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DEMS: Unit 1 > GI Polyps & Neoplasms > Flashcards

Flashcards in GI Polyps & Neoplasms Deck (25):
1

Sessile vs. Pedunculated Polyp

  • sessile = no stalk
  • pedunculated = stalk

2

Tubular vs. Villous polyp

  • tubular = smooth-ish borders
  • villous = borders look like villi
    • villous = "villanous" (worse prognosis)

3

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

4

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
       

5

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

6

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

7

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

8

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
     

9

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
     

10

Histologic features of adenomas

  1. Cells
    1. Piling up on each other (no respect!)
  2. Nuclei
    1. Darker (hyperchromasia)
    2. Progressive loss of basal-orientation
  3. Cytoplasm
    1. Reduced compared to nucleus (increased N:C ratio)
    2. Reduced mucin production
  4. Mitotic Figures
    1. Increased mitotic activity

11

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
       

12

Major genetic syndromes that increase colorectal cancer risk

  •  Sporadic (65-85%)
  • Familial Adenomatous Polyposis (FAP) (<1%)
  • Hereditary Nonpolyposis Colorectal Cancer (HNPCC) (2-3%)

13

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
     

14

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 

15

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
       

16

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
       

17

Common presentation of early colon carcinoma

–No symptoms most often
–Nonspecific findings
•Fatigue
•Weight loss
•Anemia 
 

18

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

19

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

20

Histologic features of invasive adenocarcinoma

  • gland formation
  • variable - scant mucin production
  • invade muscularis propria ==> desmoplastic (fibrotic) response 
  • "dirty necrosis" w/in some glands

21

Important prognostic factors in colorectal cancer

  1. depth of invasion
  2. presence/absence of lymph node metastasis
  3. distant metastasis

22

Sporadic colon cancer (majority): Molecular defect, target gene, predominant side, histology

  • molecular = APC/WNT pathway
  • gene = APC
  • side = left
  • histo =
    • tubular, villous
    • typical adenocarcinoma

23

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

24

FAP (majority): Molecular defect, target gene, transmission, histology

  • molecular = APC/WNT
  • gene = APC
  • transmission = AD
  • histo =
    • tubular, villouis
    • typical adenocarcinoma

25

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