1. Neoplasm of colon Dr. Amitabha Basu MD

2. Topic Terms Classification of neoplasm Classification of non-neoplastic polyps Discussion on polyps Polyps and syndrome Discussion on carcinomas

3. Terms Polyp : Mass protruded in lumen –Pedunculated –Sessile Adenomatous polyps: a polyp formed by an adenoma.

4. Classification of neoplasm of colon 1.Non neoplastic polyp 2.Neoplastic lesions 3.Adenomatous polyp 4.Carcinoma 5.Mesenchymal neoplasms 6.Lymphoma

5. Important Non-neoplastic polyp Hyperplastic polypsCommon, no malignant potential Hamartomatous polyps Juvenile polyps Peutz-Jeghers polyps

6. Hyperplastic polyp small star shaped (usually <5 mm in diameter) epithelial polyps like due drop. Location: recto sigmoid colon No malignant potential

7. Hamartomatous Polyps Juvenile polyps : Focal hamartomatous malformations of mucosa. Also called as retention polyps=1 to 3 cm in diameter. Tumor composed of Cystically dilated glands. Location: colon and rectum Clinical: spontaneous removal with stool and blood.

8. Peutz-Jeghers polyps Hamartomatous polyps that involve the mucosal epithelium, lamina propria, and muscularis mucosa. Location: mainly small intestine Associated with Peutz-Jeghers syndrome.

10. Neoplastic lesions Adenomatous polyp Carcinoma Carcinoid

11. Adenomas (adenomatous polyps) Tubular adenoma Villous adenoma

12. Adenoma Tubular adenomaVillous adenoma Pedunculated Colon, Stomach, and small intestine, ampulla of Vater Large and sessile Rectum and recto sigmoid colon 75% tubular architectureVillus projection Cancer is rareMore chance of cancer(40%) Dysplasia:+Dysplasia ; +++++++++ Presentation: asymptomatic, rectal occult bleeding (+ve guaiac test), Iron deficiency anemia

13. Tubular adenoma (a Pedunculated adenoma showing a fibro vascular stalk ) Adenomatous epithelium in an otherwise normal (mucin-secreting, clear) colonic mucosa

14. diagnosis?

15. Villous adenoma: sessile adenoma with villous architecture Dysplasia present: locate it

16. Malignant risk with an adenomatous polyp Cancer is rare in tubular adenomas < 1 cm in diameter. The risk of cancer is high (approaching 40%) in sessile villous adenomas > 4 cm in diameter. Severe dysplasia, when present, is often found in villous areas.

17. Treatment Single pedunculated polyp: polypectomy Polyposis: complete resection Sessile adenoma: recestion

18. Polyps and syndrome Various syndromes are associate with the polyps of the intestine

19. Familial Polyposis syndrome Autosomal dominant. Number: > 100. Two syndromes: –Classic FAP syndrome, patients typically develop 500 to 2500 colonic adenomas. –Variant of FAP=Gardner syndrome exhibit intestinal polyps identical to those in classic FAP ( + osteoma, epidermal cysts, fibromatosis, CA breast )

20. Familial Polyposis syndrome Study other similar picture

21. SyndromesAltered Gene Pathology in GI Tract Familial adenomatous Polyposis APC ( 5q21)Multiple adenomatous polyps Hereditary nonpolyposis colorectal carcinoma AKA: lynch syndrome Autosomal dominant familial syndrome Defects in mismatch DNA repair genes → leading to micro satellite instability Colon cancer, endometrial cancer and fewer/no polyps. Syndromes

22. Pathology in GI Tract Peutz-Jeghers syndrome Hamartomatous polyps+ multiple carcinomas + pigment in mouth, lips Juvenile polyposis syndrome Numerous Juvenile polyps Turcot syndromeMultiple adenomatous polyps, Gliomas. Cowden diseaseHamartomatous polyps + carcinoma breast Syndromes

23. Malignant Epithelial Lesions Adenocarcinoma* Carcinoid tumor

24. Colorectal carcinoma: topic Features Colorectal Carcinogenesis; –Multistep carcinogenesis Morphology

25. Features Age: Ages 60 and 79 Dietary factors: –(1) Excess dietary caloric intake. –(2) A low content of unabsorbable vegetable fiber, –(3) High content of refined carbohydrates, –(4) Intake of red meat, and –(5) Decreased intake of protective micronutrients (vitamins A, C, and E )

26. Adenoma carcinoma sequence: Multistep carcinogenesis

27. Adenoma carcinoma sequence 1.Loss of Adenomatous Polyposis Coli (APC) Gene(5q21 ) : first hit & second hit: 2 hit theory 2.Mutation of K-RAS + Loss of SMADs + Loss of p53 = adenoma formation. 3.Activation of Telomerase: invasive tumor.

28. Gross of colon cancer Proximal colon (right)Distal colon (left) Polypoid Exophytic masses Annular, encircling lesions (napkin-ring constrictions ) Obstruction is uncommon. Obstruction is common. Develop iron deficiency anemia No anemia

29. Carcinoma of the cecum. The fungating carcinoma projects into the lumen but has not caused obstruction

30. Carcinoma of the descending colon. Circumferential tumor has heaped-up edges and an ulcerated central portion. The arrows identify separate mucosal polyps

31. Microscopic morphology Features of right- and left-sided colonic adenocarcinoma are similar. Shows desmoplastic reaction. Many tumors produce mucin- PAS positive Some cancers the cells take on a signet- ring appearance

32. Invasive adenocarcinoma of colon, showing malignant glands infiltrating the muscle wall.

33. Marker and clinical CEA ( carcino embryonic antigen) –Useful for following the course of the disease. –Stool : occult blood positive ( non specific) –Alternate Constipation and diarrhea.

34. Staging of colon carcinoma Depends on: size, node involvement and metastasis. The Astler-Coller Staging System TNM

36. T Tis=Carcinoma in situ (high-grade dysplasia) or intramucosal carcinoma (lamina propria invasion) T1=Tumor invades sub mucosa T2=Extending into the muscularis propria but not penetrating through it T3=Penetrating through the muscularis propria into subserosa T4=Tumor directly invades other organs or structures

37. NM Nx= Regional lymph nodes cannot be assessed N0=No regional lymph node metastasis N1=Metastasis in 1 to 3 lymph nodes N2=Metastasis in 4 or more lymph nodes Mx=Distant metastasis cannot be assessed M0=No distant metastasis M1=Distant metastasis

38. Grading Grade depends on: # of mitosis and differentiation. Well differentiated tumor (WD) : good prognosis. Small tumor (usually < 2 cm) : usually good prognosis Low mitosis (WD): good prognosis More/ atypical mitosis: bad prognosis

39. Prognosis depends on Grading and staging – 2 of 2 Tumor with high mitosis: poor prognosis. Lymph node involvement : bad prognosis –(more the number worse is the prognosis) Distant metastasis: bad prognosis always. Poorly differentiated < undifferentiated tumor < anaplasia : poor prognosis.

40. Carcinomas arising in the anorectal canal Dominated by squamous cell carcinoma. Below the ano-rectal junction Due to chronic HPV infection

41. Carcinoid tumors Origin: Neuroendocrine cells Age: sixth decade Appendiceal (commonest) and rectal carcinoids. Other sites: Ileal, gastric, and colonic carcinoids.

42. Morphology The appendix is the most common site. Appendicular tumor: Appear as bulbous swellings of the tip, which frequently obliterate the lumen. Other place: Bronchus= Intramural masses that create small, polypoid or plateau-like elevations(<3cm) Remember the size

43. Colour Characteristic feature is a solid, yellow- tan appearance on transection. Micro: –form discrete islands, trabeculae, stands, glands. –a scant, pink granular cytoplasm and a round to oval stippled nucleus

44. Multiple protruding tumors are present at the ileocecal junction

45. Tumor cells exhibit a monotonous morphology (salt and pepper)

46. Electron micrograph showing dense core bodies in the cytoplasm Study other similar picture

47. Clinical Features: many are asymptomatic Malignant carcinoid: mets. to liver Skin Flushing & diarrhea Carcinoid syndrome: By Serotonin Gastric and pancreatic carcinoids Produce. Multiple non healing peptic ulcers. Zollinger-Ellison syndrome by Gastrin Cushing syndrome ; hypertension, weight gain, moonfaced. ACTH Appendix carcinoid → ObstructionAppendicitis (RUQ pain and neutrophilia)

48. Diagnosis and prognosis Elevated levels of 5-HT and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), are present in the blood and urine. Overall five-year survival rate for carcinoids (excluding appendiceal) is approximately 90%

49. GASTROINTESTINAL LYMPHOMA Definition ::- Primary gastrointestinal lymphomas exhibit no evidence of liver, spleen, mediastinal lymph node, or bone marrow involvement at the time of diagnosis. They are nonHodgkins lymphoma(NHL)

50. Etiology/Risk factors (1) Chronic gastritis caused by H. pylori (2) Chronic sprue like syndromes (3) Natives of the Mediterranean region (4) Infection with human immunodeficiency virus.

51. Classification: GASTROINTESTINAL LYMPHOMA B-cell lymphoma MALT lymphoma ; small tumor [t(11;18): translocation common] Starry sky: bulky tumor Burkitt lymphoma (t8;14 )

52. Morphology Location: –Stomach, Small intestine, colon Gross: plaque-like, with effacement of the overlying mucosal folds and focal ulceration. Micro: Small/Large blue round cell with scanty cytoplasm.

53. Melanosis coli DEF: Black (brown –black) pigmentation of colon. Deposit: Lipofuscin ( “wear and tear”) Etiology: laxative use Can mimic a tumor/ colitis Clinical: constipation.

54. Thank you