25. Tumors of the Small and Large Bowel Flashcards Preview

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Flashcards in 25. Tumors of the Small and Large Bowel Deck (123):
1

Though the small intestine makes up 75% the length of the GI tract, what % of the tumors are found there?

3-6%

2

What is the most common tumor of the SI?

Adenoma near the ampulla

3

What are four RFs for small intestine adenocarcinoma?

Crohn's disease
Adenomas
Celiac disease
Familial polyposis syndrome

4

What is the most common non-epithelial tumor in the GI tract? What is it derived from?

GIST
Mesenchymal origin, from interstitial cells of Cajal (pacemaker cells)

5

What are three syndromes associated with GIST?

1. Carney triad: GIST, pulmonary chondroma, extra-adrenal paragnaglioma
2. Neurofibromatosis
3. Carney-Stratakis syndrome

6

What can be used to treate GIST and CML?

Gleevec/imatinib

7

Where is GIST most commonly located?

Stomach (60%)
SI (30%)
Colon (4%)

8

What % of GIST tumors have a c-kit mutation?

85%

9

What are three specific markers for GIST?

c-kit (CD117)
DOG1
CD34

10

What are three muscle markers that can be used for GIST but are not necessarily specific?

Actin
Desmin
S-100

11

What two tyrosine kinase receptors can get mutated in GIST, and in what region of the receptor?

C-kit: juxtamembrane domain
PDGFRA: tyrosine kinase II domain

12

What are neuroendocrine tumors of the GI that secrete bioactive compounds?

Carcinoid tumors

13

What are components of carcinoid syndrome?

Vasomotor distrubances
Intestinal hypermotility (diarrhea)
Wheezing
Hepatomegaly
Cardiac involvement

14

What condition can lead to MALT lymphoma?

H. pylori gastritis

15

What is a polyp?

Epithelium-derived tumor mass which protrudes into the gut lumen

16

What are the two main types of polyp by shape?

Pedunculated polyp
Sessile polyp

17

A non-neoplastic polyp is a result of:

Abnomal mucosal maturation, inflammation, architectural distortion
**no malignant potential

18

Neoplastic polyps arise from:

Proliferation and dysplasia (adenomas)
**precursor for carcinoma

19

What are the three main types of non-neoplastic polyps?

Hamartomatous
Inflammatory
Lymphoid

20

What is a hamartoma?

Benign tumor that is composed of mature, histologically normal elements that grow in a disorganized manner due to developmental error

21

What is a choistoma?

Like a hamartoma, but in an abnormal location

22

Where do 80% of juvenile, hamartomatous polyps occur? Shape?

Rectum
Pedunculated (1-3 cm)

23

Histologic appearance of juvenile, hamartomatous polyps

Expanded lamina propria with variable inflammation
Abundant cystically dilated and tortuous glands
*non-neoplastic

24

What is Juvenile polyposis syndrome?

Over 5 juvenile polyps in the stomach, SI, colon, rectum

25

What mutations are associated with juvenile polyposis syndrome?

SMAD4 (20%)
BMPR1A (20%)
**NOT PTEN

26

Juvenile polyposis syndrome is associated with risk for:

Adenomas
10-50% lifetime incidence of colon cancer

27

What mutation is Peutz-Jeghers syndrome associated with (hamartomatous polyps)

STK11

28

What is seen in Peutz-Jeghers syndrome?

Multiple GI hamartomatous polyps
Hyperpigmentation--mucosal and cutaneous (fingers)

29

What is there an increased risk for with Peutz-Jeghers syndrome?

Intussusception
Cancer of the pancreas, breast, lung, ovary, uterus (50% cumulative lifetime risk for cancer)

30

What are the characteristics of Peutz-Jeghers Polyp?

Large and pedunculated
Connective tissue and smooth muscle extends into the polyp
Abundant glands rich in goblet cells

31

What is Cowden syndrome?

AD condition with:
- Hamatomatous GI polyps
- Facial trichilemmomas
- Oral papillomas
- Acral keratoses

32

What is Cowden syndrome associated with a risk for?

Thyroid and breast cancer
**polyps themselves have no malignant potential

33

What is Cronkhite Canada syndrome?

Non-herediatry syndrome with
- GI hamartomatous polyps
- Nail atrophy and alopecia (ectodermal abnormalities)

34

What are inflammatory polyps?

Psuedopolyps that form from regenerating mucosa adjacent to ulceration (usually with severe IBD)

35

What are lymphoid follicles?

Mucosal bumps that are caused by intramucosal lymphoid follicles (normal)

36

What are the two serrated polyps?
What are the two types of polyps with malignant potential?

Hyperplastic and sessile serrated polyps
Sessile serrated polyps and adenomatous polyps

37

What are serrated polyps?

Smooth protrusions of mucosa, usually at the tops of mucosal folds
Serrated lumnia and increased numbers of goblet cells

38

Where are most serrated polyps found?

Rectosigmoid colon

39

What is the prevelance of the two types of serrated polyps?

Hyperplastic 60-90% (MC)
Sessile serrated 10-30%

40

What kind of mutation is associated with sessile serrated polyps?

BRAF V600E mutations

41

What do adenomas/adenomatous polyps arise from?

Arise from epithelial proliferative dysplasia
Precursor lesions for adenocarcinoma

42

What are the three architectural types of adenomas/adenomatous polyps?

Tubular adenoma
Villous adenoma
Tubulovillous adenoma

43

Prevalence of adenomas?
With adenomas, __fold greater risk for developing carcinoma

Common, 40-50% after 60
4 fold

44

Morphology and location of tubular adenomas

Small and pedunculated from dysplastic epithelium (elongated, psuedostratified, hyperchromatic nuclei with loss of mucin production)
90% in the colon

45

Morphology and location of villous adenoma?

Villous projections that are large and sessile
Retrosignoid colon of older people

46

Why does invasion occur more readily with villous adneoma than tubular?

No stalk to act as a buffer zone--cancer invasion occurs directly into the colon wall, lymphatics

47

While cancer is rare in TAs under 1 cm, the risk of cancer approaches __% in sessile, villous adenomas over 4 cm

40%

48

Clinical presentation of adenomatous polyps

Asymptomatic or
Present with rectal bleeding or anemia

49

When is endoscopic removal of pendunculated adenomatous polyps sufficient?

- Resection margins negative
- No vascular or lymphatic invasion
- Carcinoma not poorly differentiated

50

Colon and rectum cancer is the ___ deadliest cancer

Second

51

98% of colorectal cancer is what type?

Adenocarcinoma

52

Where are the most common locations for colorectal cancer?

Rectosigmoid colon (55%)
Cecum and ascending colon (22%)
Transverse colon (11%)
Descending colon (6%)

53

In what geographic locations are the highest death rates from colorectal cancer?

US
Australia
New Zealand
Eastern Europe
**linked to diet

54

What dietary practices are risk factors for colorectal carcinoma?

Excess dietary intake
Low fiber
High content of refined carbs
Red meat
Decreased intake of nicronutrients
Obesity and physical inactivity

55

Presentation of right sided colon cancer? Type of lesions?

Non-obstructive
Fatigue, weakenss, IDA
**Polypoid, exophytic lesions

56

Presentation of left sided colon cancer? Type of lesions?

Obstructive
Occult bleeding, changes in BMs, abdominal discomfort
Annular "napkin ring" constrictions
**Infiltrative

57

What classic presentation is colon cancer until proven otherwise?

IDA in a older male

58

What is the idea behind the 'adenoma-carcinoma sequence'?

Populations with a high prevalence of adenomas have a high prevalence of colon cancer, and vice versa
Distribution of the two is similar

59

What is typically the first mutation to occur in the multi-hit devo of adenoma-carcinoma?

Inactivating mutation in APC (5q11)
**also beta catenin

60

What is the result of dysfunction of APC?

Increased WNT signaling, which leads to decreased cell adhesion and increased cell proliferation

61

What mutation occurs late in the multi-hit development of adeomas and carcinoma?

Loss of p53

62

Along with p53, APC, and beta catenin, what are other mutations involved in the development of colorectal cancer?

K-RAS
LOH
SMAD2 and 4

63

When colorectal cancer is insidiously infiltrative and difficult to identify grossly, what is this usually associated with?

Ulcerative colitis

64

What does that T of TMN classification represent?

Depth of invasion

65

What are the T stages of the TMN classification?

Tis: In situ (LP invasion)
T1: Invasion of submucosa
T2: Invasion of muscularis propria
T3: Penetration of muscularis propria into serosa
T4: Invasion into other structures/organs

66

What are stages 0-IV of colon carcinoma

Stage 0: in situ
Stage I: T1 or T2, N0, M0
Stage II: T3 or T4, N0, M0
Stage III: Any T, + nodes, M0
Stage IV: Any T, any N, M1

67

What is the difference between N1 and N2 in stage III?

N1: 1-3 positive LNs
N2: 4 or more positive LNs

68

What is the most important prognostic factor for colorectal carcinoma?

Stage of the tumor at the time of diagnosis

69

What is the 5 yr survival for stage I, II, III, IV?

I: 93.2%
II: 85%
III: 70%
IV: 8.1%

70

What are the different ways the colon carcinoma can metastasize?
What % of patients have mets at the time of dx?

- Direct extension into adjacent structures
- Met through LNs and vessels
**25-30%

71

What are the four non-specific agents that can be used for colorectal carcinoma (more SEs)

5FU
Capecitabine
Irinotecan
Oxaliplatin

72

What are the three drugs that can be used for targeted therapy of colorectal cancer (picked based on the mutation prolife of the cancer present)

Bevacizumab
Cetuximab
Panitumumab

73

What are the two types of biomarkers with respect to their function?

Prognostic: info about the patient's overall outcome, regardless of therapy
Predictive: info about the effects of a particular therapeutic intervention

74

What receptor stimulates key processes involved with tumor growth and progression--proliferation, angiogenesis, invasion, and metastasis?

EGFR
**overexpressed in a range of solid tumors

75

What 3 major pathways are activated by EGFR?

1. RAS-RAF-MAP kinase
2. PI3K-AKT
3. PLCy

76

What are the three domains of EGFR?

Extracellular domain
Transmembrane domain
Intracellular domain (tyrosine kinase)

77

What are the 4 subsets of EGFR?

ErbB1/EGFR/Her1
ErbB2/Her2
ErbB3/Her3
ErbB4/Her4

78

What subset of EGFR is expressed in COLON cancer, lung, and head and neck cancers?

ErbB1/EGFR/Her1

79

What are the two monoclonal antibodies to EGFR?

Cetuximab
Ranitumumab

80

It is not the EGFR expression that dictates response to anti-EGFR therapy, but rather:

Constituativly active proteins downstream of EGFR, like K-RAS, B-Raf, PI3K, and PTEN

81

What is the major negative predicator of efficiency of EGFR monocloncal antibody tx (cetuximab and reanitumab)?

K-RAS mutation **
BRAF mutation

82

What are the uncommon and autosomal dominant herediatary syndromes that involve the GI tract?

1. Peutz-Jeghers, Cowden disease, Juvenile
2. FAP- Gardner's and Turcot's syndromes
3. MYH associated polyposis (MAP)
4. Lynch syndrome

83

Inheritance and penetrance of familial adenomatous polyposis

Autosomal dominant
Very penetrant

84

How many colonic adenomas are typically present in FAP?

500-2,500 (minimum of 100)

85

Tx for FAP?

Prophylactic colectomy, because colon adenocarcinoma occurs in 100%

86

FAP is due to inheritance of germline mutations in:

APC gene in chrom 5q11

87

What % of people with FAP have no fam hx (de novo, somatic mutations)

25%

88

What is the age of onset for FAP?

median 16
Range 5-38 years
Colorectal cancer in late 30s early 40s

89

What is attenuated FAP

<100 polyps
Some residual low level of APC resulting in fewer polyps

90

What is Gardner syndrome?

Adenomatous polyposis
Osteomas
Epidermoid cysts
Desmoid tumors

91

What is Turcot syndrome?

Adenomatous polyposis
Medulloblastoma

92

Where in the chromosome coding for APC are mutation leading to classical FAP? Attenuated? Garner?

Near N terminal
Near C terminal
Between (causes desmoids)

93

What is a herediatary colorectal cancer syndrome that looks like attenuated FAP (20-100 adenomatous polyps) but is caused by a different mutation (not APC)

MYH associated polyposis (MAP)

94

Inheritance pattern for MYH associated polyposis. Age of presentation

Autosomal recessive
Older age of presentation

95

MAP is due to mutations in the MYH gene, which encodes what kind of protein?

DNA repair protein involved in base excision repair (repairs oxidation-induced DNA damage by removing A mis-paired with G)

96

What are the two common mutations in MYH associated polyposis?

494A->G
1145G->A
**present in 85-90%

97

What is lynch syndrome associated with an increased risk for?

Colorectal cancer
Extra-intestinal cancer: endometrial cancer, ureter, renal pelvis)

98

What is the genetic defect in lynch syndrome?

DNA mismatch repair genes (microsatellite instability pathway)

99

What is Muir-Torre syndrome?

Subtype of Lynch syndrome
Associated with multiple sebaceous adenomas, sebaceous carcinomas, and keratoacanthomas

100

What are two histological presentation of Lynch syndrome tumors?

Mucinous features and chronic inflammation
Mucionous faatures and signet ring features

101

What is the role of MSH2 and MSH6? PMS2 and MLH1

Find the mismatch
Read the mismatch and remove mutant strand

102

What is the dominant protein in the MSH2/6 relationship?
MLH1/PMS2?

MSH2
MLH1

103

What happens with a sporadic (12%) or hereditary (3%) loss of mismatch repair (MMR) function?

Random accumulation of mutations during cell divisions
Mutant in important oncogenes/tumor suppressor genes
Further acceleration of tumor devlopment
Cancer

104

What is negative IHC with a MSH2 mutation?

MSH2 negative
MSH6 negative

105

What is negative with a MSH6 mutation?

MSH6

106

What is negative with a PMS2 mutation?

PMS2

107

What is negative with a MLH1 mutation?

MLH1
PMS2

108

Interpretation of a tumor that is + for MSH2, MSH6, MLH1, PMS2

Sporadic cancer, LS unlikely

109

Interpretation of a tumor that is - for MLH1, PMS2? Etiology?

LS or sporadic caner
MLH1 mutation or MLH1 hypermethylation

110

Interpretation of a tumor that is - for MSH2 and MSH6? Etiology

LS
MSH2 mutation

111

Interpretation of a tumor that is - for MSH6? Etiology

LS
MSH6 mutation

112

Interpretation of a tumor that is - for PMS2? Etiology

LS
PMS

113

What are sensitive markers for defective function of mismatch repair?

Microsatellites: with DNA slippage, MMR should repair the loss of DNA. Failure of system leads to variation in the size of microsatellites

114

What are the three outcomes of microsatellite testing?

Microsatellite stable (MSS): no markers show MSI
Microsatellite instability-LOW (MSI-L): one marker shows MSI
Microsatellite instability-HIGH (MSI-H): at least 2 markers show MSI

115

What is the difference in the response of MSI-L vs MSI-H to adjuvant chemo?

MSI-L have better outcomes with adjuvant chemo
MSI-H have better outcomes without adjuvant chemo

116

What mutation has never been reported in a patient with lynch syndrome, but it present in 68% of patients with MSI CRC that is not related to lynch syndrome?

BRAF mutation

117

Do must people with MSI phenotypes and CRC have sporadic mutations or lynch syndrome?

SPORADIC

118

What are the types of cancer that can occur in the anal canal?

Basaloid carcinoma
Squamous cell carcinoma
Adenocarcinoma
Paget's disease
Small-cell carcinoma
Melanoma

119

What is the MC tumor of the appendix?

Carcinoid (20-39 yrs)

120

What is a mucocele?

Obstructed appendix containing insipissated mucin (not truely a tumor)

121

What is a mucinous cystadenoma of the appendix?

Mucus secreting epithelial tumor of the appendix

122

Where in the appendix are carcinoid tumors found?

At the distal tip

123

What is a condition that can result from mucin produced by mucinous adenocarcinoma of the appendic?

Psuedomyxoma peritonei: mucin into the peritoneal cavity, encasing the organs