Dr Nirmal P Shah

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.

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

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. 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

7. Intestinal Polyps
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.

9. 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.

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

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%.

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.

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.

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%.

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.

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.

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

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.

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

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.

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.

38. 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).

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.

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.

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

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.

47. 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%

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.

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. Overview of
Colorectal Cancer
Maryland Department of Health & Mental Hygiene
Cigarette Restitution Fund Program
Center for Cancer Surveillance and Control
Cigarette Restitution Fund Programs Unit
March, 2009

55. What is colorectal cancer?
• Cancer that begins in the
colon (bowel or large
intestine) or rectum is
known as colorectal
cancer
– The colon is about 5
feet long.
– Colorectal cancer can
occur any section of
the colon or the
rectum.

56. What causes colorectal cancer?
• It is not known exactly what causes
colorectal cancer
– But there are risk factors that increase
chances for colorectal cancer:
• Some risk factors cannot be changed---
age, personal and family history
• Some risk factors can be changed or
eliminated---tobacco use, obesity,
inactivity

57. What are the
personal and family risk factors?
• Age
– More than 90% of colorectal cancer is found
people ages 50 and over.
• Family history (in a mother, father,
brother, sister, or child):
– Colorectal cancer
– Adenomatous polyps or “adenomas”

58. Personal history of:
– Colorectal cancer
– Adenomatous polyps or
“adenomas”
• An adenoma is a growth that
can turn into cancer
– Ovarian or endometrial
cancer before age 50
– Inflammatory bowel disease
• Ulcerative colitis and Crohn
colitis
Source: NCI
Source: American Cancer Society
What are the
personal and family risk factors (cont.)?

60. Other risk factors
• Other risk factors for colorectal
cancer include:
– Smoking
– Diets high in fat
– Obesity in premenopausal women
Source: American Cancer Society

61. Race and colorectal cancer
• Compared to Caucasians, African-
Americans…
– Develop colon cancer at a younger age
– Have decreased access to screening
– Have more ‘aggressive’ colon cancer
– Have a reduced response to
chemotherapy for advanced disease
– Have reduced survival (30% mortality
increase)
Am J Gastroenterol 100:515, 2005

62. What are the signs and symptoms
for colorectal cancer?
• Early stages of colorectal cancer may have
NO signs or symptoms.
• If signs and symptoms are present, they
may include:
– Bleeding from the rectum or blood in the stool
– Marked change in bowel habits
– Abdominal mass
– Abdominal cramps or pain
– Iron deficiency anemia that is not due to other
conditions
Source: American Cancer Society

63. Who should be screened for
colorectal cancer?
• People ages 50 and over
• People under 50 with:
–Personal or family risk factors
Source: American Cancer Society
Colorectal Cancer Screening
Saves Lives!

64. How do we test for
colorectal cancer?
Tests used to look for
colorectal cancer:
– Colonoscopy
– Flexible Sigmoidoscopy
– Fecal Occult Blood Test
(FOBT)
– Double contrast barium
enema
– Other
Source: Oncolink

65. Colonoscopy
• Colonoscopy:
doctor uses a
flexible tube with a
light to look inside
your large intestine
(colon or guts).

66. Colonoscopy (cont.)
• Colonoscopy looks at the whole
colon to find and remove polyps
or to find cancer.
• The procedure takes about 30
minutes unless polyps need to be
removed.
Source: American Cancer Society

67. Different types of polyps
Sessile polyp Sessile polyp
Tubulovillous
adenoma
Biopsy forceps

68. Different types of adenomas
Sessile polyp
Tubular
adenoma
Sessile polyp
Tubulovillous
adenoma
Polyp removal

69. What should I do to get ready for
colonoscopy?
• Bowel Preparation: Before
colonoscopy, the colon must be
clean so the doctor can see inside
the entire colon.
– Clear liquid diet one to two days before
the test
– Laxatives to eliminate stool from the
colon

70. Clean colon showing adenomas
Pedunculated polyp
Tubular adenoma
Pedunculated polyp
Tubular adenoma

71. What about during and after
colonoscopy?
• Just before the test, you will be
given medications to relax you.
• After the test, you will need
someone to take you home.
• Although the procedure is safe,
colonoscopy involves slight risk
(bleeding, perforation).

72. Can I reduce my risk for
colorectal cancer?
• You can reduce your risk for
colorectal cancer:
– Get screened for colorectal cancer
– Achieve and maintain a healthy weight
– Exercise at least 30 minutes on five or more
days each week
– Eat at least five servings of vegetables and
fruits each day
– Avoid tobacco and alcohol
Source: American Cancer Society

73. THE
END
Colorectal Cancer Screening
Saves Lives!