Colonic Polyps and Tumors

Question 1

A man has a biopsy of a colonic polyp. The more ____ (villous/sessile/tubular/hyperplastic) it is, the more likely that it is malignant.


Answer 1

Villous


Question 2

Your 50-year-old patient has a history of hyperplastic polyps. On colonoscopy, where do you most expect to find new hyperplastic polyps?


Answer 2

In the rectosigmoid area


Question 3

A child with rectal discomfort has a single rectal juvenile polyp on colonoscopy. He is otherwise well. Should be polyp be urgently removed?


Answer 3

No; there is no malignant potential if it is truly the only juvenile polyp


Question 4

The malignancy risk of adenomatous polyps is not associated with ____ (degree of dysplasia/villous histology/size/symptoms).


Answer 4

Symptoms


Question 5

What type of polyp is considered a precursor for colorectal cancer?


Answer 5

Adenomatous polyps


Question 6

List these three adenomatous polyp subtypes in order of their potential for malignant transformation, from lowest to highest.


Answer 6

Tubular adenomas, tubulovillous adenoma, villous adenomas


Question 7

What two conditions are associated with the formation of hamartomatous polyps?


Answer 7

Peutz-Jeghers syndrome and juvenile polyposis


Question 8

A patient has a colonoscopy. Polyps are biopsied, and “saw tooth” crypts are seen. Is there a risk of progression to colorectal cancer?


Answer 8

Yes, as the biopsy description is consistent with serrated polyps, which are premalignant (~20% of sporadic colorectal cancer cases)


Question 9

What genetic mutations are associated with serrated polyps?


Answer 9

The CpG hypermethylation phenotype pathway with microsatellite instability, and mutations in BRAF

Question 10

A 12-year-old boy is found to have several polyps in his colon, stomach, and small bowel. For what cancer is he at risk?


Answer 10

Adenocarcinoma (this is likely juvenile polyposis syndrome)


Question 11

A man has GI tract hamartomas and dark patches around his mouth and palms. He asks if his son will be affected by this disorder. Your reply?


Answer 11

The probability is 50% (this patient has Peutz-Jeghers syndrome, an autosomal dominant disorder)


Question 12

A patient has multiple GI tract hamartomas and hyperpigmented hands, mouth, lips, and genitalia. What cancers is he at increased risk for?


Answer 12

Increasing risk for colorectal, breast, stomach, small bowel, pancreatic cancers (the patient has Peutz-Jeghers syndrome)


Question 13

A patient inherits a mutation of the APC gene on chromosome 5q. He asks about his risk for colorectal cancer. What do you tell him?


Answer 13

The patient has familial adenomatous polyposis syndrome; there is 100% progression to CRC if the colon is not removed


Question 14

A 28-year-old man with a history of familial adenomatous worries about his newborn son and asks what the inheritance pattern is.


Answer 14

Autosomal dominant (patients inherit one faulty copy of the gene and lose the other through an acquired mutation [two-hit hypothesis])


Question 15

Familial adenomatous polyposis involves mutation of the ____ gene on chromosome ____. This disease follows the ____ hypothesis.


Answer 15

APC, 5q; two-hit


Question 16

You are going to perform a colonoscopy on a patient with familial adenomatous polyposis. What do you expect to find? Is the rectum involved?


Answer 16

Thousands of polyps (pancolonic involvement) (always involving the rectum)


Question 17

A patient with bone and soft tissue tumors is found to have thousands of polyps on colonoscopy. What syndrome is suspected?


Answer 17

Gardner syndrome


Question 18

Why might you want to perform a colonoscopy on a young patient with extra teeth and abnormally pigmented retinas?


Answer 18

These are Gardner syndrome traits (FAP, osseous/soft tissue tumors, hypertrophy of retinal pigment epithelium, impacted/supernumerary teeth)


Question 19

A young patient with a history of a brain tumor has GI bleeding. What syndrome might you want to urgently screen for in your work-up?


Answer 19

Turcot syndrome (FAP + malignant CNS tumor) (Turcot = Turban)


Question 20

What is the inheritance pattern of juvenile polyposis syndrome? At what age does it typically present?


Answer 20

Autosomal dominant; less than 5 years of age

Question 21

A woman is diagnosed with endometrial cancer and has multiple relatives with skin and colorectal cancer. What syndrome do you suspect?


Answer 21

Lynch syndrome, or HNPCC (requires 3 relatives with Lynch syndrome across 2 generations, at least 1 found before age 50)


Question 22

Hereditary nonpolyposis colon cancer, or Lynch syndrome, involves mutations of DNA ____ genes. It is of autosomal ____ inheritance.


Answer 22

Mismatch repair; dominant


Question 23

If working up a patient for HNPCC, what part of the bowel do you biopsy? What gene mutation would you look for in the biopsied tissue?


Answer 23

The proximal colon (is always involved); screen for mutations of DNA mismatch repair genes with subsequent microsatellite instability


Question 24

What percentage of patients with HYPNCC will progress to have colorectal cancer?


Answer 24

Approximately 80%

Question 25

A patient is diagnosed with right-sided colon cancer. What type of symptoms would you observe in this patient to reach your diagnosis?


Answer 25

An exophytic mass, iron deficiency anemia, weight loss


Question 26

Name at least three risk factors for colorectal cancer.


Answer 26

Adenomatous and serrated polyps, familial cancer syndromes, IBD, tobacco use, diet of processed meat with low fiber


Question 27

How do you screen for colorectal cancer?


Answer 27

Colonoscopy, flexible sigmoidoscopy, or stool occult blood testing


Question 28

A patient with past history of colorectal cancer is constantly monitored for recurrence. What nonspecific serum tumor marker is used?


Answer 28

Carcinoembryonic antigen (CEA)


Question 29

A man has fevers, hypotension, and a new murmur. Blood cultures grow a streptococcal species. Why might you want to perform a colonoscopy?


Answer 29

Although rare, colorectal cancer can be associated with Streptococcus bovis bacteremia (this patient may need a colonoscopy once stabilized)


Question 30

A male patient with iron deficiency anemia is concerned about colon cancer risk. Should he be concerned? Who else should be concerned?


Answer 30

Yes, as iron deficiency anemia can be a presenting sign of colorectal cancer, from occult GI bleeding; postmenopausal females


Question 31

Put in order (from most to least common) where colorectal cancer presents: descending colon, ascending colon, rectosigmoid junction.


Answer 31

Rectosigmoid junction, ascending colon, descending colon


Question 32

A man is worried about colon cancer. He wants a screening CEA level drawn, because he is “scared of colonoscopies.” What do you tell him?


Answer 32

CEA levels cannot be used for screening—they can be used only to monitor for recurrence in previously diagnosed patients

Question 33

In the microsatellite instability pathway, what type of mutation is responsible for carcinogenesis in colonic epithelium?


Answer 33

DNA mismatch repair gene mutations, which accumulate (they occur sporadically or are defective in Lynch syndrome)


Question 34

A man with colonic polyps is found to have colorectal cancer. This process was likely set in motion by the loss of function of which gene?


Answer 34

APC gene (loss of function causes increased proliferation and decreased intracellular adhesion)


Question 35

The KRAS gene mutation leads to dysregulation of what cellular function?


Answer 35

Signal transduction (the cell will respond abnormally to growth factors, contributing to tumorigenesis)


Question 36

Both ____ and ____ gene mutations must be present for colonic adenoma formation. The ____ gene mutation alone simply puts the colon at risk.


Answer 36

APC, KRAS; APC


Question 37

Loss of function of which tumor suppressor genes is often the last step in malignant transformation of colonic epithelial cells?


Answer 37

p53, DCC


Question 38

What molecular pathway most commonly generates sporadic colorectal cancer?


Answer 38

APC/β-catenin (chromosomal instability) pathway


Question 39

What three gene mutations must generally occur for colorectal cancer to develop, and in what order do they occur?


Answer 39

In order, they are loss of APC, KRAS, and p53 & DCC (AK-53)


Question 40

A patient has a family history of Lynch syndrome due to genetic microsatellite instability. Are there any physical signs other than cancer?


Answer 40

There are none, despite the accumulation of mutations (no defined morphologic correlates)


Question 41

APC gene mutations lead to dysregulation of what cellular function? Can any gross findings be seen on colonoscopy?


Answer 41

Intercellular adhesion (there is decreased intercellular adhesion and increased proliferation); no, as the colon will appear normal


Question 42

KRAS gene mutations lead to dysregulation of what cellular function? Can any gross findings be seen on colonoscopy?


Answer 42

Intracellular signal transduction becomes unregulated; yes, as colonic adenomas may develop and be visible


Question 43

In the CRC chromosomal instability pathway, indicate whether each gene in the sequence is a tumor suppressor or a proto-oncogene.


Answer 43

APC is a tumor suppressor, KRAS is a proto-oncogene, p53 and DCC are tumor suppressors