012215 neoplasms sm and large intes Flashcards Preview

Gastrointes 3 > 012215 neoplasms sm and large intes > Flashcards

Flashcards in 012215 neoplasms sm and large intes Deck (53):
1

prevalence of neoplasms in sm intes

low

2

most common neoplasm in sm intes

adenoma (near ampulla)

3

risk factors for sm intes adenocarcinoma

Crohn's dis
adenomas
celiac dis
familial polyposis syndrome

4

tx for GIST

imatinib (85% have c-kit mutations)

5

immunohistochemical markers for GIST

CD117 (c-kit)
DOG1 (specific marker)
CD34

6

mutations in GIST

c-kit (80%)
PDGFRA (5-10%)

both are tyrosine kinase receptors--gain of fxn

7

most common non-epithelial (soft tissue) tumor in GI tract

GIST

8

sm intes neoplasms

adenoma (most common)
carcinoid and adenocarcinoma
mesenchymal tumors (rare)-lipoma, GIST, lymphoma

9

polyp

epithelium derived tumor mass which protrudes into gut lumen

10

two types of polyps-shape wise

pedunculated
sessile

11

in terms of malignant potential, what are the two types of polyps

non-neoplastic polyp (abnormal mucosal maturation, inflam, distorted architecture)--no malignant potential

neoplastic polyp-due to prolferation and dysplasia (adenomas). precursor of carcinoma

12

types of non-neoplastic poyps

hamartomatous
inflammatory
lymphoid

13

hamartoma

mature, histologically normal elements from the site growing in disorganized manner

14

chriostomas

haphazard tissue in wrong location (as opposed to hamartoma)

15

junvenile polyps

hamartomatous polyp

abundant cystically dilated glands usually w inflam

16

juvenile polyposis syndrome

multiple juvenile polyps
autosomal dominant mutations
increased risk of adenomas, colon cancer

17

Peutz Jeghers polyps

hamartomatous polyps
no malignant potential

18

Peutz-Jeghers syndrome

mutliple GI polyps--hamartomatous polyps
autosomal dominant
hyperpigmentation/freckles-appearing-mucosal (mouth) and cutaneous (fingers)
increased risk of cancer of pancreas, breast, lung, ovary, uterus

19

inflammatory polyps

regnerating mucosa adjacent to ulceration (severe IBD)

20

lymphoid polyps

mucosal bumps caused by intramucosal lymphoid follicles (normal)

21

types of colon polyps

serrated polyps:
hyperplastic polyp (benign)
sessile serrated polyp (malignant potential)

adenomatous polyp/adenoma (precursor to cancer)

22

serrated lumina

serrated polyps

23

sessile serrated tumors

high malignant potential
interval tumors--develop more quickly
BRAF V600E mutations
methylation (tumor suppressor genes shut down)
can have microsatellite instability
horizontal growth

24

how do adenomatous polyps/adenomas arise

epithelial proliferative dysplasia

25

epidemiology of adenomatous polyps

common-after age 60

26

3 architectural types of adenomas

tubular
villous
tubulovillous

27

tubular adenoma morphology

tubular glands
small, pedunculated

28

villous adenoma

villous projections
large, sessile

29

clinical symptoms of adenomatous polyps

asymptomatic or present with rectal bleeding or anemia

30

tx for adenoma

complete resection (regardless of whether carcinoma is present)

31

iron defic anemia in older male signifies

colon cancer unless proven otherwise

32

almost all colon cancers have mutations in what gene?

APC (tumor suppressor gene)

for those without an APC mutation, 50% of them have beta-catenin mutations

33

depth of invasion of colorectal carcinomas

TIS (in situ)--within mucosa
T1--submucosa
T2--muscularis propria
T3--serosa

34

staging colon carcinoma

stage 0: in situ carcinoma

stage I: T1 or T2, N0,M0
stage II: T3 or T4, N0, M0
stage III: any T, positive nodes, M0 (N1=1-3, N2=4 or more)
stage IV: any T, any N, M1 (distant mestasis)

35

currently the only proven prognostic marker to identify pts with aggressive colon carcinoma

TNM staging

36

biomarkers to guide adjuvant therapy--types?

prognostic-provide info about pts overall outcome regardless of therapy

predictive-give info about effects of particular therapeutic intervention

37

what is a key target in cancer?

EGFR (turns on cell cycle-it's a transmembrane tysorine kinase receptor)

38

what pathway is activated by EGFR

RAS-RAF-MAP kinase
and two others

39

therapeutic options of colorectal carcinoma

targeted therapy for metastatic tumors:
bevacizumab
ceubixmab
panitumumab

if targeted therapy is not effective, then do traditional chemo

surgery (if earlier stage, can completely resect out)

40

what mutations result in decreased efficacy of EGFR monocloncal antibody therapy?

KRAS
BRAF

41

familial adenomatous polyposis is inherited in what fashion?

autosomal dominant

42

mininum of how many polyps present is needed to be familial adenamtous polyposis?

100

43

outlook for FAP

colon adenocarcinoma occurs in about 100%
so prophylactic colectomy is required

44

what genetic mutation exists in FAP?

APC gene
but 25% of FAP pts have no family hx (new mutations)

45

MYH associated polyposis

hereditary colorectal cancer syndrome that has phenotypic overlap with FAP

typically 20-100 adenomatous polyps

autosomal recessive inheritance
due to mutation in MYH gene

46

MYH protein's role

DNA repair protein--base excision repair

47

Lynch syndrome/hereditary nonpolyposis colorectal cancer

increased risk of colorectal cancer and extraintestinal cancer. RISK FOR SECOND PRIMARY CANCER (endometrial cancer)

ADENOMAS occur earlier than normal population
COLONIC CARCINOMAS are often MULTIPLE and are not necessarily associated with adenomas
GENETIC DEFECT involves DNA mismatch repair genes (microsatelitte instability pathway)

48

what four genes can be defective in Lynch syndrome/hereditary nonpolyposis colorectal cancer

MLH1
PMS2
MSH2
MSH6

latter two identify mismatch. first two fix the mismatch

49

how can you clinically analyze mismatch repair of LYnch syndrome?

immunohistochemistry staining for the four different gene/proteins

50

microsatellite instability can be used how?

microsatelittes are prone to mismatches, so they are sensitive markers of defective mismatch repair fxn

51

how can microsatellite stability predict prognosis?

prognosis for high microsatelitte instability is better long term

52

with regards to adjuvant therapy/chemo, should microsatelittle stable or instable pts get it?

microsatelittle stability

53

majority of colorectal cancers have what microsatelittle instability phenotype?

microsatelittle stable/low instability