012215 neoplasms sm and large intes Flashcards
prevalence of neoplasms in sm intes
low
most common neoplasm in sm intes
adenoma (near ampulla)
risk factors for sm intes adenocarcinoma
Crohn’s dis
adenomas
celiac dis
familial polyposis syndrome
tx for GIST
imatinib (85% have c-kit mutations)
immunohistochemical markers for GIST
CD117 (c-kit)
DOG1 (specific marker)
CD34
mutations in GIST
c-kit (80%)
PDGFRA (5-10%)
both are tyrosine kinase receptors–gain of fxn
most common non-epithelial (soft tissue) tumor in GI tract
GIST
sm intes neoplasms
adenoma (most common)
carcinoid and adenocarcinoma
mesenchymal tumors (rare)-lipoma, GIST, lymphoma
polyp
epithelium derived tumor mass which protrudes into gut lumen
two types of polyps-shape wise
pedunculated
sessile
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
types of non-neoplastic poyps
hamartomatous
inflammatory
lymphoid
hamartoma
mature, histologically normal elements from the site growing in disorganized manner
chriostomas
haphazard tissue in wrong location (as opposed to hamartoma)
junvenile polyps
hamartomatous polyp
abundant cystically dilated glands usually w inflam
juvenile polyposis syndrome
multiple juvenile polyps
autosomal dominant mutations
increased risk of adenomas, colon cancer
Peutz Jeghers polyps
hamartomatous polyps
no malignant potential
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
inflammatory polyps
regnerating mucosa adjacent to ulceration (severe IBD)
lymphoid polyps
mucosal bumps caused by intramucosal lymphoid follicles (normal)
types of colon polyps
serrated polyps:
hyperplastic polyp (benign)
sessile serrated polyp (malignant potential)
adenomatous polyp/adenoma (precursor to cancer)
serrated lumina
serrated polyps
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
how do adenomatous polyps/adenomas arise
epithelial proliferative dysplasia
epidemiology of adenomatous polyps
common-after age 60
3 architectural types of adenomas
tubular
villous
tubulovillous
tubular adenoma morphology
tubular glands
small, pedunculated
villous adenoma
villous projections
large, sessile
clinical symptoms of adenomatous polyps
asymptomatic or present with rectal bleeding or anemia
tx for adenoma
complete resection (regardless of whether carcinoma is present)
iron defic anemia in older male signifies
colon cancer unless proven otherwise
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
depth of invasion of colorectal carcinomas
TIS (in situ)–within mucosa
T1–submucosa
T2–muscularis propria
T3–serosa
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)
currently the only proven prognostic marker to identify pts with aggressive colon carcinoma
TNM staging
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
what is a key target in cancer?
EGFR (turns on cell cycle-it’s a transmembrane tysorine kinase receptor)
what pathway is activated by EGFR
RAS-RAF-MAP kinase
and two others
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)
what mutations result in decreased efficacy of EGFR monocloncal antibody therapy?
KRAS
BRAF
familial adenomatous polyposis is inherited in what fashion?
autosomal dominant
mininum of how many polyps present is needed to be familial adenamtous polyposis?
100
outlook for FAP
colon adenocarcinoma occurs in about 100%
so prophylactic colectomy is required
what genetic mutation exists in FAP?
APC gene
but 25% of FAP pts have no family hx (new mutations)
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
MYH protein’s role
DNA repair protein–base excision repair
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)
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
how can you clinically analyze mismatch repair of LYnch syndrome?
immunohistochemistry staining for the four different gene/proteins
microsatellite instability can be used how?
microsatelittes are prone to mismatches, so they are sensitive markers of defective mismatch repair fxn
how can microsatellite stability predict prognosis?
prognosis for high microsatelitte instability is better long term
with regards to adjuvant therapy/chemo, should microsatelittle stable or instable pts get it?
microsatelittle stability
majority of colorectal cancers have what microsatelittle instability phenotype?
microsatelittle stable/low instability
