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Colorectal Carcinoma
Eugen DivjakMentor: A. Žmegač Horvat
Intestinal tumorsNon-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
Adenocarcinoma
98% of all cancers in large intestine almost always arise in adenomatous polyps,
generally curable by resection
Epidemiology
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
worldwide distribution highest incidence rates in United States,
Canada, Australia, New Zealand, Denmark, Sweden, and other developed countries
Etiology
genetic influences: preexisting ulcerative colitis or polyposis
syndrome hereditary nonpolyposis colorectal cancer
syndrome (HNPCC, Lynch syndrome) → germ-line mutations of DNA mismatch repair genes
Etiology
environmental influences: dietary practices
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? cyclooxygenase-2 & prostaglandin E2
Carcinogenesis
chromosome instability pathway
Carcinogenesis
mismatch repair (microsatellite instability) pathway
Morphology
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
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
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 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 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 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 evidentTis = in situ (limited to mucosa)T1 = invasion of lamina propria or submucosaT2 = invasion of muscularis propriaT3 = invasion through muscularis propria into
subserosa or nonperitonealized perimuscular tissue
T4 = invasion of other organs or structures
Lymph Nodes (N)0 = none evident1 = 1 to 3 positive pericolic nodes2 = 4 or more positive pericolic nodes3 = any positive node along a named blood vessel
Distant Metastases (M)0 = none evident1 = any distant metastasis
5-Year Survival RatesT1 = 97%T2 = 90%T3 = 78%T4 = 63%Any T; N1; M0 = 66%Any T; N2; M0 = 37%Any T; N3; M0 = data not availableAny M1 = 4%
Clinical Features detection and diagnosis:
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
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: 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