Most common benign tumours are leiomyomas adenomas vascular tumours haemangioma lymphangioma malignant tumours carcinoid tumours lymphomas adenocarcinoma Carcinoid ID: 1037561
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1. Tumours of intestine
2. SMALL INTESTINAL TUMOURSMost common benign tumours, are leiomyomas, adenomas vascular tumours (haemangioma, lymphangioma) malignant tumours, carcinoid tumours lymphomas adenocarcinoma. .
3. Carcinoid Tumour (Argentaffinoma)tumours originating from endocrine cells (synonyms:argentaffin cells, Kulchitsky cells, enterochromaffin cells)belonging to APUD cell system and are therefore also called as apudomas The endocrine cells have secretory granules which stain positively with silver salts (argentaffin granules) classified as foregut,midgut, hindgut carcinoids.
4. Tryptophan5hydroxytryptophan 5HT(potent vasodilator,smooth muscle stimulant) 5HIAA (mid gut carcinoid produce large quantity of 5HT.5HIAA)EXCRETED IN URINE
5. A number of secretory products in a functioning carcinoidi) 5-Hydroxytryptamine (5-HT, serotonin)ii) 5-Hydroxytryptophaniii) 5-Hydroxy-indole acetic acid (5-HIAA)iv) Histamine Kallikrein Bradykinin
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7. MORPHOLOGIC FEATURES. Grossly, all carcinoids are small, button-like submucosal elevations with intact or ulcerated overlying mucosa. those larger than 2 cm are more often metastasising. Ileal and gastric carcinoids are commonly multipleappendiceal carcinoids involve the tip of the organ and are solitary Cut section of all the carcinoids is bright yellow.
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9. Histologically,the tumour cells may be arranged in a variety of patterns—solid nests, sheets, cords, trabeculae and clusters, show characteristic palisading of the peripheral cells. The tumour cells are small,monotonous, having uniform nuclei and poorly-defined cell boundaries The argentaffin carcinoids show eosinophilic granules in the cytoplasm which stain positively by the argentaffin reaction. Mitotic figures are rare but all carcinoids infiltrate the bowel wall.
10. solid masses and trabeculae of uniform, monotonous, small cells with palisading of the peripheral cells.
11. CARCINOID SYNDROME.Carcinoid tumours that metastasise, to the liver, associated with the carcinoid syndrome. 1. Intermittent attacks of flushing of the skin of face2. Episodes of watery diarrhea3. Abdominal pain4. Attacks of dyspnoea due to bronchospasm5. Right-sided heart failure due to involvement of tricuspid pulmonary valves and endocardium
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13. Polyps small elevations of the mucosa. referred as sessile Polyps with stalks are termed pedunculated classified as non-neoplastic neoplastic The most common neoplastic polyp is the adenoma,============== potential to progress to cancer. The non-neoplastic polyps classified as inflammatory, hamartomatous hyperplastic.
14. INFLAMMATORY POLYPS forms part of the solitary rectal ulcer syndrome ie clinical triad of rectal bleeding mucus discharge inflammatory lesion of the anterior rectal wall cause : recurrent abrasion and ulceration of the overlying rectal mucosa Entrapment of this polyp in the fecal stream leads to mucosal prolapse
15. histologic featuressuperimposed mucosal prolapse fibromuscular hyperplasia mixed inflammatory infiltrates, Erosion epithelial hyperplasia
16. Solitary rectal ulcer syndrome.A The dilated glands, proliferative epithelium, superficial erosions, and inflammatory infiltrate are typical of an inflamatory polyp. B Epithelial hyperplasiaC Granulation tissue-like capillary proliferation within the lamina propria caused by repeated erosion and re-epithelialization
17. Hamartomatous polyps occur sporadically with 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. HAMARTOMATOUS POLYPS
18. SyndromeMean Age at Presentation (yr).Gastrointestinal LesionsSelected Extra-Gastrointestinal ManifestationsPeutz-Jeghers syndrome10–15.Arborizing polyps; Small intestine > colon > stomach; colonic adenocarcinomaSkin macules; increased risk of thyroid, breast, lung, pancreas, gonadal, and bladder cancersJuvenile polyposis<5.Juvenile polyps; risk of gastric, small intestinal, colonic, and pancreatic adenocarcinomaPulmonary arteriovenous malformations, digital clubbingCowden syndrome, Bannayan-Ruvalcaba-Riley syndrome<15.Hamartomatous polyps, lipomas, ganglioneuromas, inflammatory polyps, risk of colon cancerBenign skin tumors, benign and malignant thyroid and breast lesionsCronkhite-Canada syndrome>50.Hamartomatous colon polyps, crypt dilatation and edema in nonpolypoid mucosaNail atrophy
19. Familial adenomatous polyposis (FAP) Classic FAP10–15.Multiple adenomasCongenital RPE hypertrophy Attenuated FAP40–50Multiple adenomas Gardner syndrome10–15.Multiple adenomasOsteomas, desmoids, skin cysts Turcot syndrome10–15.Multiple adenomasCNS tumors, medulloblastoma
20. Peutz-Jeghers Syndrome autosomal dominant syndrome presents at a median age of 11 years multiple GI hamartomatous polyps and mucocutaneous hyperpigmentation. dark blue to brown macules around the mouth, eyes, nostrils, buccal mucosa, palmar surfaces of the hands, genitalia, and perianal region.. polyps can initiate intussusception,-------fatal associated with an increased risk of several malignancies, (cancers of the colon, pancreas, breast, lung, ovaries, uterus, and testicles)loss-of-function mutations in the gene LKB1/STK11 (tumor suppressor gene)
21. Morphology. most common in the small intestine, Grossly, the polyps are large and pedunculated with a lobulated contour. Histologic examination a characteristic arborizing network of connective tissue, smooth muscle, lamina propria, glands lined by normal-appearing intestinal epithelium .
22. A, Polyp surface (top) overlies stroma composed of smooth muscle bundles cutting through the lamina propria. B, Complex glandular architecture and the presence of smooth muscle are features that distinguish Peutz-Jeghers polyps from juvenile polyps
23. Juvenile polyps are focal malformations of the mucosal epithelium and lamina propria,. occur in children less than 5 years of age. located in the rectum present with rectal bleeding. prolapse ---polyp protrudes through the anal sphincter usually solitary lesions ----- retention polyps, individuals with the autosomal dominant syndrome of juvenile polyposis have from 3 to as many as 100 hamartomatous polyps Pulmonary arteriovenous malformations -------- extra-intestinal manifestation
24. Morphology. less than 3 cm . pedunculated, smooth-surfaced, reddish lesions with cystic spaces . Microscopic dilated glands filled with mucin and inflammatory debris . The remainder of the polyp is composed of lamina propria expanded by mixed inflammatory infiltrates..pathogenesis mutations in pathways that regulate cellular growth . mutation of SMAD4Dysplasia can occur-----increased risk of colonic adenocarcinoma.syndrome.
25. Juvenile polyp. surface erosion and cystically dilated crypts. B, Inspissated mucous, neutrophils, and inflammatory debris can accumulate within dilated crypts.
26. The arborization and presence of smooth muscle intermixed with lamina propria are helpful in distinguishing polyps of Peutz-Jeghers syndrome from juvenile polypsCysticaly dilated glands filled with mucin and inflammatory debris The remainder of the polyp is composed of lamina propria expanded by mixed inflammatory infiltrates
27. Colonic hyperplastic polyps epithelial proliferations in the 60-70 yr result from decreased epithelial cell turnover and delayed shedding of surface epithelial cells Morphology. Hyperplastic polyps are most commonly found in the left colon, 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, Histologically,composed of mature goblet and absorptive cells. The delayed shedding of these cells leads to crowding that creates the serrated surface architecture . , .
28. A, Polyp surface with irregular tufting of epithelial cells. B, Tufting results from epithelial overcrowding. C, Epithelial crowding produces a serrated architecture when glands are cut in cross-section.
29. neoplastic polyps ---------------- colonic adenomas benign polyps that are precursors to colorectal adenocarcinomasAdenomas are intraepithelial neoplasms pedunculated polyps to large sessile lesions surface of both types having raspberry, due to the abnormal epithelial growth pattern. Most are clinically silent large polyps produce occult bleeding and anemia villous adenomas that cause hypoproteinemic hypokalemia by secreting large amounts of protein and potassium.
30. MorphologyHistologicallycharacterized by the presence of epithelial dysplasiachanges are at the surface of the adenoma the cytologic hallmark of epithelial dysplasia is nuclear hyperchromasia elongation, and stratification.presence of large nucleoli, eosinophilic cytoplasm, reduction in the number of goblet cells. the epithelium fails to mature as cells migrate from crypt to surface.
31. Colonic adenomas. A, Pedunculated adenoma B, Adenoma with a velvety surface. have slender fibromuscular stalks containing prominent blood vessels derived from the submucosaThe stalk is usually covered by non-neoplastic epithelium
32. classified as tubular, tubulovillous, or villous based on their architecture. Tubular adenomas small, pedunculated polyps composed of small rounded, or tubular, glands villous adenomas, larger and sessile, are covered by slender villi Tubulovillous adenomas have a mixture of tubular and villous elements.
33. A, Tubular adenoma with a smooth surface and rounded glands. , crypt dilation and rupture can be seen at the bottom . B, Villous adenoma long, slender projections that are reminiscent of small intestinal villi C, Dysplastic epithelial cells (top) Compare to the nondysplastic epithelium below D, Sessile serrated adenoma lined by goblet cells without typical cytologic features of dysplasia.
34. Sessile serrated adenomas 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 serrated architecture throughout the full length of the glands, including the crypt base associated with lateral growth and crypt dilation Difference with h/p polypserrated architecture is typically confined to the surface of hyperplastic polyps
35. Intramucosal carcinomaoccurs 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 (complete polypectomy is effective therapy) Invasion beyond the muscularis mucosa ------- invasive adenocarcinoma .
36. Adenoma with intramucosal carcinoma A Cribriform glands interface directly with the lamina propria without an intervening basement membrane B Invasive adenocarcinoma (left) beneath a villous adenoma (right). Note the desmoplastic response to the invasive components
37. most colorectal adenomas are benign lesions Size is the most important characteristic that correlates with risk of malignancy cancer is extremely rare in adenomas less than 1 cm in diameter high-grade dysplasia is a risk factor for cancer in an individual polyp
38. 00:00Colorectal Carcinoma
39. Adenocarcinoma98% of all cancers in large intestine almost always arise in adenomatous polyps
40. Epidemiologypeak incidence: 60 to 70 years of ageadenomas – precursor lesions for most tumorsmales affected ≈ 20% more often than females Geographic variations. Colorectal cancer is a disease of affluent societies because
41. Etiologyenvironmental influences:dietary practiceslow content of unabsorbable vegetable fiber leading to low stool bulk ------------ colorectal cancerhigh content of refined carbohydrates remain in contact with the colonic mucosa for prolong duration -----changes the bacterial flora of the bowel, ---resulting in production of carcinogenic substances.high fat content excessive cholesterol and their metabolites which may be carcinogenic.decreased intake of protective micronutrients (vitamins A, C, and E) .
42. Etiologygenetic influences:preexisting ulcerative colitis or polyposis syndromehereditary nonpolyposis colorectal cancer syndrome (HNPCC, Lynch syndrome) → germ-line mutations of DNA mismatch repair genes
43. adenoma-carcinomasequence hypothesis:i) In a case with early invasive cancer adenoma → hyperplasia → dysplasia → carcinoma in situ →Evidences ii) Incidence of adenomas directly proportionate to the prevalence of colorectal canceriii) The risk of adenocarcinoma colon declines with endoscopic removal of all identified adenoma
44. The risk of malignancy increases with the followingadenoma-related factors:a) Number of adenomas: more related with familial polyposis coli syndrome b) Size of adenomas: large size increases the risk.c) Type of adenomas: greater villous component
45. Hereditary non-polyposis colonic cancer (HNPCC orLynch syndrome). an autosomal dominant condition associated with colorectal cancer is seen in first-degree relatives before the age of 50 years mutations in mismatch repair genes association with multiple primary cancers at different sites (e.g. endometrium, ovary), preferred location in proximal colon
46. GENETIC BASIS OF COLORECTALCARCINOGENESIS.1.Microsatellite instability mechanism 2.APC mutation/ β-catenin mechanism i) Loss of tumour suppressor APC (adenomatous polyposis coli) gene (5q) translocation of β-catenin to the nucleus activates transcription of MYC and cyclin D1, stimulate cell proliferation. Point mutation in K-RAS gene follows loss of APC gene + Loss of p53 tumour suppressor gene
47. Carcinogenesischromosome instability pathway
48. Microsatellite instability mechanism Basic mutation is loss of DNA repair gene. repetitive DNA sequences (i.e. microsatellites)become unstable during replication cycle, ------- microsatellite instability, DNA repair genes which are mutated in colon cancer TGF-β receptor gene which normally inhibits cell proliferation but in mutated form allows ----uncontrolled proliferation of colonic epithelium in adenoma.ii) BAX gene which normally causes apoptosis but by mutaiton loss of apoptosis and dysregulated growth.
49. Carcinogenesismismatch repair (microsatellite instability) pathway
50. Morphology.
51. MORPHOLOGIC FEATURES. 60% of the cases occur in the rectum, differences between the growth on the right and left half of the colonRight-sided colonic growths tend to be large, cauliflower-like, soft and friable masses projecting into the lumen (fungating polypoid carcinoma).Left-sided colonic growths,napkin-ring configuration i.e. they encircle the bowel wall circumferentially with increased fibrous tissue forming annular ring, central ulceration on the surface (carcinomatous ulcers) slightly elevated margins
52. Morphologyall colorectal carcinomas begin as in situ lesionstumors in the proximal colon: polypoid, exophytic masses
53. Morphologyin the distal colon: annular, encircling lesions that produce “napkin-ring” constrictions of the bowel and narrowing of the lumenboth forms of neoplasm Eventually penetrate the bowel wall and may appear as firm masses on the serosal surface
54. A, Right-sided growth—fungating polypoid carcinoma showing cauliflower-like growth projecting into the lumen. B, Left-sided growth—napkin-ring configuration with spread of growth into the bowel wall
55. These differences in right and left colonic growths are probably due to the liquid nature of the contents in the ascending colon leaving space for luminal growth on rightside, while the contents in left colon are more solid permitting the spread of growth into the bowel wall.early lesion in left as well as right colon are small, button-like areas of elevation.
56. Microscopically 10% are mucin-secreting colloid carcinomas . The remaining 5% tumours undifferentiated carcinoma, signet-ring cell carcinoma, adenosquamous carcinomas seen in near the anus. The histologic grades well-differentiated, moderately differentiated poorly-differentiated.
57. Colonic adenocarcinoma. A, Moderately differentiated. B, Mucin-secreting adenocarcinoma
58. SPREAD. Direct spread.circumferentially into bowel wall directly into the depth of the bowel wall to the serosa, pericolic fat, and mesentry into peritoneal cavity2. Lymphatic spread. firstly the regional lymph nodes preaortic, internal iliac and the sacral 3. Haematogenous spread. relatively late goes to liver, lungs brain, bones and ovary.
59. Clinical Features Cecal and right colonic cancers:i) Occult bleeding (melaena)ii) Change in bowel habits, more often in left-sided growthiii) Loss of weight (cachexia)iv) Loss of appetite (anorexia) fatigueiron deficiency anemialeft-sided lesions: occult bleedingchanges in bowel habitcrampy left lower quadrant discomfortiron deficiency anemia in an older man means gastrointestinal cancer until proved otherwise
60. complications obstruction and haemorrhage; perforation and secondary infection
61. .diagnosisdetection and diagnosis:digital rectal examinationfecal testing for occult blood lossbarium enema, sigmoidoscopy and colonoscopyconfirmatory biopsycomputed tomography and other radiographic studiesserum markers (elevated blood levels of carcinoembryonic antigen)molecular detection of APC mutations in epithelial cells, isolated from stool detection of abnormal patterns of methylation in DNA isolated from stool cells
62. STAGING AND PROGNOSIS. The prognosis of colorectal cancer depends upon Extent of the bowel involvementii) Presence or absence of metastasesiii) Histologic grade of the tumouriv) Location of the tumour.Three staging systems are in use:1. Dukes’ ABC staging (modified Duke’s includes stage D aswell).2. Astler-Coller staging which is a further modification ofDuke’s staging .3. TNM staging described by American Joint Committee isalso used.
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65. Pathologic staging according to Astler-Coller system
66. IMPORTANT QUESTIONS Q. Classify polyps of the intestine and describe their clinicopathological featuresQ. Differentiate between tubular and villous adenomasQ. Write briefly on hereditary cancer syndromes of colon.Q. Write briefly on colorectal carcinogenesis/adenoma–carcinoma sequenceQ. Enumerate the various modalities for diagnosing colorectal carcinomaQ. Differentiate between right-sided and left-sided colonic carcinoma.Q. Describe the clinicopathological features of carcinoid tumour of GIT