GI neoplasms 2

Question 1

How many polpys must be prsent to dx FAP?

Inheritance pattern?

Gene affected?

Answer 1

need 100

autosomal dominant

APC germile gene on 5q (but 25% sporadic)

Question 2

Where are the adenomas in FAP? what do you do for these pts?

Answer 2

most are in the colon, can be anywhere and require a prophylactic colectomy bc 100% cance of developing colon adenocarcinoma

Question 3

FAP

age of onset of polyps

Age of onset of CRC

Answer 3

Age of onset: median = 16 years, range from 5-38 w/ increasing # detected with age. Cancer at late 30s

Question 4

Varients: Attenuated FAP <100 polpys; usually on the ___ terminus while classic is at the ___

Answer 4

C

N

Question 5

adenomatous polyposis w/ osteomas, epidermoid cysts, desmoid tumors

Answer 5

Gardners syndrome: variatn of FAP

Question 6

: adenomatous polyposis with medulloblastoma

Answer 6

Turcot; variant of FAP

Question 7

hereditary colorectal cancer syndrome; phenotypic overlap with FAP; mostly attenuated FAP, 20-100 adenomatous polyps; but can have more then 100

Answer 7

MYH Associated Polyposis (MAP)

Question 8

Inheritance pattern of MAP

Mutation of MAP

Age presenation of pts

Answer 8

Auto- recessive

mutated MYH gene: 1p34.3-p32.1

Present older then FAP

Question 9

Define the role of teh MYH protein

Answer 9

DNA repair protein; base excision repair; takes our A—G mismatch

494A—> G

1145G—> A

are two common mutations

Question 10

Increased risk of colorectal cancer and extra-intestinal cancer; endometrial cancer in females (w/ sm.inets/ureter/renal pelvis)

Answer 10

Lynch sydnrome: Herediary nonpolyposis Colorectal cancer

Question 11

What is the age of onset for adenoma in Lynch compared to other syndromes?

Answer 11

Adenomas occur earlier then normal but in low #s::: Colonic carcinoma IG occurs in mulitples, not ass. w/ adenomas

Question 12

What is the defect responsible for Lynch sydrome?

Answer 12

defect often DNA mismatch repair: microsatelilite instability pathway

Question 13

Features of Lynch:

accelerated carcinogeneis (adenoma—> carcioma) in _____ yrs vs 8-10

see____ CRC pts have Lynch syndrome, risk for second primary cancer is 16% in 10 yrs

Answer 13

2 to 3

1/35

Question 14

How do first degree relatives of Lynch patients do?

Answer 14

risk for new cancer in first/second degree relative = 35-45% by age 70 but better survival rate bc most are associated with increased inflammation thus boosts host immune response to cancer

Question 15

assoicated w/ lots of sebaceous adenomas, sebaceous carcinomas and keratoacanthomas; ie SKIN cancers with sebaceous adenomas

Answer 15

Muir-Torre syndrome:

part of LYNCH!!!

Question 16

Lifetime risk of following cancers if you have MMR gene mutation

colon, male:

Colon, female:

Endometrium:

Sm intestine:

stomach

ovarian

Answer 16

colon, male: 28-50%

Colon, female: 24-50%

Endometrial: 30-50%

Sm intestine: 4-7%

stomach: 2-13%
ovarian: 3-13%

Question 17

Describe key histology in Lynch syndrome

Answer 17

Mucinous features and chronic inflammation with signet ring features

Question 18

What are my MMR or mismatch repair genes?

Answer 18

MSH1 and MSH2 recognize and fix shit

PMS2 and MSH6

Question 19

MSH2/MSH6 will:

Answer 19

identify the mismatch

Question 20

MSH1/PMS2 will

Answer 20

fix the mismatch

Question 21

*see loss of MMR funtion sporadic (___%) or hereditary (__%) leading to accumulation of mutations

Answer 21

12

3

Question 22

Staining is:

MLH1: +

PMS2: +

MSH2: +

MSH6: +

Answer 22

likely sporadic cancer

Question 23

Staining is:

MLH1: -

PMS2: -

MSH2: +

MSH6: +

Answer 23

LS or sporadic

MLH1 mucation or MLH1 hyperpigmentation

Question 24

Staining is:

MLH1: +

PMS2: +

MSH2: -

MSH6: -

Answer 24

Mutation is likely LS:

MSH2 mutation

Question 25

Staining is:

MLH1: +

PMS2: +

MSH2: +

MSH6: -

Question 26

Staining is:

MLH1: +

PMS2: -

MSH2: +

MSH6: +

Answer 26

Likely LS with PMS2 mutuation

Question 27

= repeat DNA throughout genome and IG non-coding segments

Answer 27

Microsatallites

Question 28

mutations in MMR protein—> accumulation of mutation in genome; some are in critical genes an can initiate cancer.

Answer 28

microsatelitte instability

Question 29

DNA replication enZ will ‘slip’ frequently on repeat sequences (microsatellites) and___ fixes the ‘slips’… NO____ : end up with see mutated microsatellites that change in length and act as surrogate marker for___ function

Answer 29

MMR

Question 30

Understand how to read microsatelitte instability

Answer 30

note the left shift = instability in microsatellite means may be instabilityin MMR gene

Question 31

MSI-L = microsatalite instability-LOW means see 1 maker for MSI= more likely____

Answer 31

sporadic

Question 32

MSI-H = microsatallite instability-HIGH see at least 2 markers show MSI =

Answer 32

more likely inherited

Question 33

When do we give adjuvant chemo: in MSI-L or MSI-H patients?

Answer 33

In pts with MSI-Low!!!

Question 34

BRAF has never been reported in pt with_____ syndrome but we see 68% of sporadic MSI CRC (non-lynch) do have BRAF mutation.

Answer 34

Lynch

Question 35

BRAF is useful in diagnosing:

Answer 35

MSI-H and loss of MLH-1 IHC seen in colorectoal cancer

Question 36

Most common frequenct of Micro-Sat-Instability phenotype in CRC

Answer 36

MSS/ MSI-L

while 13% are sporadic: MSI-H

Question 37

What does anal canal carcionma with basaloid differentiation look like on histology

Answer 37

sheets of basal cells

Question 38

What do Squamos cell carcinomal of anal canal look like on histology?

Answer 38

irregular nuclei, squamous looking glands

Question 39

most common cancer of appendix?

Answer 39

Carcinoid = most common (20-39 yrs)—> secretes bioactive compounds

Question 40

obstructed appendix w/ insipissate mucin; not a true tumor

Answer 40

Mucocele:

Question 41

Mucinous cystadenoma/cystadenocarcinoma:

Answer 41

mucus secreating epitheial tumor

Question 42

Psuedomyxoma peritonei=

Answer 42

jelly belly, very gelatinous looking