POLYPS OF INTESTINE

1. POLYPS OF INTESTINE Dr. farhana

2. Polyps • Polyps are most common in the colon but may occur in the esophagus, stomach, or small intestine. • Most polyps begin as small elevations of the mucosa. • These are referred to as sessile

3. As sessile polyps enlarge, several processes, including proliferation of cells adjacent to the mass and the effects of traction on the luminal protrusion, may combine to create a stalk. • Polyps with stalks are termed pedunculated. In general, intestinal polyps can be classified as non-neoplastic or neoplastic in nature.

4. The most common neoplastic polyp is the adenoma, which has the potential to progress to cancer. • The non-neoplastic polyps can be further classified as inflammatory, hamartomatous, or hyperplastic

5. INFLAMMATORY POLYPS • The polyp that forms as part of the solitary rectal ulcer syndrome is an example of a purely inflammatory lesion. • Patients present with a clinical triad of rectal bleeding, mucus discharge, and an inflammatory lesion of the anterior rectal wall.

6. An inflammatory polyp may form as a result of chronic cycles of injury and healing. • Entrapment of this polyp in the fecal stream leads to mucosal prolapse.

7. Distinctive histologic features are those of a typical inflammatory polyp with superimposed mucosal prolapse and include lamina propriafibromuscular hyperplasia, mixed inflammatory infiltrates, erosion, and epithelial hyperplasia

8. HAMARTOMATOUS POLYPS • Hamartomatous polyps occur sporadically and in the context of various genetically determined or acquired syndromes . • Hamartomas are tumor-like growths composed of mature tissues that are normally present at the site in which they develop

9. Juvenile Polyps • Juvenile polyps are focal malformations of the mucosal epithelium and lamina propria. These may be sporadic or syndromic, but the morphology of the two forms may be indistinguishable. • The vast majority of juvenile polyps occur in children less than 5 years of age.

10. The majority of juvenile polyps are located in the rectum and most present with rectal bleeding. • In some cases prolapse occurs and the polyp protrudes through the anal sphincter. • Sporadic juvenile polyps are usually solitary lesions and may be referred to as retention polyps. • In contrast, individuals with the autosomal dominant syndrome of juvenile polyposis have from 3 to as many as 100 hamartomatous polyps

11. Morphology. • Most juvenile polyps are less than 3 cm in diameter. • They are typically pedunculated, smooth-surfaced, reddish lesions with characteristic cystic spaces apparent after sectioning. • Microscopic examination shows these cysts to be dilated glands filled with mucin and inflammatory debris . • The remainder of the polyp is composed of lamina propria expanded by mixed inflammatory infiltrates. The muscularis mucosa may be normal or attenuated.

12. Peutz-Jeghers Syndrome • This rare autosomal dominant syndrome presents at a median age of 11 years with multiple GI hamartomatous polyps and mucocutaneous hyperpigmentation. • The latter takes the form of dark blue to brown macules around the mouth, eyes, nostrils, buccal mucosa, palmar surfaces of the hands, genitalia, and perianal region

13. Germline heterozygous loss-of-function mutations in the gene LKB1/STK11 are present in approximately half of individuals with familial Peutz-Jeghers syndrome as well as a subset of patients with sporadic PeutzJeghers syndrome

14. Morphology. • The polyps of Peutz-Jeghers syndrome are most common in the small intestine, although they may occur in the stomach and colon, and, with much lower frequency, in the bladder and lungs. • Grossly, the polyps are large and pedunculated with a lobulated contour. • Histologic examination demonstrates a characteristic arborizing network of connective tissue, smooth muscle, lamina propria, and glands lined by normal-appearing intestinal epithelium

15. Cowden Syndrome and Bannayan-Ruvalcaba-Riley Syndrome • Cowden syndrome and Bannayan-Ruvalcaba-Riley syndrome are autosomal dominant hamartomatous polyp syndromes associated with loss-of-function mutations in PTEN, • Cowden syndrome is characterized by macrocephaly, intestinal hamartomatous polyps, and benign skin tumors, typically trichilemmomas, papillomatous papules, and acralkeratoses.

16. A variety of other lesions derived from all three embryologic layers, including subcutaneous lipomas, leiomyomas, and hemangiomas, also occur

17. Bannayan-Ruvalcaba-Riley syndrome can be distinguished from Cowden syndrome on clinical grounds; for example, mental deficiencies and developmental delays are only seen with the Bannayan-Ruvalcaba-Riley syndrome, which also seems to be associated with a lower incidence of neoplasia than Cowden syndrome

18. Cronkhite-Canada Syndrome • is nonhereditary and most often develops in individuals over 50 years of age. • The clinical symptoms are nonspecific and include diarrhea, weight loss, abdominal pain, and weakness. • The most characteristic feature is the presence of hamartomatous polyps of the stomach, small intestine, and colorectum that are histologically indistinguishable from juvenile polyps.

19. The nonpolypoid intervening mucosa also shows cystic crypt dilatation and lamina propriaedema and inflammation. • Associated abnormalities include nail atrophy and splitting, hair loss, and areas of cutaneous hyperpigmentation and hypopigmentation

20. HYPERPLASTIC POLYPS • Colonic hyperplastic polyps are common epithelial proliferations that are typically discovered in the sixth and seventh decades of life. • they are thought to result from decreased epithelial cell turnover and delayed shedding of surface epithelial cells, leading to a “piling up” of goblet cells and absorptive cells

21. Morphology Hyperplastic polyps are most commonly found in the left colon and are typically less than 5 mm in diameter. They are smooth, nodular protrusions of the mucosa, often on the crests of mucosal folds They may occur singly but are more frequently multiple, particularly in the sigmoid colon and rectum

22. Histologically, hyperplastic polyps are composed of mature goblet and absorptive cells. • The delayed shedding of these cells leads to crowding that creates the serrated surface architecture that is the morphologic hallmark of these lesions

23. NEOPLASTIC POLYPS • Any neoplastic mass lesion in the GI tract may produce a mucosal protrusion, or polyp. This includes carcinoidtumors, stromal tumors, lymphomas, and even metastatic cancers from distant sites. • However, the most common and clinically important neoplastic polyps are colonic adenomas, benign polyps that are precursors to the majority of colorectal adenocarcinomas.

24. Adenomas are intraepithelial neoplasms that range from small, often pedunculated polyps to large sessile lesions. • There is no gender preference, and they are present in nearly 50% of adults living in the Western world by age 50. • These polyps are precursors to colorectal cancer

25. Colorectal adenomas are characterized by the presence of epithelial dysplasia. Consistent with their role as precursor lesions, the prevalence of colorectal adenomas correlates with that of colorectal carcinoma and the distributions of adenomas and adenocarcinoma within the colon are similar

26. Most adenomas are clinically silent, with the exception of large polyps that produce occult bleeding and anemia and rare villous adenomas that cause hypoproteinemichypokalemia by secreting large amounts of protein and potassium.

27. Morphology. • Typical adenomas range from 0.3 to 10 cm in diameter and can be pedunculated or sessile, with the surface of both types having a texture resembling velvet or a raspberry, due to the abnormal epithelial growth pattern. • Histologically, the cytologic hallmark of epithelial dysplasia is nuclear hyperchromasia, elongation, and stratification

28. These changes are most easily appreciated at the surface of the adenoma and are often accompanied by the presence of large nucleoli, eosinophilic cytoplasm, and a reduction in the number of goblet cells. • Notably, the epithelium fails to mature as cells migrate from crypt to surface.

29. Pedunculated adenomas have slender fibromuscular stalks containing prominent blood vessels derived from the submucosa. The stalk is usually covered by non-neoplastic epithelium, but dysplastic epithelium is sometimes present.

30. Adenomas can be classified as tubular, tubulovillous, or villous based on their architecture. • Tubular adenomas tend to be small, pedunculated polyps composed of small rounded, or tubular, glands . • villous adenomas, which are often larger and sessile, are covered by slender villi . • Tubulovillous adenomas have a mixture of tubular and villous elements.

31. Sessile serrated adenomas overlap histologically with hyperplastic polyps, but are more commonly found in the right colon. • Despite their malignant potential, sessile serrated adenomas lack typical cytologic features of dysplasia that are present in other adenomas . • Histologic criteria include serrated architecture throughout the full length of the glands, including the crypt base, associated with lateral growth and crypt dilation

32. Intramucosal carcinoma occurs when dysplastic epithelial cells breach the basement membrane to invade the lamina propria or muscularis mucosa. • Because lymphatic channels are absent in the colonic mucosa, intramucosal carcinoma has little or no metastatic potential and complete polypectomy is effective therapy .

33. Invasion beyond the muscularis mucosa, including into the submucosal stalk of a pedunculated polyp , constitutes invasive adenocarcinoma and carries a risk of spread to other sites

34. Although most colorectal adenomas are benign lesions, a small proportion may harbor invasive cancer at the time of detection. • Size is the most important characteristic that correlates with risk of malignancy

35. Familial Syndromes • Several syndromes characterized by the presence of colonic polyps and increased rates of colon cancer

36. FAMILIAL ADENOMATOUS POLYPOSIS • Familial adenomatouspolyposis (FAP) is an autosomal dominant disorder in which patients develop numerous colorectal adenomas as teenagers. • It is caused by mutations of the adenomatouspolyposis coli, or APC, gene.

37. At least 100 polyps are necessary for a diagnosis of classic FAP, and as many as several thousand may be present . • Except for their remarkable numbers, these growths are morphologically indistinguishable from sporadic adenomas. • In addition, however, flat or depressed adenomas are also prevalent in FAP, and microscopic adenomas, consisting of only one or two dysplastic glands, are frequently observed in otherwise normal-appearing mucosa.

38. Colorectal adenocarcinoma develops in 100% of untreated FAP patients, often before age 30. As a result, prophylactic colectomy is the standard therapy for individuals carrying APC mutations. • Colectomy prevents colorectal cancer, but patients remain at risk for neoplasia at other sites.

39. FAP is associated with a variety of extra-intestinal manifestations including congenital hypertrophy of the retinal pigment epithelium, which can generally be detected at birth and can be an adjunct to early screening.

40. HEREDITARY NON-POLYPOSIS COLORECTAL CANCER • Hereditary non-polyposis colorectal cancer (HNPCC), also known as Lynch syndrome, was originally described based on familial clustering of cancers at several sites including the colorectum, endometrium, stomach, ovary, ureters, brain, small bowel, hepatobiliary tract, and skin. • Colon cancers in HNPCC patients tend to occur at younger ages than sporadic colon cancers and are often located in the right colon

41. HNPCC is caused by inherited mutations in genes that encode proteins responsible for the detection, excision, and repair of errors that occur during DNA replication