pathology 6 - Colonic polyps Polyposis syndromes Lynch syndrome Colorectal cancer Molecular pathogenesis of colorectal cancer

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

adenomatous colonic polyps genes

Answer 8

APC and KRAS, which are commonly mutated via the chromosomal instability pathway in neoplastic polyps

Question 9

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

Answer 9

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

Question 10

What genetic mutations are associated with serrated polyps?

Answer 10

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

Question 11

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 11

Adenocarcinoma (this is likely juvenile polyposis syndrome)

Question 12

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 12

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

Question 13

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

Answer 13

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

Question 14

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 14

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

Question 15

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

Answer 15

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

Question 16

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

Answer 16

APC, 5q; two-hit

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

lthough 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

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

Answer 34

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

Question 35

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

Answer 35

APC, KRAS; APC

Question 36

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

Answer 36

p53, DCC

Question 37

What molecular pathway most commonly generates sporadic colorectal cancer?

Answer 37

APC/β-catenin (chromosomal instability) pathway

Question 38

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

Answer 38

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

Question 39

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

Answer 39

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

Question 40

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

Answer 40

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