Colorectal Carcinoma
Lecture 18
Colorectal Carcinoma
Adenocarcinoma 98%
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
AdenocarcinomaSquamous 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
AdenocarcinomaAdenocarcinoma 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
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
Epidemiology cont….
•worldwide distribution
• highest incidence rates in United States, Canada, Australia, New Zealand, Denmark, Sweden, and other developed countries
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 > 25percent 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
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
Etiology cont.II. Environmental influences:– A. dietary practices
1. low content of unabsorbable vegetable fiber2. corresponding high content of refined carbohydrates3. high fat content4. 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
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
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
Morphology cont.• in the distal colon: annular, encircling lesions that
produce “napkin-ring” constrictions of the bowel and narrowing of the lumen
Morphology cont.
Both forms of neoplasm eventually
penetrate the bowel wall and may appear as firm masses on the serosal surface
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
Squamous Cell Carcinoma
Squamous Cell Carcinoma of the anus:
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
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
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%
Diagnosis– digital rectal examination– fecal testing for occult blood loss– barium enema, sigmoidoscopy and colonoscopy– confirmatory biopsy– computed tomography and other radiographic
studies
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
Treatment1. Chemotherapy2. Radiotherapy3. Photodynamic therapy4. Radical surgery5. Gene therapy
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