GI Neoplasia II: Colonic Polyps/Colon Cancer: Jackson

Question 1

Describe the two categories of colonic polyps and their relative predilection to malignancy.

Answer 1

Adenomatous (70%)- can develop into cancer
sub groups: tubular, villous, tubulovillous
Non-adenomatous (30%)- very low cancer risk
sub groups: hyperplastic, other (less common)

Question 2

What is the most common, non-neoplastic polyp?

Where are they usually located?

Answer 2

Hyperplastic polyp

Sigmoid colon and rectum

Question 3

What is Peutz-Jeghers Syndrome?

Answer 3

Autosomal dominant
Present ~ 11yo
Multiple GI hamartomatous polyps (small intestine) and mucocutaneous lesions (freckles on lip)
Incr. risk of malignancies: Sex cord tumors of testes, late childhood for gastric and small intestinal cancers, 2nd/3rd decades for colon, pancreatic, breast, lung, ovarian, and uterine cancers.
40% lifetime risk.
Germline heterozygous loss-of-function mutation in gene STK11

Question 4

What are juvenile polyps?

Answer 4

Focal malformations of the epithelium and LP.

Sporadic or syndromic.

Question 5

What is the most common neoplasic polyp?
Risk factors?
Prevalence?

Answer 5

Adenomatous polyps
Old, fat, black man
25-30% by age 50 have them
Most are tubular (80%)

Question 6

Sessile Serrated Adenoma (SSA):
Malignant potential?
Location?
Morphology?
Mutations?

Answer 6

Similar in histo appearance to hyperplastic polyps but have malignant potential.
Proximal colon.
Flat lesions.
May have MSI-H or BRCA muts.

Question 7

RFs for colon cancer.

Anything protective?

Answer 7

Fat
Smoke
EtOH
Red meat

Protective:
Folate in diet, fiber

Question 8

What is the most common cancer of the GI tract?
What is its incidence in the US population?
What percent succumb to the dz?

Answer 8

Colon cancer
5% lifetime risk of colon cancer
40% die

Question 9

Describe the presentation of colon cancer at difference sites along the length of the colon.
Proximal colon:
Sigmoid:
Rectum:

Answer 9

Proximal colon: Occult bleeding, anemia
Sigmoid: Obstruction (BC descending more narrow than asc.), overt bleeding
Rectum: Tenesmus, pain, bleeding

Question 10

Describe tx of colon cancer.

Answer 10

Polypectomy may be curative if cancer localized to head of polyp.
Pre-op CT to look for mets
Remove cancer and adjacent lymphatics surgically to mitigate chances of spread.
Adjuvant chemo if nodes are positive.

Question 11

Describe the screening protocol for colon cancer.

Answer 11

Start screening at age 50 or 45 (AAs). Stop at 75.

Screen every 10 yrs

Question 12

Most cases of colon cancer are sporadic, familial, syndromic?

Answer 12

Sporadic

Question 13

Describe the genetic etiology of familial associated polyposis (FAP).

Answer 13

One allele of APC gene inherited- germ line mutation inherited in AD pattern.
Mut. present in every colon cell.
Polyp growth begins when second hit mutation occurs, causing loss of gene function.

Question 14

What is the lifetime risk of FAP developing into colorectal adenocarcinoma?

Answer 14

100% chance it will transform. Betterhave colon taken out before age 20.

Question 15

Where else besides the colon are adenomas associated w/ FAP common?

Answer 15

Near ampulla of Vater and in stomach

Question 16

HNPCC/Lynch Syndrome:
Number of polyps compared to APC?
Pattern of inheritance?
Genetic etiology?
Prevalence among colon cancers?
Age range and location?

Answer 16

Fewer polyps than in APC
AD pattern of inheritance
Faulty DNA mismatch repair gene and microsatellite instability.
2-4% of colorectal cancers, MC syndromic form.
Younger ages, found in right colon

Question 17

Describe the two sub syndromes associated w/ FAP.

Answer 17

Gardners- mult. colon polyps, osteomas, thyroid cancer, desmoid fibromas, epidermal inclusion cysts.

Turcots- (AR) polyps w/ glioblastoma/medulloblastoma

Question 18

Describe the histologic appearance of hyperplastic polyps.

Answer 18

Well-formed, elongated glands and crypts with saw-tooth or star shaped appearance due to accumulation of cells that will not die.
Mix of goblet and absorptive cells.
Bland cytology w/ eosinophilic cytoplasm (nothing special).

Question 19

What is the diagnostic criteria for differentating sessile serrated adenoma from hyperplastic polyp?
3 histo features?

Answer 19

SSA is found in right colon, HP in left.
SSA carries greater malignant potential.
1) serrated architecture throughout fill length of the glands, including the crypt base.
2) crypt dilation
3) lateral growth

Question 20

How do you diff. Peutz-Jagher polyps from juvenile polyps on histo?

Answer 20

Difference:
Complex glandular architecture and the presence of smooth muscle in Peutz-Jagher polyps.

Peutz-Jagher polyps:
Polyps are large and pedunculated.
Characteristic arborizing network of connective tissue: SM, LP, and glands lined by normal appearing intestinal epithelium

Juvenile polyps:

Question 21

The polyp ____ is the most importance characteristic that correlates w/ risk of malignancy.

Answer 21

Size

Question 22

Adenocarcinoma is one of few cancers that causes this histologic feature of involved lymph nodes:

Answer 22

Dirty necrosis

Question 23

The two most important prognostic indicators of adenocarcinoma of the colon are:

Answer 23

depth of invasion

lymph node mets

Question 24

CR adenocarcinoma likes to met to:

Worst prognosis associated with:

Answer 24

Liver, lung, peritoneum

Worst prog: liver

Question 25

Outline the mutation pathway for CRC from least advanced to most advanced lesions in the case of:
Chromosomal instability (sporadic, classic pathway 80%): 
Microsatellite instability (Lynch syndrome):
Epigenetic pathway (sessile serrated):

Answer 25

Chromosomal instability: APC---> KRAS--->SMAD2/4--->p53 (80% of cases)
Microsatellite instability (Lynch syndrome): failure of mismatch repair (early)
Epigenetic pathway: BRAF

Question 26

Describe staging for CRC.

Answer 26

T1- Tumor invades submucosa
T2- Tumor invades muscularis propria
T3- Tumor invades THROUGH muscularis propria into subserosa
T4- Tumor directly invades other organs/structures