Background and Aims
Familial adenomatous polyposis (FAP) is characterized by high risks of colonic and
extracolonic tumors. Recent studies have suggested a rising risk for gastric cancer
(GC). We sought to define the spectrum of premalignant gastric polyps in FAP, focusing
on high-grade dysplasia (HGD).
Methods
The gastric phenotypes of 118 patients diagnosed with FAP or attenuated FAP in our
Hereditary Gastrointestinal Cancer Registry were retrospectively reviewed. To analyze
the clinical features associated with the diagnosis of HGD, we established an age-
and sex-matched control group of FAP patients from our cohort without gastric HGD
in a 4:1 ratio.
Results
The spectrum and frequency of gastric polyps in individuals with FAP included fundic
gland polyps (67.9%), hyperplastic polyps/foveolar hyperplasia (19.6%), tubular adenomas
(15.2%), foveolar adenomas (10.7%), and pyloric gland adenomas (6.3%). Ten patients
(8.9%) exhibited gastric HGD at a mean age of 55 ± 13 years, and HGD was seen in all
polyp types. When compared with control subjects, HGD was associated with a high diversity
of gastric polyp histology, prior low-grade dysplasia, severe gastric polyposis, and
prior Whipple surgery (P = 2.0E-5, .003, .024, and .04, respectively). Two patients (1.7%) with HGD were diagnosed
with GC. However, the remaining 8 patients with HGD have been under surveillance for
an average of 5.8 ± 4.5 years without progression to GC.
Conclusions
Gastric HGD in FAP may be more common than previously appreciated. The natural history
of HGD is variable, and most patients with HGD do not appear to progress to GC.
Graphical abstract
Graphical Abstract
Abbreviations:
AFAP (attenuated familial adenomatous polyposis), APC (adenomatous polyposis coli), CRC (colorectal cancer), FA (foveolar adenoma), FAP (familial adenomatous polyposis), FGP (fundic gland polyp), FH (foveolar hyperplasia), GC (gastric cancer), HGD (high-grade dysplasia), HP (hyperplastic polyp), LGD (low-grade dysplasia), PGA (pyloric gland adenoma), TA (tubular adenoma)To read this article in full you will need to make a payment
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References
- Extracolonic manifestations of hereditary colorectal cancer syndromes.Clin Colon Rectal Surg. 2008; 21: 263-272
- Extracolonic manifestations of familial adenomatous polyposis: desmoid tumours, and upper gastrointestinal adenomas and carcinomas.Scand J Gastroenterol. 1998; 225: 85-91
- ACG clinical guideline: genetic testing and management of hereditary gastrointestinal cancer syndromes.Am J Gastroenterol. 2015; 110: 223-262
- Familial adenomatous polyposis.Am J Gastroenterol. 2006; 101: 385-398
- The risk of upper gastrointestinal cancer in familial adenomatous polyposis.Gastroenterology. 1992; 102: 1980-1982
- Risk of gastric cancer among Korean familial adenomatous polyposis patients. Report of three cases.Dis Colon Rectum. 1992; 35: 996-998
- Gastric cancer in FAP: a concerning rise in incidence.Fam Cancer. 2017; 16: 371-376
- Gastric tumours in FAP.Fam Cancer. 2017; 16: 363-369
- Endoscopic and histologic features associated with gastric cancer in familial adenomatous polyposis.Gastrointest Endosc. 2019; 89: 961-968
- Hereditary and familial colon cancer.Gastroenterology. 2010; 138: 2044-2058
- Duodenal adenomatosis in familial adenomatous polyposis.Gut. 2004; 53: 381-386
- Sporadic fundic gland polyps: common gastric polyps arising through activating mutations in the beta-catenin gene.Am J Pathol. 2001; 158: 1005-1010
- British Society of Gastroenterology. The management of gastric polyps.Gut. 2010; 59: 1270-1276
- Surveillance and management of upper gastrointestinal disease in familial adenomatous polyposis.Fam Cancer. 2006; 5: 263-273
- 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
- Dysplastic changes in gastric fundic gland polyps of patients with familial adenomatous polyposis.Ital J Gastroenterol Hepatol. 1999; 31: 192-197
- Fundic gland polyps in familial adenomatous polyposis: neoplasms with frequent somatic adenomatous polyposis coli gene alterations.Am J Pathol. 2000; 157: 747-754
- Fundic gland polyp dysplasia is common in familial adenomatous polyposis.Clin Gastroenterol Hepatol. 2008; 6: 180-185
- Dysplasia and dysregulation of proliferation in foveolar and surface epithelia of fundic gland polyps from patients with familial adenomatous polyposis.Am J Surg Pathol. 1998; 22: 293-298
- Role of upper gastrointestinal surveillance in patients with familial adenomatous polyposis.Gastrointest Endosc Clin North Am. 1997; 7: 99-111
- Upper gastrointestinal disease in patients with familial adenomatous polyposis.Br J Surg. 1998; 85: 742-750
- Gastric adenomas in familial adenomatous polyposis are common, but subtle, and have a benign course.Hered Cancer Clin Pract. 2014; 12: 4
- Gastric adenomas: intestinal-type and gastric-type adenomas differ in the risk of adenocarcinoma and presence of background mucosal pathology.Am J Surg Pathol. 2002; 26: 1276-1285
- Genetic alteration of colorectal adenoma-carcinoma sequence among gastric adenocarcinoma and dysplastic lesions in a patient with attenuated familial adenomatous polyposis.Mol Genet Genom Med. 2020; 8: e1348
- Gastric adenocarcinoma associated with fundic gland polyps in a patient with attenuated familial adenomatous polyposis.Am J Gastroenterol. 1999; 94: 2275-2281
- Gastric adenocarcinoma and dysplasia in fundic gland polyps of a patient with attenuated adenomatous polyposis coli.Gastroenterology. 1997; 113: 659-663
- Diagnosis, surveillance, and treatment strategies for familial adenomatous polyposis: rationale and update.Eur J Gastroenterol Hepatol. 2014; 26: 255-262
- Germline mutations in APC and MUTYH are responsible for the majority of families with attenuated familial adenomatous polyposis.Clin Genet. 2007; 71: 427-433
- Attenuated familial adenomatous polyposis: results from an international collaborative study.Colorectal Dis. 2010; 12: e243-e249
- The 2019 WHO classification of tumours of the digestive system.Histopathology. 2020; 76: 182-188
- Gastric polyps: classification and management.Arch Pathol Lab Med. 2008; 132: 633-640
- Multicenter experience with upper gastrointestinal polyps in pediatric patients with familial adenomatous polyposis.Am J Gastroenterol. 2004; 99: 681-686
- Gastric polyps: a review of clinical, endoscopic, and histopathologic features and management decisions.Gastroenterol Hepatol. 2013; 9: 640-651
- High-grade dysplasia in sporadic fundic gland polyps: clinically relevant or not?.Eur J Gastroenterol Hepatol. 2003; 15: 1153-1156
- High-grade dysplasia in sporadic fundic gland polyps: a case report and review of the literature.Eur J Gastroenterol Hepatol. 2003; 15: 1229-1233
- Pyloric gland adenoma: an entity distinct from gastric foveolar type adenoma.Am J Surg Pathol. 2009; 33: 186-193
- Gastric polyps; their morphological and endoscopical characteristics and relation to gastric carcinoma.Acta Pathol Microbiol Immunol Scand A. 1982; 90: 221-228
- Depressed adenoma of the stomach.Cancer. 1988; 62: 2197-2202
- Malignant transformation of benign epithelial gastric polyps.Am J Gastroenterol. 1995; 90: 2152-2159
- Association between histologic type of polyp and carcinoma in the stomach.Gastrointest Endosc. 1992; 38: 481-484
- Gastric polyposis and malignancy.Br J Surg. 1986; 73: 532-533
- Gastric pyloric gland adenoma: a multicentre clinicopathological study of 67 cases.Histopathology. 2018; 72: 1007-1014
- Pyloric gland adenoma: a clinico-pathological analysis of 90 cases.Virch Arch. 2003; 442: 317-321
- Immunohistochemical analysis of pyloric gland adenomas using a series of Mucin 2, Mucin 5AC, Mucin 6, CD10, Ki67 and p53.Virch Arch. 2010; 457: 529-536
- Why is the hyperplastic polyp a marker for the precancerous condition of the gastric mucosa?.Virch Arch. 2006; 448: 80-84
- Gastric polyps: relationship of size and histology to cancer risk.Am J Gastroenterol. 1996; 91: 714-717
- Malignant transformation of gastric hyperplastic polyps.Am J Gastroenterol. 1987; 82: 1016-1025
- Possible neoplastic transformation within gastric hyperplastic polyp: application of endoscopic polypectomy.Surg Endosc. 1995; 9: 714-718
- Carcinoma in gastric hyperplastic polyps: a phenotypic study.Dig Dis Sci. 1996; 41: 377-386
- Risk of neoplastic change in large gastric hyperplastic polyps and recurrence after endoscopic resection.Endoscopy. 2020; 52: 444-453
- Malignant transformation of foveolar hyperplastic polyp of the stomach: a histopathological study.Med Oncol. 2011; 28: 941-944
- Surveillance for pathology associated with cancer on endoscopy (SPACE): criteria to identify high-risk gastric polyps in familial adenomatous polyposis.Gastrointest Endosc. 2020; 92: 755-762
- Gastric foveolar hyperplasia in patients with cancer of the intact stomach.Surg Laparosc Endosc. 1994; 4: 196-199
- Long-term follow-up of patients with familial adenomatous polyposis undergoing pancreaticoduodenal surgery.J Gastrointest Surg. 2002; 6: 671-675
- Gastric epithelial dysplasia in the natural history of gastric cancer: a multicenter prospective follow-up study. Interdisciplinary Group on Gastric Epithelial Dysplasia.Gastroenterology. 1994; 107: 1288-1296
- Diagnosis and management of gastric dysplasia.Korean J Intern Med. 2016; 31: 201-209
- The management of gastric polyps.Gut. 2010; 59: 1270-1276
- High grade dysplasia of the gastric mucosa: a marker for gastric carcinoma.Gut. 1990; 31: 977-983
- Gastric dysplasia. A follow-up study.Am J Gastroenterol. 1993; 88: 1714-1719
- Gastric dysplasia. A histological follow-up study.Am J Surg Pathol. 1987; 11: 788-796
- Clinical significance of gastric dysplasia: a multicenter follow-up study.Endoscopy. 1993; 25: 265-268
- Risk of gastric carcinoma in patients with mucosal dysplasia associated with atrophic gastritis: a follow up study.J Clin Pathol. 1996; 49: 979-984
- Gastric cancer risk in patients with premalignant gastric lesions: a nationwide cohort study in the Netherlands.Gastroenterology. 2008; 134: 945-952
- High-grade dysplasia associated with fundic gland polyposis in a familial adenomatous polyposis patient, with special reference to APC mutation profiles.Mod Pathol. 2004; 17: 1421-1426
References
- Upper gastrointestinal cancer in patients with familial adenomatous polyposis.Lancet. 1989; 2: 783-785
- VarSome: the human genomic variant search engine.Bioinformatics. 2019; 35: 1978-1980
- ClinVar: improving access to variant interpretations and supporting evidence.Nucleic Acids Res. 2018; 46: D1062-D1067
- The relationship between frequencies of extracolonic manifestations and the position of APC germline mutation in patients with familial adenomatous polyposis.Jpn J Clin Oncol. 2000; 30: 82-88
- Nine novel APC mutations in Italian FAP patients.Hum Mutat. 2001; 17: 434-435
- The genetic basis of familial adenomatous polyposis and its implications for clinical practice and risk management.Appl Clin Genet. 2015; 8: 95-107
Article info
Publication history
Published online: September 13, 2022
Accepted:
September 3,
2022
Received:
June 29,
2022
Footnotes
DISCLOSURE: All authors disclosed no financial relationships.
Identification
Copyright
© 2023 by the American Society for Gastrointestinal Endoscopy
