GI Polyps & Neoplasms Flashcards
Sessile vs. Pedunculated Polyp
- sessile = no stalk
- pedunculated = stalk
Tubular vs. Villous polyp
- tubular = smooth-ish borders
- villous = borders look like villi
- villous = “villanous” (worse prognosis)
Types of non-neoplastic polyps + key association
- non-neoplastic type polyps are frequently “syndromic”, i.e. associated with a genetic syndrome that overall predisposes to cancer development
- inflammatory polyps
- hamartomatous
- juvenile
- peutz-jeghers
- hyperplastic
Characteristics of 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 ==> ulceration/erosion ==> epithelial hyperplasia
Characteristics of hamartomatous polyps
- most occur during childhood
- Hamartoma: “tumor-like” over-growth / mature tissue / developing where it is normally present (e.g. colonic tissue developing in the colon)
- Associations: Juvenile (sporadic and syndromic) and Peutz-Jeghers (syndromic)
- benign features on histo, but often have foci of dysplasia
- ==> increase risk for future GI carcinoma
Characteristics of hyperplastic polyps
Smooth, nodular lesion with flat base (sessile)
- (1) The lesion abuts muscularis mucosa (arrow) and does not have a stalk.
- (2) It is composed of crowded, mixed absorptive and goblet cells
- (3) A serrated architecture results
- (4) This is a benign, usually non-neoplastic lesion to be distinguished from SSPs
hyperplastic vs. sessile serrated polyps/adenomas
- hyperplastic
- NOT pre-malignant
- common @ L side of colon
- not dysplastic epithelium
- Sessile serrated/adenoma
- pre-malignant
- CAN progress to adenocarcinoma
- common @ R side of colon
- +/- dysplastic epithelium
- pre-malignant
Characteristics (general) of adenomas
- 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
- origin: epithelial cells
- gland-forming masses
Risk factors (related to adenomas) for malignancy
- 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
- SIZE MATTERS
- 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
Histologic features of adenomas
- Cells
- Piling up on each other (no respect!)
- Nuclei
- Darker (hyperchromasia)
- Progressive loss of basal-orientation
- Cytoplasm
- Reduced compared to nucleus (increased N:C ratio)
- Reduced mucin production
- Mitotic Figures
- Increased mitotic activity
Risk factors for colorectal cancer
- Increase Risk
- Body fatness
- Abdominal fatness
- Red/processed meat
- Alcoholic drinks
- Smoking
- Genetic predisposition
- Decrease Risk
- Physical Activity
- Foods with High Fiber
Major genetic syndromes that increase colorectal cancer risk
- Sporadic (65-85%)
- Familial Adenomatous Polyposis (FAP) (<1%)
- Hereditary Nonpolyposis Colorectal Cancer (HNPCC) (2-3%)
Main molecular pathways to 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
Characteristics of WNT/APC pathway to colorectal cancer
- Wnt protein ligands are critical for development
- drive proliferation of their target tissues/organs
- Wnt pathway regulates the levels of cytoplasmic b-catenin
- WNT binds to receptor ==> disruption of APC/beta-catenin complex (normally, this complex leads to destruction of beta-catenin/low levels of b-c) ==> elevated beta-catenin levels @ cytosol
- b-catenin translocates to nucleus ==> cell cycle initiation w/TCF (transcription factor)
- mutated/absent APC ==> cells behave as if under constant stimulation by WNT
Characteristics Familial Adenomatous Polyposis
-
APC mutations can run in families, producing Familial Adenomatous Polyposis (FAP)
- AD mutation @ APC gene ==> increased risk of colon cancer,
- Most people who acquire colon cancer without FAP acquire spontaneous somatic mutations in APC
Characteristics of Hereditary Non-Polyposis Colorectal Cancer Lynch Syndrome
- Develop colon cancer at an earlier age than sporadic forms
- Tend to be right-sided
- Inherit mutation of mismatch repair gene allele
- __acquire the second allele mutation over time leading to microsatellite instability
Common presentation of early colon carcinoma
–No symptoms most often
–Nonspecific findings
•Fatigue
•Weight loss
•Anemia
Common presentation of advancing colon carcinoma
- Change in bowel habits and indicators
- Constipation
- Urgency
- Narrowing of stool
- Cramping / pain
- Blood Loss
- Blood in stool or bleeding from rectum (BBBPR)
- Anemia (iron-deficiency)
- Unexplained weight loss
Common methods of screening/detection of colorectal neoplasm
- visualization +/- biopsy
- colonoscopy
- barium enema
- blood detection @ stool
- HemOccult of Fit test
- looking for hemorrhage of ulcerated lesion
- DNA/mutation detection in stool
- looking for shedded neoplastic cells
Histologic features of invasive adenocarcinoma
- gland formation
- variable - scant mucin production
- invade muscularis propria ==> desmoplastic (fibrotic) response
- “dirty necrosis” w/in some glands
Important prognostic factors in colorectal cancer
- depth of invasion
- presence/absence of lymph node metastasis
- distant metastasis
Sporadic colon cancer (majority): Molecular defect, target gene, predominant side, histology
- molecular = APC/WNT pathway
- gene = APC
- side = left
- histo =
- tubular, villous
- typical adenocarcinoma
Sporadic colon cancer (minority): Molecular defect, target gene, predominant side, histology
- moceluar = DNA mismatch repair
- gene =
- MSH2
- MLH1
- side = right
- histo =
- sessile serrated adenoma
- mucinous adenocarcinoma
FAP (majority): Molecular defect, target gene, transmission, histology
- molecular = APC/WNT
- gene = APC
- transmission = AD
- histo =
- tubular, villouis
- typical adenocarcinoma
HNPCC : Molecular defect, target gene, transmission, predominant site, histology
- molecular = DNA mismatch
- gene =
- MSH2
- MLH1
- transmission = autosomal
- side = right
- histo =
- sessile serrated adenoma
- mucinous adenocarcinoma
