012215 neoplasms sm and large intes

Question 1

prevalence of neoplasms in sm intes

Answer 1

low

Question 2

most common neoplasm in sm intes

Answer 2

adenoma (near ampulla)

Question 3

risk factors for sm intes adenocarcinoma

Answer 3

Crohn’s dis
adenomas
celiac dis
familial polyposis syndrome

Question 4

tx for GIST

Answer 4

imatinib (85% have c-kit mutations)

Question 5

immunohistochemical markers for GIST

Answer 5

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

Question 6

mutations in GIST

Answer 6

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

both are tyrosine kinase receptors–gain of fxn

Question 7

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

Answer 7

GIST

Question 8

sm intes neoplasms

Answer 8

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

Question 9

polyp

Answer 9

epithelium derived tumor mass which protrudes into gut lumen

Question 10

two types of polyps-shape wise

Answer 10

pedunculated

sessile

Question 11

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

Answer 11

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

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

Question 12

types of non-neoplastic poyps

Answer 12

hamartomatous
inflammatory
lymphoid

Question 13

hamartoma

Answer 13

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

Question 14

chriostomas

Answer 14

haphazard tissue in wrong location (as opposed to hamartoma)

Question 15

junvenile polyps

Answer 15

hamartomatous polyp

abundant cystically dilated glands usually w inflam

Question 16

juvenile polyposis syndrome

Answer 16

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

Question 17

Peutz Jeghers polyps

Answer 17

hamartomatous polyps

no malignant potential

Question 18

Peutz-Jeghers syndrome

Answer 18

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

Question 19

inflammatory polyps

Answer 19

regnerating mucosa adjacent to ulceration (severe IBD)

Question 20

lymphoid polyps

Answer 20

mucosal bumps caused by intramucosal lymphoid follicles (normal)

Question 21

types of colon polyps

Answer 21

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

adenomatous polyp/adenoma (precursor to cancer)

Question 22

serrated lumina

Answer 22

serrated polyps

Question 23

sessile serrated tumors

Answer 23

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

Question 24

how do adenomatous polyps/adenomas arise

Answer 24

epithelial proliferative dysplasia

Question 25

epidemiology of adenomatous polyps

Answer 25

common-after age 60

Question 26

3 architectural types of adenomas

Answer 26

tubular villous tubulovillous

Question 27

tubular adenoma morphology

Answer 27

tubular glands | small, pedunculated

Question 28

villous adenoma

Answer 28

villous projections | large, sessile

Question 29

clinical symptoms of adenomatous polyps

Answer 29

asymptomatic or present with rectal bleeding or anemia

Question 30

tx for adenoma

Answer 30

complete resection (regardless of whether carcinoma is present)

Question 31

iron defic anemia in older male signifies

Answer 31

colon cancer unless proven otherwise

Question 32

almost all colon cancers have mutations in what gene?

Answer 32

APC (tumor suppressor gene) for those without an APC mutation, 50% of them have beta-catenin mutations

Question 33

depth of invasion of colorectal carcinomas

Answer 33

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

Question 34

staging colon carcinoma

Answer 34

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)

Question 35

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

Answer 35

TNM staging

Question 36

biomarkers to guide adjuvant therapy--types?

Answer 36

prognostic-provide info about pts overall outcome regardless of therapy predictive-give info about effects of particular therapeutic intervention

Question 37

what is a key target in cancer?

Answer 37

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

Question 38

what pathway is activated by EGFR

Answer 38

RAS-RAF-MAP kinase | and two others

Question 39

therapeutic options of colorectal carcinoma

Answer 39

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)

Question 40

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

Answer 40

KRAS | BRAF

Question 41

familial adenomatous polyposis is inherited in what fashion?

Answer 41

autosomal dominant

Question 42

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

Answer 42

100

Question 43

outlook for FAP

Answer 43

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

Question 44

what genetic mutation exists in FAP?

Answer 44

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

Question 45

MYH associated polyposis

Answer 45

hereditary colorectal cancer syndrome that has phenotypic overlap with FAP typically 20-100 adenomatous polyps autosomal recessive inheritance due to mutation in MYH gene

Question 46

MYH protein's role

Answer 46

DNA repair protein--base excision repair

Question 47

Lynch syndrome/hereditary nonpolyposis colorectal cancer

Answer 47

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)

Question 48

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

Answer 48

MLH1 PMS2 MSH2 MSH6 latter two identify mismatch. first two fix the mismatch

Question 49

how can you clinically analyze mismatch repair of LYnch syndrome?

Answer 49

immunohistochemistry staining for the four different gene/proteins

Question 50

microsatellite instability can be used how?

Answer 50

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

Question 51

how can microsatellite stability predict prognosis?

Answer 51

prognosis for high microsatelitte instability is better long term

Question 52

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

Answer 52

microsatelittle stability

Question 53

majority of colorectal cancers have what microsatelittle instability phenotype?

Answer 53

microsatelittle stable/low instability