GI Tumors

Question 1

GIST

Answer 1

c-KIT (85%)

PDGFRA (5-10%)

Question 2

Juvenile polyp/syndrome

Answer 2

Auto dom
SMAD4 (20%)
BMPR1A (20%)-> both involve TGF beta signalling

Question 3

Peutz-Jeghers polyps/syndrome

Answer 3

Auto dom: STK11

Question 4

Cowden syndrome

Answer 4

Auto dom: PTEN

Question 5

Cronkhite-Canada

Answer 5

Non-hereditary; likely autoimmune

*Ectodermal abnormalities

Question 6

Sessile Serrated

Answer 6

BRAF V600E mutations
Methylation of tumor suppresor gene- shut down
MSI (+/-)

Question 7

Colorectal carcinoma - Adenocarcinoma sequence

Answer 7

Adenoma-carcinoma sequence: Normal colon -> Loss of APC/beta-catenin gene -> mucosa at risk -> K-RAS mutation -> adenoma -> loss of p53 -> carcinoma -> telomerase

> 80% of CRC have inactivated APC, many w/out APC mutation have beta-catenin mutation

Question 8

Familial Adenomatous Polyposis (FAP)

Answer 8

Auto. dominant APC mutation (chromo 5)-> proximal mutation near N terminus, less APC gene made -> no residual function ; 25% have no FamHx -> new, de novo mutations.

Question 9

Attenuated FAP

Answer 9

Mutation closer to C terminus, longer protein made so some residual APC activity is present -> mutation weakens APC but doesnt completely knock it out which is why you get less polyps

Question 10

MYH associated polyposis (MAP)

Answer 10

auto. recessive mutation in MYH gene (chromo 1); MYH = DNA repair protein (base excision repair)

Question 11

Lynch syndrome/ Hereditary Nonpolyposis Colorectal cancer

Answer 11

auto. dom. mutation in DNA mismatch repair gene; MSI pathway
NO BRAF mutations in Lynch syndrome; 68% of sporadic MSI CRC have BRAF mutation

• MSH2/MSH6 find mutation
• MLH1/PMS2 repair it

MSH2 holds onto MSH6
- MSH2 knockout (KO) also KOs MSH6
MLH1 holds onto PMS2
- MLH1 KO also KOs PMS2

Mutations in MSH2, MSH6 or PMS2 = Lynch
- However MLH1 mutation could be sporadic or Lynch

Question 12

Neuroendocrine tumor, secretes bioactive compounds
Elevated serotonin (5-HT) 5-HIAA

Answer 12

Carcinoid tumor

Question 13

Two types of intestinal polyps. Which is easier to remove?

Answer 13

Pedunculate and sessile polyps

*Pedunculated is easier to remove

Question 14

Benign tumor, focal mass (resembles tumor), d/t development error
Mature, histo normal elements -> growing in disorganized manner

Answer 14

Hamartomatous polyps

Question 15

Pedunculated, 1-3 cm (large); Kids < 5 y.o., 80% in rectum

Expanded lamina propria (LP) w/ variable inflammation, abundant cystically dilated glands glassy, mucousy appearance

Answer 15

Juvenile polyps/syndrome

Question 16

Large & pedunculated

Syndrome -> multiple polyps, hyperpigm of mucosa (mouth) & cutaneous (fingers), incr risk of intussusception & ca of pancr, breast, lung, ovary, uterus

CT and smooth muscle extends into polyp

Answer 16

Peutz-Jehgers Polyps/syndrome

Question 17

Hamartomatous polyp

Facial trichilemmomas, oral papillomas, acral keratoses
Assoc. risk of thyroid & breast ca

Answer 17

Cowden Syndrome

Question 18

Pseudopolyps -> regenerating mucosa adjacent to ulceration (severe IBD)

Answer 18

Inflammatory Polyps

Question 19

Mucosal bumps caused by intramucosal lymphoid follicles -normal

Answer 19

Lymphoid Polyps

Question 20

SMALL (1/2 in rectosigmoid colon

Answer 20

Serrated Polyps

Question 21

Majority (60-90%), no malignant potential

Grows from base of crypt. Only see serations at the ends (near the lumen) .

Distal colon

Answer 21

Hyperplastic polyps

Question 22

10-30%, HIGH MALIGNANT potential

“Interval tumor” (arise in-betw colonoscopies). These polyps were either missed or thought to be hyperplastic polyps on initial colonoscopy -> so they were never removed. Before next coloscopy they became dysplastic and eventually a cancerous mass.

Grows in middle of crypt (can see dilation at crypt base)

Proximal colon

Answer 22

Sessile serrated polyps

Question 23

Arise d/t epith proliferative dysplasia, Precursor lesion for adenocarcinoma

Asymptomatic or present w/ rectal bleeding or anemia
Intramucosal carcinoma -> invades LP, no metastatic potential; invasive when goes thru muscularis mucosa

Answer 23

Adenomatous polyps

Question 24

Three types of adenomatous polyps

Answer 24

Tubular
Villous
Tubulovillous

Question 25

Tubular glands, often small, pedunculated, single or multiple, rare >2.5 cm

Dysplastic epithelium -> elongated, pseudostratified, hyperchromatic nuclei w’ loss of mucin production. stain darker, no mucin production, haphazard gland arrangement.

90% in colon

Answer 25

Tubular polyp

Question 26

Villious projections, often large (up to 10cm dia), sessile

Most common in older ppl w/ rectosigmoid colon; risk of cancer 40% if adenoma >4 cm

more invasive potential simply because they are located more closely to lympathics (sessile so no stalk to buffer the invasive cells)

Answer 26

Villous polyp

Question 27

Treatment for tubular vs villous polyp

Answer 27

Tubular = Endoscopic removal adequate if negative resection margins and no vascular/ lymph involvement.

Villous = Endoscopic removal INADEQUATE -> colectomy.

Question 28

Right sided presentation of CRC

Answer 28

Right-sided: fatigue, weakness, iron deficiency anemia, polypoid exophytic lesions, occult blood

Question 29

Left sided presentation of CRC

Answer 29

Left-sided: occult bleeding/hematochezia, change bowel habits, abd discomfort, annular “napkin ring/apple core” constrictions

Question 30

What is the most common location of CRC?

Answer 30

Rectosigmoid > cecum/ascending > descending; difficult to identify grossly hence go unnoticed until it is a carcinoma

Question 31

Treatment options of CRC

Answer 31

Anti-EGFR (ie Cetuximab, panitumumab, bevacizumab); but K-Ras mutation = negative predictor of EGFR MOAB therapy (b/c downstream of target antibody); BRAF mutation correlates w/ poor prognosis and lack of response

Question 32

Treatment for Familial Adenomatous Polyposis

Answer 32

Prophylactic colectomy

Question 33

FAP + osteomas, epidermoid cysts, desmoid tumors

Answer 33

Gardener’s Syndrome

Question 34

FAP + medulloblastoma

Answer 34

Turcot’s Syndrome

Question 35

Treatment for Lynch Syndrome

Answer 35

Resection of course. Then….

MSS & MSI-L are treated the same way. It is beneficial to use 5FU adjuvant chemotherapy.

MSI-H do not do well when treated with 5FU adjuvant chemotherapy so dont treat them with this!

Question 36

Lynch syndrome + sebaceous adenomas/carcinomas, & keratocanthomas

Answer 36

Muir-Torre Syndrome

Question 37

Tumors of the appendix

Answer 37

Mucocele: obstructed appendix containing mucin (not truly a tumor)

Mucinous cystadenoma/cystadenocarcinoma: mucous secreting epithelial tumor; associated with diverticular formation