GI Polyps and Carcinoma Flashcards Preview

DEMS Pt 1 > GI Polyps and Carcinoma > Flashcards

Flashcards in GI Polyps and Carcinoma Deck (28)
1

Sessile polyp vs pedunclulated polyp

Pedunculated: has a stalk
Sessile: no stalk

2

Non-Neoplastic Polyps

Inflammatory Polyps

Hamartomatous Polyps: Juvenile, Peutz-Jeghers, Others: Cowden, Cronkhite-Canada

Hyperplastic Polyps

3

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

4

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

5

Peutz-Jeghers syndrome

Mucocutaneous pigmented lesions; increased risk of thyroid, breast, lung, pancreas, gonadal, and bladder cancers

6

Juvenile polyposis

Pulmonary arteriovenous malformations, digital clubbing

7

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

8

Serrated Polyps

NOT pre-malignant: Hyperplastic Polyps (generally)

Pre-malignant: Sessile serrated polyps/adenoma (alternate pathways to carcinoma than the usual adenomatous polyp).

9

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

10

Adenomatous Changes

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

11

Adenoma to cancer progression

APC mutations, beta-catenin (also APC), KRAS mut, loss of p53 and/or SMAD 2 and 4

12

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

13

Protective factors for colorectal cancer

Exercise
NSAID use
High-fiber diet

14

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

15

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

16

Adenoma formation

There is no increase in the rate of cell proliferation in
the early stage of polyp formation.

Polyps represent an increase in the size of the proliferating crypt compartment

17

FAP: Familial Adenometous Polyposis

APC mutations can run in families, producing Familial Adenomatous Polyposis (FAP)

FAP patients have increased risk of colon cancer, but these account for a small fraction of the total cases of colon cancer (~5%)

Most people who acquire colon cancer without FAP acquire spontaneous somatic mutations in APC

18

Colon Carcinoma: Symptoms / Presentation

Early Colon Carcinoma:
No symptoms most often
Nonspecific findings
Fatigue
Weight loss
Anemia

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

cetuximab

Monoclonal antibody against EGFR

20

Hereditary Non-Polyposis Colorectal Cancer aka 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

21

Definition of carcinoma and what adenomas are at risk

Invasion of dysplastic epithelial cells into and beyond the lamina propria

Adenomas at risk:
4 cm: high risk (~40% in one study) of identification of invasive component within lesion

22

Staging of colorectal cancer

TNM

T: tumor size and degree of invasion
N: Lymph node involvement
M: metastasis

23

Most important prognostic factors

Depth of invasion
Presence or absence of lymph node metastasis
Distant metastasis

24

Most common location of metastasis of colorectal cancer

liver

25

Therapy for colorectal cancer

Surgery:
Local excision – e.g. polypectomy
Colonic resection
Radiofrequency ablation
Cryosurgery

Chemotherapy:
Only treatment = palliative
Adjunctive treatment
Pre or Post-Operative

Radiation therapy:
Targeted Therapy

Monoclonal antibodies

Angiogenesis inhibitors

26

Sporadic colon cancer: pathway involved, target molecule, and histology

APC/WNT pathway (80%)
APC target molecule
Histology: Tubular, villous; typical adenocarcinoma

DNA mismatch repair (10-15%)
Target genes: MSH2, MLH1
Histology: Sessile serrated adenoma; mucinous adenocarcinoma

27

Familial Adenomatous Polyposis: pathway involved, target molecule, and histology

APC/WNT pathway (70%)
Target gene: APC
HIstology: Tubular, villous; typical adenocarcinoma

DNA mismatch repair (

28

Hereditary Nonpolyposis Colorectal Cancer
(HNPCC) / Lynch Syndrome: mechanism, target molecule, and histology

DNA mismatch repair
Target genes: MSH2, MLH1
Histology: Sessile serrated adenoma; mucinous adenocarcinoma