Introduction
Background
Adenomatous polyps are, by definition, neoplastic. Although benign, they are the direct precursors of adenocarcinomas and follow a predictable cancerous temporal course unless interrupted by treatment. They can be either pedunculated or sessile. Polyps are generally asymptomatic but may occasionally ulcerate and bleed; uncommonly, they may result in obstruction if very large. Adenomas are divided into 3 subtypes based on histologic criteria, as follows: (1) tubular, (2) tubulovillous, and (3) villous. According to World Health Organization (WHO) criteria, villous adenomas are composed of greater than 80% villous architecture. Tubular adenomas are encountered most frequently (80-86%). Tubulovillous adenomas are encountered less frequently (8-16%), and villous adenomas are encountered least frequently (5%).
Endoscopic view of a sessile polyp, which histology studies revealed to be a villous adenoma. Courtesy of H. Chaun, MD.
Endoscopic view of a sessile polyp histologically determined to be a villous adenoma. Courtesy of R. Enns, MD.
Histology of villous adenoma. Fingerlike projections stretching from the surface of a polyp downward with minimal branching. Courtesy of D. Owen, MD.
Histology of villous adenoma. Low-grade dysplasia with loss of mucin, prominent nucleoli, and hyperchromatic and elongated cells. Courtesy of D. Owen, MD.
Villous adenomas are associated more often with larger adenomas and more severe degrees of dysplasia. These adenomas occur more frequently in the rectum and rectosigmoid, although they may occur anywhere in the colon. They generally are sessile structures that appear as velvety or cauliflowerlike projections. Although rare, villous adenomas of the duodenum and the small bowel, particularly at the ampulla, can occur. Villous adenomas are of concern primarily because of the risk of malignant transformation (approximately 15-25% overall but higher once >2 cm).
The primary focus of this article is colonic villous adenomas. Where appropriate, certain aspects of small bowel villous adenomas are addressed.
Pathophysiology
Adenomas are believed to have an abnormal process of cell proliferation and apoptosis. The proliferative component is not confined to the crypt base and accumulates onto the surface and infolds downward. In villous adenomas, mesenchymal proliferation results in longer projections and larger polyps.
Clinical, autopsical, and epidemiological studies provide evidence of adenoma-to-carcinoma progression. The mean age of adenoma diagnosis is 10 years earlier than with carcinoma, and progression to carcinoma takes a minimum of 4 years. Multiple sources have provided evidence for an adenoma-to-carcinoma progression: one third of operative specimens containing colon cancer contain one or more synchronous adenomas. The risk of colon cancer is increased with the number of adenomatous polyps. Adenomatous tissue is frequently found contiguous to frank carcinoma. Patients who refuse polypectomy for adenomas develop colon cancer at a rate of about 4% after 5 years and 14% after 10 years.
Molecular genetic studies also describe an adenoma-to-carcinoma sequence through accumulation of lesions in a variety of genes, with activation of oncogenes and inactivation of tumor suppressor genes. Genetic mutations lead to progressively disordered local DNA replication. The progressive accumulation of multiple genetic mutations results in the transition from normal mucosa to adenoma to severe dysplasia and finally to carcinoma. The K-ras oncogene is described in 9% of small adenomas, 58% of adenomas larger than 1 cm, and 46% of colorectal carcinomas. Inactivation of tumor suppressor genes on arms 5q, 18q, and 17p are thought to be essential in tumorigenesis. The APC gene, on 5q, has an important role in adenoma formation. The gene is mutated in 30-60% of persons with sporadic adenomas and adenocarcinomas. Mutations in the APC gene occur early in adenoma development and are often found in aberrant crypt foci, the earliest identifiable dysplastic crypts.
Mutation on the TP53 gene, on 17p, results in malignant transformation of adenomas. The loss of TP53 is frequent in patients with adenomas (50%) and occurs in more than 75% of patients with adenocarcinomas.
The loss of the DCC (deleted in colon cancer) gene, on 18q, occurs in 50% of patients with adenomas and 70% of patients with carcinomas. The loss of the normal DCC gene is important in the transition from an intermediate adenoma to a late adenoma.
Frequency
United States
The prevalence of adenomas closely parallels the risk of colorectal cancer in a region. Adenomas are found in 30-40% of persons aged 60 years or older; in some areas, as many as 50% have adenomas.
International
In regions of low risk for colon carcinoma (eg, Costa Rica, Columbia), prevalence rates are 12%. This rate increases drastically in high-risk regions (eg, United States, Canada, western Europe, Argentina, New Zealand, Australia) to 30-40%. In some areas, rates approach 50%.
Mortality/Morbidity
The immediate risks of adenomas include hemorrhage, obstruction with intussusception, and, possibly, torsion. However, the main concern is malignant progression of the villous adenoma. Studies have defined the risk of progression of adenomas to adenocarcinoma.
- Precolonoscopy studies show the cumulative risk for carcinoma from polyps larger than 1 cm to be 4%, 14%, and 37% with 5, 10, and 20 years of follow-up, respectively. The risk for persons with carcinoma at sites other than the reference polyp is 4 times greater than that of the general population. Increasing polyp size and villous histology correlate with the development of colorectal cancer. The likelihood that an adenoma contains villous tissue, high-grade dysplasia, or invasive carcinoma is proportional to its size.
- Using complete colonoscopies, the National Polyp Study (NPS) prospectively followed 1418 patients diagnosed with 1 or more adenomas. An incidence reduction rate of 76-90% of colorectal cancers occurred, with only 10-24% of cancers that would be predicted from a reference population. This study found that the only independent predictive factors for progression from adenoma to adenocarcinoma were adenoma size and villous histology. The NPS study defined advanced polyps as larger than 1 cm or as those containing villous tissue or high-grade dysplasia.
- Overall, villous adenomas have a malignant risk of 15-25%. The risk of adenocarcinoma approaches 40% in villous adenomas larger than 4 cm in diameter. Patients with a rectosigmoid adenoma larger than 1 cm (or villous histology) had a 3.6-fold risk of developing adenocarcinoma compared to the general population. Villous adenomas of the ampulla of Vater contain carcinoma in 30-50% of cases, and carcinoma is found in 20-25% of duodenal villous adenomas.
Race
Race is not an independent factor for adenoma prevalence, although region is considered to be a factor.
- This is well described in the Hawaiian-Japanese population, which has much higher rates of adenoma than the Japanese population.
- A similar situation exists with black Americans (higher rates) and black South Africans.
Sex
Generally, adenoma risk is independent of sex, although some authorities suggest a slight male predominance.
Age
The prevalence and distribution of adenomas varies with patient age.
- The prevalence of adenomas increases with age. The prevalence of polyps at 50 years is 30%, at 60 years is 40-50%, and at 70 years is 50-65%.
- Distribution of polyps differs with age. In patients aged 55 years or younger, 75% of polyps 10 mm or larger were located distally. In patients aged 65 years and older, 50% of polyps 10 mm or larger were located proximally.
Clinical
History
Note that the vast majority of patients are asymptomatic and have unremarkable laboratory findings. Approximately two thirds of colorectal polyps are asymptomatic. Any nonspecific intestinal symptoms are more likely to be coincidental. For example, bright red rectal bleeding in a patient in whom a small colonic polyp is eventually found is still most likely to be hemorrhoidal in origin. Polyps greater than 1 cm are more likely to produce symptoms, usually rectal bleeding, abdominal pain, and a change in bowel habits.
- The most common presenting symptom is occult/overt bleeding (hematochezia) with an anemia, which may be microcytic. Polyps may bleed only intermittently into the stromal component, thus accounting for inconsistent findings.
- Nonspecific symptoms include diarrhea, constipation, and flatulence. A change in stool caliber (ie, the classic pencil-thin stools), although still described in older textbooks, is an entirely nonspecific and unreliable symptom. Pencil-thin stools, if truly present, would be secondary to large distal adenomas or frank carcinomas.
- When intense cramping occurs, torsion or episodic intussusception due to larger adenomas may be considered.
- Villous adenomas rarely cause a secretory diarrhea syndrome. The tumor usually is located at the rectosigmoid or rectum and often is 3-4 cm in diameter. Stool volumes of 350-3000 mL are reported and may cause hypovolemia and metabolic imbalances.
- Patients may have a family history of polyps and colon cancer. Using data obtained from the prospective Health Professionals Follow-Up Study, in which men underwent endoscopy between 1986 and 2004, Wark et al examined whether a family history of colorectal cancer is associated with advanced adenoma stage, defined as 1 cm or larger and a histology with villous component or carcinoma in situ, or adenoma multiplicity.1 Twenty-one percent of 3881 patients with adenoma and 13.9% of 24,959 adenoma-free men had a first-degree relative with colorectal cancer. The investigators found a number of positive associations with a family history of colorectal cancer including advanced and advanced adenomas, with the possibility of potential differences due to adenoma location, as well as the number of adenomas and presence of multiple distally located adenomas.1 Wark et al suggested that at the population level, their findings may demonstrate a greater significance of heritable factors in earlier stages of adenoma formation than at stages of adenoma advancement for at least distally located adenomas.1
- Patients with villous adenomas of the ampulla usually present with intermittent or progressive jaundice, abdominal pain, intestinal hemorrhage, or pancreatitis.
Physical
- Patients often have no findings on bedside physical examination.
- Occasionally, a palpable mass is present upon digital rectal examination.
- Jaundice may be present with villous adenoma of the ampulla.
Causes
- Genetic factors: From the NPS data, relatives of patients with polyps have an increased risk of carcinoma. This includes siblings of patients with adenomas detected prior to age 60 years or siblings of patients with adenomas detected at any age if either parent has colorectal cancer. Offer these patients screening colonoscopy every 5 years after age 40 years.
- Lifestyle and diet: Foods and vitamins that have a protective effect against adenomas include dietary fiber, plant foods, carbohydrates, and folate supplementation. Excess fat and alcohol are positively correlated with adenoma risk. A strong association exists between cigarette smoking and adenoma size. Supplemental vitamins C and E are not considered protective.
- Acromegaly: Patients with acromegaly have an increased risk of adenomas and colon cancer. Prevalence rates of 14-35% for adenomas are reported. The mechanism for increased risk is not known.
- Streptococcus bovis bacteremia: This causes an increased risk of adenomas, carcinomas, and, possibly, familial adenomatous polyposis (FAP). These patients should undergo colonoscopy. Patients with endocarditis from Streptococcus agalactiae infection are reported to have an increased risk of rectal villous adenoma and should be evaluated.
- Atherosclerosis and cholesterol: Autopsy studies report a positive correlation between the degree of atherosclerosis and adenoma size, dysplasia, and multiplicity.
- Uterosigmoidostomy sites: Patients who undergo urinary diversion procedures are at increased risk of developing polyps or carcinomas at uterosigmoidostomy sites as many as 38 years later. Prevalence rates of 29% are reported.
- Inflammatory bowel disease (IBD): In patients with IBD who develop carcinomas, 50% of the lesions are found to be juxtaposing serrated or villous adenomas. These possibly are the lesions from which the carcinomas originate. However, a dysplasia-associated lesion or mass is reported to be the premalignant lesion of adenocarcinoma in ulcerative colitis, in which the adenoma-carcinoma sequence is not preserved.
- Other conditions: Historically, some conditions have been thought to be correlated with increased incidence of polyps. These conditions include acrochordons (skin tags), breast cancer, and cholecystectomy, for which no evidence exists of an increased risk for adenoma.
More on Villous Adenoma |
 Overview: Villous Adenoma |
| Differential Diagnoses & Workup: Villous Adenoma |
| Treatment & Medication: Villous Adenoma |
| Follow-up: Villous Adenoma |
| Multimedia: Villous Adenoma |
| References |
| Further Reading |
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References
Wark PA, Wu K, van 't Veer P, Fuchs CF, Giovannucci EL. Family history of colorectal cancer: a determinant of advanced adenoma stage or adenoma multiplicity?. Int J Cancer. Jul 15 2009;125(2):413-20. [Medline].
Terhaar Sive Droste JS, Craanen ME, van der Hulst RW, et al. Colonoscopic yield of colorectal neoplasia in daily clinical practice. World J Gastroenterol. Mar 7 2009;15(9):1085-92. [Medline]. [Full Text].
Martinez ME, Baron JA, Lieberman DA, et al. A pooled analysis of advanced colorectal neoplasia diagnoses after colonoscopic polypectomy. Gastroenterology. Mar 2009;136(3):832-41. [Medline].
Denis B, Peters C, Chapelain C, et al. Diagnostic accuracy of community pathologists in the interpretation of colorectal polyps. Eur J Gastroenterol Hepatol. Aug 18 2009;epub ahead of print. [Medline].
Bokemeyer B, Bock H, Huppe D, et al. Screening colonoscopy for colorectal cancer prevention: results from a German online registry on 269000 cases. Eur J Gastroenterol Hepatol. Jun 2009;21(6):650-5. [Medline].
Cole BF, Logan RF, Halabi S, et al. Aspirin for the chemoprevention of colorectal adenomas: meta-analysis of the randomized trials. J Natl Cancer Inst. Feb 18 2009;101(4):256-66. [Medline].
Baron JA, Cole BF, Sandler RS, Haile RW, Ahnen D, Bresalier R, et al. A randomized trial of aspirin to prevent colorectal adenomas. N Engl J Med. Mar 6 2003;348(10):891-9. [Medline].
Bond JH. Colon polyps and cancer. Endoscopy. Jan 2001;33(1):46-54. [Medline].
Bond JH. Colorectal cancer update. Prevention, screening, treatment, and surveillance for high-risk groups. Med Clin North Am. Sep 2000;84(5):1163-82, viii. [Medline].
Bond JH. Polyp guideline: diagnosis, treatment, and surveillance for patients with colorectal polyps. Practice Parameters Committee of the American College of Gastroenterology. Am J Gastroenterol. Nov 2000;95(11):3053-63. [Medline].
Bond JH. Polyp guideline: diagnosis, treatment, and surveillance for patients with nonfamilial colorectal polyps. The Practice Parameters Committee of the American College of Gastroenterology. Ann Intern Med. Oct 15 1993;119(8):836-43. [Medline].
Cotton PB, Durkalski VL, Pineau BC, Palesch YY, Mauldin PD, Hoffman B, et al. Computed tomographic colonography (virtual colonoscopy): a multicenter comparison with standard colonoscopy for detection of colorectal neoplasia. JAMA. Apr 14 2004;291(14):1713-9. [Medline].
Day DW, Morson BC. The adenoma-carcinoma sequence. In: Morson BC, ed. The Pathogenesis of Colorectal Cancer. Philadelphia: WB Saunders; 1978:58-71.
DuBois RN, Giardiello FM, Smalley WE. Nonsteroidal anti-inflammatory drugs, eicosanoids, and colorectal cancer prevention. Gastroenterol Clin North Am. Dec 1996;25(4):773-91. [Medline].
Farnell MB, Sakorafas GH, Sarr MG, Rowland CM, Tsiotos GG, Farley DR, et al. Villous tumors of the duodenum: reappraisal of local vs. extended resection. J Gastrointest Surg. Jan-Feb 2000;4(1):13-21, discussion 22-3. [Medline].
Gibbs ER, Walton GF, Kent RB 3rd, Laws HL. Villous tumors of the ampulla Vater. Am Surg. Jun 1997;63(6):467-71. [Medline].
Heald RJ, Bussey HJ. Clinical experiences at St. Mark's Hospital with multiple synchronous cancers of the colon and rectum. Dis Colon Rectum. Jan-Feb 1975;18(1):6-10. [Medline].
Itzkowitz SH, Kim YS. Colonic polyps and polyposis syndromes. In: Feldman M, Scharschmidt BF, Sleisenger MH. Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology, Diagnosis, and Management. 6th ed. Philadelphia, Pa: WB Saunders; 1997:467-71.
Mandel JS, Bond JH, Church TR, Snover DC, Bradley GM, Schuman LM, et al. Reducing mortality from colorectal cancer by screening for fecal occult blood. Minnesota Colon Cancer Control Study. N Engl J Med. May 13 1993;328(19):1365-71. [Medline].
Morson BC, Dawson IMP. Gastrointestinal Pathology. Oxford: Blackwell Scientific; 1972.
O'Brien MJ, Winawer SJ, Zauber AG, Gottlieb LS, Sternberg SS, Diaz B, et al. The National Polyp Study. Patient and polyp characteristics associated with high-grade dysplasia in colorectal adenomas. Gastroenterology. Feb 1990;98(2):371-9. [Medline].
Pickhardt PJ, Choi JR, Hwang I, Butler JA, Puckett ML, Hildebrandt HA, et al. Computed tomographic virtual colonoscopy to screen for colorectal neoplasia in asymptomatic adults. N Engl J Med. Dec 4 2003;349(23):2191-200. [Medline].
Sandler RS, Halabi S, Baron JA, Budinger S, Paskett E, Keresztes R, et al. A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer. N Engl J Med. Mar 6 2003;348(10):883-90. [Medline].
Schrock TR. Colonoscopy for colorectal cancer: too much, too little, just right. ASGE Distinguished Lecture 1993. Gastrointest Endosc. Nov-Dec 1993;39(6):848-51. [Medline].
Seitz U, Bohnacker S, Seewald S, Thonke F, Brand B, Braiutigam T, et al. Is endoscopic polypectomy an adequate therapy for malignant colorectal adenomas? Presentation of 114 patients and review of the literature. Dis Colon Rectum. Nov 2004;47(11):1789-96; discussion 1796-7. [Medline].
Stryker SJ, Wolff BG, Culp CE, Libbe SD, Ilstrup DM, MacCarty RL. Natural history of untreated colonic polyps. Gastroenterology. Nov 1987;93(5):1009-13. [Medline].
Winawer SJ, Zauber AG, Fletcher RH, Stillman JS, O'Brien MJ, Levin B, et al. Guidelines for colonoscopy surveillance after polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society. Gastroenterology. May 2006;130(6):1872-85. [Medline].
Winawer SJ, Zauber AG, Ho MN, O'Brien MJ, Gottlieb LS, Sternberg SS, et al. Prevention of colorectal cancer by colonoscopic polypectomy. The National Polyp Study Workgroup. N Engl J Med. Dec 30 1993;329(27):1977-81. [Medline].
Winawer SJ, Zauber AG, Ho MN, O'Brien MJ, Gottlieb LS, Sternberg SS, et al. The National Polyp Study. Eur J Cancer Prev. Jun 1993;2 Suppl 2:83-7. [Medline].
Winawer SJ, Zauber AG, O'Brien MJ, Ho MN, Gottlieb L, Sternberg SS, et al. Randomized comparison of surveillance intervals after colonoscopic removal of newly diagnosed adenomatous polyps. The National Polyp Study Workgroup. N Engl J Med. Apr 1 1993;328(13):901-6. [Medline].
Zauber AG, Winawer SJ. Initial management and follow-up surveillance of patients with colorectal adenomas. Gastroenterol Clin North Am. Mar 1997;26(1):85-101. [Medline].
Further Reading
Clinical guidelines
Guidelines for colonoscopy surveillance after polypectomy: A consensus update by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society.
American Cancer Society - Disease Specific Society
American Gastroenterological Association Institute - Medical Specialty Society. 2006 May. 17 pages. NGC:006080
Surveillance and management of groups at increased risk of colorectal cancer.
New Zealand Guidelines Group - Private Nonprofit Organization. 2004 May. 84 pages. NGC:003655
Quality indicators for colonoscopy.
American College of Gastroenterology - Medical Specialty Society
American Society for Gastrointestinal Endoscopy - Medical Specialty Society. 2006 Apr. 13 pages. NGC:004969
Colorectal cancer screening.
Institute for Clinical Systems Improvement - Private Nonprofit Organization. 1995 May (revised 2008 Jun). 27 pages. NGC:006580
Routine aspirin and non-steroidal anti-inflammatory drug (NSAID) prophylaxis for colorectal cancer prevention.
United States Preventive Services Task Force - Independent Expert Panel. 2007 Mar. 5 pages. NGC:005452
Clinical trials
Randomised Trial of NBI for Adenoma Detection
Selenium in Treating Patients With Adenomatous Colorectal Polyps
A Prospective, Single Blinded Study for Predicting Colon Polyp Histology With Narrow Band Imaging (NBI)
Chemoprevention of Colorectal Adenomas
Prevention of Progression of Duodenal Adenomas in Patients With Familial Adenomatous Polyposis (PreDuoFAP)
Related eMedicine topics
Pancreas, Mucinous Cystic Neoplasm
Papillary Tumors
Neoplasms of the Endocrine Pancreas
Colon, Polyps
Hereditary Colorectal Cancer
Colon Cancer, Adenocarcinoma
Keywords
villous adenoma, tubulovillous adenoma, adenomatous polyps, colonic tumor, colonic neoplasm, papillary adenoma, malignancy, tubular adenoma, tubulovillous adenoma, tubulo-villous adenoma, colonoscopy, adenocarcinomas, rectal cancer, colon cancer, colonic villous adenomas
