GI neoplasms 1 Flashcards by Meghan May

SB is ____% of GI with only ___% of tumors

most common is the ____

75%

3-6%

Adenoma near ampula

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Risk factors for SI adenocarcinoma

Crohns/ Adenomas/ Celiac/ Familial polyposis Syndrome

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most common non-epi tumor of GI, from Cajal cells (mesenchymal)

GIST

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GIST is seen in which syndromes:

Seen in: Carney triad/ Neurofibromatosis/ Carney-Stratakis syndrome

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Treatement for GIST tumors

Tx: Gleevac (bc of c-kit mutation seen in 85% = tyrosine kinase and is a driver mutation. PDGFRA same)

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Location of GIST tumors

Location:

60% stomach/

30% sm.intestine

4% colon:

with a glossy grayish color

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Key histological markers in GIST

Histology: test + for ckit = CD117 in almost 100% cases

DOG1

CD34 (90% time)—> shows up dark stain

Also has different muscle markers: actin, desmin, S-100

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Pt comes in with tumors in the small intestine and your Preceptor states it is ammendable to Gleevac for tx. What type of markers would you expect it to have?

This is a GIST tumor; c-kit positive (tyr/kinase), DOG1 and CD34 +

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Tumor that secreates bioactives = vasomotor/flushing/hepatomegaly and increase serotonin 5-HT

carcinoid tumor

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Where are carcinoid tumors commonly located in the intetinal tract?

located in WALL of intestine; presents as submucosal nodule. Mass of neuroendocrine cells pushing upward

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What levels will be elevated in a pt with carcinoid tumor?

Seratonin: 5-HT

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epithelium derived tumor mass, protrudes through lumen: either pedunculate or sessile

Intestinal Polyp

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d/t abnormal mucosal maturation, inflammation, fucked arch. NO MALIG potential

Non-neoplastic =

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d/t proliferation+dysplasia (adenomas) and is precursor to carcinoma

Neoplastic

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benign, focal mass with mature, histologically normal elements in disorganized manner

Hamartoma: non neoplastic polyp

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What are my 3 non-neoplastic polyps?

Hamartomatous

Inflammatory

Lymphoid

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seen in kids

Juvenile polyps

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Describe what a juvenile polyp looks like histologically

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What is Juvenile polyposis syndrome?

Where is it located?

What gene mutation?

multple polyps >5: in stomach/sm.intest/colon/rectum

        **Auto. Dominant** of **SMAD4, BMPR1A**, r*isk of adenomas,* 10-50% lifetime risk colon,  gastric, small intestine and pancreas cancer

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multple polyps >5: in stomach/sm.intest/colon/rectum

        Auto. Dominant of SMAD4, BMPR1A, risk of adenomas, 10-50% lifetime risk colon,  gastric, small intestine and pancreas cancer

Juvenile polyposis Syndrome

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Peutz-Jeghers Polyps:____ malignant potential

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Pt has hyperpigmented mouth and fingers and multple GI polyps. Dx and inheritance pattern?

Peutyz-Jegher Syndrome = STK11; auto-Dominant

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What are risks associated with Peutz-Jeghers Syndrome?

Risk intussusseption.

Risk of cancer of: pancrease/breast/ovary/uterus/lung of 50% lifetime risk

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Describe what you see on histology and what disease this is assoicated with

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hamartomous GI polpys with facial trichilemmomas, oral papillomas, acral keratoses.

Cowden syndrome

Pt has Cowden syndrome. What is the inheritance pattern? What are associated risks? What is the maligant potential?

Cowden = hamartomatous polyps, Autosomal Dominant Assoicated with thyroid and breast cancer polyps have no maligant potential

non-hereditary, GI hamartomas, Ectodermal shit: nail atrophy + alopecia 2. Inflammatory polyps: pseudopolyps—regenarating mucosa next to ulceration (seen in bad IBD) 3. Lymphoid polyps: mucosal bumps, d/t intramucosal lymphoid follicles; NORMAL

Cronkite-Canada

pseudopolyps—regenarating mucosa next to ulceration (seen in bad IBD)

Inflammatory polyps

mucosal bumps, d/t intramucosal lymphoid follicles; NORMAL

Lymphoid polyps

Two types of serrated polyps

Hyperplastic and Sessile serrated

Describe location, histology and maligant potential of Hyperplastic Serrated polyps

Distally located no maligant potential make up 60-90% of serrated polyps and grow upward so deep, narrow stalk

Describe location, maligant potential and histology of Sessile Serrated polyps

more proximally located HIGH malignant potetial: BRAF V600 mutation; methlyation --+/- microsatalite instability Look like flasks on histology bc grow horizontal and verticle

epithelial proliferative dysplasia + precursor to adenocarcinoma ## Footnote

Adenomatous Polpys; adenomas

Three types of adenoma polpys

Epidemiology for Adenomatous polyps

seen in 40-60% population \>60. Familial pattern; 4x risk of devo adenoma if 1st degree relative had one Adenoma has 4x increase risk of devoing carcinoma with M=F

What do Tubular adenoma's look like and where are they found?

small, pedunculate w/ 90% in colon. Can be mult or single IG

Describe the histology of tubular adenomas

-dysplastic epithelium: elongated, pseudostratified, HYPERchromatic nuclei, loss of mucin production

lots of projections, large and sessile, no stalk, seen in OLDER peep in RECTOsigmoid

Villious Adenoma:

Describe histology of villous adenoma why is there such high maligant potential?

-no stalk to act as buffer in case of invasive carcinoma—\> invasion directly into colon wall —up to 10cm diameter; see fungating and slightly raised for gross

Tubular adenoma; rare to get cancer if \_\_\_\_\_ Risk approaches ____ in sessile, villous adnomas \>4cm; high grade dysplasia if present IG in\_\_\_\_\_ areas but also found in any polyp

\<1cm 40% villious

Intramucosal carcinoma = invades LP but

NO malignant potential

Invasive carcionoma IN a pedunuclated adenoma that has gone through muscularis: endoscopic removal is enough IF what 3 critera are met

resection margins are negative no lymph or vascular invasion carcinoma not poorly different

Invasive carcinoma in **Sessile** polyp: polypectomy\_\_\_\_\_, need partial colectomy

inadequte \*\*\*regardless of carcinoma presence, only tx for adenoma is complete resection!

Colorectal Cancer epidemiology

98% adnocarcinoma 9% of all cancer deaths in US Peak incidicend is 90% over age 50 99% occur singly 1-3% familila or IBD most in rectosigmoid, followed by cecum and ascending

Colorectal cancers causes fatige, weak, Fe anemia. More common in cecum, slow bleed causing progressive weakness. D/t polypoid or exophytic lesions

Right Sided (non-obstructive) colorectal cancer

What type of lesions commonly seen with right sided CRC?

polypoid or exophytic

Colorectal cancer that is obstructive, get occult bleed, change in bowel habits, ab discomfort and **Annular ‘napkin’ obstruction**. More **infiltrative**

Left sided: (obstructive) CRC

Male comes in that is in his 60s and has been tiring easily and feels weak. His labs show Fe deficinecy anemia. What do we need to rule out?

Dx as colon cancer till proven otherwise; often has aysmptomatic and insidious onset

Population w/ high prevelance of adenomas = high chance of\_\_\_\_ cancer distribution of polyps and cancer in colorectal is simular Peak age for adenomas anteda\_\_\_tes peak age for cancer; if you find cancer early, often see adenomatous tissue surrounding it Cancer risk is\_\_\_\_\_ related to # adenomas; will get cancer with FAP; thus remove polyps!

colorectal colorectal DIRECTLY

Explain pathogenesis of CRC

Multi-hit hypothesis; accumulation of mutations (more important than order) with the last to accumlate is p53

\>80% colon cancer has inactivated\_\_\_\_ and 50% w/out ACP have ____ mutations (10%) ## Footnote

ACP B-catenin

—dysfnx of APC seen in colorectal cancer leads to

increased WNT signaling, decreased cell adhesions, increase cell proliferate

Not frequent, but hard to identify grossly, associated with Ulcerative colitis, aggressive, spread early

Infiltrative colorectal cancer

Staging based on depth of invasion; T1 = T2= T3= Stage = T+N+M

1 = Submucosa 2= muscularis propria 3= Serosa

Stage 0 = Stage I: Stage II: Stage III:

Stage 0 = in situ carcinoma Stage I: T1, T2, N0, M0 Stage II: T2 or T4, NO, MO Stage III: any T, positive Nodes StageIV-mets I and II can be cured by excision III need adjuvant therapy IV is palliative care

Single most important prognostic indicator of colorectal carcinoma is

extent or STAGE at time of dx

Survival rates for Colorectal Carcinoma

I and II = 93 and 85% 5 yr surival Stage II = 70% stage IV= 8%

Where do CRC mets genrally go to?

Direct extension to adjacent structures. Mets via LN then to liver, lungs, bones 25-30% pts have METS when they present

Options for targeted therapy in mCRC

Targeted Therapy: to the tumor cell w/ Bevacizumab, Cetuximab, Pantiumamb

\_\_\_\_\_\_ gives info about pt overall outcome, regardless of therapy \_\_\_\_\_\_: info about effects of particular therapeutic intervention

Prognostic: Predictive:

activation stims key processes in tumor growth & progression; key for proliferation, angiogenesis, invasion, metastasis

EGFR

What 3 major pathways are activated in EGFR?

RAS-RAF-MAP kinase PI3K-AKT PLC-gamma that are overexposed in range of solid tumors: there is a transmembrane domain and intracellular domain

What are our key EGFRs involved in colon and breast cancer?

ErbB1/EGFR/Her1 in colon B2/Her2/Neu in breast

What happens in EGFR signal transduction?

turn on STAT or RAS/RAF/MAPK path to induce gene transcription = **anti-apoptosis, metastasis, angiogenesis and proliferation and maturation**

Monoclonal anti-EGFR tx:\_\_\_\_\_ and\_\_\_\_\_\_ used in treatement but no correlation with EGFR expression and response: Doesn’t work for pts with\_\_\_\_ mutation bc that’s downstream

Cetuximab pantumumab KRAS

There is a lack of correlation btween anti-EGFR therapy and

EGFR expression

If a patient has ______ then giving them anti-EGFR mAB won't help their cancer

KRAS

this mutant tumor is associated with lower progression free surival and overall survival compated to WT tumor

BRAF mutant

how don't does the anti-EGFR therapy work?

only for 12-18 months and only in tumors that don't have downstream effector molecule mutations

\_\_\_\_\_mutaiton is major NEGATIVE predictor for efficacy in EFGR therapy and\_\_\_\_ correlates w/ poor prognosis

KRAS BRAF