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

1
Q

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

A

Villous

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2
Q

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

A

In the rectosigmoid area

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3
Q

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

A

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

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4
Q

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

A

Symptoms

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5
Q

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

A

Adenomatous polyps

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6
Q

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

A

Tubular adenomas, tubulovillous adenoma, villous adenomas

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7
Q

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

A

Peutz-Jeghers syndrome and juvenile polyposis

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8
Q

adenomatous colonic polyps genes

A

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

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9
Q

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

A

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

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10
Q

What genetic mutations are associated with serrated polyps?

A

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

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11
Q

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?

A

Adenocarcinoma (this is likely juvenile polyposis syndrome)

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12
Q

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?

A

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

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13
Q

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

A

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

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14
Q

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?

A

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

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15
Q

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

A

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

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16
Q

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

A

APC, 5q; two-hit

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17
Q

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

A

Gardner syndrome

18
Q

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

A

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

19
Q

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?

A

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

20
Q

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

A

Autosomal dominant; less than 5 years of age

21
Q

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

A

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

22
Q

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

A

Mismatch repair; dominant

23
Q

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?

A

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

24
Q

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

A

Approximately 80%

25
Q

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

A

An exophytic mass, iron deficiency anemia, weight loss

26
Q

Name at least three risk factors for colorectal cancer

A

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

27
Q

How do you screen for colorectal cancer?

A

Colonoscopy, flexible sigmoidoscopy, or stool occult blood testing

28
Q

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

A

Carcinoembryonic antigen (CEA)

29
Q

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

A

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

30
Q

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

A

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

31
Q

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

A

Rectosigmoid junction, ascending colon, descending colon

32
Q

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?

A

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

33
Q

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

A

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

34
Q

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

A

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

35
Q

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

A

APC, KRAS; APC

36
Q

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

A

p53, DCC

37
Q

What molecular pathway most commonly generates sporadic colorectal cancer?

A

APC/β-catenin (chromosomal instability) pathway

38
Q

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

A

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

39
Q

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

A

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

40
Q

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

A

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