Liver / Pancreas Flashcards
1
Q
What is the immunoprofile of solid pseudopapillary neoplasm?
A
POSITIVE: Beta-catenin (nuclear) LEF1 TFE3 CD99 (perinuclear dot-like) PR+ Synaptophysin +/-
NEGATIVE
ER
Chromogranin
2
Q
What gene fusion identifies fibrolamellar carcinoma of the liver?
(name 2 genes involved and chromosome)
A
Deletion on chromosome 19 leading to fusion of
DNAJB1-PRKACA
3
Q
Name 8 histologic subtypes of HCC
A
Steatohepatitic Clear Cell Macrotrabecular Massive Scirrhous Chromophobe Fibrolamellar Neutrophil-rich Lymphocyte-rich
4
Q
List 3 inherited diseases that can cause HCC.
A
Hemochromatosis
glycogen storage disease
hereditary tyrosinemia
Others:
Wilson
Alpha-1-antitrypsin
5
Q
List at least 5 manifestations of acute liver failure.
A
Encephalopathy Jaundice/cholestasis Coagulopathy Portal Hypertension Hepatorenal syndrome
6
Q
List 2 PREHEPATIC causes of portal hypertension.
A
- Obstructive thrombosis of portal vein
- Structural abnormalities (such as narrowing of portal vein before it ramifies in the liver).
Robbins table 18.2
7
Q
List the 4 leading causes of chronic liver failure.
A
Hepatitis B
Hepatitis C
Non-alcoholic fatty liver disease
Alcoholic liver disease.
8
Q
List intrahepatic causes of portal hypertension (9)
A
Cirrhosis (from any cause)
Nodular regenerative hyperplasia
Primary biliary cholangitis
Schistosomiasis
Massive fatty change
Diffuse, fibrosing granulomatous disease (e.g. sarcoid)
Infiltrative malignancy (primary or met)
Focal malignancy with invasion into portal vein (esp. HCC)
Amyloidosis
9
Q
List 3 post-hepatic causes of portal hypertension.
A
Severe right-sided heart failure
Constrictive pericarditis
Hepatic vein outflow obstruction.
10
Q
List the 4 main major clinical consequences of portal hypertension.
A
Hepatic encephalopathy
Esophageal varices / portosystemic shunts
Ascites
Congestive Splenomegaly
(Robbins fig. 18.7 & p. 829)
11
Q
Define acute liver failure.
A
Acute liver illness associated with:
Encephalopathy
Coagulopathy
that occurs WITHIN 26 WEEKS of the initial liver injury
and in the ABSENCE of pre-existing liver disease.
Robbins 10th p. 826.
12
Q
What is the protein content in ascites due to portal hypertension? (what is the serum-ascites albumin gradient)
A
SEROUS fluid
<3g/dL of protein (albumin)
serum-ascites albumin gradient of more than 1.1g/dL
(serum albumin is more concentrated)
13
Q
Name two pulmonary complications of liver failure and portal hypertension.
A
- Hepatopulmonary syndrome (vasodilation, right-left shunt –> V/Q mismatch, hypoxemia, worse in upright position and poor prognostic sign).
- Portopulmonary hypertension (pulmonary arterial htn; vasoconstriction & remodeling; dyspnea on exertion and clubbing).
14
Q
Name four histologic types of pancreatic carcinoma that are NOT graded.
A
Acinar cell carcinoma
Acinar cell cystadenocarcinoma
Serous cystadenocarcinoma
Solid-pseudopapillary neoplasm
15
Q
List 4 entities that are classified as Tis (T stage in-situ) of the pancreas.
A
High-grade Pancreatic intraepithelial neoplasia (PanIn-3)
Intraductal papillary mucinous neoplasm with high-grade dysplasia (IPMN)
Intraductal tubulopapillary neoplasm with high-grade dysplasia
Mucinous cystic neoplasm with high-grade dysplasia
16
Q
Invasion of what extrapancreatic structures is considered to be T4?
A
SMA
Celiac axis
Common hepatic artery
17
Q
How many lymph nodes should be assessed in a Whipple specimen?
A
12
18
Q
List two indications for pancreatic transplant.
A
Chronic pancreatitis
Diabetes resistant to insulin therapy.
19
Q
What are the diagnostic serum markers of the Hepatitis A-E viruses?
What are other ways to test for them, other than serum, when applicable?
A
A: Serum IgM antibodies
B: HBsAg or HBcAg antibodies
PCR for HBV DNA
C: ELISA for HCV antibodies
PCR for HCV RNA
D: Serum IgM and IgG antibodies
PCR for HCD RNA
E: Serum IgM and IgG
PCR for HEV RNA
Robbins p. 836
Table 18.3
20
Q
What are the FOUR (general) features required for a diagnosis of autoimmune hepatitis?
A
Autoantibodies
Elevation of serum IgG
Exclusion of other etiologies (e.g. viral hepatitis)
Supportive histology
Robbins table 18.4
p. 840
21
Q
What are the antibodies seen in autoimmune hepatitis, and how are they scored?
A
ANA, ASMA, LKM > 1:80 = 2 points
ANA, ASMA, LKM > 1:40 = 1 point
SLA/LP positive = 0 points
(SLA/LP: may also be seen, but doesn’t get any points)
22
Q
How is autoimmune hepatitis classified?
A
Type 1 & Type 2
Type 1: Antinuclear (ANA) and anti-smooth muscle actin (SMA) antibodies. May also see anti-SLA /LPA (soluble liver antigen/liver pancreas antigen)
Type 2: children; LKM-1 antibodies (anti-liver kidney microsome) directed against CYP2D6
& anti-liver cytosol (ACL-1) antibodies.
Serum IgG may be elevated in both.
23
Q
What is the outcome of untreated autoimmune hepatitis?
A
Without immunosuppresion: high risk of progression to cirrhosis, hepatocellular carcinoma. May need liver transplant.
24
Q
What is the most common cause of acute liver failure necessitating transplantation (in the US)?
What is the most common cause of chronic liver disease?
A
Acetaminophen toxicity
- Robbins 842
NAFLD
- Robbins 846
25
List 3 drugs that can cause microvesicular steatosis
tetracycline
valproic acid
zidovudine
The microvesicular steatosis is due to mitochondrial dysfunction.
Robbins 842
26
List 4 drugs that can cause a steatohepatitis-like reaction
methotrexate
tamoxifen
amiodarone
irinotecan
27
How do you distinguish a primary hepatocellular liver injury vs a cholestatic pattern of injury?
Serum markers!
Hepatocellular: ALT >5x upper limit of normal
or ALT/ALP (alk phos) ratio >5
Cholestatic: ALP (alk phos) >2x upper limit of normal
ALT/ALP ratio <2
mixed: increased ALT and ALP with ratio between 2 and 5.
robbins 842
28
What are the two mechanisms of liver injury in drug-induced liver injury?
1. Direct hepatotoxicity: dpse-dependent phenomenon of the drug or its metabolite directly on the liver, example acetominophen.
2. Idiosyncratic hypersensitivity reaction (unpredictable)
29
Name three forms of alcohol-induced liver injury
Steatosis
Alcoholic steato-hepatitis
Fibrosis (cirrhosis)
30
List 3 factors that influence the severity of alcoholic liver disease
Gender: females more susceptible (estrogen plays a role)
Ethnicity
Comorbidities - iron overload, NASH, HCV and HBV synergize with alcohol
31
List 3 factors that contribute to the mechanism of alcoholic liver disease
Acetaldehyde
CYP2E1 induction
Methionine metabolism
Robbins p. 843
32
What is the usual pattern of steatosis in alcoholic steatosis?
MACROvesicular
Exception: unusually, there can be alcoholic foamy degeneration, a form of microvesicular steatosis with chronic heavy alcohol use.
33
What are the (3) major histologic features of alcoholic hepatitis?
Ballooned hepatocytes: Essential for the diagnosis; injured hepatocytes; cytoplasmic damage --> Mallory hyaline.
Inflammation and necrosis: neutrophils; lobular lymphocytic infiltrates; macrophages
Perivenular/pericellular fibrosis: starts in zone 3, pericellular or perisinusoidal fibrosis with a chicken wire appearance.
34
how do the serum markers in alcoholic hepatitis differ from those in other chronic liver diseases?
ALCOHOL: AST > ALT (>2:1)
Chronic liver disease: ALT > AST
35
list causes of death in alcoholic liver disease
Hepatic coma
Massive GI hemorrhage
Intercurrent infection (at risk for this)
Hepatorenal syndrome (vasodilation: reduced GFR)
Hepatocellular carcinoma
36
What is the clinical setting of NAFLD?
Metabolic syndrome - patients who are not alcoholic AND who do NOT have another cause for steatosis (eg. HCV, Wilson, meds).
37
What are the WHO criteria for the metabolic syndrome?
```
One of:
Diabetes
Impaired glucose tolerance
Impaired fasting glucose
insulin resistance
```
```
TWO of:
BP >140/90
Dyslipidemia (high triglycerides and low HDL)
Central obesity (BMI >30)
Microalbuminuria
```
38
What are the key morphologic features of NASH?
- (Hard to distinguish from alcoholic hepatitis)
Required for diagnosis = LIVER BIOPSY showing:
- steatosis: >5% of hepatocytes
- Lobular inflammation
- Ballooned hepatocytes
Also:
Fibrosis, usually develops around central vein in chicken wire pattern (just like alcoholic hepatitis);
other causes must be EXCLUDED, ex. viral, autoimmune, or other metabolic diseases of the liver.
39
How does pediatric NAFLD differ from adult NAFLD?
more diffuse steatosis
portal (rather than central) fibrosis
ballooned hepatocytes may not be present.
40
What is NASH?
A subset of NAFLD with inflammation and ballooned hepatocytes, with a greater risk for advanced fibrosis, decompensated liver failure and hepatocellular carcinoma.
41
List four genes implicated in the pathogenesis of hereditary hemochromatosis.
Genes encoding HFE - most common in adult hemochromatosis - governs intestinal absorption of dietary iron by regulating hepcidin synthesis. Usually C282Y in caucasians; H63D worldwide.
transferrin receptor 2 (TfR2) - rare
hepcidin (HAMP) - juvenile form
Genes encoding HJV (hemojuvelin: juvenile hemochromatosis)
42
List causes of secondary hemochromatosis:
secondary iron overload due to:
Parenteral iron overload (transfusions)
- hemolytic anemias like sickle cell
- severe thalassemia
- bone marrow failure (aplastic anemia)
Increased iron uptake:
- Beta-thalassemia
- Myelodysplastic syndrome
Increased oral intake of iron:
- Bantu siderosis
Congenital atransferrinemia
Chronic liver disease
- alcoholic liver disease
- porphyria cutanea tarda
Neonatal hemochromatosis (in utero)
Robbins table 18.7 p. 848
43
What is the pathogenesis of hemochromatosis?
abnormal intestinal absorption of iron
disease manifests after 20g of iron stored
main regulator of iron absorption: hepcidin (encoded by HAMP)
deficiency of hepcidin causes overload.
Loss of hepcidin due to loss-of-function mutations in HAMP, HJV, TFR2, HFE
Mechanisms of liver injury:
- lipid peroxidation via iron-catalyzed free radical reactions
- stimulation of collagen formation by activation of hepatic stellate cells
- interaction of ROS and iron with DNA
44
What is the mechanism of iron overload in hematopoetic disorders?
Ineffective hematopoesis in beta-thalassemia and myelodysplastic syndrome --> chronically elevated levels of erythroferrone, a hormone involved in regulating of iron uptake from gut.
45
Deposition of hemosiderin in hemochromatosis is seen in which organs?
```
Liver
pancreas
myocardium
pituitary gland, adrenal gland
thyroid, parathyroid
joints
skin
```
46
What are the three major characteristic features of hemochromatosis?
1. deposition of hemosiderin in organs, esp. liver
2. cirrhosis
3. pancreatic fibrosis.
47
Where does hemosiderin deposit first in the liver?
periportal
48
What is the cause of increased skin pigmentation in hemochromatosis?
increased melanin deposition
49
What are the 4 major clinical presentations of hemochromatosis?
diabetes
skin pigmentation
cardiac dysfunction
cirrhosis with hepatomegaly (then shrinkage; risk of HCC)
50
What are the two most common causes of secondary hemochromatosis?
myelodysplastic syndrome
Thalassemia
- transfusions and increased absorption due to high erythroferrone levels.
51
What is the gene mutated in Wilson disease?
ATP7B
Loss-of-function mutation leads to impaired copper excretion into bile and a failure to incorporate copper into ceruloplasmin.
52
What are three test results that support a diagnosis of Wilson disease?
Decreased serum ceruloplasmin
Increased hepatic copper content (most sensitive and accurate)
Increased urinary excretion of copper (most specific test)
also: demonstration of Keyser-Fleischer rings by slit lamp exam
53
What are the morphologic features of Wilson disease in the liver?
- variable
Fatty change (steatosis)
Acute liver failure
Chronic hepatitis with PORTAL inflammation and hepatocyte necrosis (features of steatohepatitis - ballooning, Mallory hyaline, perisinusoidal fibrosis)
Eventually, cirrhosis
54
What brain structure is typically involved in Wilson disease?
Basal ganglia
Patients with neurologic involvement develop Keyser-Fleischer rings: green-brown deposits of copper is Descemet's membrane in limbus of cornea.
55
what are the 3 mechanisms of liver injury due to copper deposition in Wilson disease?
1. formation of free radicals
2. binding sulfhydryl groups of cellular proteins
3. displacing other metals from hepatic metalloenzymes.
56
What is the function of the normal alpha-1-antitrypsin protein?
Inhibits proteases:
neutrophil elastase
cathepsin G
Proteinase 3
57
What is the normal / wild type genotype of alpha-1-antitrypsin?
PiMM
58
What is the most common clinically significant mutation in the alpha-1-antitrypsin gene?
PiZ
Expression is autosomal Codominant
PiZZ: Worst phenotype (because two Z alleles), only 10% of circulating enzyme
PiMZ: have one normal allele, so intermediate disease
PiMM: wild type
Compound heterozygote
59
What is the characteristic histology of alpha-1-antitrypsin disease in the liver?
PAS+ diastase-resistant globules
may present with neonatal hepatitis
number of globules does not correlate with disease severity.
EM: shows misfolded proteins accumulated in the endoplasmic reticulum.
A1AT can progress to CIRRHOSIS.
60
What are the 4 major components of bile?
Bilirubin: toxic end product of hemoglobin degradation that is excreted in bile.
Bile salts
Cholesterol
Phospholipids
61
Name 5 syndromes associated with hereditary hyperbilirubinemia.
Crigler-Najjar type 1 (fatal around birth)
Crigler-Najjar type 2
Rotor syndrome
Gilbert syndrome
Dubin-Johnson syndrome
62
List the 3 most common causes of pediatric large bile duct obstruction.
Biliary atresia (extrahepatic)
Cystic fibrosis
Choledochal cyst
Unrelieved obstruction --> "biliary cirrhosis"
63
At what age should neonatal physiologic jaundice be resolved? After this age, jaundice must be evaluated for what disorder?
List causes of this disorder.
After 14-21 days, physiologic jaundice is resolved.
Beyond this date, babies with jaundice should be evaluated for neonatal cholestasis.
Causes of neonatal cholestasis:
1. Obstructive causes:
Biliary atresia
Cystic fibrosis
Choledochal cyst
```
2. Non-obstructive etiologies:
Cystic fibrosis
Paucity of bile ducts (Alagille syndrome)
Infectious/metabolic disorders
bile transporter defects
alpha-1-antitrypsin
idiopathic neonatal hepatitis
Neonatal infections - CMV, bacterial sepsis, urinary tract infection, syphilis
```
see table 18.9
Robbins 856
64
What methods must be used to diagnose neonatal cholestasis?
Ultrasound - small or absent gallbladder; fibrosis at porta hepatis
HIDA scan - failure of technetium99 to be excreted in bile
Biopsy - features of obstruction - portal edema, ductular reaction, neutrophils.
65
```
Compare and contrast PBC and PSC, with attention to:
age
gender
associated conditions
serology
radiology
duct lesion
```
PBC: 50s; 90% female
Associated with Sjogren (70%); thyroid; scleroderma
Serology: AMA (95%) against E2 of pyruvate dehydrogenase complex; 40-50% ANA +
Radiology: normal
Duct lesion: florid duct lesion; ductopenia; poorly-formed granulomas.
PSC: 30s, 70% male
Associated with ulcerative colitis
Serology: 65% ANCA + ; 6% ANA +
Radiology: beading, strictures of large ducts; pruning of small ducts.
Duct lesion: inflammatory destruction of extrahepatic and large intrahepatic ducts, fibrotic obliteration of medium and small intrahepatic ducts, ductular reaction in smaller portal tracts. SCLEROSIS - degenerating bile ducts in onion-skin scarring lesion.
66
What are the diagnostic criteria for PBC?
TWO of :
1. elevated alk. phos. for >6 months
2. positive serum AMA
3. characteristic histologic findings.
67
What is a dreaded complication of PSC?
cholangiocarcinoma
68
What are the most common causes of large bile duct obstruction in adults?
Neoplasm in the head of the pancreas
Gallstones
Strictures (from previous surgeries or ischemic injury)
69
List three causes of cholestasis due to sepsis.
Direct effect of intrahepatic bacterial infection
circulating microbial products
ischemia secondary to septic hypotension
70
List 4 risk factors for cholangiocarcinoma.
Liver fluke (esp. Clonorchis and Opisthorcis)
Hepatolithiasis
Primary Sclerosing Cholangitis (PSC)
Fibropolycystic disease (congenital hepatic fibrosis, often associated with Autosomal Recessive Polycystic Kidney Disease)
? Choledochal cyst
71
What is a choledochal cyst, and what disease/syndrome is it associated with?
Congenital dilatation of the Common Bile Duct.
Presents as jaundice, abdo pain, usually by age 10.
Females > males
SYNDROME: Caroli disease: cystic dilatation of the intrahepatic biliary tree, with congenital hepatic fibrosis.
72
What three histologic findings are seen in Fibropolycystic disease?
(FPD = congenital malformation of biliary tree, often in association with ARPKD)
1. Von Meyenburg complexes
2. Single or multiple intrahepatic or extrahepatic biliary cysts
3. Congenital hepatic fibrosis
Robbins p. 860
73
What is the most common cause of small portal vein branch obstruction?
schistosomiasis!
74
What is the most common cause of intrahepatic portal vein obstruction?
List 4 other causes of obstruction to sinusoidal blood flow.
Cirrhosis
Sickle cell disease
Disseminated intravascular coagulation (DIC)
Eclampsia
Diffuse intrasinusoidal metastatic tumor
Robbins p. 862
75
Define peliosis hepatis.
Sinusoidal dilatation that occurs in any condition in which efflux of hepatic blood is impeded. (pathogenesis unknown)
Robbins p. 862.
76
Define Budd-Chiari syndrome and list associated conditions.
Obstruction of major hepatic veins leading to liver enlargement, ascites, pain. High mortality.
Gross: swollen, red-purple with tense capsule; hemorrhagic liver necrosis
Micro: centrilobular congestion, necrosis; major veins with thrombi. Pericentral/sinusoidal fibrosis in cases that develop more slowly/chronically.
```
Associations:
myeloproliferative neoplasms (ex. Polycythemia vera)
```
inherited disorders of coagulation
antiphospholipid antibody syndrome
paroxysmal nocturnal hemoglobinuria
intraabdominal cancers (esp. hepatocellular carcinoma)
77
Define sinusoidal obstruction syndrome, and give two settings in which it occurs.
Obstruction of hepatic veins secondary to sloughed sinusoidal endothelium, with 80% mortality, in the setting of :
- drinking Jamaican bush tea
- chemotherapy
- within 3 weeks of hematopoetic stem cell transplant
Injured, sloughed endothelium obstructs sinusoidal blood flow, and associated debris accumulates in the terminal hepatic vein.
78
Define nutmeg liver.
Centrilobular hemorrhagic necrosis secondary to left-sided cardiac failure or shock, leading to hepatic hypoperfusion and hypoxia of hepatocytes around central veins.
MICRO: viable periportal hepatocytes
necrotic or atrophic pericentral hepatocytes, with suffusion of blood through the centrilobular region.
79
What is the most common cause of jaundice in pregnancy?
Viral hepatitis (A, B, C or B & D)
Hep. E not as common but has 20% mortality in pregnancy.
may also see: Listeria abscess in liver, rarely HSV hepatitis.
80
List 3 hepatic pathologies associated with pregnancy.
Pre-eclampsia / HELLP (hemolysis, elevated liver enzymes, low platelets
Acute fatty liver of pregnancy
Intrahepatic cholestasis of pregnancy
Robbins pp. 864 - 865.
81
Define acute fatty liver of pregnancy and describe the pathogenesis.
Maternal hepatic dysfunction secondary to a fetus with homozygous deficiency for long-chain-3-hydroxyacylCoA, that produces metabolites toxic to the mother.
Must be diagnosed on biopsy: pattern is MICROVESICULAR steatosis; but may resemble viral hepatitis.
Usually mild but can be rapidly fatal.
82
What is the most common benign liver tumor?
Cavernous hemangioma
83
List clinical associations with hepatocellular adenoma.
Young women on oral contraceptives
Anabolic steroids
obesity & metabolic syndrome
84
List the three molecular subtypes of hepatocellular adenoma.
1. HNF1-alpha inactivated
2. Inflammatory
3. Beta-catenin activated
85
What are the molecular findings in HNF1-alpha-inactivated hepatocellular adenoma?
Biallelic inactivation of HNF1-a
90% Somatic, women
10% germline, also have Maturity-Onset Diabetes of the Young (MODY type 3)
CYP1B1 mutations may also predispose to HNF1a inactivated type. (WHO table)
86
What is the risk of hepatocellular carcinoma with the various molecular subtypes of adenoma?
HNF1a: low risk
Inflammatory: low risk
Beta-catenin inactivated: Exon 3 HIGH RISK; Exons 7/8 low/no risk.
87
What is the most common mutation seen in inflammatory type hepatocellular adenoma, and what is the pathway involved?
gp130 mutation, a co-receptor for IL6 --> activation of JAK/STAT pathway
88
What are the immunohistochemical profiles of the various subtypes of hepatocellular adenoma?
```
HNF1alpha:
shows loss of LFABP (a protein regulated by HNF1a)
B-catenin -
Glutamine synthetase -
SAA -
```
Beta-catenin activated:
LFABP1+
Beta-catenin +/- focal - one nucleus is enough to call +
Glutamine synthetase + (strong diffuse, vs. maplike in FNH)
SAA -
```
Inflammatory:
LFABP +
Beta-catenin -
Glutamine synethetase - (~10% positive = beta-catenin inactivated, higher risk)
SAA, CRP +
```
Unclassified: LFABP +, all else negative
ddx FNH: with maplike glutamine synthetase, LFABP+, all else negative.
89
Name two syndromes associated with hepatoblastoma.
FAP
Beckwith-Wiedemann
90
List risk factors for hepatocellular carcinoma.
Chronic viral hepatitis B , C infection
Hereditary hemochromatosis
alpha-1-antitrypsin
glycogen storage disease
Tyrosinemia
NAFLD
Aflatoxin
Wilson disease
rarely can arise in hepatocellular adenoma (beta-catenin activated subtype)
91
What 3 histologic features characterize steatohepatitis?
1. inflammation in the background
2. steatosis
3. ballooning degeneration.
92
List risk factors for intrahepatic cholangiocarcinoma.
Fibropolycystic liver disease
chronic inflammatory conditions - PSC, liver flukes, hepatolithiasis
Liver disease that predispose to HCC - HBV, HCV, NAFLD
93
What is a Klatskin tumor?
Extrahepatic biliary adenocarcinoma occurring at the junction of the right and left hepatic ducts.
Robbins 871
94
Name three risk factors for intrahepatic angiosarcoma.
Exposures:
vinyl chloride
Thorotrast
arsenic
95
List congenital anomalies of the gallbladder.
Agenesis
Duplication
Septum
Aberrant location
Folded fundus (phyrgian cap) = most common
Choledochal cysts
96
List 6 histologic variants of pancreatic ductal adenocarcinoma
Adenosquamous carcinoma and SCC
Colloid carcinoma
Hepatoid carcinoma
Medullary carcinoma
Invasive micropapillary
Signet ring / poorly cohesive
Undifferentiated
97
List three precursor lesions to ductal adenocarcinoma of the pancreas
1. PanIN
2. IPMN
3. Mucinous Cystic Neoplasm (MCN)
98
List the molecular changes involved in pancreatic intraepithelial neoplasia
KRAS --> CDKN2A/p16 --> inactivation of p53, SMAD4
SMAD4 relatively specific; can use immunohistochemistry.
Robbins p. 891.
99
List 3 intraductal neoplasms of the pancreas.
IPMN (intraductal papillary mucinous neoplasm)
Intraductal oncocytic papillary neoplasm (IOPN)
Intraductal tubular papillary neoplasm (ITPN)
100
What is the oncogenic mutation seen in 80% of IPMNs?
KRAS; (same as in MCN)
GNAS also seen in 2/3 of IPMNS, not seen in other pancreatic cysts.
101
List three subtypes of IPMN, and one immunostain that helps you for each one.
1. Gastric (70%); most low grade.
Immuno: MUC5AC and MUC6
Intestinal (20%) usually with high grade foci
Immuno: CK20
Pancreaticobiliary (least common, high grade)
Immuno: EMA (MUC1)
102
What is the main feature that distinguishes IPMN from PanIN?
SIZE! Also differentiation/cell type.
PanIN: <0.5cm
- almost all have gastric diff
IPMNs: usually >1.0cm
- can be gastric, intestinal, pancreaticobiliary
- GNAS mutations.
Lesions between 0.5 - 1.0cm: "incipient IPMN"
103
How is PanIN staged?
High-grade PanIN = Tis
can be surrogate marker for carcinoma elsewhere in the pancreas. Low grade is not meaningful.
104
What are the main features and immunostaining pattern of MCN?
Women, body or tail, age ~48
NOT connected to pancreatic ducts
Columnar mucin-producing cells;
Ovarian-type Stroma
Positive for PR and Inhibin
105
What are the main gross, histological and clinical features of serous cystadenoma?
Gross:
- small cysts /microcystic (millimetric) or macro/unicystic
- central scar (with multicystic);
- straw-colored fluid
Histo:
- clear cuboidal cells, single layer, with well-defined cytoplasmic borders and small round nucleus.
- glycogen
- PAS+ diastase sensitive
Clinical:
- F>M 3:1
- Mostly BODY or TAIL;
- VHL association
106
Classic clinical features and mutations in solid pseudopapillary neoplasm
Classic histology of SPN
Immunoprofile of SPN
F:M = 9:1
Young; avg. 25 years
Anywhere in pancreas
BETA CATENIN mutation
Histology:
- sheets; clear-eosinophilic cytoplasm
- uniform nuclei with grooves
- decliate vasculature
- necrosis and hemorrhage typical
- foam cells & cholesterol crystals
- INTRACYTOPLASMIC GLOBULES (alpha-1-antitrypsin +)
Immuno: Beta-catenin, CD10 (cytoplasmic dots), CD56; E-cad loss; PR positive but ER negative;
70% synapto
70% cyclin D1
107
What is the telltale clinical presentation seen in 10-15% of patients with Acinar Cell Carcinoma of the pancreas?
Lipase hypersection, aka. metastatic fat necrosis syndrome
Lipase (produced by acinar cells) released into the circulation.
--> fat necrosis, peripheral eosinophilia, polyarthralgias.
108
What is the immunoprofile of Acinar cell carcinoma of the pancreas?
```
POSITIVE for:
BCL10
Trypsin
Chmotrypsin
Lipase
1/3 also positive for synapto/chromo.
PAS positive, resistant to diastase digestion (zymogen granules)
```
109
List (6) familial syndromes associated with hereditary pancreatic neuroendocrine neoplasms.
(10-20% of PanNets syndromic)
MEN1
VHL
NF1
Tuberous Sclerosis
Glucagon cell hyperplasia & neoplasia
Familial insulinomatosis
110
List 4 causes of acute pancreatitis
Four categories:
1. Metabolic:
- alcohol
- hyperlipoproteinemia
- hypercalcemia
- drugs (NSAIDS, others)
- genetic (SPIN1, PRSS1, CFTR)
2. Mechanical:
- gallstones
- iatrogenic (ERCP with dye)
- trauma
- occlusion of ducts by Ascaris
3. Vascular:
- shock
- atheroembolism
- vasculitis (polyarteritis nodosa)
4. Infectious:
- mumps
- coxsackie
- mycoplasma pneumonia
+/- 5. idiopathic.
111
List 5 IgG4 related diseases
```
Autoimmune pancreatitis
Chronic sialadenitis
Sclerosing cholangitis
Riedel thyroiditis
orbital pseudolymphoma
Retroperitoneal fibrosis
Sclerosing mesenteritis
Mediastinal fibrosis
```
112
What is the serum marker in Type 1 Pancreatitis?
IgG4
Also, for pancreatitis in general, lipase and amylase;
hypocalcemia may result from saponification of necrotic fat.
113
Contrast the histologic features of Type 1 and Type 2 pancreatitis
Type 1: (elderly men)
Lymphoplasmacytic sclerosing inflammation; phlebitis; IgG4 plasma cells 30-50 IgG4/HPF
Ratio >40
Type 2: (younger, M=F)
granulocyte epithelial lesions (GELs) --> neutrophils
idiopathic duct-centric pancreatitis
neutrophils and 0-10 IgG4+ plasma cells per HPF.
associated with IBD.
114
List 3 NON-HEPATOTROPIC viruses that cause acute liver failure in the setting of HIV.
CMV
Herpes
adenovirus
Robbins p. 826
115
List two complications of hepatitis B, other than cirrhosis
Polyarteritis nodosa (PAN)
Membranoproliferative glomerulonephritis type 1 (MPGN1)
