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Arch Surg. 2007;142(9):902.

Answer: Serrated Adenomatous Polyposis
Over the last 15 years, better understanding of the relationship between colorectal polyps and colorectal cancer has challenged the traditional neoplastic pathway from adenoma to carcinoma.¹ Historically, clinicians have considered hyperplastic polyps to have no malignant potential. However, in 1990, pathologists Longacre and Fenoglio-Preiser² described mixed hyperplastic adenomatous polyps that demonstrated serrated glands with varying degrees of dysplasia. These so-called serrated adenomas were identified throughout the colon, sometimes in association with hyperplastic polyposis and frank carcinoma. Most serrated adenomas are in the sigmoid (20%) and rectum (33%), with a prevalence of 1% to 7% at colonoscopy.^3-4 Studies of their morphology and classification have led investigators to propose a "serrated neoplasia pathway."^5-6

Serrated adenomatous polyposis was described by Torlakovic and Snover⁷ in patients with putative hyperplastic polyposis with or without carcinoma. Endoscopic examination revealed sheets of colorectal polyps consistent with familial adenomatous polyposis (FAP), but pathologic examination showed apparent hyperplasia and morphologic evidence of serrated adenoma. Torlakovic and Snover noted that 47% of cases of hyperplastic/metaplastic polyposis in the literature were associated with adenocarcinoma, giving credence to the hypothesis that serrated adenomas are premalignant lesions. Because our 57-year-old patient had biopsy-proven serrated adenoma, endoscopic evidence of more than 100 polyps, and no family history of FAP, the most reasonable diagnosis was serrated adenomatous polyposis.

With the sporadic loss of the second copy of the tumor suppression gene adenomatous polyposis coli, patients with FAP develop multiple adenomatous polyps (>100), usually with progression to colorectal carcinoma by their late thirties.¹ In addition, these patients are at risk for extracolonic neoplasms.^{1, 6} Patients with FAP have a low incidence of serrated adenoma (2.2% of biopsied polyps) and are more likely to have tubular adenoma (83%).⁸

Hereditary nonpolyposis colorectal cancer syndrome tends to occur in patients in their fifth decade who do not have polyposis (<100 polyps). With 1 defective DNA mismatch gene already, these patients develop colorectal cancer when they acquire mutations in the second copy of mismatch repair genes, which results in accumulation of genomic mutations.¹

Hereditary mixed polyposis syndrome, an autosomal dominant disease with high penetrance, is associated with increased risk of colorectal cancer. Hereditary mixed polyposis syndrome was identified initially in a large Ashkenazi Jewish family in 1989.⁹ Patients usually have fewer than 15 colon polyps at initial colonoscopy, with different histological subtypes that include serrated adenoma. These patients present with their first polyp at a mean age of 28 years; colorectal cancer is diagnosed in the fifth or sixth decade of life.

Changing opinions regarding potentially premalignant colorectal polyps have generated several recommendations for the clinician. Closer surveillance is indicated for patients with hyperplastic-appearing polyps larger than 1 cm, more than 20 hyperplastic polyps (especially in a proximal location), or polyps associated with dysplasia. In addition, mixed polyps, serrated adenomas, sessile serrated polyps, or sessile serrated adenomas should be completely excised via colonoscopy, and the patient should undergo close surveillance.¹⁰

AUTHOR INFORMATION

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Correspondence: Anton J. Bilchik, MD, PhD, John Wayne Cancer Institute, 2200 Santa Monica Blvd, Santa Monica, CA 90404 (bilchika{at}jwci.org).

Accepted for Publication: September 7, 2006.

Author Contributions: Study concept and design: Kavanagh. Acquisition of data: Kavanagh, Amadpour, and Bilchik. Analysis and interpretation of data: Ahmad. Drafting of the manuscript: Kavanagh. Critical revision of the manuscript for important intellectual content: Ahmad, Amadpour, and Bilchik. Administrative, technical, and material support: Kavanagh and Ahmad. Study supervision: Bilchik.

Financial Disclosure: None reported.

Funding/Support: This work was supported by funding from the Rod Fasone Memorial Cancer Fund, Indianapolis, Indiana; the Henry L. Guenther Foundation, Los Angeles, California; the William Randolph Hearst Foundation, San Francisco, California; the Davidow Charitable Fund, Los Angeles; The Point Grey Charitable Trust, Gary Coull Trustee, Hong Kong, China; and Mr and Mrs Sheldon E. Stunkel and Carolyn Dirks, Los Angeles.

REFERENCES

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1. Burgart LJ. Colorectal polyps and other precursor lesions: need for an expanded view. Gastroenterol Clin North Am. 2002;31(4):959-970. FULL TEXT | PUBMED 2. Longacre TA, Fenoglio-Preiser CM. Mixed hyperplastic adenomatous polyps/serrated adenoma: a distinct form of colorectal neoplasia. Am J Surg Pathol. 1990;14(6):524-537. WEB OF SCIENCE | PUBMED 3. Chandra A, Sheikh AA, Cerar A; et al. Clinico-pathological aspects of colorectal serrated adenomas. World J Gastroenterol. 2006;12(17):2770-2772. WEB OF SCIENCE | PUBMED 4. Jaramillo E, Watanabe M, Rubio C; et al. Small colorectal serrated adenomas: endoscopic findings. Endoscopy. 1997;29(1):1-3. WEB OF SCIENCE | PUBMED 5. Torlakovic E, Skovlund E, Snover DC; et al. Morphologic reappraisal of serrated polyps. Am J Surg Pathol. 2003;27(1):65-81. FULL TEXT | WEB OF SCIENCE | PUBMED 6. Jass JR. Serrated route to colorectal cancer: back street or super highway? J Pathol. 2001;193(3):283-285. FULL TEXT | WEB OF SCIENCE | PUBMED 7. Torlakovic E, Snover DC. Serrated adenomatous polyposis in humans. Gastroenterology. 1996;110(3):748-755. FULL TEXT | WEB OF SCIENCE | PUBMED 8. Matsumoto T, Iida M, Kobori Y; et al. Serrated adenoma in familial adenomatous polyposis: relation to germline APC gene mutation. Gut. 2002;50(3):402-404. FREE FULL TEXT 9. Rozen P, Samuel Z, Brazowski E. A prospective study of the clinical, genetic, screening, and pathologic features of a family with hereditary mixed polyposis syndrome. Am J Gastroenterol. 2003;98(10):2317-2320. FULL TEXT | WEB OF SCIENCE | PUBMED 10. Cunningham KS, Riddell RH. Serrated mucosal lesions of the colorectum. Curr Opin Gastroenterol. 2006;22(1):48-53. WEB OF SCIENCE | PUBMED

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Maihgan A. Kavanagh, Aziz Ahmad, Moe Amadpour, and Anton J. Bilchik
Arch Surg. 2007;142(9):901.
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