Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Familial Adenomatous Polyposis Workup

  • Author: Mohammad Wehbi, MD; Chief Editor: BS Anand, MD  more...
 
Updated: Mar 06, 2015
 

Approach Considerations

2015 ACG guidelines on genetic testing and management of hereditary gastrointestinal cancer syndromes

The American College of Gastroenterology (ACG) released the following recommendations for the management of patients with hereditary gastrointestinal cancer syndromes—and they specifically discuss genetic testing and management of Lynch syndrome, familial adenomatous polyposis (FAP), attenuated familial adenomatous polyposis (AFAP), MUTYH-associated polyposis (MAP), Peutz-Jeghers syndrome, juvenile polyposis syndrome, Cowden syndrome, serrated (hyperplastic) polyposis syndrome, hereditary pancreatic cancer, and hereditary gastric cancer[13] :

  • The initial assessment is the collection of a family history of cancers and premalignant gastrointestinal conditions and should provide enough information to develop a preliminary determination of the risk of a familial predisposition to cancer.
  • Age at diagnosis and lineage (maternal and/or paternal) should be documented for all diagnoses, especially in first- and second-degree relatives.
  • When indicated, genetic testing for a germline mutation should be done on the most informative candidate(s) identified through the family history evaluation and/or tumor analysis to confirm a diagnosis and allow for predictive testing of at-risk relatives.
  • Genetic testing should be conducted in the context of pre- and post-test genetic counseling to ensure the patient's informed decision making.
  • Patients who meet clinical criteria for a syndrome as well as those with identified pathogenic germline mutations should receive appropriate surveillance measures in order to minimize their overall risk of developing syndrome-specific cancers.
Next

Imaging Studies

Flexible sigmoidoscopy: Visualization of more than 100 polyps usually establishes the diagnosis because of the diffuse nature of the polyposis.

Colonoscopy is usually reserved for patients thought to have AAPC because of the higher incidence of right-sided polyps (proximal colonic involvement).

Front- and side-viewing esophagogastroduodenoscopy is recommended if sigmoidoscopy or the colonoscopy establishes the diagnosis of FAP. It is an essential component of the surveillance program in FAP, especially in that the second most common cancer involves the duodenum. This test helps to evaluate the presence of gastric, duodenal, and periampullary adenomas. It is recommended every 1-3 years. Benign gastric polyps are part of the spectrum of FAP. They are usually confined to the fundus.

Dental and skull x-ray films are recommended in patients thought to have a Gardner variant of FAP. The films help to detect osteomas and dental abnormalities.

Barium studies may be performed to visualize intestinal polyposis.

Periodic ultrasounds or abdominal computed tomography scans are used to check for intra-abdominal desmoid tumors and pancreatic cancer.

Periodic ultrasound of the thyroid: This imaging study is considered because of the increased risk of thyroid cancer. It can supplement the recommended annual physical examination of the thyroid.

Previous
Next

Histologic Findings

Characteristic pathology of a polyp from patients with FAP is a tubular adenoma.

Previous
Next

Laboratory Studies

Laboratory tests include the following:

  • Complete blood count (CBC)
  • Alpha-fetoprotein (AFP) blood test - For children with FAP until age 5 years as part of a screening program for hepatoblastoma

Genetic testing

Three genetic tests are available.[11] Patients should receive genetic counseling from a trained individual prior to the performance of these tests.

In vitro protein synthesis assay

This is the genetic test of choice for the proband patient (patient with FAP). This test is commercially available. DNA from peripheral blood is analyzed for a truncated APC gene product.

Because of the size of the APC protein, it is analyzed in 5 overlapping segments. If the proband has a mutation, other family members can be tested (after genetic counseling) for the identical mutation. The test generally has 100% accuracy in detecting other gene carriers in the family.

Gene sequencing

APC gene sequencing is the most accurate test. However, it is hard logistically and, hence, is only reserved for research purposes.

Linkage testing

DNA markers near or in the APC locus are used to identify mutant gene carriers. This test requires 2 affected family members to achieve an appropriate linkage relationship resulting in 90% accuracy. As a result, this is not appropriate logistically

Genetic testing for a germline mutation in the APC gene should be considered in individuals with 10-20 adenomas in their lifetime, furthermore in patients with a strong family history of polyposis; larger numbers of adenomas is associated with a greater the likelihood of FAP.[12, 14, 15, 16]

Counseling and screening of first-degree relatives

Offer genetic counseling before any genetic testing is performed. The patients and their family members should be made aware of the limitations of genetic testing and the associated consequences. Genetic counseling should be performed by someone familiar with FAP and the genetic tests available.

A few patients with clinical FAP have a genetic mutation that cannot be identified, and their first-degree relatives cannot be screened genetically and will require life-time clinical screenings.[17]

Previous
Next

Procedures

Representative polyps should be removed by endoscopic polypectomy to confirm the diagnosis by histologic examination.[2, 18, 19]

Previous
 
 
Contributor Information and Disclosures
Author

Mohammad Wehbi, MD Associate Professor of Medicine, Associate Program Director, Department of Gastroenterology, Emory University School of Medicine; Section Chief of Gastroenterology, Atlanta Veterans Affairs Medical Center

Mohammad Wehbi, MD is a member of the following medical societies: American College of Physicians, American Gastroenterological Association, American Medical Association

Disclosure: Nothing to disclose.

Coauthor(s)

John M Carethers, MD Professor of Medicine, Chief, Division of Gastroenterology, Department of Medicine, University of California, San Diego, School of Medicine

John M Carethers, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for Cancer Research, American College of Gastroenterology, American College of Physicians, American Gastroenterological Association

Disclosure: Nothing to disclose.

Vincent W Yang, MD, PhD R Bruce Logue Professor, Director, Division of Digestive Diseases, Department of Medicine, Professor of Hematology and Oncology, Winship Cancer Institute, Emory University School of Medicine

Vincent W Yang, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, Association of American Physicians, American Gastroenterological Association, American Society for Clinical Investigation

Disclosure: Nothing to disclose.

Kamil Obideen, MD Assistant Professor of Medicine, Division of Digestive Diseases, Emory University School of Medicine; Consulting Staff, Division of Gastrointestinal Endoscopy, Atlanta Veterans Affairs Medical Center

Kamil Obideen, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Jae W Nam, MD Fellow in Gastroenterology, Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine; Consulting Staff, Department of Critical Care, Decatur Hospital

Jae W Nam, MD is a member of the following medical societies: American College of Gastroenterology

Disclosure: Nothing to disclose.

Sunil Dacha, MBBS, MD House Staff, Division of Digestive Disease, Emory University School of Medicine

Sunil Dacha, MBBS, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

BS Anand, MD Professor, Department of Internal Medicine, Division of Gastroenterology, Baylor College of Medicine

BS Anand, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Additional Contributors

John Gunn Lee, MD Director of Pancreaticobiliary Service, Associate Professor, Department of Internal Medicine, Division of Gastroenterology, University of California at Irvine School of Medicine

John Gunn Lee, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Acknowledgements

Simmy Bank, MD Chair, Professor, Department of Internal Medicine, Division of Gastroenterology, Long Island Jewish Hospital, Albert Einstein College of Medicine

Disclosure: Nothing to disclose.

Nicole M Griglione, MD Fellow in Gastroenterology, Department of Medicine, Emory University School of Medicine

Nicole M Griglione, MD is a member of the following medical societies: American Medical Association and Illinois State Medical Society

Disclosure: Nothing to disclose.

References
  1. Schulmann K, Pox C, Tannapfel A, Schmiegel W. The patient with multiple intestinal polyps. Best Practice & Research Clinical Gastroenterology. June 2007. 21(3):409-426. [Full Text].

  2. Dekker E, Boparai KS, Poley JW, et al. High resolution endoscopy and the additional value of chromoendoscopy in the evaluation of duodenal adenomatosis in patients with familial adenomatous polyposis. Endoscopy. 2009 Aug. 41(8):666-9. [Medline].

  3. Zhang J, Ahmad S, Mao Y. BubR1 and APC/EB1 cooperate to maintain metaphase chromosome alignment. J Cell Biol. 2007 Aug 27. 178(5):773-84. [Medline]. [Full Text].

  4. Newton KF, Mallinson EK, Bowen J, et al. Genotype-phenotype correlation in colorectal polyposis. Clin Genet. 2012 Jun. 81(6):521-31. [Medline].

  5. Nieuwenhuis MH, 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 Feb. 6(2):215-9. [Medline].

  6. Will OC, Hansmann A, Phillips RK, et al. Adrenal incidentaloma in familial adenomatous polyposis: a long-term follow-up study and schema for management. Dis Colon Rectum. 2009 Sep. 52(9):1637-44. [Medline].

  7. Ponti G, Losi L, Pellacani G, et al. Wnt pathway, angiogenetic and hormonal markers in sporadic and familial adenomatous polyposis-associated juvenile nasopharyngeal angiofibromas (JNA). Applied Immunohistochemistry & Molecular Morphology. January 25, 2008. 6(2):215-9. [Full Text].

  8. 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 Feb. 6(2):180-5. [Medline].

  9. Tajika M, Nakamura T, Nakahara O, Kawai H, Komori K, Hirai T. Prevalence of adenomas and carcinomas in the ileal pouch after proctocolectomy in patients with familial adenomatous polyposis. J Gastrointest Surg. 2009 Jul. 13(7):1266-73. [Medline].

  10. Wachsmannova-Matelova L, Stevurkova V, Adamcikova Z, Holec V, Zajac V. Different phenotype manifestation of familial adenomatous polyposis in families with APC mutation at codon 1309. Neoplasma. 2009. 56(6):486-9. [Medline].

  11. Duncan RE, Gillam L, Savulescu J, Williamson R, Rogers JG, Delatycki MB. The challenge of developmentally appropriate care: predictive genetic testing in young people for familial adenomatous polyposis. Fam Cancer. 2010 Mar. 9(1):27-35. [Medline].

  12. American Gastroenterological Association. American Gastroenterological Association medical position statement: hereditary colorectal cancer and genetic testing. Gastroenterology. 2001 Jul. 121(1):195-7. [Medline].

  13. Syngal S, Brand RE, Church JM, Giardiello FM, Hampel HL, Burt RW. ACG Clinical Guideline: Genetic Testing and Management of Hereditary Gastrointestinal Cancer Syndromes. Am J Gastroenterol. 2015 Feb. 110(2):223-62. [Medline].

  14. Giardiello FM, Brensinger JD, Petersen GM. AGA technical review on hereditary colorectal cancer and genetic testing. Gastroenterology. 2001 Jul. 121(1):198-213. [Medline].

  15. Rex DK, Johnson DA, Anderson JC, Schoenfeld PS, Burke CA, Inadomi JM. American College of Gastroenterology guidelines for colorectal cancer screening 2009 [corrected]. Am J Gastroenterol. 2009 Mar. 104(3):739-50. [Medline].

  16. Burt RW, Barthel JS, Dunn KB, et al. NCCN clinical practice guidelines in oncology. Colorectal cancer screening. J Natl Compr Canc Netw. 2010 Jan. 8(1):8-61. [Medline].

  17. Lynch PM. Jurisprudential considerations in the evaluation and screening of high-risk patients. Rozen P, Winawer SJ. In Secondary Prevention of Colorectal Cancer. Karger: Basel; 1986. 55-63.

  18. McEwen JE, McCarty K, Reilly PR. A survey of medical directors of life insurance companies concerning use of genetic information. Am J Hum Genet. 1993 Jul. 53(1):33-45. [Medline].

  19. Friederich P, van Heumen BW, Nagtegaal ID, et al. Increased epithelial cell proliferation in the ileal pouch mucosa of patients with familial adenomatous polyposis. Virchows Arch. 2007 Sep. 451(3):659-67. [Medline]. [Full Text].

  20. Durno CA, Wong J, Berk T, Alingary N, Cohen Z, Esplen MJ. Quality of life and functional outcome for individuals who underwent very early colectomy for familial adenomatous polyposis. Dis Colon Rectum. 2012 Apr. 55(4):436-43. [Medline].

  21. Rodriguez-Bigas MA, Vasen HF, O'Malley L, Rosenblatt MJ, Farrell C, Weber TK. Health, life, and disability insurance and hereditary nonpolyposis colorectal cancer. Am J Hum Genet. 1998 Mar. 62(3):736-7. [Medline].

  22. Iaquinto G, Fornasarig M, Quaia M, et al. Capsule endoscopy is useful and safe for small-bowel surveillance in familial adenomatous polyposis. Gastrointest Endosc. 2008 Jan. 67(1):61-7. [Medline].

  23. Johnson MD, Mackey R, Brown N, Church J, Burke C, Walsh RM. Outcome based on management for duodenal adenomas: sporadic versus familial disease. J Gastrointest Surg. 2010 Feb. 14(2):229-35. [Medline].

  24. Ishikawa H, Wakabayashi K, Suzuki S, et al. Preventive effects of low-dose aspirin on colorectal adenoma growth in patients with familial adenomatous polyposis: double-blind, randomized clinical trial. Canc Med. 2012. 2:50-56.

  25. Jacoby RF, Cole CE, Hawk ET, Lubet RA. Ursodeoxycholate/Sulindac combination treatment effectively prevents intestinal adenomas in a mouse model of polyposis. Gastroenterology. 2004 Sep. 127(3):838-44. [Medline].

  26. Parc Y, Desaint B, Flejou JF, Lefevre JH, Serfaty L, Vienne A. The effect of ursodesoxycholic acid on duodenal adenomas in familial adenomatous polyposis: a prospective randomized placebo-control trial. Colorectal Dis. 2012 Jul. 14(7):854-60. [Medline].

  27. Half E, Bercovich D, Rozen P. Familial adenomatous polyposis. Orphanet J Rare Dis. 2009. 4:22. [Medline].

  28. Bresalier RS. Sleisenger and Fordtran's Gastrointestinal and Liver Disease. 2006. 2759-2810.

  29. Nieuwenhuis MH, Douma KF, Bleiker EM, Aaronson NK, Clevers H, Vasen HF. Clinical evidence for an association between familial adenomatous polyposis and type II diabetes. Int J Cancer. 2012 Sep 15. 131(6):1488-9. [Medline].

  30. Tonelli F, Ficari F, Bargellini T, Valanzano R. Ileal pouch adenomas and carcinomas after restorative proctocolectomy for familial adenomatous polyposis. Dis Colon Rectum. 2012 Mar. 55(3):322-9. [Medline].

  31. Brosens LA, Keller JJ, Offerhaus GJ, Goggins M, Giardiello FM. Prevention and management of duodenal polyps in familial adenomatous polyposis. Gut. 2005 Jul. 54(7):1034-43. [Medline]. [Full Text].

  32. Burt R, Neklason DW. Genetic testing for inherited colon cancer. Gastroenterology. 2005 May. 128(6):1696-716. [Medline].

  33. Doxey BW, Kuwada SK, Burt RW. Inherited polyposis syndromes: molecular mechanisms, clinicopathology, and genetic testing. Clin Gastroenterol Hepatol. 2005 Jul. 3(7):633-41. [Medline].

  34. Galiatsatos P, Foulkes WD. Familial adenomatous polyposis. Am J Gastroenterol. 2006 Feb. 101(2):385-98. [Medline].

 
Previous
Next
 
Colectomy specimen obtained from a patient with familial adenomatous polyposis. Note the presence of numerous synchronous adenomatous polyps lining the luminal surface.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.