.
        • Yamaguchi T.
        • Tanakaya K.
        • et al.
        Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the clinical practice of hereditary colorectal cancer (translated version).
        J Anus Rectum Colon. 2018; 2: S1-S51
        • Monahan K.J.
        • Bradshaw N.
        • Dolwani S.
        • et al.
        Guidelines for the management of hereditary colorectal cancer from the British Society of Gastroenterology (BSG)/Association of Coloproctology of Great Britain and Ireland (ACPGBI)/United Kingdom Cancer Genetics Group (UKCGG).
        Gut. 2020; 69: 411-444
        • Syngal S.
        • Brand R.E.
        • Church J.M.
        • et al.
        ACG clinical guideline: genetic testing and management of hereditary gastrointestinal cancer syndromes.
        Am J Gastroenterol. 2015; 110 (quiz 263): 223-262
        • Leone P.J.
        • Mankaney G.
        • Sarvapelli S.
        • et al.
        Endoscopic and histologic features associated with gastric cancer in familial adenomatous polyposis.
        Gastrointest Endosc. 2019; 89: 961-968
        • Straub S.F.
        • Drage M.G.
        • Gonzalez R.S.
        Comparison of dysplastic fundic gland polyps in patients with and without familial adenomatous polyposis.
        Histopathology. 2018; 72: 1172-1179
        • Choi W.T.
        • Brown I.
        • Ushiku T.
        • et al.
        Gastric pyloric gland adenoma: a multicentre clinicopathological study of 67 cases.
        Histopathology. 2018; 72: 1007-1014
        • Yang J.
        • Gurudu S.R.
        • Koptiuch C.
        • et al.
        American Society for Gastrointestinal Endoscopy guideline on the role of endoscopy in familial adenomatous polyposis syndromes.
        Gastrointest Endosc. 2020; 91: 963-982
        • Kim Y.J.
        • Park J.C.
        • Kim J.H.
        • et al.
        Histologic diagnosis based on forceps biopsy is not adequate for determining endoscopic treatment of gastric adenomatous lesions.
        Endoscopy. 2010; 42: 620-626
      2. Japanese classification of gastric carcinoma: 3rd English ed.
        Gastric Cancer. 2011; 14: 101-112
        • Kimura K.
        • Takemoto T.
        An endoscopic recognition of the atrophic border and its significance in chronic gastritis.
        Endoscopy. 1969; 1: 87-97
        • Haruma K.
        • Kato M.
        • Inoue K.
        • et al.
        Kyoto classification of gastritis.
        1st ed. Nihon Medical Center, Tokyo, Japan2017
      3. WHO Classification of Tumours, 5th ed. Digestive system tumours. International Agency for Research on Cancer, Lyon; 2019.

        • Tajima Y.
        • Shimoda T.
        • Nakanishi Y.
        • et al.
        Gastric and intestinal phenotypic marker expression in gastric carcinomas and its prognostic significance: immunohistochemical analysis of 136 lesions.
        Oncology. 2001; 61: 212-220
        • Shiroshita H.
        • Watanabe H.
        • Ajioka Y.
        • et al.
        Re-evaluation of mucin phenotypes of gastric minute well-differentiated-type adenocarcinomas using a series of HGM, MUC5AC, MUC6, M-GGMC, MUC2 and CD10 stains.
        Pathol Int. 2004; 54: 311-321
        • Mabuchi N.
        • Niwa Y.
        • Hirooka Y.
        • et al.
        Characteristics of gastric and intestinal mucin phenotypes of gastric carcinoma.
        Hepatogastroenterology. 2008; 55: 2277-2281
        • de Boer W.B.
        • Ee H.
        • Kumarasinghe M.P.
        Neoplastic lesions of gastric adenocarcinoma and proximal polyposis syndrome (GAPPS) are gastric phenotype.
        Am J Surg Pathol. 2018; 42: 1-8
        • Powell S.M.
        • Petersen G.M.
        • Krush A.J.
        • et al.
        Molecular diagnosis of familial adenomatous polyposis.
        N Engl J Med. 1993; 329: 1982-1987
        • Arnason T.
        • Liang W.Y.
        • Alfaro E.
        • et al.
        Morphology and natural history of familial adenomatous polyposis-associated dysplastic fundic gland polyps.
        Histopathology. 2014; 65: 353-362
        • Martin I.
        • Roos V.H.
        • Anele C.
        • et al.
        Gastric adenomas and their management in familial adenomatous polyposis.
        Endoscopy. Epub 2020 Sep 17;
        • Kabashima A.
        • Yao T.
        • Sugimachi K.
        • et al.
        Relationship between biologic behavior and phenotypic expression in intramucosal gastric carcinomas.
        Hum Pathol. 2002; 33: 80-86
        • Koseki K.
        • Takizawa T.
        • Koike M.
        • et al.
        Distinction of differentiated type early gastric carcinoma with gastric type mucin expression.
        Cancer. 2000; 89: 724-732
        • Yoshida N.
        • Doyama H.
        • Yano T.
        • et al.
        Early gastric cancer detection in high-risk patients: a multicentre randomised controlled trial on the effect of second-generation narrow band imaging.
        Gut. 2021; 70: 67-75
        • Kotani S.
        • Miyaoka Y.
        • Fujiwara A.
        • et al.
        Intestinal-type gastric adenocarcinoma without Helicobacter pylori infection successfully treated with endoscopic submucosal dissection.
        Clin J Gastroenterol. 2016; 9: 228-232
        • Yoshii S.
        • Hayashi Y.
        • Takehara T.
        Helicobacter pylori-negative early gastric adenocarcinoma with complete intestinal mucus phenotype mimicking verrucous gastritis.
        Dig Endosc. 2017; 29: 235-236
        • Ozaki Y.
        • Suto H.
        • Nosaka T.
        • et al.
        A case of Helicobacter pylori-negative intramucosal well-differentiated gastric adenocarcinoma with intestinal phenotype.
        Clin J Gastroenterol. 2015; 8: 18-21
        • Tatsugami M.
        • Ito M.
        • Tanaka S.
        • et al.
        Bile acid promotes intestinal metaplasia and gastric carcinogenesis.
        Cancer Epidemiol Biomarkers Prev. 2012; 21: 2101-2107
        • Matsuhisa T.
        • Arakawa T.
        • Watanabe T.
        • et al.
        Relation between bile acid reflux into the stomach and the risk of atrophic gastritis and intestinal metaplasia: a multicenter study of 2283 cases.
        Dig Endosc. 2013; 25: 519-525
        • Schlemper R.J.
        • Riddell R.H.
        • Kato Y.
        • et al.
        The Vienna classification of gastrointestinal epithelial neoplasia.
        Gut. 2000; 47: 251-255
        • Warren J.R.
        • Marshall B.
        Unidentified curved bacilli on gastric epithelium in active chronic gastritis.
        Lancet. 1983; 1: 1273-1275
        • Plummer M.
        • Franceschi S.
        • Vignat J.
        • et al.
        Global burden of gastric cancer attributable to Helicobacter pylori.
        Int J Cancer. 2015; 136: 487-490
        • Kato M.
        • Kaise M.
        • Yonezawa J.
        • et al.
        Magnifying endoscopy with narrow-band imaging achieves superior accuracy in the differential diagnosis of superficial gastric lesions identified with white-light endoscopy: a prospective study.
        Gastrointest Endosc. 2010; 72: 523-529
        • Friedl W.
        • Caspari R.
        • Sengteller M.
        • et al.
        Can APC mutation analysis contribute to therapeutic decisions in familial adenomatous polyposis? Experience from 680 FAP families.
        Gut. 2001; 48: 515-521
        • Nieuwenhuis M.H.
        • De Vos Tot Nederveen Cappel W.
        • Botma A.
        • et al.
        Desmoid tumors in a Dutch cohort of patients with familial adenomatous polyposis.
        Clin Gastroenterol Hepatol. 2008; 6: 215-219
        • Uchino S.
        • Ishikawa H.
        • Miyauchi A.
        • et al.
        Age- and gender-specific risk of thyroid cancer in patients with familial adenomatous polyposis.
        J Clin Endocrinol Metab. 2016; 101: 4611-4617
        • Kennedy R.D.
        • Potter D.D.
        • Moir C.R.
        • et al.
        The natural history of familial adenomatous polyposis syndrome: a 24 year review of a single center experience in screening, diagnosis, and outcomes.
        J Pediatr Surg. 2014; 49: 82-86
        • Michils G.
        • Tejpar S.
        • Thoelen R.
        • et al.
        Large deletions of the APC gene in 15% of mutation-negative patients with classical polyposis (FAP): a Belgian study.
        Hum Mutat. 2005; 25: 125-134
        • Nagase H.
        • Miyoshi Y.
        • Horii A.
        • et al.
        Correlation between the location of germ-line mutations in the APC gene and the number of colorectal polyps in familial adenomatous polyposis patients.
        Cancer Res. 1992; 52: 4055-4057
        • Nugent K.P.
        • Phillips R.K.
        • Hodgson S.V.
        • et al.
        Phenotypic expression in familial adenomatous polyposis: partial prediction by mutation analysis.
        Gut. 1994; 35: 1622-1623
        • Dobbie Z.
        • Spycher M.
        • Mary J.L.
        • et al.
        Correlation between the development of extracolonic manifestations in FAP patients and mutations beyond codon 1403 in the APC gene.
        J Med Genet. 1996; 33: 274-280
        • Wallis Y.L.
        • Morton D.G.
        • McKeown C.M.
        • et al.
        Molecular analysis of the APC gene in 205 families: extended genotype-phenotype correlations in FAP and evidence for the role of APC amino acid changes in colorectal cancer predisposition.
        J Med Genet. 1999; 36: 14-20

      Linked Article

      • Finding the needle in a haystack: approach to detection of high-risk gastric lesions in familial adenomatous polyposis
        Gastrointestinal EndoscopyVol. 94Issue 6
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          Familial adenomatous polyposis (FAP) is known as a hereditary colorectal cancer syndrome. Although the description is historically precise, given the near-universal risk of colorectal cancer unless colectomy is performed, perhaps it should be rebranded as a GI neoplasia syndrome. Risk-reducing surgical removal of the colorectum, facilitated by the presymptomatic identification of affected relatives, followed by postoperative lower GI surveillance of the remaining rectum or ileal pouch, has resulted in a substantial reduction in the incidence of and mortality from colorectal cancer in FAP.
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