Synonyms and related keywords
intestinal polyp, intestinal lumen, neoplastic polyp, nonneoplastic polyp, colorectal carcinoma, familial adenomatous polyposis, FAP, hereditary nonpolyposis colorectal cancer, HNPCC, hamartomas of the intestine, Peutz-Jeghers syndrome, familial juvenile polyposis
Author: Dennis Ahnen, MD, Director of Gastroenterology Training Program, Professor, Department of Medicine, Divisions of Gastroenterology and Medical Oncology, University of Colorado Health Science Center
Coauthor(s): John Riopelle, DO, Fellow, Department of Medicine, Division of Gastroenterology/Hepatology, University of Colorado Health Sciences Center
Dennis Ahnen, MD, is a member of the following medical societies: American Association for Advancement of Science, American Association for Cancer Research, American College of Physicians, American Federation for Medical Research, and American Gastroenterological Association
Editor(s): Rajeev Vasudeva, MD, FACG, Director, Clinical Professor, Department of Internal Medicine, Division of Digestive Diseases and Nutrition, University of South Carolina School of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, Pharmacy, eMedicine; Douglas M Heuman, MD, FACP, Director of Hepatology, McGuire Veterans Affairs Medical Center, Professor, Department of Internal Medicine, Division of Gastroenterology, Medical College of Virginia; Alex J Mechaber, MD, FACP, Director of Clinical Skills Program, Assistant Professor, Department of Internal Medicine, Division of General Internal Medicine, University of Miami School of Medicine; and Julian Katz, MD, Professor, Department of Internal Medicine, Division of Gastroenterology, MCP Hahnemann University
Background: The term intestinal polyp is used to describe any projection arising from flat mucosa into the intestinal lumen. Polyps can be broadly classified as neoplastic and nonneoplastic. Neoplastic polyps can be further classified as either adenomatous (premalignant) or malignant. Approximately 95% of all colorectal carcinomas are believed to arise from adenomas, a finding that underscores the importance of treatment and surveillance of adenomas of the gastrointestinal tract.
Adenomas represent approximately 60% of all polyps removed during colonoscopic examination of the colon. The cancer risk of adenomas is related to their macroscopic appearance (ie, size, attachment, location) as well as their microscopic architecture and degree of dysplasia. These descriptors are used clinically to predict the malignant potential of a polyp and to guide both treatment and future surveillance intervals.
Pathophysiology: The colonic mucosa is a self-renewing epithelium that is a very tightly regulated balance between cell proliferation at the base of a crypt, maturation as colonocytes migrate up the crypt, and extrusion of senescent and/or apoptotic cells from the upper crypt into the lumen. This entire process takes approximately 3-6 days.
Adenomatous cells are characterized by loss of normal growth control. They continue to proliferate as they reach the top of the crypt, and they are not extruded into the lumen. Instead, they multiply and eventually fold back into the surrounding normal mucosa, inducing a response in the mesenchymal tissue that helps shape the microscopic architecture of the adenoma. The rate of growth and progression of adenomas to cancer is variable, but, typically, this occurs in 5-10 years. Patients with heritable forms of the disease, such as familial adenomatous polyposis (FAP) or hereditary nonpolyposis colorectal cancer (HNPCC), can have a more rapid rate of adenoma formation and progression to cancer.
The adenoma-carcinoma sequence is thought to be a genetically driven process characterized by the occurrence over time of successive cycles of somatic mutation and clonal expansion of cells that have acquired a survival advantage. The first mutation in this process often involves inactivating mutations of the adenomatous polyposis coli (APC) tumor suppressor gene (inherited mutations in the APC gene cause FAP, and somatic mutations in the APC gene occur in about 80% of sporadic adenomas). Additional and progressive mutations occur in cells of the adenoma, including activating mutations of the oncogenes (Ki-ras) and inactivating mutations of tumor suppressor genes (ie, TP53) and/or DNA repair genes (ie, MSH2, MLH1). Epigenetic silencing of tumor suppressor and DNA repair genes by methylation may also contribute to this molecular process.
Some of these individual mutations lead to clones of cells that have acquired a survival advantage over surrounding cells, leading to a clone of mutant cells. Subsequent cycles of mutation and clonal expansion ultimately lead to adenoma growth, increased severity of dysplasia, and, ultimately, acquisition of the invasive and metastatic characteristics of an adenocarcinoma.
- In the US: Colonoscopic and autopsy series suggest an overall prevalence of adenomatous polyps of 40-50% by age 50-60 years. The prevalence of colonic adenomas increases with age and varies depending on the inherent risk of colorectal cancer in a given population.
- Internationally: Significant geographic variation occurs throughout the world. For example, 2 different ethnic groups from genetically homogeneous regions in Japan have as much as a 20% difference in the prevalence of adenomas in people aged 50 years.
Mortality/Morbidity: Except for the rare adenoma that causes a clinically significant hemorrhage or obstruction, morbidity and mortality are primarily related to the carcinoma that can arise from an adenoma. The National Polyp Study, a large multicenter trial, has demonstrated that detection and removal of adenomas can be expected to substantially decrease the incidence of colorectal cancer.
Race: Although substantial variations in adenoma risk occur among different populations, race itself does not appear to be an independent determinant of risk. Dietary and environmental factors may have a role in explaining some of the differences observed throughout the world; Hawaiian-Japanese men have a high prevalence of adenomas, whereas some Japanese men have low risk. Similarly, blacks in New Orleans have a high risk for adenomas, while South African rural blacks are at low risk for developing adenomas.
Sex: Some studies suggest that adenoma prevalence can be up to 30% higher in men than in women.
Age: The prevalence of adenomas increases progressively with age. Adenomas are uncommon in people younger than 30 years unless associated with a significant family history or familial syndrome. Most studies suggest that sporadic adenoma prevalence begins to increase substantially in people aged 40-50 years and continues to increase through age 80 years.
History: Most adenomas are asymptomatic and are identified primarily by colorectal cancer screening tests or by colonic imaging tests ordered for unrelated reasons. The most common symptoms and signs, usually occurring from large adenomas, include the following:
- Rectal bleeding, overt and occult
- Change in bowel habits
- Abdominal pain
- Rectal prolapse
- Occasional bowel obstruction from a large adenoma
- A large villous adenoma causing a profuse watery diarrhea (rare)
Physical: Physical examination findings are usually benign. A large rectal polyp or flat adenoma can sometimes be detected on digital rectal examination.
- Genetic predisposition: Two rare autosomal dominantly inherited forms of colon cancer that arise in adenomatous polyps have been well described and are thought to account for about 3% of all colorectal cancers. In addition, adenomatous change can occur in the hamartomatous polyposis syndromes.
- FAP is caused by inheritance of a germ line mutation in the APC gene. FAP is characterized by the appearance of hundreds to thousands of adenomas of the colon during adolescence (average age at polyp formation is approximately 15 y) and a nearly 100% risk of colon cancer (average age at cancer development is approximately 40 y) if the colon is not removed. FAP accounts for less than 1% of the total colorectal cancer risk in the United States.
- HNPCC is caused by inheritance of a germ line mutation in one of several DNA repair genes (eg, MSH2, MLH1, MSH6, PMS1, PMS2). Only a few colon adenomas develop in patients with HNPCC, but those that do occur appear to have a very high rate of progression to colorectal cancer. The cancers in HNPCC occur at a younger age (mean age is 44 y), occur more commonly in the proximal colon (60-70% proximal to splenic flexure), and more commonly are multiple rather than sporadic colorectal cancers.
- Multiple hamartomas of the intestine occur in the rare autosomal dominant syndromes of Peutz-Jeghers syndrome and familial juvenile polyposis. Adenomatous change can occur within the hamartomas and lead to adenocarcinoma, most commonly of the colon and small intestine.
- Family history: Any patient with a first-degree relative who has a colorectal adenoma or cancer is at a moderately increased (ie, 1.5- to 2-fold) risk for developing an adenoma.
- Diet and/or lifestyle: Obesity; lack of physical activity; diets high in total calories, fat, and meat; and diets low in vegetables, fruit, and fiber are associated with a moderately increased risk of colorectal adenomas and cancer. Alcohol use and cigarette smoking also increase the risk of adenomas. Acromegaly and ureterosigmoidostomy are both associated with increased risk of adenomas.
Colon Cancer, Adenocarcinoma
Familial Adenomatous Polyposis
Intestinal Polypoid Adenomas
Other Problems to be Considered:
The differential diagnosis of adenomas includes the other polypoid lesions of the gastrointestinal tract. Usually, neoplastic and nonneoplastic mucosal lesions can be endoscopically differentiated from the submucosal polypoid lesions.
Pneumatosis cystoides intestinalis
Colitis cystica profunda
- Fecal occult blood test: Large adenomas can bleed intermittently. Depending on the age of the patients tested, 10-40% of asymptomatic patients with a positive result on a fecal occult blood test have an adenoma. Quantitative testing of stool for blood has been tried, but it does not appear to have a role in screening or diagnosis of colonic adenomas at this time. Newer immunologically based tests designed to detect only human blood in stool are becoming available and are expected to increase the specificity of the test.
- Stool testing for genetic alterations: Stool testing for genetic alterations that occur in adenomas is being studied. Thus far, the stool tests are more sensitive for cancers and advanced adenomas than for small tubular adenomas
- CBC count: Patients with an adenoma occasionally can present with a microcytic (iron deficiency) anemia due to chronic blood loss.
- Iron studies: Low serum iron and ferritin and an increased total iron-binding capacity (TIBC) can be observed because of blood loss in some patients with colonic adenomas and carcinomas.
- Barium enema (BE) imaging of the colon can detect polyps, but these are usually found when the test is ordered for another indication. Air contrast barium enema (ACBE) is more sensitive than single contrast technique for detection of polyps. BE is included as an acceptable screening or surveillance test for colorectal cancer in the recommendations of the American Cancer Society and other organizations, but prospective controlled studies of its use in a screening program are lacking. BE is generally regarded as less sensitive than colonoscopy in detecting adenomas less than 1 cm in size, and some studies indicate that it is not as accurate as colonoscopy for even larger lesions. As a result, BE is usually considered an alternative to colonoscopy for evaluation of the entire colon.
- CT or magnetic resonance (MR) colonography (virtual colonoscopy) is being evaluated for the detection of adenomas and carcinomas of the colon. Thus far, virtual colonoscopy has lower sensitivity than colonoscopy for small (<1 cm) adenomas and has a high false-positive rate, but the technology is improving rapidly.
- New stool screening technology aimed at detecting some of the more common genetic alterations found in adenomas is being investigated. Currently, the stool DNA testing is more sensitive for colon cancers and advanced adenomas than for small tubular adenomas.
Histologic Findings: Adenomas are classified based on their size, architecture, and degree of dysplasia.
- Adequate bowel cleansing is necessary prior to many procedures. Several preparations are marketed for bowel cleansing (eg, polyethylene glycol 3350 [GoLYTELY, NuLYTELY], magnesium citrate [Citroma], senna [X-Prep]) in preparing patients for surgery or gastrointestinal procedures such as endoscopy, colonoscopy, and barium x-ray studies. Bowel cleansing preparations may be used with various dietary preparations (eg, clear liquid diet 1-2 d before surgery or procedure) and are convenient to administer on an outpatient basis.
- Flexible sigmoidoscopy is recommended for screening of average-risk individuals for colorectal cancer and adenomas. Flexible sigmoidoscopy can be used to visualize the left colon, where about half of all colonic adenomas and cancers are located. It is more available and less expensive and it has a lower risk than colonoscopy. Flexible sigmoidoscopy screening of the average-risk population older than 50 years could decrease the colorectal cancer mortality rate by about 40-50% and incidence by 30-40%.
- Colonoscopic screening for colorectal cancer and adenomas is generally recommended for high-risk individuals such as those with 2 or more first-degree relatives with colorectal cancer or those with a single first-degree relative with colorectal cancer occurring at a young age (ie, <50 y). Enthusiasm in the gastroenterology community for offering colonoscopy screening to average-risk individuals is increasing. Medicare has recently added colorectal screening using colonoscopy every 10 years as a covered benefit for average-risk individuals. The entire colon can be visualized using colonoscopy, and mortality rates related to colorectal cancer could be reduced by up to 80% by the routine use of colonoscopic screening and removal of adenomas. Widespread colonoscopic screening would be expensive, and the compliance rate for such a screening program is not known. Currently, the number of trained endoscopists is insufficient to perform colonoscopy screening in the average-risk population.
- Colonoscopic polypectomy is the procedure of choice for treatment of colonic adenomas, and colonoscopy is usually recommended for continued surveillance of patients with previously removed adenomas. The National Polyp Study showed that regular surveillance colonoscopy with polypectomy decreased the incidence of colorectal cancer by 76-90% compared to 3 historic control groups.
- Chromoendoscopy using methylene blue with or without the use of a magnifying endoscope is being used in some centers to improve the accuracy of diagnosing colonic polyps and to identify small adenomas and aberrant crypt foci. The surface architecture of adenomas (ie, brainlike appearance with gyri) is different from that of hyperplastic polyps (ie, chickenwire fence–like). Thus, magnifying chromoendoscopy can potentially be used to distinguish these 2 types of colonic polyps.
Size: Most adenomas are small (<1 cm). Large adenomas (>1 cm) tend toward more severe dysplasia and more worrisome architecture, and the risk of malignant potential is increased.
Architecture: Traditionally, adenomas are described as tubular, tubulovillous, or villous, primarily based on the overall percentage of villous component. Risk of malignancy increases with increased villous composition of the polyp.
- Tubular adenomas are variously defined as those that contain 0-25% villous tissue. About 70-85% of all adenomas are tubular; they tend to be smaller than villous adenomas.
- Tubulovillous adenomas contain approximately 25-75% villous tissue. These adenomas represent 10-25% of all adenomas; they tend to be intermediate in size.
- Villous adenomas contain more than 75% villous tissue. These adenomas represent 5% of all adenomas; they tend to be larger and have the greatest malignancy potential.
- Two other architectural types exist as well.
- Flat types are primarily in familial groups. They are not raised and are usually small erythematous plaques that are multiple, often have multiple foci of high-grade dysplasia, and can be associated with small adenocarcinomas.
- Mixed hyperplastic (serrated) types make up less than 1% of all polyps. They have hyperplastic architecture with evidence of dysplasia and are associated with high frequency of high-grade dysplasia.
Staging: Dysplasia is a neoplastic change in histology. All adenomas are dysplastic; they display degrees of hyperchromasia, nucleolar prominence, nuclear pleomorphism, and increased mitoses. Dysplasias are classified as either low-grade or high-grade. Invasive carcinoma is distinguished from dysplasia by invasion of neoplastic tissue beyond the muscularis mucosa.
- Low-grade - Basal or stratified nuclei, crowded glands, less goblet cells and mucin
- High-grade - Loss of glandular architecture, increased mitoses (includes previously termed carcinoma in situ and intramucosal carcinoma)
Medical Care: Excision and complete removal of adenomatous tissue during colonoscopy is considered the treatment of choice and the ultimate goal of therapy in an attempt to decrease the risk for development of colorectal carcinoma. Several techniques for removal are used, including biopsy forceps and snare excision (with and without electrocautery) as well as simple fulguration and piecemeal excision of large polyps.
Sulindac, a nonsteroidal anti-inflammatory drug (NSAID), has been shown to significantly reduce the number and size of adenomas in patients with FAP. The selective cyclooxygenase-2 (COX-2) inhibitor celecoxib has also been shown to cause modest regression of colonic adenomas in patients with FAP, and the Food and Drug Administration (FDA) has approved it for the treatment of FAP adenomas.
Several case-control and cohort studies indicate that the regular use of aspirin or other NSAIDs is associated with a lower rate of colorectal cancer mortality, but whether the association is causal is unclear. Trials are underway to determine if aspirin or other NSAIDs can prevent new adenoma formation, but none of these studies is yet complete. As a result, NSAIDs are not currently recommended for either treatment or prevention of sporadic colonic adenomas.
Surgical Care: Surgical intervention is usually not required in the management of adenomatous polyps. Rarely, a large (>2 cm) sessile adenoma may not be amenable to endoscopic resection or adequate biopsy and may require surgery. Large rectal adenomas can be removed via intraoperative transanal resection. More proximal lesions may require laparoscopy or laparotomy with segmental colonic resection and evaluation of lymph nodes.
Consultations: Most colonoscopy and polyp treatment is performed by gastroenterologists or colorectal surgeons who work closely with primary care physicians and pathologists to coordinate diagnosis, treatment, and follow-up of adenomas.
Diet: Observational epidemiologic studies have implicated several dietary factors as potentially modulating the prevalence of adenomas. A recent summary by the American College of Gastroenterology makes the following recommendations: a low-fat (25-30% of total calories) high-fiber (20-30 g/d) diet with 5 servings per day of fruits and vegetables, maintenance of normal body weight, no excessive use of alcohol, total abstinence from tobacco, and calcium carbonate supplementation (3 g/d).
- Fat: Consumption of dietary fat is associated with the prevalence of adenomas in several epidemiological studies. Consuming more than 40% of calories from fat is associated with increased risk, while consuming less than 15% of calories from fat is associated with a decreased risk of adenomas. Intervention trials have thus far failed to demonstrate a beneficial effect of a low-fat diet for the prevention of colonic adenomas. The underlying pathophysiology, demonstrated in animal models, likely involves increased production of cholesterol and bile acids by the liver, producing larger amounts of these substances in the colon. Bacterial flora subsequently convert the excess fat-derived substances into oxidized bile acids and cholesterol metabolites, which may exert a tumorigenic effect on colonic epithelium.
- Fiber: High-fiber diets are associated with a decreased incidence of adenomas in observational studies, but intervention trials have thus far failed to show a benefit of fiber supplements for the prevention of new adenomas. The focus of recent attempts to explain the effect of fiber on adenoma formation has centered on fermentation of poorly soluble fiber by colonic bacterial flora. This process produces short-chain fatty acids, which are important substrates for colonic epithelial metabolism as well as potential inhibitors of tumorigenesis.
- Dietary supplements: Multiple studies assessing the effects of supplements such as vitamins A, C, and E; folate; and selenium show no benefit in reducing the risk of adenoma formation in patients with previous adenomas. The only supplement recommended, 3 g daily of calcium carbonate, is shown to be associated with a 24% reduction of recurrent adenomas in patients with one or more previously resected adenomas.
Activity: Multiple epidemiologic studies suggest a protective effect of regular physical activity on colonic cancer risk. No intervention studies have directly evaluated the relationship between physical activity and adenoma or carcinoma risk.
The goals of pharmacotherapy are to reduce morbidity and to prevent complications.
Drug Category: Nonsteroidal anti-inflammatory drugs (NSAIDs) -- Growing evidence suggests a protective role for NSAIDs against the development of colorectal cancer. In addition, a significant effect in reversing adenoma growth has been illustrated with the use of sulindac and celecoxib in patients with FAP. The mechanism of NSAID-induced polyp regression is not known, but it may involve the selective induction of apoptotic cell death in the adenomatous mucosa.
|Sulindac (Clinoril) -- Sulindac is a sulfoxide, which is metabolized to the anti-inflammatory sulfide metabolite and a sulfone metabolite. Both metabolites are known to have apoptotic activity on colonic epithelial cells, but whether this is required for the chemoregressive activity of these drugs is not known. Multiple systemic effects, including analgesia, antipyretic, and anti-inflammatory, mostly mediated by inhibition of prostaglandin synthesis. |
|150-200 mg PO bid |
|Not established |
|Documented hypersensitivity; hypersensitivity to aspirin, iodides, or other NSAIDs; GI bleed; renal insufficiency; sulfa intolerance |
|Sulindac may increase effects of phenytoin and anticoagulants; decreases effects of loop diuretics; lithium and probenecid may increase NSAID effect and toxicity |
|C - Safety for use during pregnancy has not been established. |
|Category D in third trimester of pregnancy; acute renal insufficiency, hyperkalemia, hyponatremia, interstitial nephritis, and renal papillary necrosis may occur; increases risk of acute renal failure in preexisting renal disease or compromised renal perfusion; low WBC counts occur rarely and usually return to reference range in ongoing therapy; discontinuation of therapy may be necessary if persistent leukopenia, granulocytopenia, or thrombocytopenia occur; caution in anticoagulation defects or if receiving anticoagulant therapy|
|Celecoxib (Celebrex) -- Inhibits primarily COX-2. COX-2 is considered an inducible isoenzyme, induced during pain and inflammatory stimuli. Inhibition of COX-1 may contribute to NSAID GI toxicity. At therapeutic concentrations, COX-1 isoenzyme is not inhibited, thus GI toxicity may be decreased. Multiple systemic effects, including analgesia, antipyretic, and anti-inflammatory, mostly mediated by selective inhibition of prostaglandin synthesis. |
|400 mg PO bid for colonic adenomas in FAP |
|Not established |
|Documented hypersensitivity; hypersensitivity to NSAIDS or sulfonamides |
|Coadministration with fluconazole may cause increase in celecoxib plasma concentrations because of inhibition of celecoxib metabolism; coadministration of celecoxib with rifampin may decrease celecoxib plasma concentrations |
|B - Usually safe but benefits must outweigh the risks. |
|Category D in third trimester of pregnancy; may cause fluid retention and peripheral edema; caution in compromised cardiac function, hypertension, and conditions predisposing to fluid retention; severe heart failure and hyponatremia may occur because circulatory hemodynamics may deteriorate; NSAIDs may mask usual signs of infection; caution in the presence of existing controlled infections; evaluate symptoms and signs suggesting liver dysfunction or in abnormal liver laboratory results|
Further Inpatient Care:
- Flexible sigmoidoscopy and colonoscopy generally are outpatient procedures. Inpatient care rarely is required for the diagnosis and treatment of adenomas.
Further Outpatient Care:
- In general, a 3-year interval for surveillance colonoscopy is safe and cost-effective for most patients after removal of adenomas. Specific clinical scenarios dictate alterations from this general guideline.
- Large (>2 cm) sessile polyps or multiple adenomas found on initial colonoscopy warrant repeat colonoscopy 3-6 months after initial diagnosis to ensure complete removal of all adenomatous tissue.
- If either the endoscopist or the pathologist is unsure that the polyp has been completely removed, a repeat colonoscopy in 3-6 months is recommended.
- A suboptimal examination at colonoscopy or multiple (>4) adenomas indicates need for follow-up colonoscopy in 1 year or sooner.
- If the 3-year follow-up examination reveals no recurrent adenomas, repeat colonoscopy is recommended every 5 years.
- Follow-up of single tubular adenomas less than 1 cm is debated and patient-specific, depending primarily on comorbidities and age.
- Observational epidemiologic studies have implicated several dietary factors as potentially modulating the prevalence of adenomas. A recent summary by the American College of Gastroenterology makes the following recommendations: a low-fat (25-30% of total calories) high-fiber (20-30 g/d) diet with 5 servings per day of fruits and vegetables, maintenance of normal body weight, no excessive use of alcohol, total abstinence from tobacco, and calcium carbonate supplementation (3 g/d).
- The only intervention proven to decrease the incidence of recurrent sporadic adenomas is calcium carbonate (3 g/d).
- Growing evidence suggests a protective role for NSAIDs against the development of colorectal cancer. In addition, a significant effect in reversing adenoma growth has been illustrated with the use of sulindac and celecoxib in patients with FAP.
- The primary complication associated with adenomas is the potential development of colorectal cancer. Less than 5% of all adenomas progress to cancer. The risk of progression to cancer rises with increasing size, villous component, and degree of dysplasia.
- Complications of colonoscopy include perforation and bleeding. A diagnostic colonoscopy carries a complication risk of about 0.1%; polypectomy substantially increases the risk of complications to up to 0.2% for perforation and 1% for bleeding.
- Almost all cases of colorectal cancer arise from an adenoma; excision of adenomas reduces the incidence of colorectal cancer. Adherence to guidelines for surveillance of adenomas is expected to substantially reduce the risk of developing colon cancer.
- A sustained public awareness campaign emphasizing the importance of early detection of adenomas in the prevention of colorectal cancer has been supported by all major gastroenterology associations.
- Dietary recommendations such as those outlined in the section above on treatment have been promoted by the National Cancer Institute, the American Cancer Society, and many other organizations.
- Patients diagnosed with adenomas who are not properly monitored have an increased risk of developing metachronous adenomas and/or colorectal cancer.
Caption: Picture 1. Intestinal polypoid adenomas. Endoscopic view of pedunculated polyp.
Caption: Picture 2. Intestinal polypoid adenomas. Endoscopic view of sessile polyp.
Caption: Picture 3. Intestinal polypoid adenomas. Tubular adenoma, low-power view. Courtesy of G. Warren, MD, Rose Medical Center, Denver, Colo.
Caption: Picture 4. Intestinal polypoid adenomas. Villous adenoma, low-power view. Courtesy of G. Warren, MD, Rose Medical Center, Denver, Colo.
Caption: Picture 5. Intestinal polypoid adenomas. High-power view of adenomatous polyp with low-grade dysplasia. Courtesy of G. Warren, MD, Rose Medical Center, Denver, Colo.
Caption: Picture 6. Intestinal polypoid adenomas. Villous adenoma with grade IV invasive carcinoma. Courtesy of G. Warren, Rose Medical Center, Denver, Colo.
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