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Flashcards in GI Tumors Deck (37):
1

GIST

c-KIT (85%)
PDGFRA (5-10%)

2

Juvenile polyp/syndrome

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

3

Peutz-Jeghers polyps/syndrome

Auto dom: STK11

4

Cowden syndrome

Auto dom: PTEN

5

Cronkhite-Canada

Non-hereditary; likely autoimmune

*Ectodermal abnormalities

6

Sessile Serrated

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

7

Colorectal carcinoma - Adenocarcinoma sequence

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

8

Familial Adenomatous Polyposis (FAP)

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.

9

Attenuated FAP

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

10

MYH associated polyposis (MAP)

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

11

Lynch syndrome/ Hereditary Nonpolyposis Colorectal cancer

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

12

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

Carcinoid tumor

13

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

Pedunculate and sessile polyps

*Pedunculated is easier to remove

14

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

Hamartomatous polyps

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

Juvenile polyps/syndrome

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

Peutz-Jehgers Polyps/syndrome

17

Hamartomatous polyp

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

Cowden Syndrome

18

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

Inflammatory Polyps

19

Mucosal bumps caused by intramucosal lymphoid follicles -normal

Lymphoid Polyps

20

SMALL (1/2 in rectosigmoid colon

Serrated Polyps

21

Majority (60-90%), no malignant potential

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

Distal colon

Hyperplastic polyps

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

Sessile serrated polyps

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

Adenomatous polyps

24

Three types of adenomatous polyps

Tubular
Villous
Tubulovillous

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

Tubular polyp

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)

Villous polyp

27

Treatment for tubular vs villous polyp

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

Villous = Endoscopic removal INADEQUATE -> colectomy.

28

Right sided presentation of CRC

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

29

Left sided presentation of CRC

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

30

What is the most common location of CRC?

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

31

Treatment options of CRC

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

32

Treatment for Familial Adenomatous Polyposis

Prophylactic colectomy

33

FAP + osteomas, epidermoid cysts, desmoid tumors

Gardener's Syndrome

34

FAP + medulloblastoma

Turcot's Syndrome

35

Treatment for Lynch Syndrome

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!

36

Lynch syndrome + sebaceous adenomas/carcinomas, & keratocanthomas

Muir-Torre Syndrome

37

Tumors of the appendix

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

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