L18 colorectal carcinoma

1. Colorectal Carcinoma
Lecture 18

2. Colorectal
Carcinoma
Adenocarcinoma 98%

4. Intestinal tumors
Non-neoplastic Polyps
Hyperplastic polyps
Hamartomatous polyps
Juvenile polyps
Peutz-Jeghers polyps
Inflammatory polyps
Lymphoid polyps
Neoplastic Epithelial Lesions
Benign polyps
Adenomas
Malignant lesions
Adenocarcinoma
Squamous cell carcinoma of the anus
Other Tumors
Gastrointestinal stromal tumors
Carcinoid tumor
Lymphoma
Epithelial tumors of the intestines:
major cause of morbidity and mortality worldwide
Colon, including rectum:
host to more primary neoplasms than any other
organ in the body

5. Adenocarcinoma
Adenocarcinoma is a cancer of an epithelium that
originates in glandular tissue, adeno means gland.
•98% of all cancers in large intestine almost always
arise in adenomatous polyps, generally
curable by resection

6. EpidEmiology
•Old age: peak incidence: 60 to 70 years of age
•< 20% cases before age of 50
•adenomas – presumed precursor lesions
for most tumors
•males affected ≈ 20% more often than
females

7. Epidemiology cont….
•worldwide distribution
•highest incidence rates in United States,
Canada, Australia, New Zealand, Denmark,
Sweden, and other developed countries

8. Risk Factors for High grade dysplasia and cancer
Large Size - > 1 cm in diameter are risk factor for
containing CRC
Villous histology – adenomatous polyps with > 25
percent villous histology are a risk factor for
developing CRC
High-grade dysplasia – adenomas with high-grade
dysplasia often coexist with areas of invasive cancer
in the polyp.
Number of polyps: three or more is a risk factor

9. Etiology
•I. Genetic influences:
–preexisting ulcerative colitis or polyposis syndrome
–hereditary nonpolyposis colorectal cancer syndrome
(HNPCC, Lynch syndrome) → germ-line mutations of
DNA mismatch repair genes

11. Etiology cont.
II. Environmental influences:
–A. dietary practices
1.low content of unabsorbable vegetable fiber
2.corresponding high content of refined carbohydrates
3.high fat content
4.decreased intake of protective micronutrients (vitamins
A, C, and E)
–B. use of Aspirin
®
and other NSAIDs: protective
effect against colon cancer?
•cyclooxygenase-2 & prostaglandin E2

12. Morphology
•25% : in cecum or ascending colon
•25%: in rectum and distal sigmoid
•25%: in descending colon and proximal
sigmoid
•25%: scattered elsewhere
•multiple carcinomas present → often at
widely disparate sites in the colon

13. Morphology cont.
•all colorectal carcinomas begin as in situ lesions
•tumors in the proximal colon: polypoid, exophytic
masses that extend along one wall of the cecum and ascending
colon

14. Morphology cont.
•in the distal colon: annular, encircling lesions that
produce “napkin-ring” constrictions of the bowel and
narrowing of the lumen

15. Morphology cont.
Both forms of neoplasm eventually
penetrate the bowel wall and
may appear as firm masses on the
serosal surface

16. Morphology cont.
•
all colon carcinomas - microscopically similar
•almost all - adenocarcinomas
•range from well-differentiated to
undifferentiated, frankly anaplastic masses
•many tumors produce mucin
•secretions dissect through the gut wall, facilitate
extension of the cancer and worsen the
prognosis

17. Squamous Cell
Carcinoma
Squamous Cell Carcinoma of the anus:
Cancers of the anal zone are
predominantly squamous cell in
origin.

18. Clinical Features
•may remain asymptomatic for years
•symptoms develop insidiously
•cecal and right colonic cancers:
–fatigue
–weakness
–iron deficiency anemia
•left-sided lesions:
–occult bleeding
–changes in bowel habit
–crampy left lower quadrant discomfort

19. Clinical features cont.
Anemia in females may arise from gynecologic
causes, but it is a clinical maxim that
iron deficiency anemia in an older man means
gastrointestinal cancer until proved otherwise

20. Clinical Features
•spread by direct extension into
adjacent structures and by metastasis
through lymphatics and blood vessels
•favored sites for metastasis:
–regional lymph nodes
–liver
–lungs
–bones
–other sites including serosal
membrane of the peritoneal cavity
•carcinomas of the anal region →
locally invasive, metastasize to
regional lymph nodes and distant
sites
TNM Staging of Colon Cancer
Tumor (T)
T0 = none evident
Tis = in situ (limited to mucosa)
T1 = invasion of lamina propria or submucosa
T2 = invasion of muscularis propria
T3 = invasion through muscularis propria into
subserosa or nonperitonealized perimuscular
tissue
T4 = invasion of other organs or structures
Lymph Nodes (N)
0 = none evident
1 = 1 to 3 positive pericolic nodes
2 = 4 or more positive pericolic nodes
3 = any positive node along a named blood vessel
Distant Metastases (M)
0 = none evident
1 = any distant metastasis
5-Year Survival Rates
T1 = 97%
T2 = 90%
T3 = 78%
T4 = 63%
Any T; N1; M0 = 66%
Any T; N2; M0 = 37%
Any T; N3; M0 = data not available
Any M1 = 4%

21. Diagnosis
–digital rectal examination
–fecal testing for occult blood loss
–barium enema, sigmoidoscopy and colonoscopy
–confirmatory biopsy
–computed tomography and other radiographic
studies

22. Diagnosis cont.
–serum markers (elevated blood levels of
carcinoembryonic antigen)
–molecular detection of APC mutations in epithelial
cells, isolated from stools
–tests under development: detection of abnormal
patterns of methylation in DNA isolated from stool
cells

23. Treatment
1.Chemotherapy
2.Radiotherapy
3.Photodynamic therapy
4.Radical surgery
5.Gene therapy