Colon Polyps

Colon polyps can turn into colon cancer.

Colon polyps are growths that occur on the inner lining of the large intestine (colon) and usually protrude into the colon. Polyps form when the genetic material within the cells lining the colon changes and becomes abnormal (mutates).

Normally, the immature cells lining the colon are programmed to divide (multiply), mature, and then die in a very consistent and timely fashion. However, the genetic changes that occur in the lining cells prevent the cells from maturing, and the cells do not die. This leads to an accumulation of immature, genetically abnormal cells, which eventually results in the formation of polyps. The mutations may occur as a sporadic event after birth or they may be present from before birth.

Picture of colon polyps and colon cancer (colorectal).

Most polyps are protrusions from the lining of the intestine:

• Polypoid polyps look like a mushroom but flop around inside the intestine because they are attached to the lining of the colon by a thin stalk.
• Sessile polyps do not have a stalk and are attached to the lining by a broad base.
• Flat polyps are the least common type of colon polyp and are flat or even slightly depressed. These may be difficult to identify because they are not as prominent as polypoid or sessile polyps with the commonly available methods of diagnosing polyps.

Not all colon polyps are the same. There are different histologic types, that is, the cells that make up the polyp have different characteristics when viewed under the microscope. They also vary in size, number, and location. Most importantly, they vary in their tendency to become cancerous (malignant).

Adenomatous polyps

The most common type of polyp is the adenoma or adenomatous polyp. It is an important type of polyp not only because it is the most common, but because it is the most common cause of colon cancer.

• The likelihood that an adenoma will develop into (or has already developed into) cancer is partially dependent on its size; the larger the polyp, the more likely it is that the polyp is or will become malignant (concern about the malignant potential increases with a polyp greater than one centimeter in size).
• It also matters if there is a single polyp or multiple polyps. Patients with multiple polyps—even if they are not malignant when examined under the microscope—are more likely to develop additional polyps in the future that may become malignant. Concern about this increasing malignant potential begins when there are three or more polyps.
• Finally, the malignant potential of an adenomatous polyp is related to how the cells of the polyp organize themselves as seen under the microscope. Cells that organize themselves into tubular structures (tubular adenomas) are less likely to become cancerous than cells that organize themselves into finger-like structures (villous adenomas).

Most adenomatous polyps are considered sporadic, that is, they do not stem from a recognized genetic mutation that is present at birth (are not familial). Nevertheless, the risk of having colon polyps greater than one centimeter in size or developing colon cancer is two-fold greater if a first-degree relative has colon polyps greater than one centimeter in size. Therefore, there is likely to be a genetic factor working even in sporadic adenomatous polyps.

Genetic adenomatous polyp syndromes

There are several familial, genetic conditions in which the mutations or the development of mutations are programmed into an individual's genes from before birth, and passed down from parent to child.

In the most common of these conditions, hundreds to thousands of adenomatous polyps form (familial adenomatous polyposis or FAP) as a result of a mutation in the APC gene. It is important to recognize these polyposis syndromes and the exact genetic abnormality that causes them, if possible since the malignant potential of these polyps is much greater than that of individuals without the genetic abnormality. (Eighty percent or more of these patients develop colon cancer.) Even though these syndromes are responsible for only a few percent of all colon cancers, recognition of a polyposis syndrome identifies patients in whom screening for additional polyps needs to be done more frequently so that new polyps and cancers can be discovered and treated early. It may even be recommended that the entire colon be removed to prevent cancer.

In addition, genetic testing can be done for relatives of the patient to determine whether or not the relative has the same mutation as the patient and, therefore, is very likely to develop polyps and cancer. Relatives with the same mutation then can be screened for the presence of polyps and cancer, preferably starting the colorectal cancer screening at an earlier age than would normally be done because cancers in these syndromes develop at an earlier age than cancers not associated with a syndrome. Because of the autosomal dominant mode of transmission of the gene and its effects, only one parent needs to have the FAP gene to pass on to his or her children, and therefore, there is a 50/50 chance that each of his or her children will have FAP.

There is an uncommon form of FAP in which the number of polyps is less than classic FAP—less than 100—called attenuated FAP. The mutation in the APC gene in attenuated FAP is different than the mutation in classic FAP. Patients with many polyps but not the numbers seen in FAP should be identified and tested for the mutation. Unlike FAP, which is an autosomal dominant syndrome, attenuated FAP is a recessive mutation so that an individual needs to inherit one mutated gene from each parent to develop polyps and colon cancer, and because of the rarity of the mutation, this occurs rarely.

Another syndrome of polyps and colon cancer is the MYH polyposis syndrome. Individuals with MYH polyposis develop less than 100 polyps at a young age and are at high risk for developing colon cancer. It is caused by mutations in a different gene than FAP, the MYH gene; however, the mutation occurs sporadically due to spontaneous mutations, and, therefore, a hereditary pattern is not apparent in parents, although it may be seen in siblings. Because it is an autosomal recessive gene that requires a mutated gene from each parent, the MYH polyposis syndrome is rare.

Hyperplastic polyps

The second most common type of colon polyp is the hyperplastic polyp. It is important to recognize these polyps and to differentiate them from adenomatous polyps since they have little or no potential to become cancerous unless they are located in the proximal (ascending colon), or show a particular histologic pattern under the microscope (a serrated appearance). Nevertheless, there are uncommon genetic syndromes in which patients form many hyperplastic polyps. These patients may be at a similar risk for developing colon cancer as patients with multiple adenomatous polyps, particularly if the polyps are large, serrated, located in the ascending colon, and there is a family history of colon cancer. Hyperplastic polyps may coexist with adenomatous polyps.

Other types of colon polyps

Much less common types of colon polyps exist, and their potential for becoming cancerous varies greatly, for example, hamartomatous, juvenile, and inflammatory polyps.

Most colon polyps (95%) do not cause symptoms or signs and are discovered during screening or surveillance colonoscopy.

When symptoms or signs occur, they may include:

• Red blood mixed in with or on the surface of the stool
• Black stools if the polyp is bleeding substantially and is located in the proximal colon (cecum and ascending colon)
• Iron deficiency anemia if the bleeding has been slow and occurs over a prolonged period.
• Weakness, light-headedness, fainting, pale skin, and rapid heart rate due to iron deficiency anemia
• The presence of invisible (occult) blood in stool is tested when screening for colon cancer at visits to a doctor's office (Because of the tendency of polyps to bleed slowly, intermittently, and in small amounts, occult blood testing of stool often is used to screen for colon cancer.)
• Rarely diarrhea when large villous polyps secrete fluid into the intestine
• Rarely constipation if the polyp is very large and obstructs the colon
• Rarely intussusception, a condition in which a polyp drags the portion of the colon to which it is attached into the more distal colon (i.e., telescopes into the more distal colon) and leads to obstruction of the colon. This can cause all of the signs and symptoms of intestinal obstruction including abdominal pain and distention, nausea, and vomiting.

How common are colon polyps?

Colon polyps are very common. They increase in prevalence as people age; by age 60, one-third or more of people will have at least one polyp. If a person has a colon polyp, he or she is more likely to have additional polyps elsewhere in the colon and is more likely to form new polyps at a later time. In a small subset of patients with colon polyps, there is a familial, genetic abnormality that causes patients and other members of their families to develop larger numbers of polyps, to develop them at an early age, and to more frequently have them become cancerous.

Why are colon polyps significant?

Colon polyps are important because they may give rise to colon cancer (colorectal cancer). The type of polyp predicts who is more likely to develop further polyps and colon cancer. Polyps cause other problems (to be discussed), but it is the deadly nature of colon cancer that is of most concern.

Benign polyps become malignant polyps (cancer) with further mutations and changes in the cell's genetic material (genes). The cells begin to divide and reproduce uncontrollably, sometimes giving rise to a larger polyp. Initially, the increasingly, genetically abnormal cells are limited to the layer of cells that line the inside of the colon. The cells then develop the ability to invade deeper into the wall of the colon. Individual cells also develop the ability to break off from the polyp and spread into lymph channels through the wall of the colon to the local lymph nodes and then throughout the body, a process referred to as metastasis although this is unusual unless the cancer has invaded into the wall of the colon.

The transition from benign to malignant polyps can be seen under the microscope. In the earlier phase of the transition, called low-grade dysplasia (dysplasia=abnormal formation), the cells and their relationships with one another become abnormal. When the cells and their relationships become even more abnormal, it is termed high-grade dysplasia. High-grade dysplasia is of greater concern because the cells are cancerous although they are limited to the innermost lining of the colon; with rare exceptions, they have not yet developed the ability to invade and metastasize (spread to other parts of the body). If they are not removed, invasion and metastasis may occur.

Although most colon cancers arise from polyps, some do not. Some arise within the wall of the colon. These cancers may be flat or even depressed (excavated). They are more difficult to identify and treat, and they are more likely to spread into the wall of the colon and nearby lymph nodes than cancers originating in polyps. This is particularly true of serrated adenomatous polyps, which usually are flat rather than polypoid in appearance.

There also is a familial, genetic syndrome called hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) in which colon cancers occur with very high incidence (80% or more of patients). There are few or no polyps to identify in these patients. Moreover, the cancers occur at a younger age, often before the time screening for colon cancer is recommended to begin, and the syndrome is not recognized until a family member develops cancer usually at a young age.

HNPCC is suspected because other family members also have colon cancer and certain criteria are met (Amsterdam or Bethesda criteria), or cancer shows a particular pattern under the microscope with special stains. If HNPCC is suspected, genetic testing on cancer can be done to identify the hereditary mutation and other family members can be tested for the same mutation. If present, the family members can undergo a screening colonoscopy and follow-up surveillance colonoscopies. HNPCC may be associated with cancers in tissues outside the colon as well. Fortunately, HNPCC is responsible for only a few percent of all colon cancers.

Colon polyps can vary in size from a few millimeters to several centimeters. The larger the polyp the more likely it is that there will be cancer within the polyp or that the polyp will later become cancerous.

There are several means to diagnose colon polyps:

Endoscopic colonoscopy

Endoscopic colonoscopy involves the use of a colonoscope, a flexible tube approximately five feet in length with a light and camera at the end, and a hollow channel through which instruments can be passed. The colonoscope is passed via the anus into the colon and then through the colon until the proximal end of the colon -- the cecum -- is reached. On withdrawal of the colonoscope, the lining of the colon is observed for polyps and other abnormalities. These may be biopsied or removed using electrocautery and then examined under the microscope. Colonoscopy identifies 95% of polyps, small and large, though occasionally polyps are missed if they are small, hidden by folds in the colon's lining, are flat, or the colonoscopy is hurried.

Virtual colonoscopy

A virtual colonoscopy involves the use of either computerized tomography (CT) or magnetic resonance imaging (MRI). The colon is filled with either a liquid contrast agent or air, and CT or MRI is performed. Computerized reconstruction of either the CT or MRI images provides a virtual image that mimics the view obtained by a colonoscopy. Virtual colonoscopy is very good at finding polyps but not as good as colonoscopy; it can miss polyps less than one centimeter in size, although the need to identify these smaller polyps is debated since they infrequently are malignant. MRI has an advantage over CT because it does not expose the patient to radiation. It is more expensive, however, and there is less experience with MRI than with CT. The problem with both CT and MRI virtual colonoscopy is that if a polyp is found that should be removed, a colonoscopy then must be done at a later time to remove it.

Barium enema

A barium enema is an older method of diagnosing colon polyps. During a barium enema, the colon is filled with barium, and multiple X-rays of the colon are taken as the patient changes position. A barium enema is a good way to diagnose polyps and is relatively inexpensive; however, it can easily miss small polyps and exposes patients to radiation. Moreover, the skills and experience necessary to do a barium enema properly have declined among radiologists because barium enemas are less frequently ordered now that colonoscopy and virtual colonoscopy are available. Finally, like virtual colonoscopy, if polyps are found, a colonoscopy must be done to remove the polyp.

Flexible sigmoidoscopy

Flexible sigmoidoscopy uses a shortened version of a colonoscope, approximately three feet in length. It can examine only the distal third to one-half of the colon. Like the colonoscope, it can be used to identify, biopsy, and remove polyps without radiation exposure. For screening purposes, since the sigmoidoscope cannot examine the entire colon, it usually is combined with either less frequent colonoscopy or frequent stool occult blood tests to identify polyps beyond its reach.

Several expert groups have made recommendations for surveillance in individuals who have been found to have polyps on their initial examination, which usually is endoscopic colonoscopy but occasionally virtual colonoscopy or flexible sigmoidoscopy. The recommendations vary slightly from group to group but not in important ways. They all make recommendations based on factors such as the family history of polyps and colon cancer, the number of polyps that are found, the size of the polyps, and the polyps' histology.

By using these factors, the interval between surveillance procedures can be tailored to the risk of developing further polyps and malignancy in the future—the higher the risk, the shorter the interval between surveillance procedures. The recommendations that follow are modified from the guidelines proposed by the U.S. Multi-Society Task Force on Colorectal Cancer published in 2012.

Second examination

• If no polyps are found on the first examination it is recommended that a second examination should be done 10 years later.
• If the only polyps that are found are hyperplastic, and they are limited to the rectum and sigmoid colon and they are all less than one centimeter in size, a second examination is recommended in 10 years.
• If one or two tubular adenomas are found and they are less than one centimeter in size, a second examination is recommended in five years through a longer interval may be reasonable as well.
• If three to ten adenomas are found, it is recommended that a second examination be done in three years.
• If more than ten adenomas are found, it is recommended that a second examination be done in three years or less.
• If one or more tubular adenomas are found that are greater than one centimeter in size, a second examination is recommended in three years.
• If one or more adenomas are found of any size and their histology is villous, a second examination is recommended in three years.
• If one or more adenomas are found and any show high-grade dysplasia, a second examination is recommended in three years.
• If serrated polyps are found, recommendations are less secure because much less information is available about the future risk of polyps and cancers. Concerns are greater (and the interval to the next examination should be shorter) if the polyps are proximal (in the ascending colon), are larger (more than one centimeter in size), and particularly if they show dysplasia.

Additional examinations

Adenomas can be classified as low-risk (LRA) and high-risk (HRA) for cancer.

• LRA is defined as one to two tubular adenomas less than one centimeter in size.
• HRA is defined as three or more adenomas, with one tubular adenoma greater than one centimeter in size, or an adenoma with villous histology or high-grade dysplasia.

Recommendations regarding when to have the third and subsequent examinations depend on the presence of LRA or HRA on the first and second examinations and can vary between three and 10 years.

Genetics and genetic testing have become important aspects in the evaluation of both colon polyps and colon cancer.

Every patient with a colon polyp should have a careful family history taken. If necessary, individuals or families can be referred to doctors who specialize in the genetics of diseases and can help with decisions about genetic testing and screening. This is especially important in patients with multiple polyps, several family members with polyps or colon cancer, or a family member with early onset of colon cancer (before age 50).

A family history of colon polyps and colon cancer is an important clue to the possible presence of a familial, genetic syndrome. If a syndrome is suspected, individuals can be tested for known mutations, and they can begin surveillance colonoscopies starting at an earlier age; however, there are still syndromes for which mutations are unknown and for which cannot be tested.

Nevertheless, even in these latter families, there is a benefit; family members are made aware of the possibility of an unidentifiable syndrome and may begin surveillance colonoscopies early. Patients with FAP often have other polyps with malignant potential in the gastrointestinal tract and develop polyps and/or cancers in other gastrointestinal and non-gastrointestinal tissues. They require further screening to determine if the non-colonic polyps have malignant potential and if cancer has developed outside of the gastrointestinal tract.

Genetics also may be used in other ways. In families with FAP or HNPCC, if the genetic abnormality is identified in the initial family member with polyps or cancer, other family members can be identified with the same abnormality and then can begin early colon cancer screening.

Most polyps can be removed through the endoscope. They are then examined under a microscope. It is important to determine whether or not they contain cancer if they are of a type that has malignant potential, and if they have characteristics that make them more likely to be associated with cancer, either in another polyp at the same time or in polyps that may form in the future (for example, are villous or serrated).

The results of the colonoscopy and histologic examination are important because they determine the need for increased frequency of screening colonoscopy in the future (for example, adenomatous polyps).

• If there is cancer already present in the polyp it is important to determine how deep into the wall of the colon cancer has spread.
• If it extends deeply, it is more likely that the cancer has spread to lymph nodes further away. In such cases, it may be necessary to do an additional endoscopic resection of the area of the colon where the polyp was or to surgically remove the section of the colon, to be certain that all of the cancer has been removed. Nearby lymph nodes also may be removed and examined to identify any spread of cancer beyond the colon.
• If a genetic mutation is suspected, it is looked for by genetic testing on a portion of the biopsy, and, if present, relatives should be screened for the same mutation. If present, the relatives should undergo screening colonoscopy and more frequent surveillance colonoscopy.

It is recommended that patients with FAP and other polyp syndromes consider having their colons removed prophylactically to prevent the development of cancer.

Because of concern regarding the transition of polyps to cancer, attempts have been made to determine if treatments with theoretical potential prevent polyps. The problem with most studies is that they are retrospective, observational studies which are not sufficient as proof. The long period (many years) that it takes for polyps to form makes long-term studies mandatory, but such studies have been difficult to do except in the case of familial, genetic polyposis syndromes, and, because of the differences in their causes, it is not clear if what applies to them applies to the more common sporadic adenomas.

• Several associations have been explored for antioxidants including selenium, beta carotene, and vitamins A, C, and E. Most of the studies that have been done do not support the role of these agents in preventing polyps or in preventing colon cancer. A limited amount of support is available for the use of selenium to prevent polyps, but selenium is not recommended for use outside of experimental trials.
• Supplemental dietary calcium has been demonstrated in one study to prevent the formation of polyps. The benefit was seen with the supplementation of 1200 mg of calcium per day. There is some concern about using calcium since higher dietary and supplemental levels are associated with an increase in vascular disease. The intake of calcium that was studied was higher than the recommended intake of calcium, 800 mg per day.
• The best support for a treatment to prevent polyps is with nonsteroidal anti-inflammatory drugs (NSAIDs), a class of drugs that includes aspirin, ibuprofen (Motrin, Advil), celecoxib (Celebrex), and many others. Aspirin has been shown in several studies to reduce the formation of polyps by 30% to 50%. The effect is likely to occur with higher doses of aspirin (more than the 81-325 mg that is recommended for cardiovascular disease prevention), and there is concern about aspirin's side effect of gastrointestinal bleeding at these doses.
  • Celecoxib (Celebrex), a "COX-2 selective NSAID" or Cox-2 inhibitor has been shown to reduce colon polyps by 30% to 50% as well, but there is a lingering concern about the possible cardiovascular side effects that may be seen with most NSAIDs (though the data supporting this side effect is conflicting). It may be used in patients with genetic polyposis syndromes who choose not to have their colons removed. Celecoxib might be considered in patients with a low risk for cardiovascular disease who develop adenomatous polyps frequently.
  • Sulindac (Clinoril), a "non-selective NSAID" has been shown to prevent polyps in patients with sporadic adenoma as well as genetic syndromes. As with celecoxib, there is concern about cardiovascular side effects and gastrointestinal ulceration and bleeding.

Given the available information, it is not recommended that patients at average risk for the formation of additional polyps be treated for prevention because of concern that the risks of treatment, primarily intestinal bleeding, and cardiovascular disease, may outweigh the benefit of polyp prevention. It may be reasonable to treat patients who are at higher than average risk for polyps in which the benefit may outweigh the risks. Such patients might include those with frequent polyp formation, particularly those who have demonstrated cancerous changes in the polyps, or patients who already have had colon cancer. Studies on these types of patients are eagerly awaited.