Villous Adenoma

Updated: Oct 24, 2016
  • Author: Alnoor Ramji, MD, FRCPC; Chief Editor: Burt Cagir, MD, FACS  more...
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Overview

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%).

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. See the images below.

Endoscopic view of a sessile polyp, which histolog 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 Endoscopic view of a sessile polyp histologically determined to be a villous adenoma. Courtesy of R. Enns, MD.

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.

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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.

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Epidemiology

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%.

In Austrian patients undergoing colonoscopy screening, the prevalence for advanced adenomas was comparable between men aged 45 to 49 years and women aged 55 to 59 years. [1]

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. Note the following:

  • 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.
  • Using prospective analyses on retrospectively collected medical record data of 110,452 primary care patients eligible for colorectal screening, Fairley et al reported that baseline adenomas with high-risk features were predictive of recurrent adenoma and colorectal cancer. [2] High-risk features were defined as more than 3 adenomas, a minimum of 1 adenoma larger than 10 mm, the presence of high-grade dysplasia, or villous features. Five hundred thirty-seven of 3,300 patients had removal of adenomas on screening colonoscopy had recurrent adenomas; of these, 354 patients had adenomas with high-risk features. Combined, high-risk features added 22.8% to the probability of correctly predicting colorectal cancer. [2]

Race-related demographics

Race is not an independent factor for adenoma prevalence, although region is considered to be a factor. Note the following:

  • 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-related demographics

Generally, adenoma risk is independent of sex, although some authorities suggest a slight male predominance.

Age-related demographics

The prevalence and distribution of adenomas varies with patient age. Note the following:

  • 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.
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