Fa: Gastrointestinal - Pathology - 5

Front 1

Who is most likely to get colorectal cancer?

Back 1

- Most patients >50 years
- 25% have a family history

Front 2

What genetic syndromes can contribute to Colorectal Cancer?

Back 2

- Familial Adenomatous Polyposis (FAP)
- Gardner Syndrome
- Turcot Syndrome
- Hereditary Non-Polyposis Colorectal Cancer (HNPCC / Lynch Syndrome)

Front 3

How are the different genetic syndromes that can cause Colorectal Cancer inherited?

Back 3

All Autosomal Dominant

Front 4

What mutation is responsible for Familial Adenomatous Polyposis (FAP)? Location?

Back 4

Autosomal Dominant mutation of APC gene on chromosome 5q
- Requires 2-hits

Front 5

If you have 2 hits of the mutated APC gene on chromosome 5q, what do you have? What will it cause?

Back 5

Familial Adenomatous Polyposis (FAP)
- 100% progress to Colorectal Cancer unless the colon is resected

Front 6

What are the signs of Familial Adenomatous Polyposis (FAP)?

Back 6

- Thousands of polyps arise starting at a young age
- Pancolonic
- Always involves RECTUM

Front 7

What is it called if you have Familial Adenomatous Polyposis (FAP) + osseous and soft tissue tumors, with congenital hypertrophy of retinal pigment epithelium?

Back 7

Gardner Syndrome

Front 8

What is it called if you have Familial Adenomatous Polyposis (FAP) + a malignant CNS tumor?

Back 8

Turcot Syndrome (think TURban)

Front 9

What mutation is responsible for Hereditary Non-Polyposis Colorectal Cancer (HNPCC / Lynch Syndrome)?

Back 9

Autosomal dominant mutation of DNA mismatch repair genes

Front 10

If you have a mutation of DNA mismatch repair genes, what do you have? What will it cause?

Back 10

Hereditary Non-Polyposis Colorectal Cancer (HNPCC / Lynch Syndrome)
- 80% progress to Colorectal Cancer (CRC)

Front 11

Which part of the colon is affected by Hereditary Non-Polyposis Colorectal Cancer (HNPCC / Lynch Syndrome)?

Back 11

Proximal colon is ALWAYS involved

Front 12

What mutations cause a predisposition for colorectal cancer?

Back 12

- Mutation of APC gene on chromosome 5q → Familial Adenomatous Polyposis (FAP) → 100% progress to CRC
- Mutation of DNA mismatch repair genes → Hereditary Non-Polyposis Colorectal Cancer (HNPCC / Lynch Syndrome) → 80% progress to CRC

Front 13

What is Gardner Syndrome?

Back 13

Familial Adenomatous Polyposis (FAP) + osseous and soft tissue tumors, congenital hypertrophy of retinal pigment epithelium

Front 14

What is Turcot Syndrome?

Back 14

Familial Adenomatous Polyposis (FAP) + malignant CNS tumor (TURcot = TURban)

Front 15

What are the risk factors for Colorectal Cancer?

Back 15

- Inflammatory Bowel Disease
- Tobacco use
- Large villous adenomas (polyps)
- Juvenile polyposis syndrome
- Peutz-Jeghers Syndrome (hamatromatous polyps)

Front 16

What part of the colon is most commonly affected by Colorectal Cancer?

Back 16

Rectosigmoid > Ascending > Descending

Front 17

What are the characteristics of Colorectal Cancer in the ascending colon?

Back 17

- Exophytic mass
- Iron deficiency anemia
- Weight loss

RIGHT SIDE BLEEDS, left side obstructs

Front 18

What are the characteristics of Colorectal Cancer in the descending colon?

Back 18

- Infiltrating mass
- Partial obstruction
- Colicky pain
- Hematochezia

Right side bleeds, LEFT SIDE OBSTRUCTS

Front 19

What is a rare presentation of Colorectal Cancer?

Back 19

Streptococcus bovis bacteremia
- S. bovis colonizes the gut
- Can also cause subacute endocarditis

Bovis in the Blood = Cancer in the Colon

Front 20

If you have a patient with iron deficiency anemia who is male or postmenopausal female, what must you rule out?

Back 20

Colorectal Cancer

Front 21

How should patients be screened for Colorectal Cancer?

Back 21

- Screen patients >50 years old
- Colonoscopy or stool occult blood test

Front 22

What finding occurs in Colorectal Cancer on barium enema x-ray?

Back 22

"Apple core" lesion

Front 23

Your patient gets a barium enema x-ray, and this is the finding in the sigmoid colon, what do you think of?

Back 23

Apple core lesion → think Colorectal Cancer

Front 24

What tumor marker is good for monitoring recurrence of Colorectal Cancer? Can it be used for screening?

Back 24

CEA tumor marker can be used to monitor for recurrence, but not useful for screening

Front 25

What are the two molecular pathways that lead to Colorectal Cancer? How common?

Back 25

- Microsatellite instability pathway (~15%)
- APC / β-catenin (chromosomal instability) pathway (~85%)

Front 26

What is wrong in the microsatellite instability pathway? What does it cause?

Back 26

- DNA mismatch repair gene mutations → sporadic and HNPCC syndrome
- Mutations accumulate, but no defined morphologic correlates
- Responsible for 15% of cases of CRC

Front 27

What is wrong in the APC/β-catenin pathway? What does it cause?

Back 27

- Chromosomal instability → sporadic cancer
- Responsible for 85% of cases of CRC

- Normal colon → loss of APC gene →
- Colon at risk → K-ras mutation →
- Adenoma → Loss of tumor suppressor gene(s) (p53, DCC) →
- Carcinoma

Front 28

What gene events occur in the APC/β-catenin pathway leading to colorectal cancer

Back 28

Order of gene events: AK-53

- Normal colon → loss of APC gene (↓ intercellular adhesion and ↑ proliferation) →
- Colon at risk → K-ras mutation (unregulated intracellular signal transduction) →
- Adenoma → Loss of tumor suppressor gene(s) (p53, DCC) (increased tumorigenesis) →
- Carcinoma

Front 29

What are the implications of the loss of the APC gene in the progression to colorectal cancer?

Back 29

- Decreased intercellular adhesions
- Increased proliferations
- Colon at risk

Front 30

What are the implications of the K-RAS mutation after loss of the APC gene in the progression to colorectal cancer?

Back 30

- Unregulated intracellular signal transduction
- At risk colon → Adenoma

Front 31

What are the implications of the loss of tumor suppressor genes (p53, DCC), after the K-RAS mutation and loss of the APC gene in the progression to colorectal cancer?

Back 31

- Increased tumorigenesis
- Adenoma → Carcinoma

Front 32

What are the signs of portal hypertension?

Back 32

- Esophageal varices → hematemesis and melena
- Peptic ulcer → melena
- Splenomegaly
- Caput medusae, ascites
- Portal hypertensive gastropathy
- Anorectal varices

Front 33

What are the signs of liver cell failure?

Back 33

- Hepatic encephalopathy
- Scleral icterus
- Fetor hepaticus (breath smells musty)
- Spider nevi (d/t ↑ Estrogen)
- Gynecomastia (d/t ↑ Estrogen)
- Jaundice
- Testicular atrophy (d/t ↑ Estrogen)
- Liver "flap" = asterixis (coarse hand tremor)
- Bleeding tendency (↓ clotting factors, ↑ prothrombin time)
- Anemia
- Ankle edema

Front 34

What is the term for the diffuse fibrosis and nodular regeneration that destroys the normal architecture of the liver?

Back 34

Cirrhosis

Front 35

What are the characteristics of cirrhosis?

Back 35

- Diffuse fibrosis
- Nodular regeneration
- Destroys normal architecture of liver

Front 36

What does cirrhosis put you at risk for?

Back 36

Increased risk for Hepatocellular Carcinoma (HCC)

Front 37

What are the most common causes of cirrhosis?

Back 37

- Alcohol (60-70%)
- Viral hepatitis
- Biliary disease
- Hemochromatosis

Front 38

What can alleviate portal hypertensino?

Back 38

Portosystemic shunts:
- Esophageal varices
- Caput medusae

Front 39

What are these signs indicative of?
- Esophageal varices
- Hematemesis
- Peptic ulcer
- Melena
- Splenomegaly
- Caput medusae, ascites
- Portal gastropathy
- Anorectal varices

Back 39

Portal Hypertension

Front 40

What are these signs indicative of?
- Hepatic encephalopathy
- Scleral icterus
- Fetor hepaticus (breath smells musty)
- Spider nevi
- Gynecomastia
- Jaundice
- Testicular atrophy
- Liver "flap" = asterixis (coarse hand tremor)
- Bleeding tendency (↓ clotting factors, ↑ prothrombin time)
- Anemia
- Ankle edema

Back 40

Liver cell failure

Front 41

What does this CT show?

Back 41

Nodularity (arrows) of the liver contour secondary to regenerating macronodules = Cirrhosis

Front 42

What does this slide show?

Back 42

Cirrhosis, microscopic: typical regenerative nodules (arrow 1) and bridging fibrosis (arrow 2)

Front 43

What are the serum markers of liver and pancreas pathology?

Back 43

- Alkaline phosphatase (ALP)
- Aminotransferases (AST and ALT) - often called liver enzymes
- Ceruloplasmin
- γ-Glutamyl Transpeptidase (GGT)
- Amylase
- Lipase

Front 44

What is the major diagnostic use of Alkaline Phosphatase (ALP)?

Back 44

- Obstructive hepatobiliary disease
- HCC
- Bone disease

Front 45

What is the major diagnostic use of Aminotransferases (AST and ALT) - often called "liver enzymes"?

Back 45

- Viral hepatitis (ALT > AST)
- Alcoholic hepatitis (AST > ALT)

Front 46

What is the major diagnostic use of Ceruloplasmin?

Back 46

↓ in Wilson Disease

Front 47

What is the major diagnostic use of γ-Glutamyl Transpeptidase (GGT)?

Back 47

↑ in various liver and biliary diseases (just as ALP can), but not in bone disease; associated with alcohol use

Front 48

What is the major diagnostic use of Amylase?

Back 48

- Acute pancreatitis
- Mumps

Front 49

What is the major diagnostic use of Lipase?

Back 49

Acute Pancreatitis (most specific)

Front 50

Which serum marker is most specific to acute pancreatitis?

Back 50

Lipase

Front 51

What can develop in children to take aspirin?

Back 51

Reye Syndrome - rare, often fatal childhood hepatoencephalopathy

Front 52

What are these findings associated with:
- Hepatoencephalopathy
- Mitochondrial abnormalities
- Fatty liver (microvesicular fatty change)
- Hypoglycemia
- Vomiting
- Hepatomegaly
- Coma

Cause?

Back 52

Reye Syndrome - associated with viral infection (especially VZV and influenza B) that has been treated with aspirin

Front 53

What is the mechanism by which aspirin causes Reye Syndrome?

Back 53

Aspirin metabolites ↓ β-oxidation by reversible inhibition of mitochondrial enzyme

Front 54

What are the signs of Reye Syndrome?

Back 54

- Hepatoencephalopathy (often fatal)
- Mitochondrial abnormalities
- Fatty liver (microvesicular fatty change)
- Hypoglycemia
- Vomiting
- Hepatomegaly
- Coma

Front 55

What is the only exception for use of aspirin in children?

Back 55

Kawasaki disease

Front 56

What are the stages of alcoholic liver disease?

Back 56

- Hepatic steatosis
- Alcoholic hepatitis
- Alcoholic cirrhosis