GI Polyps and Carcinoma Flashcards
Sessile polyp vs pedunclulated polyp
Pedunculated: has a stalk
Sessile: no stalk
Non-Neoplastic Polyps
Inflammatory Polyps
Hamartomatous Polyps: Juvenile, Peutz-Jeghers, Others: Cowden, Cronkhite-Canada
Hyperplastic Polyps
Inflammatory polyps
Often present with bleeding
Often due to mucosal prolapse (very common in the rectum)
Cycles of injury and healing result in “polyp” formation = inflamed colonic mucosa with ulceration/erosion, epithelial hyperplasia
Hamartomatous Polyps
Tissue that does belong there but is overgrown and a little disorganized
Most occur in childhood
Think about syndromes
Polyps: Variable locations in lower GI system
Benign features histologically but syndromic juvenile polyps often have foci of dysplasia
May portend
Risk of future GI carcinoma (increase frequency of screening)
Both Peutz-Jeghers and Juvenile polyposis = 40% cumulative risk for CA
Extra-GI manifestations
Need to consider familial screening (genetic counseling) in some cases
Peutz-Jeghers syndrome
Mucocutaneous pigmented lesions; increased risk of thyroid, breast, lung, pancreas, gonadal, and bladder cancers
Juvenile polyposis
Pulmonary arteriovenous malformations, digital clubbing
Hyperplastic Polyps
Delayed maturation with overgrowth of epithelium (SERRATED appearance)
Increasing incidence with age
Small in size
No dysplasia but need to distinguish from “sessile serrated polyp/adenoma” (SSP) which ARE pre-malignant
Serrated Polyps
NOT pre-malignant: Hyperplastic Polyps (generally)
Pre-malignant: Sessile serrated polyps/adenoma (alternate pathways to carcinoma than the usual adenomatous polyp).
Adenomas (non-serrated)
Size is variable – range from a few mm to several cm (10 cm or more)
Present in nearly 50% of Western adults by age 50
Present throughout the colon
Have epithelial cytologic dysplasia ranging from low grade to high grade (carcinoma in situ)
Villous adenomas contain foci of invasion more frequently than tubular adenomas but SIZE MATTERS (size is the most important characteristic that correlates with risk of malignancy overall in the patient)
Presence of high grade dysplasia increases risk of malignant transformation in that polyp but not in the rest of the colon
Adenomatous Changes
- Cells
- Piling up on each other (no respect!)
- Nuclei
- Darker
(hyperchromasia) - Progressive loss of basal-orientation
- Darker
- Cytoplasm - Reduced compared to nucleus
(increased N:C ratio)- Reduced mucin production
- Mitotic Figures - Increased mitotic activity
Adenoma to cancer progression
APC mutations, beta-catenin (also APC), KRAS mut, loss of p53 and/or SMAD 2 and 4
Risk factors for colorectal cancer
High-risk: Age Country of birth FAP/HNPCC Long-standing ulcerative colitis
Moderate-risk:
HIgh-red mean diet
previous denoma or cancer
pelvic irradiation
Mild risk: High fat diet smoking and alcohol Obesity Cholecystectomy
Protective factors for colorectal cancer
Exercise
NSAID use
High-fiber diet
Main Molecular Pathways for colorectal cancer
WNT/APC/beta-catenin – classical adenoma-carcinoma sequence
K-Ras/MAP kinase/PI3 kinase signaling pathways—activating mutations
Microsatellite Instability – defects in mismatch repair proteins
Also: epigenetic events such as methylation-induced gene silencing…enhances progression along these pathways
The WNT Pathway
APC and beta-catenin are part of WNT pathway
Wnt protein ligands are critical for development
Animals lacking Wnt homologs fail to develop entire organs. The fly homolog of human wnt-1 is wingless
Wnt ligands drive proliferation of their target tissues/organs
The Wnt pathway regulates the levels of cytoplasmic beta-catenin
Without WNT signaling: Phosphorylated beta-catenin is ubiquitylated and degraded in proteasome
With WNT signaling: unphosphorylated beta-catenin accumulates, migrates to nucleus, and displaces groucho causing transcription of WNT-responsive genes
