Gi #24: Liver Pathology 2

Front 1

Based on the fact that there is predominately centrilobular necrosis and the portal area is relatively intact, what drug-induced liver disease do you think this is?

Do you see inflammatory cells? What agent would work synergisticaly to damage the liver?

Back 1

Tylenol (Acetaminophen) toxicity --> centrilobular necrosis. No lymphocytes, not much inflammation.

Alcohol works synergistically.

Front 2

If you found out that this person had never drunk a drop of alcohol in his life, what comorbidities do you suspect they would have?

Back 2

This is NAFLD (looks indistinguishable from alcoholic steatosis).

You see steatosis with sinusoidal/pericellular fibrosis and pericentral fibrosis (around central vein). Can also find ballooning degeneration, mallory bodies, & polys.

Suspect Metabolic syndrome (Diabetes, insulin resistance, obesity, HTN, dyslipidemia).

Front 3

This person had a positive prussian blue stain on histology. What do you think is their genetic profile?

Back 3

Hereditary Hemochromatosis- autosomal recessive mutation in HFE (that regulates hepcidin). Looks like chocolate liver.

Hepcidin levels are reduced leading to increased iron absorption. Fe directly toxic to liver cells --> "bronzed diabetes" and cirrhosis.

Front 4

These organ system diseases are consistent with what gene mutation?

What stain would be appropriate to use in this situation?

Back 4

Wilson's disease- accumulate copper in body (liver, brain, basal nuclei) --> hepatitis with neuropsych symptoms (and Keiser Flecher ring)

Auto Recessive ATP7B gene mutation (transporter needed to bind CU2+ to cerulosplasmin and excrete both out of the cell). Use RHODADINE stain

Front 5

This is a rhodadine stain. What serum and urine lab levels would help confirm a diagnosis?

Interestingly, what disease process do these individuals NOT have to worry about progressing to?

Back 5

Wilson's disease-

Serum = LOW ceruloplasmin and LOW cu2+ (because they are trapped)
Urine = High urinary Cu2+ excretion

Does NOT progress to HCC.

Front 6

This person has a biopsy stained with PAS. What is the genetic defect? What is this person's genotype?

Besides liver conditions (cholestasis, cirrhosis, hepatitis), what is another frequent comorbidity in these pts?

Back 6

Alpha1-antitrypsin deficiency. PiZZ genotype.

They are unable to fold the protease inhibitor normally, and it gets clumped up in the ER of cells. Also can get emphysema and lung problems (unable to inhibit elastase).

*Protein electrophoresis testing is diagnostic!!

Front 7

Based on this histology and EM, what syndrome do you think this is?

What is the typical clinical scenario?

Back 7

Reye Syndrome (child <4 OD's on Aspirin, becomes irritable, vomits, lethargic, and hepatomegaly).

Note the MICROvesicular steatosis, and swollen mitochondria, irregular mitochondria with loss of cristae on EM. This is a MITOCHONDRIAL HEPATOPATHY.

Front 8

What are the following symptoms of cholestasis?

What changes do you expect on a histologic level?

Back 8

Jaundice (↑ Bilirubin), Pruritis (from ↑ bile acids), Skin xanthomas (accumulate cholesterol), ↑ Alk Phos, ↑ GGT

Histology: enlarged hepatocytes, dilated canalicular spaces, apoptotic cells, Kupffer cells filled with bile pigment

Front 9

What are some Extrahepatic Bile duct disorders?

Back 9

1. Choledocholithiasis (stone in common bile duct)
2.Cholangitis (stone in CBD that causes inflammation
3. Congenital biliary atresia (absence of extrahepatic bile duct- in newborn)

Front 10

This is the liver of a newborn that had severe jaundice, dark urine, light (acholic) stools, and an enlarged liver.

What changes might you suspect on the histology?

Back 10

Congenital Biliary Atresia (there is no extrahepatic bile duct, bile accumulates in the liver). *remember, neonatal hepatitis can present the same but different histology/liver biopsy!

Extrahepatic biliary obstruction- bile ductular proliferation, edema/distended portal tract, bile accumulation, and inflammation

Front 11

This is from a newborn with severe jaundice, dark urine, light (acholic stools) and an enlarged liver.

What condition is it? What condition presents in the same way but has different histology

Back 11

This is Neonatal Hepatitis (from infection, toxins/metabolic, idiopathic). Looks clinically like Congenital Biliary Atresia.

*key histologic difference = Panlobular Giant Cells (Hepatocytes that are multinucleated)

Front 12

What are two diseases of Intrahepatic Biliary Tract?

Back 12

Primary Biliary Cirrhosis (destruction of small & medium sized bile ducts)

Primary Sclerosing Cholangitis (destruction of large intrahepatic bile ducts as well as extrahepatic duct)

Front 13

What condition is shown based on the pathology?

What demographic is typically affected and what associated serology would you expect to see?

Back 13

This is a FLORID duct lesion (lymphoplasmacytic infiltrate around small bile duct). You can also get upstream bile duct proliferation when there's bile duct destruction.

Middle aged women, with other autoimmune disease (sjogren, scleroderma, thyroiditis). They will have elevated AMA (antimitochondrial antibodies), as well as Alk Phos and GGT.

*liver is cirrhotic and green

Front 14

What condition is shown based on pathology?

What demographic is typically affected and what associated serology might you see? What is the radiologic appearance?

Back 14

Primary Sclerosing Cholangitis- complete obliteration of bile ducts replaced by fibrous whorls (onion-skin fibrosis). This is seen early on (later on just cirrhosis/fibrosis).

Seen in younger males, associated with UC (patients can have positive ANCA and HLA-DR alleles). Radiology: shows strictures and dilations (beading)

Front 15

Is this a rare finding? why or why not?

Back 15

Rare- because liver has dual blood supply.

Front 16

What are some examples of conditions that can cause impaired blood flow through the liver (hint: one is shown above)?

Back 16

Sickle cell disease (causing occlusion). There is also DIC (causing occlusion of sinusoids) and eclampsia of pregnancy (leading to occlusion/ necrosis).

Front 17

What type of heart failure does the above individual have? How can you tell?

What if this heart failure progressed --- what would it look like?

Back 17

Right sided heart failure- causing passive CENTRILOBULAR congestion (because blood backs up & there's impaired outflow of blood from liver-- sinusoids become dilated with blood).

Eventually you get CARDIAC SCLEROSIS (which is centrilobular fibrosis with "Reversed lobulation" - i.e. central vein-to central vein septa).

Front 18

What is this classically associated with?

Back 18

Hemorrhagic necrosis (nutmeg liver) --> can be due to left and right sided heart failure. Basically portal tracts preserved but there is centrilobular necrosis.

Front 19

What condition does this person have?

What are some risk factors that can lead to this?

Back 19

Peliosis Hepatitis (note the dilation of sinusoids. Cystic spaces lined with endothelial cells)

This is most commonly due to Anabolic steroid use. *above - gross image showing dilated cystic areas that can rupture --> fatal hemorrhage

Front 20

What acute condition is demonstrated here (on gross pathology and histology)?

What other liver conditions can it look like? What would the chronic form of this condition look like?

Back 20

Acute Budd-Chiari. Thrombi of hepatic veins --> cause centrilobular congestion and necrosis (looks like heart failure or Acetaminophen injury).

Chronic Budd-Chiari (shown above) --> Reversed lobulation (takes on characteristics like cardiac sclerosis)

Front 21

What is shown here? What group of individuals is this commonly seen in?

Back 21

Focal Nodular Hyperplasia (FNH)- incidental finding in women of reproductive age (not neoplasm!). Just a localized nodular regeneration of liver parenchyma.

Front 22

What type of condition is this associated with? Should we be worried about cancer?

Back 22

Macroregenerative nodules (not premalignant- but appears in cirrhosis).

Front 23

What is the most common benign tumor of the liver? What is the most common subtype of this tumor?

Back 23

Hemangioma = most common benign tumor

Cavernous hemangioma (vascular spaces lined by endothelium) is the most common subtype

Front 24

Is this malignant or benign? What risk factor is it commonly associated with and what demographic does it affect?

Back 24

Benign (Hepatic adenoma). You can tell because there's an increase in hepatocytes but still 1-2 cell thickness. Also portal triads are absent.

Though benign, you still have to follow it surgically (of B-catenin mutation, risk of cancer).

Typically in Women of childbearing age who take OCPs.

Front 25

What type of malignant tumor is this? Name an infectious cause, a food contaminant cause, and a metabolic cause that can lead to this?

What is the most common malignant lesion in the liver?

Back 25

Hepatocellular carcinoma (note the soft tumor on a cirrhotic background. also bile producing). Infectious = Hep B, Food contaminant = Aflatoxin (from aspergillus, peanut mold), Metabolic = HH or a1AT

Most common malignant lesion = METASTATIC TUMORS (from colon, lung, breast, pancreas)

Front 26

Is this benign or malignant? How can you tell?

What serum value might be elevated in this condition?

Back 26

Malignant- it is hepatocellular carcinoma. Note that the plates are wide (4-5 cells thick, rather than 1-2).

AFP (alpha feto protein) elevated in about 50% of cases. *note- if tumor is bile producing as shown above, it is an HCC*

Front 27

A patient is brought to you with this biopsy. What is the prognosis?

Back 27

Good! Even though it is a hepatocellular carcinoma- this is Fibrolamellar Variant (seen in young people).

THERE IS NO UNDERLYING CIRRHOSIS! But the tumor itself if firm!! (very unusual). See the dense stromal response (desmoplastic rxn)

Front 28

Based on gross appearance, what type of liver cancer is this?

What are some risk factors for this cancer? What is the typical age at presentation and the prognosis?

Back 28

Cholangiocarinoma (it is hard and whitish and we TYPICALLY don't see a cirrhotic background).

Risk factors = PSC, thorotrast (imaging contrast), HC, liver fluke, NOT COMMONLY ASSOCIATED WITH CIRRHOSIS

Front 29

How does this cancer tend to spread? How does this differ from HCC?

What lab finding will be elevated in these patients?

Back 29

Cholangiocarcinoma (CCA)- spreads via lymphatics. HCC spreads hematogenously (through veins-- can enter the Right atrium of heart!)

Elevated CEA- carcinoembryonic antigen. (not AFP like HCC).

*note: here you see glandular formation ad a marked desmoplastic response. These are firm tumors.