Fundic gland polyposis

Fundic gland polyposis is a medical syndrome where the fundus of the stomach develops many polyps. The condition has been described both in patients with polyposis conditions of the colon (including familial adenomatous polyposis), and in patients in whom it occurs sporadically.Declich P, Tavani E, Ferrara A, Caruso S, Bellone S. Sporadic fundic gland polyps: clinico-pathologic features and associated diseases. "Pol J Pathol." 2005;56(3):131-7. PMID 16334981]

Clinical presentation

Most patients with fundic gland polyposis do not have any symptoms, and the diagnosis is made on gastroscopy done for other reasons. Retrospective analysis of patients with sporadic fundic gland polyposis shows that a high percentage do have symptoms, but that this is more likely to be related to the underlying disease responsible for the polyposis [Church JM, McGannon E, Hull-Boiner S, Sivak MV, Van Stolk R, Jagelman DG, Fazio VW, Oakley JR, Lavery IC, Milsom JW. Gastroduodenal polyps in patients with familial adenomatous polyposis. Dis Colon Rectum. 1992 Dec;35(12):1170-3. PMID 1335405] . These symptoms include:
*epigastric pain
*nausea
*vomiting
*weight loss

The polyps on endoscopy are usually tiny, numerous and sessileDeclich P, Ambrosiani L, Grassini R, Tavani E, Bellone S, Bortoli A, Gozzini C, Prada A. Fundic gland polyps: a still elusive entity on the eve of the year 2000. "Pol J Pathol." 2000;51(1):3-8. PMID 10833897] , and usually scattered throughout the fundus of the stomach, where parietal cells are more numerous. They have the same colour as the gastric mucosa, and never have a stalk Burt RW. Gastric fundic gland polyps. "Gastroenterology." 2003 Nov;125(5):1462-9. PMID 14598262.] . When the polyps are biopsied, the pathology typically shows shortened gastric pits, and both superficial and deep cystic lesions in the fundic glands. As sometimes parietal cell hyperplasia may develop deep dilations of gland [Declich P, Ambrosiani L, Bellone S, Tavani E, Grassini R, Prada A, Bortoli A, Gozzini C, Omazzi B. Parietal cell hyperplasia with deep cystic dilations: a lesion closely mimicking fundic gland polyps. "Am J Gastroenterol." 2000 Feb;95(2):566-8. PMID 10685784 ] , one should be really strict in the diagnosis of FGPs (i.e. the presence of deep and superficial dilations). Unfrequently, the two lesions may coexist . Foci of dysplasia can sometimes be seen.

Epidemiology and disease associations

Fundic gland polyposis is found in 0.8 to 1.9% of patients who undergo esophagogastroduodenoscopy, and are more common in middle aged women [Weston BR, Helper DJ, Rex DK. Positive predictive value of endoscopic features deemed typical of gastric fundic gland polyps. "J Clin Gastroenterol." 2003 May-Jun;36(5):399-402. PMID 12702980] .

The most important consideration in evaluating patients with fundic gland polyposis is determining whether there is an underlying congenital cause for the condition, or whether the condition was acquired. This is to ascertain the risk of development of gastric cancer, and to ascertain the risk of concomitant colon cancer.

Fundic gland polyposis can be found in association with the following congenital conditions :
*familial adenomatous polyposis
*attenuated familial adenomatous polyposis syndromes
*Peutz-Jeghers syndrome
*Cowden's syndrome
*juvenile polyposis

The following are acquired causes for fundic gland polyposis :
*chronic use of proton pump inhibitors(proposed by some authors, denied by others) [LinksFreeman HJ. Proton pump inhibitors and an emerging epidemic of gastric fundic gland polyposis. "World J Gastroenterol." 2008 Mar 7;14(9):1318-20. PMID 18322941] [Declich P, Omazzi B, Tavani E, Bellone S, Gozzini C, Bortoli A, Prada A. Fundic gland polyps and PPI: the Mozart effect of gastrointestinal pathology? "Pol J Pathol." 2006;57(4):181-2. PMID 17285759] [Vieth M, Stolte M. Fundic gland polyps are not induced by proton pump inhibitor therapy."Am J Clin Pathol." 2001 Nov;116(5):716-20. PMID 11710689 ] [Declich P, Tavani E, Ferrara A, Prada A, Caruso S, Bellone S, Bortoli A, Porcellati M, Gozzini C. Sporadic fundic gland polyps, GERD and omeprazole usage: is there a little piece of information missed? "Pol J Pathol." 2001;52(1-2):63-4. PMID 11505682 ]

*Zollinger-Ellison syndrome [Declich P, Bellone S, Ambrosiani L, Bortoli A, Gozzini C, Tavani E, Grassini R, Prada A. Fundic gland polyps: do they arise as a by-product of hypergastrinemia in patients with Zollinger-Ellison syndrome? "Hum Pathol." 2000 Jul;31(7):889-90. PMID 10923933 ] [Aprile MR, Azzoni C, Gibril F, Jensen RT, Bordi C.Intramucosal cysts in the gastric body of patients with Zollinger-Ellison syndrome. "Hum Pathol." 2000 Feb;31(2):140-8. PMID 10685627]
*atrophic gastritis

"Helicobacter pylori" infection does not correlate with fundic gland polyposis, and may cause polyp regression [Watanabe N, Seno H, Nakajima T, Yazumi S, Miyamoto S, Matsumoto S, Itoh T, Kawanami C, Okazaki K, Chiba T. Regression of fundic gland polyps following acquisition of Helicobacter pylori. "Gut." 2002 Nov;51(5):742-5. PMID 12377817] .

Pathophysiology

The development of polyps depends on the underlying disorder.

In sporadic cases of fundic gland polyposis, there is usually a driving force for parietal cell hypertrophy; for example in chronic proton pump inhibitor use, the cause is up-regulation of gastrin from acid suppression. Mutations in the β-catenin gene are associated as a risk for polyp development [Abraham SC, Nobukawa B, Giardiello FM, Hamilton SR, Wu TT. Sporadic fundic gland polyps: common gastric polyps arising through activating mutations in the beta-catenin gene. Am J Pathol. 2001 Mar;158(3):1005-10. PMID 11238048.]

In familial adenomatous polyposis, the abnormality is a mutation in the APC gene, resulting in its inactivity. Attenuated FAP can occur from other mutations in the APC gene, and causes a phenotype wherein colonic polyps may be few in number

Both the β-catenin gene and the APC gene are involved in the same cell growth signalling pathway, but the APC gene is known to have a significantly higher association with the development of colorectal tumors [Chung DC. The genetic basis of colorectal cancer: insights into critical pathways of tumorigenesis. "Gastroenterology" 2000;119: 854–865. PMID 10982779] .

Cancer risk and the need for screening

There is a risk of development of cancer with fundic gland polyposis Sebastian S, Qasim A, McLoughlin R, O'Morain CA, O'Connor HJ. Fundic gland polyps: not so trivial entity and worth evaluation. "Gastroenterology". 2004 May;126(5):1497-8. PMID 15131828] , but it varies based on the underlying cause of the polyposis. The risk is highest with congenital polyposis syndromes, and is lowest in acquired causesJalving M, Koornstra JJ, Gotz JM, van der Waaij LA, de Jong S, Zwart N, Karrenbeld A, Kleibeuker JH. High-grade dysplasia in sporadic fundic gland polyps: a case report and review of the literature. "Eur J Gastroenterol Hepatol." 2003 Nov;15(11):1229-33. PMID 14560158] . As a result, it is recommend that patients with multiple fundic polyps have a colonoscopy to evaluate the colon . If there are polyps seen on colonoscopy, genetic testing and testing of family members is recommended .

It is still unclear which patients would benefit with surveillance gastroscopy, but most physicians recommend endoscopy every one to three years to survey polyps for dysplasia or cancer . In the event of high grade dysplasia, polypectomy, which is done through the endoscopy, or partial gastrectomy may be recommended. One study showed the benefit of NSAID therapy in regression of gastric polyps, but the efficacy of this strategy (given the side effects of NSAIDs) is still spurious [Esaki M, Matsumoto T, Mizuno M, Kobori Y, Yoshimura R, Yao T, Iida M. Effect of sulindac treatment for attenuated familial adenomatous polyposis with a new germline APC mutation at codon 161: report of a case. "Dis Colon Rectum". 2002 Oct;45(10):1397-402. PMID 12394442] .

References