GI - Pathology (Colon Polyps & Cancer)

Question 1

What are colonic polyps, and what is their classic appearance?

Answer 1

Masses protruding into gut lumen => sawtooth appearance

Question 2

What percentage of colonic polyps are non-neoplastic? What are the 2 histologic forms in which colonic polyps can occur?

Answer 2

90% are non-neoplastic; Can be tubular or villous

Question 3

Where in the colon are colonic polyps often found?

Answer 3

Often rectosigmoid

Question 4

What kind of colonic polyps are precancerous? To what kind of cancer is it a precursor?

Answer 4

Adenomatous polyps are precancerous.; Precursor to colorectal cancer

Question 5

What are 3 factors/determinants associated with malignant risk?

Answer 5

Malignant risk is associated with (1) increased size, (2) villous histology, and (3) increased epithelial dysplasia. The more villous the polyp, the more likely it is to be malignant (Think: “villous = villainous”)

Question 6

How do polyps often present? What are 3 other symptoms that may characterize the presentation of polyps? Which of these is specific to villous adenomas?

Answer 6

Polyp symptoms - often asymptomatic, lower GI bleed, partial obstruction, secretory diarrhea (villous adenomas)

Question 7

What is the most common non-neoplastic polyp in the colon? What percentage of these polyps are found in the rectosigmoid colon?

Answer 7

Hyperplastic; Most common non-neoplastic polyp in colon (> 50% found in rectosigmoid colon).

Question 8

In what patient population do Juvenile colonic polyp lesions mostly occur, and how? Where in the GI tract do most occur, and at what percentage?

Answer 8

Mostly sporadic lesions in children < 5 years old. 80% in rectum.

Question 9

Describe the contexts for the malignant potential of juvenile colonic polyps.

Answer 9

If single, no malignant potential; Juvenile polyposis syndrome - multiple juvenile polyps in GI tract, increased risk of adenocarcinoma

Question 10

What findings define Peutz-Jeghers syndrome? What kind of syndrome is it?

Answer 10

Peutz-Jeghers syndrome - autosomal dominant syndrome featuring multiple nonmalignant hamartomas throughout GI tract, along with hyperpigmented mouths, lips, hands, genitalia.

Question 11

What risk does Peutz-Jeghers syndrome increase?

Answer 11

Associated with increase risk of CRC and other visceral malignancies

Question 12

What is the age range of most colorectal cancer patients? What percentage of these patients have a family history?

Answer 12

Most patients are > 50 years old. ~25% have a family history.

Question 13

What are 4 genetic conditions related to colorectal cancer?

Answer 13

(1) Familial adenomatous polyposis (FAP) (2) Gardner syndrome (3) Turcot syndrome (4) Hereditary nonpolyposis colorectal cancer

Question 14

What mutation characterizes familial adenomatous polyposis (FAP)? What hypothesis is relevant here?

Answer 14

Autosomal dominant mutation of APC gene on chromosome 5q. 2-hit hypothesis.

Question 15

At what rate does FAP progress to CRC? What intervention prevents progression?

Answer 15

100% progress to CRC unless colon is resected

Question 16

In FAP, how many polyps arise, and at what age? What extent of the colon does it involve? What part of the GI tract in always involved in FAP?

Answer 16

Thousands of polyps arise starting at a young age; pancolonic; always involves rectum

Question 17

What defines Gardner syndrome?

Answer 17

FAP + osseous and soft tissue tumors, congenital hypertrophy of retinal pigment epithelium

Question 18

What defines Turcot syndrome?

Answer 18

FAP + malignant CNS tumor; Think: “Turcot = Turban”

Question 19

What is another name for Hereditary nonpolyposis colorectal cancer? What mutation does it involve?

Answer 19

Hereditary nonpolyposis colorectal cancer (HNPCC/Lynch syndrome) - autosomal dominant mutation of DNA mismatch repair genes

Question 20

What percentage of HNPCC progresses to CRC?

Answer 20

~80% progress to CRC

Question 21

What part of the colon is always involved in HNPCC?

Answer 21

Proximal colon is always involved

Question 22

Besides genetic conditions, what are 5 additional risk factors for colorectal cancer?

Answer 22

(1) IBD (2) Tobacco (3) Large villous adenoma (4) Juvenille polyposis syndrome (5) Peutz-Jeghers syndrome

Question 23

List the portions of the colon in which colorectal cancer presents in order of most to least common.

Answer 23

Rectosigmoid > Ascending > Descending

Question 24

What are 3 signs/symptoms in the presentation of ascending colorectal cancer?

Answer 24

Ascending - exophytic mass, iron deficiency anemia, weight loss

Question 25

What are 4 signs/symptoms in the presentation of descending colorectal cancer?

Answer 25

Descending - infiltrating mass, partial obstruction, colicky pain, hematochezia

Question 26

Contrast the main distinguishing finding in right-sided versus left-sided colorectal cancer.

Answer 26

Right side bleeds; Left side obstructs

Question 27

Colorectal cancer rarely presents as what infectious condition?

Answer 27

Rarely presents as Streptococcus bovis bacteremia

Question 28

What hematologic finding raises suspicion for colorectal cancer, and in what patient populations?

Answer 28

Iron deficiency anemia in males (especially > 50 years old) and postmenopausal females raises suspicion.

Question 29

At what age should patients be screened for colorectal cancer, and how?

Answer 29

Screen patients > 50 years old with colonoscopy or stool occult blood test

Question 30

What imaging finding characterizes colorectal cancer?

Answer 30

“Apple core” lesion seen on barium enema x-ray

Question 31

What tumor marker is associated with colorectal cancer? How is it used? What is its limitation?

Answer 31

CEA tumor marker: good for monitoring recurrence, not useful for screening

Question 32

What are the 2 molecular pathways that lead to CRC? What percentage of CRC cases are due to each?

Answer 32

(1) Microsatellite instability pathway (~15%) (2) APC/Beta-catenin (chromosomal instability) pathway (~85%)

Question 33

What is the pathophysiology of the microsatellite instability pathway to CRC? What syndrome(s) result(s)?

Answer 33

DNA mismatch repair gene mutations => sporadic and HNPCC syndrome. Mutations accumulated, but no defined morphologic correlates.

Question 34

What is another name for the APC/Beta-catenin pathway to CRC? Again, what percentage of CRC cases does it cause? What kind of cancer results?

Answer 34

APC/Beta-catenin (chromosomal instability) pathway (85%) => sporadic cancer

Question 35

Draw a diagram illustrating the order of gene events in the APC/Beta-catenin (chromosomal instability) pathway to CRC and their effects.

Answer 35

See p. 359 in First Aid 2014 for visual at bottom of page; Think: Order of gene events - “AK-53”

Question 36

What effects does loss of APC gene have in the APC/Beta-catenin (chromosomal instability) pathway to CRC?

Answer 36

Decreased intercellular adhesion and increased proliferation; Normal colon => Colon at risk

Question 37

What effects does K-RAS mutation have in the APC/Beta-catenin (chromosomal instability) pathway to CRC?

Answer 37

Unregulated intracellular signal transduction; Colon at risk => Adenoma

Question 38

What effects does loss of tumor suppressor gene(s) have in the APC/Beta-catenin (chromosomal instability) pathway to CRC? What tumor suppressor genes are lost?

Answer 38

Increased tumorigenesis; Adenoma => Carcinoma; Loss of tumor suppressor gene(s) (p53, DCC)