Pathology - GI Cancers Flashcards
(104 cards)
1
Q
Two main variants of esophageal carcinomas?
A
- Adenocarcinoma
- Squamous cell carcinoma
2
Q
Risk factors for Adenocarcinoma? (3)
A
- Long standing GERD
- Barrett’s esophagus
- Tobacco use
3
Q
Protective factors against Adenocarcinoma?
A
Diets rich in fruits and vegetables
4
Q
Risk factors for Squamous Carcinoma? (7)
A
- Alcohol and tobacco use
- Poverty
- Caustic esophageal injury
- Achalasia
- Tylosis
- Plummer-Vinson syndrome
- Frequent consumption of very hot beverages
5
Q
Are esophageal carcinomas common?
A
Yes relatively common - very deadly
6
Q
Epithelial clones identified in nondysplastic Barrett metaplasia persist and __________ during progression to dysplasia and invasive carcinoma
A
Accumulate mutations
7
Q
What mutations are present in esophageal carcinoma? (3)
A
- Over expression of p53
- Amplification of: c-ERB-B2, cyclin D1, cyclin E genes
- Mutation of RB
8
Q
Where does esophageal adenocarcinoma usually occur?
A
Distal 1/3 of the esophagus and may invade adjacent gastric cardia
9
Q
In adenocarcinoma. tumors resemble what kind of cells? What do they produce?
A
Intestinal cells; mucin and form glands
10
Q
Etiology of squamous cell carcinoma?
A
Loss of several tumor suppressor genes, including p53 and p16/INK4a
11
Q
Half of squamous cell carcinomas occur where?
A
Middle 1/3 of the esophagus
12
Q
How do early lesions of squamous cell carcinomas appear?
A
Small, grey-white, plaque-like thickenings
13
Q
With progression, squamous cell tumor can ______ into and obstruct the lumen or _____ and infiltrate
A
protrude; ulcerate
14
Q
What surrounding structures may squamous cell carcinoma invade?
A
- respiratory tree, causing pneumonia
- aorta, causing catastrophic exsanguination
- mediastinum and pericardium
15
Q
Clinical features of esophageal carcinomas? (5)
A
- Dysphagia
- Odynophagia
- Obstruction
- Weight loss
- Hemorrage and sepsis (may occur)
16
Q
Prognosis of esophageal carcinomas?
A
Poor – 5 year survival is 10% - 25% due to frequency of metastasis
17
Q
75% of all gastric polyps are either ________ or ________
A
Inflammatory or hyperplastic
18
Q
Gastric polyps usually develop in association with what?
A
Chronic gastritis
19
Q
What increases the likelihood for presence of malignancy?
A
Larger polyps
20
Q
Gastric adenomas make up ___% of gastric polyps
A
10%
21
Q
Epidemiology of gastric adenoma?
A
- Incidence increases with age
- M > F
- Age: 50-60 yo.
22
Q
Gastric adenomas have a greater risk of cancer than ________
A
Colonic carcinomas
23
Q
Etiology of gastric adenoma?
A
- Gastric atrophy
- Intestinal metaplasia
24
Q
Where are gastric adenoma solitary lesions most commonly located?
A
Stomach antrum - higher malignant potential in the fundus
25
what is risk of progression to adenocarcinoma related to?
Size of lesion
26
Majority of adenomas composed of what?
Intestinal-type columnar epithelium
27
How are gastric adenocarcinomas classified? What are the classifications?
Classified based on location
- Diffuse = diffuse infiltrative growth patterns
- Intestinal = composed of glandular structures
28
Adenocarcinomas comprises what percent of gastric cancers?
90%
29
Why is it thought that incidence of gastric adenocarcinoma has decreased in North America?
Related to reduced rates of H. pylori infection and environmental factors
30
Gastric adenocarcinoma tends to develop in what setting?
Chronic inflammation
31
Genes of interest in gastric adenocarcinoma? (3)
- p53 mutations common
- lof of E-cadherin
- Intestinal - mutations that increase signalling of ent pathway
32
Characteristic of advanced cancers?
Penetration below the submucosa into the muscular wall
33
Intestinal gastric adenocarconioma?
Composed of malignant cells forming neoplastic intestinal glands - resemble colonic adenocarcinoma
34
Diffuse gastric adenocarcinoma?
Gastric-type mucous cells that don't form glands but permeate the mucosa = form signet-ring cells
35
Clinical features of gastric adenocarcinoma? (initial and advanced)
- Sx similar to PUD or chronic gastritis until advanced
- Advanced: weight loss, anorexia, altered bowel habits, anemia
36
Prognosis of gastric adenocarcinoma?
- If caught early, surgical resection results in 90% 5- year survival
- If advanced, 5-year survival is 20%
37
Common metastasis of gastric adenocarcinoma? (2)
- Supraclavicular sentinel lymph node
- Ovaries
38
Most common site for lymphoma outside of lymph nodes?
Stomach (gastric lymphoma)
39
Where does gastric lymphoma arise?
Sites of chronic inflammation (most commonly from chronic H. pylori)
40
Where does gastric lymphoma originate?
Originate in GI tract at sites of pre-existing MALT
41
Gastric lymphoma tends to be _____ lymphoma
B-cell
42
Pathology of B-cell lymphomas? (3)
- Dense lymphocytic infiltrate LP
- Neoplastic lymphocytes infiltrate gastric glands
- reactive-appearing B-cell follicles present
43
Prognosis of gastric lymphoma?
- 90% 5-year survival if caught at an early stage
- 30-40% if discovered at more advanced stages
43
Clinical features of gastric lymphomas? (7)
- Underlying B-12 deficiency and anemia
- Fatigue
- Low-grade fever
- Nausea
- Constipation
- Epigastric pain
- Weight loss
44
Why are clinical findings of gastric lymphomas those of underlying B12 deficiency?
Autoimmune deficiencies = lose intrinsic factor
45
Most common neoplastic polyps?
Colonic adenomas
46
Benign polyps are precursors to what?
Colorectal adenocarcinomas
47
Risk factors for colonic adenomas?
- 50% of adults in western world by age 50
- If you have a relative with it, typically screened at 10 years before youngest age that relative was diagnosed
48
Although adenomas exhibit _________, majority do not progress to adenocarcinomas?
Epithelial dysplasia
49
Metaplasia?
Turns into a different kind of cell (eg. stomach cell becomes an esophageal cell)
50
Dysplasia?
Transforms into an abnormal version of ITSELF
51
What will you see with dysplasia?
- Nuclear hyperchromasia, elongation
- Epithelium fails to mature actively = REDUCTION IN GOBLET CELLS
52
What is the most important characteristic that correlated with risk of malignancy of colorectal adenocarcinoma?
Size
53
Most common malignancy of GI tract and major cause of morbidity and mortality worldwide?
Adenocarcinoma of the colon
54
Peak incidence of adenocarcinoma of the colon?
60-70 yo.
55
What is most closely associated with increased colorectal cancer rates?
Dietary factors - low intake of un-absorbable vegetable fiber and high intake of refined carbs and fats
56
Reduced fiber content leads to what?
Decreased stool bulk and altered composition of intestinal microbiota
57
What do deficiencies of vitamins A, C, and E do?
They are free radical scavengers - so more damage by oxidants
58
High fat intake enhances what?
Hepatic synthesis of cholesterol and bile acids
59
What may be protective against adenocarcinoma of the colon?
COX-2 inhibitors
60
Two genetic pathways of adenocarcinoma?
1. APC/beta-catenin pathways associated with WNT
2. Microsatellite instability pathway
61
What mutation is also common in adenocarcinoma of the colon? (proto-oncogene)
BRAF
62
80% of sporadic colon tumors typically include mutation of ____ in the neoplastic process
APC
63
What is APC a key negative regulator of?
Beta-catenin
64
What happens with loss of APC function?
Beta-catenin accumulates and translocates to the nucleus
65
What does beta-catenin activate?
MYC and cyclin D1 = promote proliferation
66
Additional mutations following APC mutation?
KRAS and p53 lof
67
What is micro-satellite instability?
Loss of mismatch repair genes, mutations accumulate in micro-satellite repeats
68
Some microsatellite sequences are located in the coding or promoter region of genes involved in regulation of cell growth including: (2)
- Type II TGF-beta receptor
- Pro-apoptotic protein BAX
69
Distribution of adenocarcinoma of the colon?
Distributed equally over entire colon
70
Tumors in proximal colon grow as what?
Polyploid, exophytic masses that extend along walls of the viscus
71
Carcinomas in distal colon tend to be what kind of lesions? What do they produce?
- Annular lesions
- Napkin-ring constrictions and luminal narrowing
72
Adenocarcinomas in the distal colon can be palpated in what exams? What do they feel like?
- DRE
- Firm palpable masses
73
Clinical features of cecal and other right-sided colon cancers? (3)
- Bleeding leading to iron deficiency anemia
- Fatigue
- Weakness
74
Clinical features of left-sided colorectal carcinomas? (3)
- Occult bleeding
- Changes in bowel habits
- Cramping in LLQ
75
Most important prognostic factors for adenocarcinoma of the colon?
- Depth of invasion
- Presence or absence of lymph node metastases
76
Most common site of metastatic lesions of adenocarcinoma of the colon? What is it a result of?
Liver - Result of portal drainage of colon
77
Adenocarcinoma of the colon matastases?
- Regional lymph nodes
- Lungs
- Bones
78
When hepatic adenomas present as intra-hepatic masses, what may they be mistaken for?
Ominous hepatocellular carcinomas
79
What type of adenomas have a tendency to rupture during pregnancy? What may this cause?
Subcapsular adenomas - may cause intraperitoneal hemorrage
80
Epidemiology of hepatic adenomas?
Tend to occur in young women who have used oral contraceptives (but usually regress when terminated)
81
Primary carcinomas of the liver?
Hepatocellular carcinoma (HCC)
82
Where do hepatocellular carcinoma cases happen most?
Countries with high rates of chronic HBV infection
83
Risk factors for hepatic carcinoma?
- Long standing cirrhosis
- Chronic viral infection
- Chronic alcoholism
- Food contaminants
84
What is Aflatoxin?
Produced by fungus, which contaminates peanuts and grains and mutates p53
85
Common driver mutations in hepatic carcinoma? (3)
- Activating mutations in Beta-catenin genes
- TERT mutations – upregulated telomerase
- Inactivating mutations to p53
86
Why is cirrhosis the major risk factor for HCC?
Repeated cycles of cell death and regeneration
87
Tumor will often be well differentiated and can secrete what?
Bile
88
What do hepatic carcinomas do early?
Invade vascular structures - migrate along portal vein or vena cava
89
What are hepatic carcinomas less dependent on for metastasis?
Lymph node infiltration
90
Clinical features of hepatic carcinoma? (4)
- Ill defined upper abdominal pain
- Malaise and fatigue
- Weight loss
- Abdominal fullness
91
Prognosis of hepatic carcinoma?
Poor - majority of patients pass away within first 2 years
92
Majority of pancreatic cysts are what type?
Non-neoplastic pseudocysts
93
4th leading cause of cancer deaths?
Pancreatic cancer (ductal adeno-carcinoma)
94
Risk factor for pancreatic cancer?
- SMOKING
- Chronic pancreatitis
- Diabetes
95
What do 90% of pancreatic cancers begin as?
Intraepithelial neoplasia
96
Most frequently altered oncogene in pancreatic cancer?
KRAS
97
Genetic alterations in pancreatic cancer?
- KRAS
- Inactivation of CDKN2A (encodes p16)
- Inactivates p53
98
Where do most pancreatic cancers arise?
In the head of the gland (60%)
99
Ductal adenocarcinomas that form glandular structures secrete what?
Mucin
100
Characteristic features of ductal adenocarcinoma?
- Highly invasive
- Elicits an intense non-neoplastic host reaction
101
Clinical features of pancreatic cancer? (3)
- Typically silent until tumor causes obstruction
- Jaundice (post) from obstruction of common bile duct
- Weight loss, anorexia, malaise
102
Prognosis of pancreatic cancer?
Poor - 5-year survival rate less than 5%
103
Higher mortality rate of any cancer?
Pancreatic cancer
