1. Tumors of the small and large intestines
Non-neoplastic polyps
Neoplastic ( epithelial) polyps
Mesenchymal lesions
Lymphoma

2. Tumors of the small and large intestine
Epithelial tumors are a major cause of morbidity and mortality worldwide
The colorectal cancer is the GIT segment most commonly affected by tumors
It is the host to more primary tumors than any other tumor of the body.
Colonic carcinoma is second to bronchogenic carcinoma as a cause of death in USA.
Adenocarcinoma in colorectum represent 70% of all malignancy of GIT
Benign tumors, primarily epithelial, are present in 25 to 50% of older adults. 1

3. Terminology of Intestinal Tumors
Polyps and Polyposis Syndromes
Polyp is a mucosal growth that protrude into the lumen of gut. It could be sessile or pedunculated
Polyps may be formed as the result of abnormal mucosal maturation, inflammation, or as epithelial proliferation with dysplasia 2

4. Terminology of Intestinal Tumors
Polypoid lesions is the inflammatory masses, hamartomas and tumors arising from the submucosa or muscle coat, but also protruding into the lumen.
Polyposis is multiple polyps.
Polyposis syndrome is hereditary, characterized by the presence of multiple pedunculated or sessile tumors of the mucosa

5. Tumors of the small and large intestine Classification
Non-neoplastic polyps
Hyperplastic polyps
Hamartomatous polyps (Juvenile & Peutz-Jeghers polyps)
Inflammatory polyps
Lymphoid polyps
Neoplastic ( epithelial) polyps
Benign polyps (adenoma)
Malignant lesions
Adenocarcinoma
Carcinoid
Anal zone carcinoma
Mesenchymal lesions
GIT stromal tumors (benign & malignant)
Others ( lipoma, neuroma, angioma, Kaposi sarcoma)
Lymphoma

6. Non-Neoplastic Polyps
Intestinal Polyps
Non-Neoplastic Polyps
Represent 90% of all epithelial polypi found in large intestine.
Found in more than half of all persons age 60 years or older.
Types: 1. Hyperplastic polyp.
2. Hamartomatous polyp (Juvenile & Peutz- Jeghers)
3. Inflammatory polyp
4. Lymphoid polyp 3

7. Intestinal Polyps Asymtomatic
1] Hyperplastic Polyp
Asymtomatic
> 50% are located in the rectosigmoid, 20% in the ascending colon.
Smooth, moist, round, small (0.5cm) sessile lesions.
Multiple polyps are frequent.
Composed of well-formed glands and crypts lined by differentiated goblet or absorptive cells.
Pure hyperplastic polyps have no malignant potential.
Larger hyperplastic polyps; foci of adenomatous change.

8. Non-Neoplastic Polyp 2] Hamartomatous polyp
Juvenile Polyps (retention polyp)
Developmental malformations affecting the glands and lamina propria, having no malignant potential.
commonly occur in children under 5 years old in the rectum. In adult called retention polyp.
Painless rectal bleeding after defecation.
Large, rounded, smooth lesions with a stalk
Histology: mucus-filled, cystically dilated tubules lined by normal or inflamed mucosa.
Juvenile polyposis syndrome. Occurrence of multiple hamartomatous polyps throughout the GI tract. 4

9. 2] Hamartomatous Polyps
Non-Neoplatic Polyps
2] Hamartomatous Polyps
Peutz-Jehgers polyps
Uncommon hamartomatous polyps accompanied by mucosal and cutaneous pigmentation around the lips, oral mucosa, face and genitalia.
Rare, autosomal dominant.
Caused by germ-line mutation in the LKB1 gene, which encodes a serine threonine kinase.
Polyps tend to be large and pedunculated.
May occur anywhere in the GI tract.
Have an increased risk of developing carcinoma of the pancreas, breast, lung, ovary and uterus. 5

10. hamartomatous polyp

11. Non-Neoplastic Polyps
3] Inflammatory Polyps
Occur in patients with longstanding IBD, especially in chronic ulcerative colitis.
Usually multiple.
Represent an exuberant reparative response to longstanding mucosal injury called pseudopolyps 6

12. 4] Lymphoid polyps

13. Neoplastic Polyps (Adenomas)
Adenomatous Polyp
Occur mainly in large bowel.
Prevalence: 20% to 30% before age 40, 50% after age 60.
Males and females are equally affected
Spordic and familial
Vary from small pedunculated to large sessile
Epithelium proliferation and dysplastia with loss of basal orientation of nuclei (pseudostratified).
Divided into:
Tubular adenoma has less than 25% villous architecture
Villous adenoma villous architecture over 50%
Tubulovillous adenoma villous architecture between 25 and 50%. 7

14. All adenomatous lesions arise as the result of epithelial proliferation and dysplasia, which may range from mild to so severe as to represent transformation to carcinoma.

15. Neoplastic Polyps 1] Tubular adenoma
Represents 75% of all neoplastic polyps.
Occurs sporadicaly and in well defined hereditary syndromes.
Average age is 60 years
75 % occur in the distal colon and rectum.
More than 50% occur singly.
Size: few millimeters (sessile) to many centimeters (have stalk).
Stalk has a central core of fibrovascular tissue, covered with dysplastic colonic mucosa.
Severe dysplasia and invasive carcinoma may supervene. 8

16. Tubular adenoma

17. Neoplastic Polyps 2] Villous Adenoma
The least common, largest and most ominous of epithelial polyps.
Age: 60 to 65 years, M:F ratio roughly equal.
Present with rectal bleeding or anemia, large ones may secrete copious amounts of mucoid material rich in protein.
75% located in rectosigmoid area. 10

18. Neoplastic Polyps 2] Villous Adenoma Morphology
Size: 1 to 10 cm in diameter.
Most are broad, sessile, velvety lesions projecting 1 to 3 cm.
Frondlike papillary projections of adenomatous epithelium with a delicate fibrovascular core.
All degree of dysplasia with frank invasive carcinoma in up to 40%. 10

19. Neoplastic Polyps 3] Tubulovillous adenoma
Intermmediate in size, frequency of having a stalk, degree of dysplasia and malignant potential between tubular and villous adenomas. 11

20. Neoplastic Polyps Clinical features
The smaller adenomas are usually asymptomatic, occult bleeding.
Villous adenomas are much more frequently symptomatic because of overt or occult rectal bleeding or mucoid material rich in protein and potassium to produce hypoproteinemia or hypokalemia.
Adenomas in the immediate vicinity of the ampulla of Vater may produce biliary obstruction.

21. Relationship of Neoplastic Polyps to Carcinoma
Adenoma to carcinoma sequence is documented by several observations and genetic alterations.
The probability of carcinoma occuring in a neoplastic polyp is related to:
1. The size of the polyp.
2. The relative proportion of its villous features.
3. The presence of significant cytologic atypia
(dysplasia) in the neoplastic cells. 12

22. Familial Polyposis Syndrome
Patients have genetic tendencies to develop neoplastic polyps, most often autosomal dominant.
Familial polyposis coli (FPC)
Genetic defect ch5 q21.
Innumerable neoplastic polyps in the colon (500 to 2500)
Polyps are also found elsewhere in alimentary tract
Most polyps are tubular adenomas
The risk of colorectal cancer is 100% by midlife.
Gardener’s syndrome
Polyposis coli, multiple osteomas, epidermal cysts, and fibromatosis.
Turcot syndrome
Polyposis coli, glioma and fibromatosis 13

24. Malignant Tumors of Large Intestine Adenocarcinoma
Constitutes 98% of all cancers in the large intestine.
Worldwide distribution, highest incidence in west.
Causes 15% of all cancer-related death in the USA.
The mortality rate and incidence is higher in blacks.
Peak incidence in the sixth to seventh decade. 14

25. Malignant Tumors of Large Intestine Adenocarcinoma
Predisposing factors: IBD, polyposis syndrome.
Male:female ratio is 2:1 in rectal cancer, roughly equal in colon cancer, generally males are affected about 20% more than females.
Diet appears to play an important role in the risk for colon cancer:
- Low content of unabsorpable vegetable fibre.
- High content of refined carbohydrates.
- High fat content.
- ? Increased intake of nitrites, nitrates (nitrosamines).
- Reduced intake of vit A, C & E.
The use of aspirin and NSAID (cyclooxygenase-2 inhibitors) exerts a protective effect against colon cancer

26. When colorectal cancer is found in a young person, preexisting ulcerative colitis or one of the polyposis syndromes must be suspected.
Individuals with hereditary nonpolyposis colorectal cancer syndrome (HNPCC, also known as Lynch syndrome), caused by germ-line mutations of DNA mismatch repair genes, are at a high risk of developing colorectal cancers.
(HNPCC patients are also at risk of developing other tumors, such as cholangiocarcinomas.)

27. Malignant Tumors of Large Intestine Adenocarcinoma
Colorectal carcinogenesis
Two pathogenetically distinct pathways for the development of colon cancer, both seem to result from accumulation of multiple mutations
The APC/B-catenin pathway
chromosomal instability that results in stepwise accumulation of mutations in a series of oncogenes and tumor suppressor genes.
Localized colon epithelial proliferation followed by the formation of small adenomas, become more dysplastic, and ultimately develop into invasive cancers.

28. Malignant Tumors of Large Intestine Adenocarcinoma
Colorectal carcinogenesis
This adenoma-carcinoma sequence accounts for aboout 80% of sporadic colorectal cancers.

29. Malignant Tumors of Large Intestine Adenocarcinoma
The DNA mismatch repair genes pathway:
10% to 15% of sporadic cases.
There is accumulation of mutations (as in the APC/B-catenin schema) but the involved genes are different.
Unlike in the adenoma-carcinoma sequence, there are no clearly identifiable morphologic correlates

30. Malignant Tumors of Large Intestine Adenocarcinoma
In DNA mismatch repair genes pathway defective DNA repair caused by inactivation of DNA mismatch repair genes is the fundamental and the most likely initiating event in colorectal cancers
Inherited mutations in one of five DNA mismatch repair genes (MSH2, MSH6, MLH1, PMS1, AND PMS2) give rise to the hereditary non polyposis colon carcinoma (HNPCC)
MLH1 gene is the one most commonly involved in sporadic colon carcinomas

31. Malignant Tumors of Large Intestine Adenocarcinoma
Microsatellite instability (MSI) is the molecular signature of defective DNA mismatch repair
Most microsatellite sequences are in noncoding regions of the genes so mutations in these genes are probably harmless.
However, some micorsatellite sequences are located in the coding or promoter region of genes involved in regulation of cell growth.

32. HNPCC

33. Colorectal Carcinoma Morphology
Sixty to 70% of colorectal carcinomas are in the rectum, rectosigmoid and sigmoid colon.
Left-sided carcinomas tend to be annular, encircling lesions with early symptoms of obstruction.
Neoplasms start superficially, slowly invading the deeper layers with ulceration and eventually metastasis. 15

35. Colorectal Carcinoma Morphology
Right-sided carcinomas tend to grow as polypoid, fungating masses, obstruction is uncommon.
Invasion of the wall and extend to the mesentery, regional lymph nodes and more distal sites.
Mucinous adenocarcinoma secret abundant mucin that may dissect through cleavage planes in the wall.
Small cell undifferentiated carcinomas are rare (arising from neuroendocrine cells)
In UC, poorly differentiated infiltrative adenocarcinoma without an exophytic growth. 16

38. Left-sided lesions tend to present earlier but
Colorectal Carcinoma
Clinical features
The condition tends to be present for a considerable time before producing symptoms.
Left-sided lesions tend to present earlier but
also have a more infiltrative growth pattern and a poorer prognosis.
Right-sided lesions tend to present with weakness, malaise, weight loss, unexplained anemia (secondary to early bleeding). 17

39. Colorectal Carcinoma Spread: - direct extension. - metastasis through:
- lymphatic
- blood vessels
- favored sites are regional lymph node, liver, lungs, bones.
Serum levels of carcinoembryonic antigen (CEA) are related to tumor size and extent of spread. They are helpful in monitoring for recurrence of tumor after resection.
Overall 5-year survival is 35 to 49% in the United States. 18

43. Colorectal Neoplasm Other Tumors
Malignant spindle cell (mesenchymal) tumors and lymphomas.
Grossly and microscopically resemble those arising elsewhere in the GI tract.
Carcinoid tumors may arise anywhere in the colon, especially the rectum.
Squamous cell carcinomas are largely limited to the rectal canal. Initially present as plaque-like lesions, later becoming ulcerated or fungating.
Malignant melanoma at the anal verge. 19

44. Small Intestinal Neoplasms
3-6% of GIT neoplasm, slight preponderance to benign tumors.
BENIGN
Discovered incidentally, leiomyoma, adenoma and lipoma
Large lesions may cause obstruction, bleeding, intussusception, volvulus.
ADENOMAS
Single or multiple polyps, most often in the duodenum and ileum.
There is a risk of malignancy with larger adenomatous polyps.
MALIGNANT
In descending order of frequency: carcinoid, adenocarcinomas, lymphomas and leiomyosarcomas.
Leiomyosarcomas have tyrosine kinase receptors, can be treated by STI-571 20

45. Small Intestinal Neoplasms
Adenocarcinoma of small intestine
Tumors grow as polypoid fungating ulcerating mass or encircling pattern
Site: duodenum ( ampulla of Vater)
Presentation: abdominal cramping pain, vomiting and weight loss
Patients present late
5 years survival is 70% after en bloc resection

46. Small Intestinal Neoplasms
Carcinoid Tumors
Neoplasms arising from endocrine cells Kulchitsky or enterochromaffin cells found along the length of GIT mucosa. Cells have an affinity for silver salts.
60 to 80% appendix and terminal ileum: 10 to 20% rectum, the remainder in the stomach, duodenum or esophagus.
Other Location: Lungs, pancreas, biliary tract, ovaries and liver.
Peak age: 6th decade, comprise 2% of colorectal carcinoma and 50% of small intestinal carcinoma.
Tumors in the appendix and rectum, although spreading locally, seldom metastasize.
Ileal, gastric, and colonic carcinoids are frequently malignant. 21

47. Gastric and ileal carcinoids are frequently multiple.
Carcinoid Tumors
Morphology
Round submucosal elevations that are bright yellow or yellow-gray, may be deeply infiltrative and penetrate muscle to the serosa.
Gastric and ileal carcinoids are frequently multiple.
Tumor cells arranged in trabecular, insular, glandular or undifferentiated patterns are monotonously similar to each other with regular round nuclei
Ultrastructral features: neurosecretory electron dense bodies in the cytoplasm

48. Small Intestinal Neoplasms
Carcinoid Tumor
Clinical features
Asymptomatic
May cause obstruction, intussusception or bleeding.
May elaborate hormones: Zollinger-Ellison, Cushing’s carcinoid or other syndromes.
5 years survival rate is 90%, small bowel Carcinoid with liver metastasis the 5 years survival rate is better than 50% 22

49. Small Intestinal Neoplasms
Carcinoid tumor
Carcinoid syndrome
Syndrome occur in 1% of all pt. with carcinoid & in 20% of those of widespread metastasis
Paroxymal flushing, episodes of asthma-like wheezing, right-sided heart failure, attacks of watery diarrhea, abdominal pain, edema and pellagra-like lesions of the skin and oral mucosa.
The principal chemical mediator is serotonin (5-hydroxy-tryptamine-5HT).
5-HT is decarboxylated in the liver and lungs to
5-hydroxy-indoleacetic acid (5HIAA)
The syndrome is classically associated with ileal carcinoids with hepatic metastases. 23

50. Small Intestinal Neoplasms
Lymphoma
Up to 40% of lymphomas arise in sites other than lymph nodes, gut is the most.
1% to 4% of all gastrointestinal malignancies are lymphomas.
Primary GIT lymphomas exhibit no evidence of liver, spleen, or bone marrow involvement at the time of diagnosis.

51. Small Intestinal Neoplasms
Lymphoma
Sporadic lymphoma arise from the B cells of mucosa-associated lymphoid tissue (MALT).
This usually affects adults, lacks a sex predilection, and may arise anywhere in the gut: stomach - 55% to 60% -
small intestine - 25% to 30% -
proximal colon - 10% to 15% -
distal colon - up to 10% -

52. Small Intestinal Neoplasms
Lymphoma
Gastric MALT lymphomas arise in the setting of mucosal lymphoid activation, as a result of Helicobacter associated chronic gastritis.
Celiac disease is associated with a higher than normal risk of T-cell lymphomas.

53. Small Intestinal Neoplasms
Lymphoma
Primary GIT lymphomas have a better prognosis than do those arising in other sites.
Treatment: combined surgery, chemotherapy, and radiation therapy.

54. Thank you