GI Tumors Flashcards
GIST
c-KIT (85%)
PDGFRA (5-10%)
Juvenile polyp/syndrome
Auto dom
SMAD4 (20%)
BMPR1A (20%)-> both involve TGF beta signalling
Peutz-Jeghers polyps/syndrome
Auto dom: STK11
Cowden syndrome
Auto dom: PTEN
Cronkhite-Canada
Non-hereditary; likely autoimmune
*Ectodermal abnormalities
Sessile Serrated
BRAF V600E mutations
Methylation of tumor suppresor gene- shut down
MSI (+/-)
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
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.
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
MYH associated polyposis (MAP)
auto. recessive mutation in MYH gene (chromo 1); MYH = DNA repair protein (base excision repair)
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
Neuroendocrine tumor, secretes bioactive compounds Elevated serotonin (5-HT) 5-HIAA
Carcinoid tumor
Two types of intestinal polyps. Which is easier to remove?
Pedunculate and sessile polyps
*Pedunculated is easier to remove
Benign tumor, focal mass (resembles tumor), d/t development error
Mature, histo normal elements -> growing in disorganized manner
Hamartomatous polyps
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
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
Hamartomatous polyp
Facial trichilemmomas, oral papillomas, acral keratoses
Assoc. risk of thyroid & breast ca
Cowden Syndrome
Pseudopolyps -> regenerating mucosa adjacent to ulceration (severe IBD)
Inflammatory Polyps
Mucosal bumps caused by intramucosal lymphoid follicles -normal
Lymphoid Polyps
SMALL (1/2 in rectosigmoid colon
Serrated Polyps
Majority (60-90%), no malignant potential
Grows from base of crypt. Only see serations at the ends (near the lumen) .
Distal colon
Hyperplastic polyps
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
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
Three types of adenomatous polyps
Tubular
Villous
Tubulovillous
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
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
Treatment for tubular vs villous polyp
Tubular = Endoscopic removal adequate if negative resection margins and no vascular/ lymph involvement.
Villous = Endoscopic removal INADEQUATE -> colectomy.
Right sided presentation of CRC
Right-sided: fatigue, weakness, iron deficiency anemia, polypoid exophytic lesions, occult blood
Left sided presentation of CRC
Left-sided: occult bleeding/hematochezia, change bowel habits, abd discomfort, annular “napkin ring/apple core” constrictions
What is the most common location of CRC?
Rectosigmoid > cecum/ascending > descending; difficult to identify grossly hence go unnoticed until it is a carcinoma
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
Treatment for Familial Adenomatous Polyposis
Prophylactic colectomy
FAP + osteomas, epidermoid cysts, desmoid tumors
Gardener’s Syndrome
FAP + medulloblastoma
Turcot’s Syndrome
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!
Lynch syndrome + sebaceous adenomas/carcinomas, & keratocanthomas
Muir-Torre Syndrome
Tumors of the appendix
Mucocele: obstructed appendix containing mucin (not truly a tumor)
Mucinous cystadenoma/cystadenocarcinoma: mucous secreting epithelial tumor; associated with diverticular formation
