VHJOE Editor:

John Deutsch, MD
St. Mary's Duluth Clinic

International Editor:

Manoop S. Bhutani, MD
MD Anderson Cancer Center
Houston, TX

Editorial Board:

William R. Brugge, MD
Massachusetts General Hospital

Peter R. McNally, DO
Denver, CO

Thomas J. Savides, MD
University of California,
San Diego

C. Mel Wilcox, MD
University of Alabama, Birmingham

Video capture on VHS tape and digitization using Adobe Premiere 1.5

Abstract:

A patient with familial adenomatous polyposis and multiple upper intestinal adenomas including dysplastic fundic polyps is presented and management discussed.

Case:

A 44-year-old woman with familial adenomatous polyposis (FAP) had endoscopic surveillance of her upper gastrointestinal tract:

She was a member of a large family with FAP/Gardnerís syndrome. Five years prior to this encounter she had a total colectomy and partial resection of an intraabdominal desmoid tumors. She had previous upper endoscopies which had revealed multiple duodenal and gastric adenomas as well as fundic gland polyps. An enlarged right adrenal gland had previously been identified with biopsy suggesting adenoma.

She had a history of early breast cancer and had undergone a mastectomy.

Her APC gene had been sequenced and a mutation was identified as: 4393delAG

Family History includes multiple family members over 3 generations with manifestations of FAP.

Medications included Tamoxifen 10 mg a day.

Her physical exam was significant for truncal obesity, but no other findings outside of the sequelae of previous colon and breast surgery.

Endoscopic surveillance of the upper gastrointestinal tract was performed using Olympus GIF H180 gastroscope. The ampulla was examined using an Olympus JF 160 duodenoscope. Figure 1 shows the duodenum, Figure 2 the ampulla, Video 1 shows the gastric antrum and Video 2 shows the gastric fundus. Biopsies of the duodenal wall, ampulla and antrum revealed adenomatous dysplasia (Figures 3-5). Biopsies of the proximal stomach revealed fundic glands also with low grade adenomatous dysplasia (Figure 6).

She is currently involved in an ongoing upper gastrointestinal surveillance program with removal of all visible adenomas using endoscopic methods.

Figure 1
Figure 2

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Video 2

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Figure 3a
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Figure 5a
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Figure 6a
Figure 6b

Discussion

Gardner's Syndrome, adenomatous polyposis coli (APC), and familial adenomatous polyposis (FAP) are terms for an inherited cancer syndrome involving mutations on chromosome 5q21-q221-3. This condition is expressed as multiple colon polyps, a high risk of colon cancer development and various extracolonic manifestations.

The inherited defect is generally a truncation mutation in the APC gene. This large gene consists of over 8,000 nucleotides arranged in 15 exons. In addition to colonic disease, the lifetime risk of an upper GI malignancy in FAP is approximately 5-10%. Benign manifestations of FAP include desmoids tumors, adrenal adenomas, osteomas, and fundic gland polyps. Fundic gland polyposis in this syndrome is extremely common, occurring in up to 90% of FAP patients1,4.

Since duodenal and gastric cancers can occur in APC, surveillance of the upper gastrointestinal tract is recommended in these patients5,6. However, the fundic gland polyposis creates a somewhat unique problem in that the polyps may be extensive, dysplasia may be common, but the overall gastric cancer risk in the fundic glands is relatively low7.

Fundic gland polyps are small sessile lesions that occur in the acid producing part of the stomach. They can be broadly broken down into two categories- sporadic and those associated with APC. Sporadic fundic gland polyps are being found in increasing frequency, possibly related to the widespread use of proton pump inhibitor medications8. These sporadic polyps often contain mutations in the beta-catenin gene9. It is rare to develop dysplasia in sporadic fundic gland polyps. However, when dysplasia is found in sporadic fundic polyps, reports suggest that there frequently is an acquired mutation in the FAP gene10. A few case reports suggest progression of sporadic fundic gland polyps from low grade to high grade dysplasia11,12, but cancer rarely, if ever, occurs.

In contrast to the sporadic polyps, fundic gland polyposis in FAP may show low grade dysplasia in 40% of patients8. High grade dysplasia has been reported in 3%8 and cancer has been reported to occur in fundic gland polyps of patients with FAP13.

In the duodenum, the modified Spigelman classification scheme (Table 1) helps guide management of adenomas in FAP patients and can be used as a guide when considering aggressive measures. Surgery (duodenectomy or pancreatoduodenectomy) is recommended by some authors for a score of 9 or more14,15. However, the guidelines for gastrectomy in fundic gland dysplasia in FAP are less well defined. Periodic surveillance rather than prophylactic surgery is generally recommended, with removal of the largest fundic polyps, and daily use of proton pump inhibitor medicines8.

This patient illustrates the findings of premalignant upper gastrointestinal dysplasia as found in FAP. Careful follow up surveillance is being performed in this patient.

Table 1: Spigelman Classification Scheme

Column A (1 point) B (2 points) C (3 points)
Polyp
Number
1 - 4 5 - 20 More than 20
Polyp
Size in mm
Less than 4 5 - 10 Greater than 10
Polyp
Histology
Tubular Tubulovillous Villous
Polyp
Dysplasia
Low Grade   High Grade

References:

1. Galiatsatos P, Foulkes WD. Familial adenomatous polyposis. Am J Gastroenterol. 2006 101:385-98. <Related link>

2. Fearnhead NS, Britton MP, Bodmer WF. The ABC of APC. Hum Mol Genet. 2001 10:721-33. <Related link>

3. Polakis P. The adenomatous polyposis coli (APC) tumor suppressor. Biochim Biophys Acta. 1997 1332:F127-47. <Related link>

4. 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 35:1170-3. <Related link>

5. Hirota WK, Zuckerman MJ, Adler DG, Davila RE, Egan J, Leighton JA, Qureshi WA, Rajan E, Fanelli R, Wheeler-Harbaugh J, Baron TH, Faigel DO. ASGE guideline:the role of endoscopy in the surveillance of premalignant conditions of the upper GI tract. Gastrointest Endosc 2006; 563:570-580. <Related link>

6. Gallagher MC, Phillips RK, Bulow S. Surveillance and management of upper gastrointestinal disease in Familial Adenomatous Polyposis. Fam Cancer. 2006;5(3):263-273. <Related link>

7. Bianchi LK, Burke CA, Bennett AE, Lopez R, Hasson H, Church JM. Fundic gland polyp dysplasia is common in familial adenomatous polyposis. Clin Gastroenterol Hepatol. 2008 6:180-185. <Related link>

8. Freeman HJ. Proton pump inhibitors and an emerging epidemic of gastric fundic gland polyposis. World J Gastroenterol. 2008 14:1318-1320 <Related link>

9. Torbenson M, Lee JH, Cruz-Correa M, Ravich W, Rastgar K, Abraham SC, Wu TT Sporadic fundic gland polyposis: a clinical, histological, and molecular analysis. Mod Pathol. 2002 15:718-723. <Related link>

10. Abraham SC, Park SJ, Mugartegui L, Hamilton SR, Wu TT. Sporadic fundic gland polyps with epithelial dysplasia : evidence for preferential targeting for mutations in the adenomatous polyposis coli gene. Am J Pathol. 2002 161:1735-1742 <Related link>

11. Stolte M, Vieth M, Ebert MP. High-grade dysplasia in sporadic fundic gland polyps: clinically relevant or not? Eur J Gastroenterol Hepatol. 2003 15:1153-1156. <Related link>

12. Jalving M, Koornstra JJ Gotz JM, van der Waaij LA, deJong 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 15:1229-1233. <Related link>

13. Garrean S, Hering J, Saied A, Jani J, Espat NJ. Gastric adenocarcinoma arising from fundic gland polyps in a patient with familial adenomatous polyposis syndrome. Am Surg. 2008 74:79-83. <Related link>

14. Saurin J, Gutknecht C, Napoleon B, Chavillion A, Ecochard R, Scoazec JY, Ponchon T, and Chayvialle JA. Surveillance of duodenal adenomas in familial adenomatous polyposis reveals high cumulative risk of advanced disease. J Clin Oncol 2004; 22:493-498. <Related link>

15. Burke C. Risk Stratification for Periampullary Carcinoma in Patients With Familial Adenomatous Polyposis: Does Theodore Know What to Do Now? Gastroenterology 2001; 121:1246-1248. <Related link>

 

 

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