Liver Pathology

Front 1

The clinical presentation in infants or neonates who have this serpinopathy include giant cell hepatitis and paucity of intrahepatic bile ducts. In adults, the spectrum of related diseases includes chronic hepatitis, cirrhosis, liver cell dysplasia, and HCC.

Back 1

Alpha-1-antitrypsin deficiency

Front 2

What are the 3 histological components of acute rejection?

Back 2

Acute Rejection:
1. Immune cell infiltrate: T-cells predominate, but the infiltrate is heterogeneous with eosinophils (specific), and fewer numbers of plasma cells and neutrophils.
2. Bile duct damage with intraepithelial lymphocytes
3. Endotheliitis affecting portal vein branches but can also involve central veins and sinusoids.

Front 3

This lesion is characterized by 3 components: immune cell infiltrate consisting predominantly of T-cells but also with mixed inflammation including eosinophils; bile duct damage by intraepithelial lymphocytes; and endotheliitis.

Back 3

Acute rejection

Front 4

What do the following terms mean?
1. PiMM
2. PiZZ
3. PiSZ
4. PiMZ

Back 4

1. PiMM: wild type for AAT
2. PiZZ: homozygous for AAT deficiency
3. PiSZ: heterozygous for AAT deficiency
4. PiMZ: heterozygous for AAT deficiency

NOTE: Pi stands for protease inhibitor; M is wild-type; Z is diseased

Front 5

What are the 3 typical histological features of autoimmune hepatitis?

Back 5

Autoimmune hepatitis:
1. Interface hepatitis: lymphoplasmacytic infiltrates extending into the periportal region
2. Abundant plasma cells
3. Regenerative liver cell rosettes: rounded groups of hepatocytes surrounded by lymphocytes and plasma cells

Front 6

This lesion has the following 3 characteristics:
1. interface hepatitis
2. abundant plasma cells
3. regenerative liver cell rosettes

Back 6

Autoimmune hepatitis

Front 7

This subtype of autoimmune hepatitis usually presents in young women with positive ANA (anti-nuclear antibody), anti-SMA (anti-smooth muscle antibody), or both.

Back 7

Type 1 Autoimmune Hepatitis

Front 8

Type 1 autoimmune hepatitis usually presents with what antibodies?

Back 8

ANA (anti-nuclear antibody)
Anti-SMA (anti-smooth muscle antibody)
or both

Front 9

This type of autoimmune hepatitis presents with anti-LKM (liver-kidney microsome).

Back 9

Type 2 Autoimmune Hepatitis

Front 10

Type 2 autoimmune hepatitis usually presents with what antibody?

Back 10

Anti-LKM (liver-kidney microsome)

Front 11

This type of autoimmune hepatitis presents with anti-SLA (soluble liver antigen).

Back 11

Type 3 Autoimmune Hepatitis

Front 12

Type 3 autoimmune hepatitis presents with what antibody?

Back 12

Anti-SLA (soluble liver antigen)

Front 13

This subcapsular liver lesion is grossly white/tan and nodular. It is usually less than 1 cm in diameter. The lesion is made up of medium-sized, regular bile duct structures embedded in well formed fibrous stroma. The glands are separated from one another by stroma. The cytology is benign. The edge of the lesion often contains aggregated lymphocytes within the fibrous stroma. The bile ducts do not have any contents.

Back 13

Bile duct adenoma

Front 14

This subcapsular liver lesion consists of dilated and irregularly shaped bile ducts containing inspissated bile or mucin.

Back 14

Bile duct hamartoma (AKA von Meyenburg's complex; bile duct malformation)

Front 15

This lesion is characterized by generalized lobular disarray with disruption of the normal radiating liver cell plate pattern by diffuse lymphocytic inflammation within the sinusoids and in the portal tracts. Hepatocytes show ballooning and apoptosis. Tan-staining ceroid laden Kupffer cells within sinusoids can be seen around the central vein.

Back 15

Acute hepatitis (either drug or viral)

Front 16

What antibody is associated with primary biliary cirrhosis?

Back 16

AMA (anti-mitochondrial antibodies)

Front 17

What disease is associated with AMA (anti-mitochondrial antibodies)?

Back 17

Primary biliary cirrhosis

Front 18

What antibody is associated with primary sclerosing cholangitis?

Back 18

P-ANCA (perinuclear antineutrophoil cytoplasmic antibody)

Front 19

P-ANCA (perinuclear antineutrophil cytoplasmic antibody) is associated with what disease?

Back 19

Primary sclerosing cholangitis

Front 20

While in adults, bile ductular cholestasis is virtually pathognomonic for ____, in children, the finding is seen in the setting of ____.

Back 20

While in adults, bile ductular cholestasis is virtually pathognomonic for SEPSIS, in children, the finding is seen in the setting of EXTRAHEPATIC BILIARY ATRESIA.

Front 21

What is the liver biopsy finding pathognomonic for sepsis (but not often found) in adults?

Back 21

bile ductular cholestasis

Front 23

Chronic hepatitis (e.g. HCV, HBV, AIH), PBC, and PSC can all present with this histological finding.

Back 23

Portal lymphoid aggregates

Front 24

What is the most common cause of portal lymphoid aggregates?

Back 24

Chronic hepatitis C

NOTE: other causes include chronic hepatitis (viral or autoimmune), PBC, PSC

Front 25

Between primary biliary cirrhosis and primary sclerosing cholangitis, which one is associated with ulcerative colitis?

Back 25

primary sclerosing cholangitis

Front 26

Primary sclerosing cholangitis is associated with what GI AI disease?

Back 26

UC

NOTE: 60-80% of PSC have UC, 20% have no IBD, and less than 10% have Crohn's disease

Front 27

What percentage of people with UC have PSC?

What percentage of people with PSC have UC?

Back 27

4% of UC have PSC

60-80% of PSC have UC

Front 28

This disease is characterized by ductopenia (arterioles in portal tracts without bile ductules), periportal lymphocytic interface hepatitis, periductal "onion skin" fibrosis, fibro-obliterative cholangitis (rounded scars at the sites of former bile ducts), pale and swollen periportal hepatocytes (i.e. pseudoxanthomatous change or cholate stasis due to the detergent action resulting from chronic retention of bile salts).

Back 28

Primary sclerosing cholangitis

Front 29

Congenital web of the inferior vena cava or Budd-Chiari syndrome are characterized by what histology?

Back 29

Congenital web of the inferior vena cava and Bud-Chiari syndrome are both outflow tract obstructions characterized by perivenular sinusoidal dilation and congestion around central venules. No significant portal changes are evident other than a possible mild chronic inflammation.

Front 30

Chronic acetominophen use is characterized by what histology?

Back 30

Chronic acetominophen use is characterized by perivenular necrosis in the centrilobular (around central venule) area.

Note: In addition to perivenular hepatocyte necrosis, in acute acetominphen poisoning, tan-staining Kupffer cells containing phagocytic remnants of dead hepatocytes are seen in the centrilobular region.

Front 31

This hepatic lesion is characterized grossly as a well-circumscribed solitary nodule with central scar and fibrosis. Microscopically, this lesion is characterized by proliferated bile ductular structures at the edges of the radiating central scar.

Back 31

Focal nodular hyperplasia

Front 32

This lesion is associated with OCP.

Back 32

Hepatic adenoma

Front 33

Macrovesicular or microvesciular steatosis?
EtOH

Back 33

Macro

Front 34

Macrovesicular or microvesciular steatosis?
Obesity/DM2/Hyperlipidemia/Metabolicsyndrome

Back 34

Macro

Front 35

Macrovesicular or microvesciular steatosis?
Corticosteroid therapy

Back 35

Macro

Front 36

Macrovesicular or microvesciular steatosis?
Deficient diet (TPN)

Back 36

Marco

Front 37

Macrovesicular or microvesciular steatosis?
Antiretroviral drugs (HAART)

Back 37

Micro

Front 38

Macrovesicular or microvesciular steatosis?
Acute fatty liver of pregnancy

Back 38

Micro

Front 39

Macrovesicular or microvesciular steatosis?
Reye's syndrome

Back 39

Micro

Front 40

Macrovesicular or microvesciular steatosis?
Tetracycline toxicity

Back 40

Micro

Front 41

Macrovesicular or microvesciular steatosis?
Valproic acid toxicity

Back 41

Micro

Front 42

Macrovesicular or microvesciular steatosis?
Mushrooms

Back 42

Micro

Front 43

This lesion is characterized by diffuse non-caseating granuloma formation in portal tracts with reactive fibrosis.

Back 43

Sarcoidosis involving the liver

NOTE: PBC presents with focal rather than diffuse portal granuloma

Front 44

People who have iron overload due to chronic transfusions (e.g. sickle cell anemia, thalassemia) tend to store iron in what histological pattern in the liver?

Back 44

Extensive Kupffer cell iron with mild to moderate iron in hepatocytes. Hepatocytes in the periportal area store more iron than the ones in the cetrilobular (central venule, zone 3) area.

Front 45

What is the iron liver histology of a person with HFE-related hereditary hemochromatosis.

Back 45

Iron is primarily in hepatocytes with little or no Kupffer cell hemosiderin until the later stages of disease when there is periportal fibrosis or cirrhosis.

Front 46

What is the liver histology of a person with oral iron overload?

Back 46

Iron stores primarily occurs in both portal macrophages and Kupffer cells.

Front 47

This lesion grows in a sheet-like pattern with mildly thickened plates. Venous and arterial channels are interspersed but there are no bile ducts.

Back 47

Hepatic adenoma

Front 48

What mutation is associated with hepatic adenoma?

Back 48

HNF-1-alpha (hepatocyte nuclear factor 1 alpha)

Front 49

HNF-1-alpha (hepatocyte nuclear factor 1 alpha) mutations are associated with what hepatic lesion?

Back 49

Hepatic adenoma

Front 50

What mutations are associated with cholangiocarcinoma?

Back 50

KRAS and c-myc

Front 51

KRAS and c-myc mutations are associated with what hepatic lesion?

Back 51

Cholangiocarcinoma

Front 52

What mutation is associated with hepatocellular carcinoma?

Back 52

p53

Front 53

p53 mutation is associated with what hepatic lesion?

Back 53

Hepatocellular carcinoma

Front 54

What mutation is associated with Alagille's syndrome (syndromic paucity of intrahepatic bile ducts)?

Back 54

Jagged-1

Front 55

Jagged-1 mutation is associated with what hepatic syndrome?

Back 55

Alagille's syndrome (syndromic paucity of intrahepatic bile ducts.)

Front 56

This lesion is found in childhood typically before age 2 and is characterized by thickened cords of hepatocytes with clear (glycogenated) and eosinophilic cytoplasm rendering a "light" and dark" or herringbone pattern. Extramedullary hematopoiesis is present in sinusoids.

Back 56

Hepatoblastoma, fetal epithelial type

Front 57

This hepatic lesion is found in childhood, characterized by hepatocytes with increased N:C ratio and mitotic figures growing in tubular structures.

Back 57

Hepatoblastoma, embryonal type

Front 58

IHC for HCC:
HepPar1
Polyclonal CEA
CD34
AFP
CK7
CK20
CK8/18

Back 58

IHC for HCC:
HepPar1: diffuse cytoplasmic +
Polyclonal CEA: canalicular +
CD34: vascular +
AFP: diffuse cytoplasmic + (can be -)
CK7: - (can be +)
CK20: - (can be +)
CK8/18: +

Front 59

After liver injury due to this cause, on liver biopsy, there is mild ballooning of centrilobular hepatocytes, mild cholestasis in centrilobular hepatocytes and bile canaliculi as well as lipopeliosis (large lipid vacuoles from necrotic hepatocytes released into sinusoids).

Back 59

Ischemia-reperfusion injury

Front 60

What are the liver findings in eclampsia?

Back 60

Finbrin in portal vessels and sinusoids. Necrosis with hemorrhage in more severe cases.

Front 61

What gene is mutated in benign recurrent intrahepatic cholestasis? What chromosome is it on?

Back 61

FIC-1 (AKA ABCB11) on chromosome 18

Front 62

What is the typical histology of benign recurrent intrahepatic cholestasis?

Back 62

Canalicular cholestasis

Front 63

These patients present with multiple episodes of jaundice since childhood, each time resolving without medical therapy.

Back 63

Benign recurrent intrahepatic cholestasis

Front 65

What are 5 causes of chronic hepatitis?

Back 65

- Viral hepatitis (B, C, D)
- Autoimmune hepatitis
- Alpha-1-antitrypsin deficiency
- Wilson's disease
- Drug hepatotoxicity

Front 66

This disease may result in ground-glass cytoplasmic inclusions within hepatocytes which stain positively with orcein and Victoria blue stains.

Back 66

HBV

NOTE: The inclusion represent HBsAg embedded within cisternae of rough endoplasmic reticulum. Other conditions in which ground-glass inclusions occur include Lafora's disease (myoclonus epilepsy), cyanamide aversion therapy of alcoholism, fibrinogen storeage disease and hepatocellular glycogenosis.

Front 67

Mutation in what gene is responsible for Wilson's disease? What is the function of the protein of the mutated gene?

Back 67

Gene = ATP7B

Protein: copper-transporting ATPase located in the trans-Golgi network of the liver

Front 68

Why is ceruloplasmin low in Wilson's disease?

Back 68

Ceruloplasmin is rapidly degraded because copper has failed to be incorporated due to a mutation in the copper ATPase gene (ATP7B).

Front 69

What constitutes Mallory bodies?

Back 69

ubiquitinated cytokeratins 8/18 and other proteins which represent byproducts of cellular stress.

NOTE: Mallory bodies can be found in a variety of lesions including alcoholic and non-alcoholic steatohepatitis, Wilson's disease, PBC, and HCC.

Front 70

Megamitochondria are associated with what condition?

Back 70

Alcoholic liver disease. Megamitochondria are visible as rounded eosinophilic intracytoplasmic bodies on H&E. On aniline blue, they are bright red.

Note: Recently has been described in nonalcoholic steatohepatitis

Front 71

What are the liver findings in HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome?

Back 71

Nonspecific inflammation
Glycogenated hepatocyte nuclei
Periportal fibrin/necrosis

Front 72

Cholangiocarcinoma is a known complication of PBC or PSC?

Back 72

PSC

Front 74

PBC or PSC?
Females, 40-60 years old

Back 74

PBC

Front 75

PBC or PSC?
HLA-DR

Back 75

PBC

Front 76

PBC or PSC?
Associated with other AI diseases such as Hashimoto's, Sjogren's, Rheumatoid arthritis, scleroderma

Back 76

PBC

Front 77

PBC or PSC?
Granulomas

Back 77

PBC

Front 78

PBC or PSC?
Males, 25-60 years old

Back 78

PSC

Front 79

PBC or PSC?
Cholangiocarcinoma

Back 79

PSC

Front 80

PBC or PSC?
String of beads on cholangiogram

Back 80

PSC

Front 81

What chromosome is alpha-1-antitripsin on?

Back 81

14

Front 82

What is the point mutation in hemochromatosis that causes the most iron overload? The least?

Back 82

Most: C282Y (cysteine to tyrosine)
Least: H63D (histidine to aspartate)

Front 83

What chromosome is ATP7B (Wilson's disease) on?

Back 83

Chromosome 13