14a Small intestinal tumors

Question 0

GIST

Answer 0

Gastrointestinal Stromal Tumor
C-Kit/CD117 (intracellular domain) mutations in 85% - DOG1 positive
60% stomach 30% small intestine 4% colon
* Most common non-epithelial tumor in the GI tract
* Interstital cells of cajal
* Carney triad, neurofibromatosis, Carne stratakis syndrome

Gleevec (imatinib) clinically useful for GIST and CML

Question 1

Small intestinal adenocarcinomas

Answer 1

Risk factors: Crohns, adenomas, CD, FAP

Question 2

Carcinoid Tumor

Answer 2

Neuroendocrine- secretion of bioactive compounds

• Carcinoid syndrome- vasomotor disturbances, intestinal hypermobility, wheezing, hepatomegaly, cardiac involvement’
• Excess 5HT

Question 3

Polyp classifications

Answer 3

Pedunculated vs. sessile

Non-neoplastic vs. neoplastic

Question 4

Non-neoplastic polyps

Answer 4

Hamartomatous polyp
Inflammatory polyp
Lymphoid polyp

Question 5

Hamartoma

Answer 5

Benign focal mass of mature histologically normal tissue growing in a disorganized manner

• developmental error
• Not to be confused with choristoma(rafts of tissue that doesnt belong)

Question 6

Juvenile hamartomatous polyp

Answer 6

• Kids<5 yrs old
• 80% in rectum
• 1-3cm pedunculated mass of expanded LP with variable inflammation
• Cystically dilated w/tortourous glands

Question 7

Juvenile polyposus syndrome

Answer 7

*Multiple juvenile polyps (>5, can be 50-100)
*Stomach to rectum AD: SMAD4 (20%) BMPR1A(20%)
*Increased rrisk of adenoma
10-50% lifetime colon cancer risk- also gastric, pancreatic, and small intestine

Question 8

Peutz-Jeghers Polyps

Answer 8

Multiple Hamartomatous polyps - Large pedunculated wth CT and SM in polyp- Abundant glands rich in goblet cells
*AD STK11
*Multiple GI polyps
*mucosal and cutaneous(hands) hyperpigmentation
*Increased intussucception
*increased risk of pancreatic, breast, lung, ovarian cancers
50% LIFETIME CANCER RISK

Question 9

Cowdens syndrome

Answer 9

• AD disorder with hamartomatous polyps
• Facial trichelemmomas, oral papillomas, acral keratoses
• increased breast and thyroid cancer risk

Question 10

Cronkhite- Canada syndrome

Answer 10

Non-hereditary
HI hamartomatous polyps
Ectodermal abnormalities- nail atrophy/ alopecia

Question 11

Other Non-neoplastic polyps

Answer 11

Inflammatory pseudo-polyps
-regenerating mucosa near ulceration

Lymphoid polyps
- normal mucosal bumps created by intramucosal lymphoid follicles

Question 12

Serrated Polyps

Answer 12

Smooth portrusions at tops of folds- rectosigmoid
*small with serrated lumina

HYPERPLASTIC (60-90%)
Distal with no malignant potential
serrated tips

SESSILE SERRATED(10-30%)
Proximal with BRAF V600E mutations
Malignant potential
Altered methylation
Microsatallite instability
"flask like appearance"
Cystically dilated glands

Question 13

Adenomatous polyps

Answer 13

Epithelial proliferative dysplasia (40-50% prevalence by age 60)

• Tubular
• villous
• Tubulovillous

4X greater chance if you have 1st deg relative
4X cancer risk

Question 14

Tubular adenoma

Answer 14

Tubular glands - small pedunculated polyp <1cm = low cancer risk

Question 15

Villous Adenoma

Answer 15

Villous projections- often a large sessile polyp
recto-sigmoid of aged patients
up to 10cm in diameter
Histo: Crowded villous projections
*40% cancer risk if >4cm
*associated with high grade dysplasia

Question 16

Colorectal cancer

Answer 16

98% adenocarcinoma: 90% diagnosed after age 50
Rectosigmoid> right colon>transverse>descending
*Highest death in US, Australia, New Zeland, Eastern europe- manly diet
*>80% have APC inactivation, 10% B-catenin (both WNT- decreased adhesion increased prolif)
Loss p53 occurs late in most GI cancers

Question 17

Colorectal clinical

Answer 17

Right sided are usually non obstructive with insidous onset
Left sided obstructive- can have constrictions (apple core appearance on barium enema), occult bleeding, pain, bowel changes

Pseudostratified elongated nuclei- like adenomas but with more stroma

Question 18

TNM

Answer 18

T: is-mucosa only, 1 submucosa, 2 MP, 3 into serosa, 4other structures

N: 0-no nodes, 1- 1-3 nodes, 2-4 or more

M: 0-no mets

Question 19

Stage

Answer 19

0: CIS
1: T12 93% survival
2: T34 N0M0 85% survival
3: Tx Nx M0 70% survival
4: METs 8.1% survival

Question 20

Colon cancer mets

Answer 20

Regional LN, Liver, Lung, bone

20-30% have distant mets at presentation

Question 21

EGFR

Answer 21

Associated with many aspects of Colon cancer

US of RAS, PI3K/AKT, PLC

Question 22

Panitumab

Answer 22

EGFR antibody- useful for non-Ras*

Question 23

Cetuximab

Answer 23

EGFR drug, less effective with BRAF*

Question 24

FAP

Answer 24

Autosomal Dominant
Onset median at 16yrs (5-38)
Cancer onset 30-40 YO

Subsets:
Attenuated FAP:<100 polyps
Gardeners: Osteomas, epidermoid cysts, desmoids
Turcot: Medulloblastoma

Question 25

MAP

Answer 25

MYH associated polyposis(Base excision repair)
Similar to FAP: 20-100 adenomatous polyps
Autosomal recessive

Question 26

Lynch syndrome

Answer 26

Hereditary nonpolyposis colorectal cancer
*Colon, endometrial, intestinal, ureteral, renal pelvis
*accelerated carcinogenesis (2-3 yr instead of 8-10)
Can have multiple synchronous colon cancerrs
DNA mismatch (MSH2/6, PMS2, MLH1) and Microsatallite instability
More treatable cancers

Question 27

Muir-Torre

Answer 27

Lynch associated wth sebaceous adenmas, sebaceous carcinomas, keratoacanthomas

Question 28

Microsatallite instability

Answer 28

Slippage of chromosomes with deletion of long runs of aaaaaaa or ttttttt
*Only give adjuvant chemo if microsatallite instability is low

Question 29

BRAF mutations

Answer 29

Common in Non Lynch MSI colorectal cancers

Question 30

Appendix toumors

Answer 30

Carcinoids
Mucocoele
Mucinous cystadenoma- very mucinous epithlial villi in appendix
Can be malignant adenocarcinoma as well.

Question 31

Pseudomyxoma Peritonei

Answer 31

“jelly belly”

Large myxoid stroma from mucinous cystadenoma