Colon- Polyps to Cancer Flashcards Preview

GI- Week 2 > Colon- Polyps to Cancer > Flashcards

Flashcards in Colon- Polyps to Cancer Deck (83):
1

What are the main types of colonic polyps?

A image thumb
2

What are main histologic types of colonic polyps?

adenomatous (70%)- include tubular, villous, tubulovillous, and sessile serrated adenomas (these CAN develop into cancer)

non aenomatous (30%)- include hyperplastic, hamatomatous (Peutz-Jeghers syndrome), and Juvenile poylps (very low risk of developing into cancer)

3

What kind of polyp is this?

Q image thumb

Non-adenomatous hyperplastic polyp

4

Describe Non-adenomatous hyperplastic polyps

These are the most common non-neoplastic polyp, usually diminutive in size, and located usually in the rectum or sigmoid colon (No malignant potential in small distal hyperplastic polyps)

5

How do hamartomatous polyps form?

Hamartomatous polyps occur sporadically or as components of various genetically determined or acquired syndromes (Peutz-Jeghers syndrome)

6

Describe Peurz-Jeghers Syndrome

This is an AD syndrome that presents around 11 y/o with multiple GI hamartomatous polyps in the small intestine and mucocutanoeus lesions on the buccal mucosa (below)

A image thumb
7

What mutation is common in Peutz-Jeghers Syndrome?

loss of function in gene STK11

 

8

Peutz-Jeghers syndrome is associated with a markedly increased risk of several malignancies. Name some.

•sex cord tumors of the testes;

•late childhood for gastric and small intestinal cancers; and the second and third decades of life for colon, pancreatic, breast, lung, ovarian, and uterine cancers

•Regular surveillance is recommended beginning at birth

9

What is this?

Q image thumb

10

When and where do juvenile poylps most commonly occur?

In the rectum of children under 5 y/o (presents with rectal bleeding)

11

How do juvenile polyps form?

Morphogenesis in­completely understood. It has been proposed that mucosal hyperplasia is the initiating event

12

What are some complications of juvenile polyps?

•Intussusception, intestinal obstruction, or polyp prolapse (through the anal sphincter) may occur. Some malignant potential as well

13

How common is dysplastic transformation of a juvenile polyp?

Rare in sporadic polyps, but in contrast juvenile polyposis syndrome, 30% to 40% of patients with juvenile polyposis develop colonic adenocarcinoma by age 45

•Individuals with the autosomal dominant syndrome can have from 3 to as many as 100 hamartomatous polyps. A minority can undergo malignant transformation. 

14

What is the most common mutation seen in juvenile polyps?

SMAD4

15

What are the risk factors for adenomatous polyp formation?

Age, abdominal obesity, male sex, and African American race are risk factors (Prevalence of 25-30 % at age 50)

16

Remember that adenomatous polyps can appear grossly as sessile, pedunculated, flat, or even depressed and 

histologically can be tubular (80%), villous (5-15%), or mixed 

A image thumb
17

Which types of adenomatous polyps have the most malignant potential?

villous is more likely than tubular due to typically being larger and Villous are usually sessile and more likely to infiltrate (larger= more likely to transform)

 

18

What is the difference between sessile serrated adenomas (SSAs) and hyperplastic polyps?

SSAs have some histological features of hyperplastic polyps but have malignant potential 

Below: Narrow-band imaging to enhance vascular pattern to ID SSA polyp

A image thumb
19

T or F. SSAs are more common in the right/ascending colon

T.

20

SSAs are most likely to have ____ or ____ mutations

MSI-H or BRAC

21

Tx for a polyp?

polypectomy

22

What is the most common GI malignancy?

Colorectal cancer

23

What are the risk factors for CRC?

-age is most important

-fam Hx, chronic colitis, adenoma, previous colorectal neoplasia 

-living in a developing country (high fat, low fiber diet)

-lack of physical activity

-red meat consumption

-obesity

-cigs and alcohol

24

What things decrease the risk of CRC?

-multivitamins containing folic acid

-aspirin and other NSAIDs

-postmenopausal hormone use

-calcium and folate

-selenium

-veggies, fruits, and fiber

•Incidence of CRC has declined by 30% in last decade in patients> age 50

25

Q image thumb

A image thumb
26

Age is the most common risk factor for colon cancer*****

Need to start screening at age 50 (AA may be earlier-screen at age 45)

Q image thumb

A image thumb
27

How is CRC in the right/ascending colon most likely to present?

The right colon has a larger lumen and thus is less likely to cause obstruction than the descending colon so the main presenting symptoms are most commonly:

-anemia (decreased hemoglobin)

-abdominal pain

-changed bowel habits

-rarely rectal bleeding (21%)

28

How is CRC in the left/descending colon most likely to present?

-abdominal pain (84%)

-changed bowel habits (86%)

-obstruction (27%)

rectal bleeding (44%)

29

How is CRC in the rectum most likely to present?

rectal bleeding (80%)

-abdominal pain (60%) and changed bowel habits 

-tenemus

A image thumb
30

Bairum enemas arent used as much anymore

Q image thumb

A image thumb
31

What are the main goals of CRC screening?

Q image thumb

1) Decrease mortality from colon cancer

2) Prevent colon cancer by removing adenomatous polyps

32

What are the main barriers to CRC screening?

1)Limited access to medical care or colonoscopy

2)Patient preference-bowel prep, time off from work for colonoscopy

3) Risk and expense of screening tests

** Best test for individual patient is test that gets done

**Only 60 % of patients currently get screening between age of 50 and 75

33

What are the screening options for average risk CRC pts?

Avergae pt= no GI symptoms or bleeding. Start screening at 50 and options include 10 yr colonoscopy for screening, a CT colography every 5 yrs, a sigmoidoscopy + barium enema. IF any are positive, move to colonoscopy 

A image thumb
34

What are the screening options for high risk CRC pts?

High risk can ONLY do a colonoscopy, not any alternatives for screening

35

What are the main stool based CRC screening tests?

FOBT (Fecal Occult Blood Test)

FIT (Fecal Immunochemistry Test)

36

Describe FOBTs

Requires 3 stool samples done yearly using a stool card that can be stained for occult blood. Positive test has 20% chance of having large polyp or cancer

•80% false positive rate (Low sensitivity for detecting CRC)

37

Describe FITs

•Responds to only human hemoglobin (doesnt depend on diet)

•Does not detect UGI bleeding

•Requires 1 or 2 stool samples

•May detect as little as 0.3gmHb/gm stool

•More expensive than Guiac and More sensitive and specific than Guiac tests

•Done yearly for screening

38

Q image thumb

39

As shown, the majority of CRC is sporadic with age being the predominant risk factor

Q image thumb

40

What does this image most likely show?

Q image thumb

Hereditary non-polyposis colon carcinoma/ Lynch syndrome (note how the cecum is not covered in polyps like in FAP)

41

Describe Hereditary non-polyposis colon carcinoma/ Lynch syndrome

AD condition that accounts for 2% to 4% of all colorectal cancers, making it the most common syndromic form of colon cancer. 

42

When does Hereditary non-polyposis colon carcinoma/ Lynch syndrome present?

•Tend to occur at younger ages than sporadic colon cancers and are often located in the right colon.

•Compared to familial adenomatous polyposis (FAP), in HNPCC there are fewer polyps and an older age for development of carcinoma. 

43

What causes Lynch syndrome?

faulty DNA mismatch repair genes, and most HNPCC tumors demonstrate microsatellite instability (variations in dinucleotide repeat sequences).

44

What criteria is used for clinical diagnosis of Lynch syndrome?

bethesda criteria

45

What are the Bethesda criteria?

NOTE: Currently most GI pathology leaders are screening every colorectal adenocarcinoma for MSI

1. CRC diagnosed in individual under 50 years of age.

2. Presence of other HNPCC-associated tumors*, regardless of age.

3. CRC with the MSI-H histology, in patient <60 years of age.

4. CRC in 1 or more first-degree relatives with an HNPCC-related tumor, with 1 of the cancers being diagnosed under age 50 years.

5. CRC diagnosed in 2 or more 1st or 2nd degree relatives with HNPCC-related tumors, regardless of age.

*  endometrial, ovarian, gastric, hepatobiliary, small bowel, transitional cell carcinoma of the renal pelvis or ureter.

46

What is this?

Q image thumb

FAP, familial adenomatous polyposis 

47

Describe FAP

Syndrome characterized by almost complete carpeting of the of the mucosal surface of the colon with small adenomatous polyps with tubular-like adenoma microscopic appearances

48

Are the polyps of FAP confined to the colon?

No, Adenomas may develop elsewhere in the GI tract, particularly adjacent to the ampulla of Vater and in the stomach

A image thumb
49

What causes FAP?

germline mutations of the APC gene in every cell of the colon in one allele, and then polyp growth begins when the second allele is somatically mutated

50

How is FAP managed?

This AD syndrome is managed by total prophylatic colectomy (generally before age 20)

NOTE: Colorectal adenocarcinoma develops in 100% of untreated FAP patients, often before age 30 and nearly always by age 50

51

What are the clinical variants of FAP?

-Turcot Syndrome

-Gardner Syndrome

52

What is Turcot Syndrome?

FAP + CNS tumors, often medulloblastomas

53

What is Gardner Syndrome?

FAP + desmoid tumors, osteoms, dental anomalies, soft tissue skin tumors, and/or congenital hypertrophy of the retinal pigment epithelium (CHRPE)

54

Q image thumb

55

What is this?

Q image thumb

Hyperplastic colonic polyp

•Well-formed, elongated glands and crypts with saw tooth or star-shaped appearance - due to decreased epithelial cell turnover, delayed shedding of surface cells and piling up of cells

•Mixture of goblet cells (with abundant mucin) and absorptive cells

Bland cytology with eosinophilic cytoplasm

56

What is this?

Q image thumb

Sessile Serrated Adenoma - Appears similar to hyperplastic poylps, but are marked by:

serrated architecture throughout the full length of the glands, including the crypt base,

crypt dilation, and

lateral growth (boot shaped crypts)

57

SSAs are most common in the _____ colon

Ascending

NOTE: These have malignant potential but lack typical cytologic features of dysplasia

58

What is this?

Q image thumb

Polyps seen in Peutz-Jeghers Syndrome. These are large and pedunculated, with characteristic arborizing (tree-like) networks of CT, as well as smooth muscle, lamina propria, and glands lined by normal-appearing intestinal epithelium 

A image thumb
59

Describe juvenile poylps

•Most are less than 3 cm in diameter and are pedunculated, smooth-surfaced, reddish lesions with characteristic cystic spaces. 

60

How do juvenile polyps appear histologically?

-Surface erosion

-Dilated glands filled with mucin and inflammatory debris

-Lamina propria expanded by mixed inflammatory infiltrates. 

Bottom right: Inspissated mucous, neutrophils, and inflammatory debris can accumulate within dilated crypts

A image thumb
61

Q image thumb

62

What is this?

Q image thumb

Tubular Adenoma -  tend to be small, pedunculated polyps composed of rounded, or tubular, glands 

63

What is this?

Q image thumb

Tubulovillous adenomas have a mixture of tubular and villous elements

1-20% villous component, higher rate of p53 and Kras mutation and MGMT loss

64

What is this?

Q image thumb

Villous adenomas, which are often larger and sessile, are covered by slender villi 

These have cauliflower-like appearance is due to the elongated glandular structures covered by dysplastic epithelium

A image thumb
65

Note about adenomatous poylps

These categories have little clinical significance in isolation.

Although villous adenomas contain foci of invasion more frequently than tubular adenomas, villous architecture alone does not increase cancer risk when polyp size is considered

66

What is the most important characteristic of polyps that correlates with risk of malignancy?

 Polyp Size

67

Q image thumb

68

Q image thumb

Note the two main types of colonic adenocarcinoma

A image thumb
69

What is a unique characteristic of metastatic CR adenocarcinoma?

Dirty necrosis, sloughing of material into the glands 

A image thumb
70

Although poorly differentiated and mucinous colonic adenocarcinoma histologies are associated with poor prognosis, the two most important prognostic factors are what?

depth of invasion and the presence of lymph node metastases (to the subcapsular sinuses most commonly).

71

Where does CRC like to MET to?

liver, lung, and peritoneum

NOTE: With the exception of brain metastasis, liver metastasis had the worst prognosis (median survival time, 9 months). 

72

Q image thumb

A image thumb
73

What is the classic (80% of sporadic colon cancers) pathway for CRC development?

Normal epithelium - APC - small tubular adenoma - KRAS - intermediate adenoma - SMAD2/4 -  advanced adenoma - p53 -  adenocarcinoma

74

What is the MSI/Lynch Syndrome pathway for CRC development?

Normal epithelium - Failure of MMR - small tubular adenoma - MSI (DNA mismatch repair) - adenocarcinoma

75

What is the Epigenetic/CpG island hypermethylation pathway for CRC development?

Normal epithelium - BRAF mutation/hypermethylation MLH1 - hyperplastic polyp - MSI - SSA - MSI - adenocarcinoma

BRAF mutation is almost exclusively seen in sporadic MSI tumors that are presumed to develop through the serrated tumorigenic pathway, but has never been reported in Lynch syndrome.

76

Q image thumb

77

What does APC normally do?

bind to and degrade B-catenin

78

What happens when APC is mutated in FAP?

Steps with loss of APC function:

1.β-catenin accumulates and translocates to the nucleus (stain positive in the nucleus),

2. where it forms a complex with the DNA-binding factor TCF and activates the transcription of genes, including MYC and cyclin D1, that

3. promote proliferation. 

79

B. 

Q image thumb

A.

A image thumb
80

E. 

Q image thumb

C. 

A image thumb
81

C. 

Q image thumb

82

B. 

Q image thumb

B. 

A image thumb
83

Q image thumb

A image thumb