Colon Cancer B&B

Question 1

describe the location and appearance of hyperplastic polyps

Answer 1

benign, most common type of polyp, common in rectosigmoid colon

have normal cellular structure (no dysplasia) with saw-tooth/ serrated pattern - finger-like projections made of normal mucosal cells

Question 2

how can adenomatous polyps be subclassified?

Answer 2

dysplastic polyps with malignant potential

classified by shape - sessile vs pedunculated

classified by histology - tubular vs villous

Question 3

sessile vs pedunculated adenomatous polyp

Answer 3

sessile = broad based with extensions into colon

pedunculated = stalk with ball at end

Question 4

tubular vs villous adenomatous polyps

Answer 4

tubular (most common) = adenomatous epithelium forming tubules

villous = long projections extending from surface (finger-like), high risk of development into colon cancer

Question 5

which types of GI polyps can cause diarrhea?

Answer 5

villous adenomatous polyps (often sessile - broad base with extensions)

can cause secretory diarrhea via excessive mucous secretion —> may lead to hypokalemia

Question 6

which type of polyp carries a high risk of development into cancer?

Answer 6

villous (histological classification): long projections extending from surface (finger-like)

may cause secretory diarrhea due to excessive mucous production

Question 7

child with 10+ polyps raises concern for…

Answer 7

juvenile polyposis syndrome - have increased risk of colon cancer, surveillance via colonoscopy

Question 8

Peutz-Jeghers Syndrome

Answer 8

AD disorder presenting in children causing multiple hamartomas throughout GI tract —> increased risk of gastric, small intestine, and colon cancer

also causes pigmented spots on lips and buccal mucosa

Question 9

Child presents due to concern of many pigmented spots on the lips and around the buccal mucosa. What might workup of the GI tract reveal?

Answer 9

Peutz-Jeghers Syndrome: AD disorder presenting in children causing multiple hamartomas throughout GI tract —> increased risk of gastric, small intestine, and colon cancer

also causes pigmented spots on lips and buccal mucosa

Question 10

what are the 3 major concepts to remember about the genetics of colon cancer?

Answer 10

1. pathway to colon cancer is either chromosomal instability or micro-satellite instability
2. cyclooxygenase-2 expression is increased in colon cancer
3. DCC gene is mutated in advanced colorectal cancer [Deleted in Colorectal Cancer gene]

Question 11

what is the genetic basis of the “adenoma-carcinoma sequence”?

Answer 11

sequence of somatic mutations that occur with aging which lead to colon cancer (10-40 years), all which have to do with chromosomal instability

more common in left-sided tumors (descending colon, sigmoid, rectum)

Question 12

what are the steps (3) of the “adenoma-carcinoma sequence”? (chromosomal instability pathway)

Answer 12

1. APC mutation - tumor suppressor, prevents beta-catenin accumulation —> increased risk for polyps
2. K-RAS mutation - proto-oncogene —> adenoma polyp formation
3. p53 mutation - tumor suppressor —> tumor cell growth

Question 13

what is the function of APC tumor suppressor

Answer 13

prevents accumulation of beta-catenin (which activates oncogenes)

Question 14

which mutation is present in patients with familial adenomatous polyposis (FAP)?

Answer 14

AD germline mutation in APC gene on chromosome 5q

100% always progresses to colon cancer because there are manyyyy polyps visible on colonoscopy

tx = colectomy

Question 15

Gardner’s Syndrome

Answer 15

familial adenomatous polyposis (FAP, mutation in APC gene) + multiple extra-colonic manifestations

—> osteomas (benign), esp. in mandible
—> cysts (epidermal, fibromas, lipomas)
—> hypertrophy of retinal pigment

Question 16

Pt w/ mutation in APC gene presents with a bone growth in their mandible, as well as multiple fibromas and lipomas. Slit lamp exam reveals a flat dark spot in the retina. Dx?

Answer 16

Gardner’s Syndrome: familial adenomatous polyposis (FAP, mutation in APC gene) + multiple extra-colonic manifestations

—> osteomas (benign), esp. in mandible
—> cysts (epidermal, fibromas, lipomas)
—> hypertrophy of retinal pigment

Question 17

Turcot Syndrome

Answer 17

familial adenomatous polyposis (FAP, mutation in APC gene) + brain tumors (medulloblastomas, gliomas)

Question 18

Pt w/ known mutation in the APC gene is found to have a brain tumor. Biopsy reveals Homer-Wright rosettes. Dx?

Answer 18

Turcot Syndrome: familial adenomatous polyposis (FAP, mutation in APC gene) + brain tumors (medulloblastomas, gliomas)

[recall Homer-Wright rosettes = medulloblastoma]

Question 19

Gardner Syndrome vs Turcot Syndrome

Answer 19

both are subtypes of familial adenomatous polyposis (FAP, mutation in APC gene)

Gardner’s Syndrome: polyps + multiple extra-colonic cysts

Turcot Syndrome: polyps + brain tumors (medulloblastomas, gliomas)

Question 20

what type of genetic dysfunction leads to colon cancers in the proximal (right) vs distal (left) sections?

Answer 20

proximal (right) - microsatellite instability (less common, “de novo”)

distal (left) - chromosomal instability (somatic, adenoma-carcinoma sequence)

Question 21

Pt with R-sided colon cancer and a 1st degree family member also with cancer raises suspicion for…

Answer 21

Hereditary Non-Polyposis Colorectal Cancer (HNPCC) / Lynch Syndrome: inherited mutation of DNA mismatch repair enzyme predisposes to colon cancer via microsatellite instability

cancer arises without pre-existing adenomatous polyp (“non-polyposis”), and usually right-sided (proximal colon)

also increased risk of endometrial cancer (most common), ovarian, stomach, etc

Question 22

increased expression of _____ is common in colon cancer cells, esp. left-sided (distal colon) cancers

Answer 22

cyclooxygenase-2: converts arachidonic acid into thromboxanes + prostaglandins

Question 23

the gene that is frequently mutated in advanced colorectal cancers is found on chromosome ____

Answer 23

DCC (Deleted in Colorectal Cancer) gene: tumor suppressor found on chromosome 18q

Question 24

how do the symptoms of colon cancer differ depending on if the tumor is right or left sided?

Answer 24

right-sided (proximal, via microsatellite instability): “exophytic” tumors (stick out) —> slow bleeding, iron deficiency anemia, weight loss

left-sided (distal, via adenoma-carcinoma sequence): circumferential lesions (smaller lumen) —> LLQ pain, blood-streaked stool, pencil-thin stools

Question 25

most common site of metastasis of colon cancer

Answer 25

—> liver - will produce multiple lesions

Question 26

which bacteria is strongly associated with colon cancer?

Answer 26

Strep Bovis: Gram+ cocci, gamma hemolytic, Lancefield Group D, normal colonic bacteria

rarely causes bacteremia/endocarditis, which is then strongly associated with colon cancer [next test after it is identified = colonoscopy]

Question 27

which tumor marker is used to monitor disease burden in patients with colon cancer?

Answer 27

CEA (carcinoembryonic antigen) - elevated in colon cancer and other tumors (pancreas), has poor sensitivity/specificity but is useful for monitoring disease burden in patients with established disease or to detect relapse