Colorectal Carcinoma
Eugen Divjak
Mentor: A. Žmegač Horvat
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Intestinal tumors
Non-neoplastic Polyps
Hyperplastic polyps
Hamartomatous polyps
Juvenile polyps
Peutz-Jeghers polyps
Epithelial tumors of the intestines:
major cause of morbidity and
mortality worldwide
Inflammatory polyps
Lymphoid polyps
Neoplastic Epithelial Lesions
Benign polyps
Adenomas
Colon, including rectum:
host to more primary neoplasms
than any other organ in the body
Malignant lesions
Adenocarcinoma
Squamous cell carcinoma of the anus
Other Tumors
Gastrointestinal stromal tumors
Carcinoid tumor
Lymphoma
Adenocarcinoma
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98% of all cancers in large intestine
almost always arise in adenomatous polyps,
generally curable by resection
Epidemiology
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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
Epidemiology
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worldwide distribution
highest incidence rates in United States,
Canada, Australia, New Zealand, Denmark,
Sweden, and other developed countries
Etiology
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genetic influences:
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preexisting ulcerative colitis or polyposis
syndrome
hereditary nonpolyposis colorectal cancer
syndrome (HNPCC, Lynch syndrome) → germline mutations of DNA mismatch repair genes
Etiology
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environmental influences:
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dietary practices
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low content of unabsorbable vegetable fiber
corresponding high content of refined carbohydrates
high fat content
decreased intake of protective micronutrients (vitamins
A, C, and E)
use of Aspirin® and other NSAIDs: protective
effect against colon cancer?
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cyclooxygenase-2 & prostaglandin E2
Carcinogenesis
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chromosome instability pathway
Carcinogenesis
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mismatch repair (microsatellite instability) pathway
Morphology
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25% of colorectal carcinomas: in cecum or
ascending colon
similar proportion: in rectum and distal
sigmoid
25%: in descending colon and proximal
sigmoid
remainder scattered elsewhere
multiple carcinomas present → often at
widely disparate sites in the colon
Morphology
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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
Morphology
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in the distal colon: annular, encircling lesions that
produce “napkin-ring” constrictions of the bowel and
narrowing of the lumen
both forms of neoplasm eventually penetrate the
bowel wall and may appear as firm masses on the
serosal surface
Morphology
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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
cancers of the anal zone are predominantly
squamous cell in origin
Clinical Features
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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
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
Clinical Features
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spread by direct extension into
adjacent structures and by
metastasis through lymphatics
and blood vessels
favored sites for metastasis:
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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%
Clinical Features
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detection and diagnosis:
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digital rectal examination
fecal testing for occult blood loss
barium enema, sigmoidoscopy
and colonoscopy
confirmatory biopsy
computed tomography and other
radiographic studies
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
Therapy
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chemotherapy
radiotherapy
photodynamic therapy
radical surgery
gene therapy
True or false?
98% of all cancers in the large intestine are adenocarcinomas.
Use of Aspirin® and other NSAIDs may cause development of
colon cancer.
Chromosome instability and the mismatch repair are two
carcinogenesis pathways.
Tumors in the proximal colon tend to be annular, encircling
lesions that produce “napkin-ring” constrictions of the bowel
and narrowing of the lumen, while those in the distal colon
tend to grow as polypoid, exophytic masses.
Colorectal carcinoma may remain asymptomatic for years.
References:
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http://www.liebertonline.com/doi/abs/10.1089/pho.2008.2238
http://clincancerres.aacrjournals.org/cgi/content/abstract/5/9/2359
Elsevier. Kumar et al: Robbins Basic Pathology 8e