A Multidisciplinary Approach to the Diagnosis and Management of Multiple Colorectal Polyps

Encountering numerous colorectal polyps during a colo-noscopy should prompt consideration of several potential diagnoses, which may have very different treatment strategies. The case report by Gallegos and associates, which describes a patient with cap polyposis, offers an opportunity to review the multiple steps required in the diagnostic evaluation of patients with multiple colorectal polyps.¹

Endoscopic Examination

An endoscopic examination is often the first opportunity for gathering data. Although finding multiple polyps during an endoscopy may be startling, the endoscopist should make every effort to document the following polyp characteristics in as much detail as possible, as this information will guide medical and/or surgical management.

Number and Size of Polyps

How many polyps are signified by the phrase “multiple polyps”? It is more informative to provide an estimate of the polyp count (eg, 5, 10, 20, 100, or 1,000+ polyps). Is it possible to remove all of the polyps endoscopically? If so, the endoscopist should attempt to biopsy or remove many of the larger polyps—to rule out malignancy—and repeat the colonoscopy within several months to clear the smaller polyps. If endoscopic removal of all polyps does not appear to be feasible, it is still important for the endos-copist to attempt to biopsy or resect several polyps that are representative of different parts of the colon and rectum, as pathologic diagnosis influences clinical management.

Location of Polyps

Are the polyps located primarily in the right or left side of the colon? Approximately how many polyps are in the rectum, and is it possible to remove all of the rectal polyps? Documenting the extent of the rectal polyp burden is important for making decisions regarding surgical management, as the presence of multiple neoplastic lesions in the rectum may indicate the need for procto-colectomy, whereas rectal sparing may support the use of subtotal colectomy.

Appearance and Morphology of Polyps and the Colonic Mucosa

Are the polyps pedunculated, sessile, lobulated, or flat? Do the polyps appear similar to typical adenomas? Does the intervening colonic mucosa around polyps appear normal or abnormal?

Tissue Biopsies

Tissue is essential for making a diagnosis. The endoscopist should strive to sample and/or remove several representative polyps from different locations, as the architecture and morphology of the lesions can provide important clues regarding their underlying etiology. Resecting a polyp with a snare usually provides the pathologist with enough tissue to evaluate its morphology. It is also important to obtain biopsies of the intervening colonic mucosa to assess whether the mucosa is normal or whether it has inflammatory or neoplastic components, which might suggest an underlying process.

Pathologic Evaluation

Histology is often the key to diagnosis, as the type of polyp generally determines further evaluation and management.²

Neoplastic Polyps (Sessile Serrated Polyps, Adenomas, and Carcinomas)

Adenomas are potentially premalignant lesions and are at risk for progression to adenocarcinomas. Adenomas may be classified as tubular, villous, tubulovillous, or serrated. Adenomas that are villous, have high-grade dysplasia, and/or measure at least 10 mm in size are considered to be advanced adenomas. The presence of multiple (>20) colorectal adenomas should raise suspicion of a genetic polyposis syndrome.

Hyperplastic Polyps

As hyperplastic polyps are generally considered to be non-neoplastic, small polyps do not require additional evaluation. However, hyperplastic polyps that are large in size (>10 mm) or number (>30) may be associated with an increased risk of colorectal cancer.^3,4 It is recommended that large, right-sided hyperplastic polyps be managed in the same way as adenomas.

Hamartomatous Polyps

Juvenile polyps and Peutz-Jeghers polyps are the predominant types of hamartomatous lesions and have unique histologic features. If 5 or more hamartomas are detected in a child or adult, the presence of a genetic syndrome should be considered. Hamartomatous polyps can also be a feature of Cronkhite-Canada syndrome, which often presents with systemic symptoms (including protein-losing enteropathy) and does not have a genetic etiology.

Inflammatory Polyps

Inflammatory polyps occur most commonly in inflammatory bowel disease and are often referred to as pseu-dopolyps. They can also develop in the setting of chronic colonic inflammation, as occurs in infectious or ischemic colitis, chronic mucosal prolapse, Cronkhite-Canada syndrome, and cap polyposis.

Other Mucosal and Submucosal Lesions

Several “benign” entities can produce polyp-like lesions; however, other neoplasms can also present with the appearance of polyposis (such as lymphoma).

If the endoscopist still has questions regarding the histologic diagnosis of a polyp, it may be helpful to obtain a second opinion from an institution with expertise in gastrointestinal pathology.

Clinical Management

Additional Endoscopic Evaluation

Often, the initial colonoscopy does not provide sufficient data or tissue to establish a definitive diagnosis. A repeat colonoscopy may be necessary to document the extent of colonic involvement and/or to biopsy or resect additional polyps. Patients with multiple colorectal adenomas or hamartomas should undergo an upper endoscopy to rule out polyps in the upper gastrointestinal tract. Individuals with Peutz-Jeghers–type polyps may also benefit from endoscopic or radiologic imaging to exclude small-bowel polyps. If a polyposis syndrome is diagnosed, the endos-copist should consider whether the polyp burden can be best managed through repeat endoscopies or surgical resection of the colon. If a patient has adenomas that can be cleared endoscopically, the patient should be followed closely with frequent endoscopic surveillance.⁵

Medical Treatment

If polyps are inflammatory, disease-focused medical treatment should be initiated. The first step should be to rule out infectious etiologies. If a systemic inflammatory process—such as inflammatory bowel disease, Cronkhite-Canada syndrome, or cap polyposis—is suspected, corti-costeroids may be considered. If polyps are dysplastic or at risk for neoplastic transformation—or if inflammatory symptoms are refractory to medical management (as in many cases of cap polyposis)—surgical options should be considered.

Genetic Evaluation

Genetic evaluation is recommended for individuals who have more than 20 cumulative colorectal adenomas, more than 5 gastrointestinal hamartomas, or a family history of cancer or polyps suggestive of a genetic syndrome.⁶ Diagnosis of genetic polyposis syndromes is important for appropriate treatment and surveillance of both the patient and the patient's family members. Genetic testing is available for a number of different hereditary syndromes associated with colorectal polyposis. As diagnosis and management of patients with hereditary cancer syndromes can be complicated, it is often helpful to refer these individuals to specialized centers that have expertise in genetic evaluation and counseling.

Surgical Management

Surgery should be considered in the setting of genetic polyposis syndromes when polyps are not amenable to endoscopic management. If symptoms of diarrhea or protein-losing enteropathy are refractory to medical management—as in the case of cap polyposis reported by Gallegos and coworkers—surgical treatment should be con-sidered.¹ The diagnosis of adenocarcinoma or advanced dysplasia, particularly in the setting of other neoplastic polyps or inflammatory bowel disease, is a strong indication for surgical resection.

Genetic Polyposis Syndromes

Adenomatous Polyposis Syndromes

Familial Adenomatous Polyposis Familial adenomatous polyposis (FAP) is implicated in 1% of colorectal cancer cases.⁷ Patients with classic FAP have hundreds to thousands of adenomas carpeting the colon. Patients with attenuated FAP have fewer than 100 polyps, and these polyps tend to develop later in life. Classic FAP is associated with a nearly-100% lifetime risk for developing colorectal cancer if the colon is not removed. There is an associated increased risk of thyroid, stomach, and small intestinal tumors, as well as bone and soft tissue tumors (Gardner syndrome) and brain tumors (Turcot syndrome). Approximately 90% of patients with classic FAP carry mutations in the APC tumor suppressor gene. Colorectal screening starts at 10–12 years of age for carriers of APC gene mutations and other at-risk individuals. Colectomy is recommended once polyps become too numerous to remove endoscopically. Most individuals with classic polyposis require total procto-colectomy. Individuals who have attenuated polyposis with rectal sparing may consider subtotal colectomy with continued surveillance of the rectal remnant every 6–12 months. Upper endoscopy, including examination of the ampulla, is recommended every 1–3 years for surveillance of duodenal and ampullary adenomas; in addition, annual surveillance of the thyroid is recommended.

MUTYH-Associated Polyposis The clinical phenotype of MUTYH-associated polyposis (MAP) may be similar to attenuated or classic FAP. MAP is caused by biallelic mutations in the MUTYH gene and demonstrates autosomal recessive inheritance. Screening recommendations are generally similar to those associated with FAP.⁸

Hamartomatous Polyposis Syndromes

Juvenile Polyposis Syndrome Juvenile polyposis syndrome (JPS) can be associated with autosomal dominant mutations in 1 of several genes (SMAD4, BMPR1A, and ENG), which encode proteins involved in the transforming growth factor–β signaling pathway.⁹ Patients often present in childhood with gastrointestinal bleeding or obstruction and have an increased risk of gastrointestinal malignancy.

Peutz-Jeghers Syndrome Patients with Peutz-Jeghers syndrome (PJS) typically have multiple gastrointestinal hamartomas, characteristic mucocutaneous pigmentation, and an increased risk for various gastrointestinal and other malignancies (including breast, lung, pancreatic, and sex cord tumors). PJS is caused by an autosomal dominant mutation in the STK11 tumor suppressor gene. Surveillance recommendations include upper and lower endoscopy, evaluation of the small intestine with radiographic tests and/or capsule endoscopy, and breast and gynecologic cancer screening.¹⁰

Cowden Syndrome Cowden syndrome is caused by an autosomal dominant mutation in the PTEN tumor suppressor gene. Although gastrointestinal hamartomas are described in some of these patients, the risks for early-onset breast, thyroid, and endometrial cancer are higher than the risk for colorectal cancer. Surveillance includes screening for colorectal, breast, thyroid, and endometrial cancer.

Conclusion

The cap polyposis case reported by Gallegos and colleagues illustrates the importance of having a systematic plan for evaluating patients with multiple colorectal polyps.¹ In this case report, the endoscopic examination provided sufficient tissue to determine that the polyps were inflammatory, and the normal biopsies of the intervening colorectal mucosa excluded other inflammatory conditions, such as inflammatory bowel disease and Cronkhite-Canada syndrome. Although the diagnosis of cap polyposis is rare, most endoscopists encounter patients with multiple colorectal polyps. A systematic and multidisciplinary approach to evaluation of such patients is necessary, as the differential diagnosis for colorectal polyposis encompasses genetic syndromes and underlying inflammatory conditions that often require coordinated endoscopic, medical, and surgical management.