Hepatobilliary Pathology Flashcards
Stages of Liver Disease
Healthy liver –> fatty liver –> liver fibrosis –> cirrhosis
- Fatty liver —deposits of fat lead to liver enlargement
- Liver fibrosis —scar tissue forms
- Cirrhosis —growth of connective tissue destroys liver cells
Some stages are reversible and some are not
Liver dysfunction
Several etiologies
- Acquired infections and conditions
- Lifestyle habits
Liver Functions
> Produces most of the substances that regulate blood clotting
Produces bile, a compound needed to digest fat and to absorb vitamins A, D, E, K
Removes potentially toxic byproducts of certain medications
Prevents shortages of nutrients by storing vitamins, minerals, and sugar
Metabolizes/breaks down nutrients from food to produce energy when needed
Produces most proteins needed by the body
Helps your body fight infection by removing bacteria from the blood
Symptoms of Liver Dysfunction
Yellowing of the skin and eyes (jaundice)
Spider-like blood vessels
Itching
Fluid build-up, swelling of the legs (edema)
Mental confusion
Problems associated with liver disease
Risk of bleeding
Alterations in the metabolism/toxicity
Hepatitis definition
Inflammation of the liver that may result from Viral hepatitis, infectious mononucleosis, secondary syphilis and tuberculosis, or prolonged use of toxic substances (drugs — acetaminophen, alcohol, ketoconazole (antifungal),
methyldopa, methotrexate)
Viral Hepatitis
Acute viral hepatitis is the most common
Different types (A, B, C, D, E, and G)
Diagnostic markers
- White blood cell count, prothrombin time, and liver enzymes
- Lymphocytosis***
o Neutrophils fight bacterial infections, but lymphocytes fight viruses, so
lymphocytes will be elevated
- Elevation in AST and ALT, alkaline phosphatase
- Elevated serum bilirubin
Hepatitis A
A viral infection of the liver spread when fecal matter enters the mouth
- May last several weeks and can be debilitating, but most people recover completely
- Preventable with careful hand washing, keeping toilets and bathrooms clean, avoiding
infected water sources
Diagnosis: Diagnose with IgM anti hepatitis A virus serology
- Coagulation profile — PT mild elevation is common with HAV infection
- Transmission usually precedes symptoms by 2 weeks when stool concentrations are
highest
Signs and Symptoms
- Clinical jaundice in 70% of cases with HAV
- GI — nausea, vomiting, right upper quadrant pain
- Hepatomegaly and Splenomegaly
- Clay-colored stools (light colored stools)
Accumulation of bilirubin in the plasma, epithelium, and urine (leading to color change)
Hepatitis B
Diagnosis — CBC, coagulation profile, serology, HBV DNA
- Transmission —nonsterile tattooing needles, contaminated dialysis equipment,
contaminated vaccination equipment, nonsterile dental practices, contaminated drug
needs, nonsterile body piercing equipment
- Usually full recovery
- But some people can have different stages
o Non-progressive —chronic
o Progressive — cirrhosis
o Fulminant
o Carrier — asymptomatic
HBeAg
—envelop antigen, indicative of active replication
HBsAg
—Hepatitis B surface Antigen
o Appears before symptoms
o Disappears in 3- 6 months
o Persists in carriers
Anti-HBs
Anti-HBs is the Hep B surface antibody
o Seen after acute disease
o 3-6 months after HBs Ag disappears
o LIFELONG PROTECTION —Immunity
o Vaccination
Anti-HBc — Anti HBc Antibody
Total hepatitis B core antibody
o Appears at the onset of symptoms in acute Hep B and persists for life
o Indicates previous or ongoing infection with hepatitis B virus in an undefined
frame
IgM anti HBc
Positivity indicates recent infection with hepatitis B virus less than 6 months
o Acute infection
What is the susceptibility for Hep. B in a patient with:
HBsAg (-)
Anti-HBc (-)
Anti-HBs (-)
SUSCEPTIBLE
What is the susceptibility for Hep. B in a patient with:
HBsAg (-)
Anti-HBc (+)
Anti-HBs (+)
Immune due to hepatitis B
vaccination
What is the susceptibility for Hep. B in a patient with: HBsAg (+) Anti-HBc (+) IgM anti-HBc (+) Anti-HBs (-)
Acutely infected
What is the susceptibility for Hep. B in a patient with: HBsAg (+) Anti-HBc (+) IgM anti-HBc (-) Anti-HBs (-)
Chronically infected
Hepatitis C Virus
ssRNA virus
Diagnosis — antibodies, serum markers, and viral genotyping
- Antibodies are not protective
o Can get the disease again!
- 55-85% develop chronic disease
- More than 75% of American adults with Hep C are baby boomers
o A big proportion, and a worldwide problem!
Extra-hepatic manifestations of HCV
- Vasculitis
- Renal complications
- Skin manifestations
ex.
-Spider angiomata
- Caput medusa
- Terry nails —white nails with a “ground glass” appearance and small bands of normal
pink nail along the top edges
Extra-hepatic manifestations of HBV
- PAN — polyarteritis nodosa
- Systemic necrotizing vasculitis of medium or occasionally small muscular arteries
- Multiple aneurysms
- Transmural necrotizing inflammation — fibrinoid necrosis
- Affects middle aged or older adults
- Pathogenesis — idiopathic
Presentation of HBV
- Weight loss
- Myalgia, weakness, leg tenderness
- Polyneuropathy or mononeuropathy
- Elevated diastolic BP >90mmHg
- Positive HBV infection
- Arteriographic abnormality
PAN (polyarteritis nodosa)
Mononeuritis with motor and sensory deficits
- Asymmetric
- Progress to branches
- Renal involvement common
- HTN may develop
- Skin lesions and motor weakness (wrist or foot drop)
- No diagnostic lab test, diagnose by biopsy and ateriogram (will see microaneurysms and
abrupt cut off)
Hepatitis D
ssRNA virus
- Diagnosis — IgM and IgG antibodies, HDV, RNA serum
- Transmission — parenteral
- Incubation — 2-12 weeks
- No vaccine
- Prognosis poor when associated with HBV
For Hepatitis, it acute or chronic infection? Would you do elective dental work?
If acute, NO
With pain, only do palliative treatment!
Avoid acetaminophen
o If chronic, is it under control?
Hard to know if it’s under control unless the patient does regular blood
work
What about bleeding? Ask how long it takes to stop bleeding when they
get a cut to help determine if it’s controlled or not
Dental Management of patients with Hepatitis
- Lab tests?
o PT and PTT to assess bleeding/coagulation in patients with liver disease
o Platelets will also help you tell if its alcoholic liver disease
Avoid anything that is metabolized in the liver or is difficult to metabolize such as antibiotics or pain meds.
Cancers with Metastasis in the Mandible
Liver cancer
Breast cancer
Prostate Cancer
Melanoma
Alcoholic Liver Disease
Etiology —alcohol ingestion
- Unknown amount of alcohol that predicts the development of ADL
- Other coexistent liver diseases
- Cirrhosis — hepatic failure
- Esophagitis, gastritis, generalized malnutrition
- Weight loss and protein deficiency (coagulation factors)
- Impairment of glucose metabolism
- Renal failure
- Portal hypertension
Clinical Presentation of Alcoholic Liver Disease
Enlarged parotid glands Spider angiomas Jaundice Ascites Hematemesis Hepatomegaly Splenomegaly Epigastric pain
Later stage –> thrombocytopenia and coagulation disorders.
Oral Complications of Alcoholic Liver Disease
Poor oral hygiene Oral neglect Glossitis Candidiasis Gingival bleeding Petechiae Parotid enlargement Impaired healing, Infections Dental attrition Xerostomia Oral cancer
o Alcohol causes problems with platelets, which can cause petechiae that is seen orally
Chronic Liver Disease
Vitamin K —important for coagulation factors II (prothrombin), VII, IX and X.
- Fat soluble vitamin
- Requires proper liver function to be absorbed by the intestines
- In general, with chronic liver disease, we get problems with synthesis of coagulation
factors, but also malabsorption
Child-Pugh score — Child-Turcotte-Pugh score or Child Criteria
Assess the prognosis of chronic liver disease, mainly cirrhosis
- Look at level of bilirubin, serum albumin, PT or INR, ascites, and hepatic encephalopathy
- Use these to do a simple classification of the level of severity of liver disease
- Class A = 5-6 points, least severe liver disease
- Class B = 7-9 points, moderately severe liver disease
- Class C = 10-15 points, most severe liver disease
o May not be a candidate for a transplant anymore because of high risk
Compound in energy drinks that causes ACUTE Hepatitis (not viral)
NIACIN
save in pharmaceutical dose but can cause liver toxicity in excess
L.A. Metabolized Primarily by the Liver
Lidocaine, Mepivacaine, Prilocaine, Bupivacaine
o Mepivacaine is second choice LA after Lidocaine, doesn’t have epinephrine
o Most of these agents appear to be safe for use in patients with liver disease
when given in appropriate amounts
Generally shouldn’t use more than 3 carpules
Analgesics Metabolized Primarily by the Liver
Acetaminophen, Codeine, Aspirin, Ibuprofen
Limit dose or avoid (only in severe cases)
o Acetaminophen can be taken for many different types of pain, which resulted in overuse and frequent hospitalization for liver disease in the past
o Max dose was reduced from 4000mg to 3000mg, and for most people we
recommend no more than 2000mg
o Also shouldn’t combine medications!
Sedatives/Antibiotics Metabolized Primarily by the Liver
Sedatives —Diazepam (Valium), Barbiturates
- Antibiotics —Ampicillin, Metronidazole
o Amoxicillin with Metronidazole is often used to treat perio disease, but this is NOT ok for someone with liver disease
Stellate Cells
Located in the Space of Disse
In its quiescent form, it is a lipid (vitamin A) storing cell
The principal cell type involved in generalized scar formation / deposition (acute and chronic)
Involved especially in alcoholic and non-alcoholic fatty liver disease
Main Patterns of Hepatic Injury
Degeneration and intracellular accumulation Necrosis and apoptosis Regeneration Inflammation Cirrhosis Ductular reaction
Degeneration and intracellular accumulation
If moderate and the agent is removed, may be reversible
Due to toxic or immunologic factors
Accumulation of
- fat droplets (steatosis)
- copper
- iron
- bilirubin (cholestasis)
Appearance:
- ballooning degeneration
- single large droplet
- multiple tiny droplets
EXAMPLES: Alcoholic liver disease Acute fatty liver of pregnancy Wilson’s disease Reye syndrome
Reye syndrome
rare but serious condition
- affects young children with viral illness
- use of aspirin was linked with it (90% of cases)
- hepatic fatty change + rapidly progressing encephalopathy
- starts with rash on palms and soles, vomiting, confusion, lethargy
- could be lethal or followed by mild to severe permanent brain damage
Necrosis and apoptosis
Irreversible changes
Apoptosis
- Shrunken, pyknotic hepatocytes + Acidophilic (apoptotic) bodies
Necrosis
- Cell membrane deterioration
- Swelling and rupture of hepatocytes
- Defective osmotic regulation
- Accumulation of macrophages
Types of necrosis
- Coagulative necrosis – in ischemia
- Hydropic degeneration – viral hepatitis
- Focal necrosis – viral or drug-induced
- Zonal necrosis (zone 1-3) –
- Bridging necrosis – inflammation or toxic
- Piecemeal necrosis – viral (chronic), autoimmune, steatohepatitis
- Submassive necrosis
- Massive necrosis
Inflammation
Due to a wide array of factors (e.g. viral, toxins, drugs, autoimmune)
Acute or chronic
Necrosis of hepatocytes may precede or follow the inflammation
Periportal or into the parenchima of liver (zone 1)
Regeneration
Under normal circumstances, very little liver proliferation
After liver injury (or resection), proliferation occurs as a compensation for tissue loss
Regeneration of lost hepatocytes occurs primarily by mitotic replication of hepatocytes adjacent to those that have died
Replicative senescence of hepatocytes may occur in time in chronic disease
Cells of the canals of Hering (oval cells) represent reserve progenitor cells for both hepatocytes and bile duct cells
Ductular (ductal) reaction
Progenitor cells for bile duct cells. Most prominent in cirrhosis.
Fibrosis
In response to inflammation or direct response to a toxic agent
Initially may develop portal, periportal, pericentral or pericellular
Later in time, bridging fibrosis
Cirrhosis
Etiology
- Alcohol abuse
- Non-alcoholic fatty liver disease (NAFLD)
- Chronic hepatitis B and C
- Autoimmune hepatitis
- Biliary disease
- Metabolic disease
- Cryptogenic (10% of cases)
Four pathological processes
1) Hepatocellular death
2) Vascular changes
3) Progressive fibrosis
4) Regeneration (nodules)
Coexist in various degrees Affect diffusely the liver The hepatic architecture is disrupted Usually most changes are irreversible All liver functions are affected
Symptomatology
About 40% of patients are asymptomatic until the
advanced stages of the disease
Symptomatic patients:
- non-specific symptomatology
- symptoms and signs suggestive for cirrhosis
Laboratory tests
Abnormal results even in asymptomatic patients
Complications Progressive (chronic) liver failure Portal hypertension (and risk of rupture of esophageal varices) Hepatocellular carcinoma (HCC)
Clinical Syndromes
HEPATIC FAILURE
CIRRHOSIS
PORTAL HYPERTENSION
CHOLESTASIS
Three situations of heart failure
1) Acute liver failure with massive hepatic necrosis:
Rare but life-threatening
Fulminant (≤ 8 weeks) or subfulminant (≤ 26 weeks)
b/w onset and hepatic encephalopathy in the absence
of pre-existing liver disease
Massive hepatic necrosis (toxic or immune mediated)
Liver larger or smaller than normal
Caused by Acetaminophen (50% cases), Amanita phalloides, Autoimmune hepatitis, and Acute viral hepatitis
2) Chronic:
Progressive evolution of chronic liver disease that ends in cirrhosis
3) Hepatic dysfunction without overt necrosis:
Reye syndrome
Tetracycline toxicity
Acute fatty liver of pregnancy (diffuse microvesicular steatosis due to mitochondrial dysfunction) – third
trimester and early postpartum
Hepatic encephalopathy
a disorder of neurotransmission in the central nervous
system and neuromuscular system.
Elevated ammonia levels in blood and the central nervous system correlate with impaired neuronal function and cerebral edema.
Encephalopathy may progress over days, weeks, or months following acute injury.
Pathophysiology
Severe loss of hepatocellular function
Shunting of blood from portal to systemic circulation leading to ammonia in the blood
Disturbances in consciousness, ranging from subtle behavioral abnormalities, to marked
confusion and stupor, to deep coma and death.
Asterixis IS A PARTICULAR SIGN!!**
Acetaminophen-induced centrilobular necrosis
This is a zone 3 necrosis (accumulating effect)
Onset: first with nausea, vomiting, and often jaundice.
Later: encephalopathy, multisystem failure.
Liver initially enlarged, then it shrinks dramatically.
Serum liver transaminases are initially very elevated;
then decline (not a sign of improvement!).
Worsening jaundice.
Coagulation defects (low level of vitamin K)
Death occurs without liver transplantation.
Hepato-renal syndrome
Renal failure without preexisting kidney condition (exceptions exist)
Liver and kidneys may be affected by same agents or processes
From mild to severe
Renal function promptly improves if hepatic functions improved
Decreased renal perfusion
Decreased glomerular filtration rate
Oliguria (although the ability to concentrate the urine is retained)
High levels of blood urea nitrogen and creatinine
Sodium retention
Ascites (refractory to diuretic therapy)
Impaired free-water excretion
PORTAL HYPERTENSION
increased resistance in the portal blood flow
can have intrahepatic and posthepatic causes;
Intrahepatic include cirrohosis, nodular regeneration hyperplasia, malignancy, amyloidosis, etc.
Posthepatic causes include SEVERE RIGHT SIDED HEART FAILURE, constrictive percarditis, hepatic vein outlow obstruction
four major clinical consequences of portal hypertension are:
(1) hepatic encephalopathy
(2) portosystemic venous shunts
(3) ascites
(4) congestive splenomegaly
Sites of porto-caval anastomoses
1) Distal third of esophagus (esophageal varices)
2) Rectum (internal hemorrhoids)
3) Paraumbilical area (caput medusae)
4) Retroperitoneum
Metabolic Liver Disease
Acquired:
• Non alcoholic fatty liver disease
Inherited metabolic diseases:
• Hemochromatosis
• Wilson disease
• α1‐antitrypsin deficiency
Hemochromatosis
Total iron is tightly regulated by intestinal absorption
Excessive accumulation of iron in the liver and pancreas
> Also heart, joints, adrenals, thyroid, skin
Primary or secondary
Secondary: Consequence of parenteral administration (blood transfusions), hemodialysis, sickle cell**
Neonatal (congenital):
• Unknown etiology
• Severe liver disease and extrahepatic deposition
• Liver injury in utero → hemosiderin accumulation
• May be related to maternal immune injury towards fetal liver
The adult form of hemochromatosis is almost always
caused by mutations of HFE gene
Symptoms of Hemochromatosis
Symptoms usually first appear in the fifth to sixth
decades of life
• Male predominance (5‐7 : 1)
• Earlier clinical presentation in males
• Diagnosed by high levels of serum Iron and ferritin
• The classic triad might not develop until late in
the course of the disease
1. pigment cirrhosis with hepatomegaly
2. skin pigmentation
3. diabetes mellitus
• Death results from cirrhosis or cardiac disease
• Hepatocellular Ca: risk is 200‐fold than gen pop
• Treatment for Fe overload does not remove risk
• Treated by phlebotomy and iron removal
Wilson Disease
• Autosomal recessive disorder • Impaired copper excretion into bile and failure to incorporate copper into ceruloplasmin • α‐2 globubin + Cu = Celuloplasmin • Low ceruloplasmin levels in WD • Accumulation of toxic levels of copper in many organs, principally the ‐ liver ‐ brain ‐ eye
• Diagnosis based on:
• Decreased serum ceruloplasmin (Serum Cu may be
normal, increased or decreased)
• Increased Urinary excretion of Cu
• Increased hepatic content of Cu
• Kayser Fleischer rings
• Treatment: Long term Copper chelation with D‐
penicillamine or liver transplant (if cirrhosis)
Symptoms of Wilson Disease
Kayser Fleischer Rings in eyes Putamen atrophy / cavitation Cirrhosis Slurred speech Diminished movement control (tremors like Parkinsons) Mild behavior change Frank psychosis
Alpha‐1 Antitrypsin Deficiency
• Autosomal recessive disorder
• Liver derived AAT provides 90% of
elastase inhibition in plasma
- Clinically:
- Early onset emphysema (<45 y)
- Unexplained liver disease w/ cirrhosis
Changes in Bilirubin lead to what urine/feces color changes?
Prehepatic cause (hemolysis): dark feces and dark urine
Hepatic tissue damage: pale feces and dark urine
Posthepatic: clay colored feces (no color) and urine is pale
Jaundice
The balance between bilirubin production and clearance is disturbed by one or more of the following mechanisms:
- Excessive extrahepatic production of bilirubin
- Reduced hepatocyte uptake
- Impaired conjugation
- Decreased hepatocellular excretion
- Impaired bile flow
- *1, 2 & 3: Unconjugated hyperbilirubinemia
- *4 & 5: Predominantly conjugated hyperbilirubinemia
Hemolytic disease of the newborn
(erythroblastosis fetalis) may lead to accumulation of
unconjugated bilirubin in the brain
• Rh incompatibility
• May cause severe neurologic damage (kernicterus)
Neonatal jaundice
mild unconjugated hyperbilirubinemia
Treatment: Phototherapy
• Works through isomerization that changes trans‐
bilirubin into water‐soluble cis‐bilirubin isomer
Cholestasis
Impaired bile formation and bile flow →
accumulation of bile pigment in the liver parenchyma
• Extrahepatic or intrahepatic obstruction of bile channels
• Defects in hepatocyte bile secretion
• Clinical symptoms: Jaundice, pruritus, skin xanthomas (focal accumulation of cholesterol), intestinal malabsorption
• Characteristic lab finding:
• Elevated serum alkaline phosphatase and γ‐glutamyl
transpeptidase (GGT)
• Enzymes present on the apical membranes of hepatocytes and bile duct epithelial cells
Intrahepatic Biliary Disease
Two entities:
1) Primary Biliary Cirrhosis (PBC)»_space; issue starts in liver
2) Primary Sclerosing Cholangitis (PSC)»_space; starts in liver and then there’s thickening and inflammation of the bile duct
Primary Biliary Cirrhosis (PBC)
- Inflammatory autoimmune mainly affecting medium‐sized intrahepatic bile ducts
- Unknown pathogenesis
- Portal inflammation, scarring, and eventual development of cirrhosis and liver failure (cirrhosis develops after many years)
- Seen in middle age with a predominance in females and in conjunction with other autoimmune conditions
Insidious onset • Fatigue and pruritus • Hepatomegaly • Eyelid xanthelasmas / Hyperpigmentation • Inflammatory arthropathy
• ↑ Serum alkaline phosphatase and cholesterol
• Antimitochondrial antibodies in 90% to 95% of
patients which is HIGHLY characteristic of PBC and ESSENTIAL for diagnosis
• Causes of death:
‐ liver failure
‐ massive variceal hemorrhage
‐ intercurrent infection
• Increased risk to develop hepatocellular carcinomas
Primary Sclerosing Cholangitis (PSC)
• Characterized by inflammation and obliterative
fibrosis of intrahepatic and extrahepatic bile ducts,
with dilation of preserved segments
• Immunologically mediated injury to bile ducts
• Commonly seen in association with Inflammatory
bowel disease, particularly ulcerative colitis
•BEADING There’s alternating dilations and strictures, creating the appearance of beads that can be seen radiographically
•Concentric periductal fibrosis around affected
ducts (“onion‐skin fibrosis”)
Cholelithiasis (gallstones)
- 10% to 20% of adults in developed countries
- > 80% are “silent”
• Two main types of gallstones
1) About 90% are cholesterol stones containing >50%
of crystalline cholesterol monohydrate
• Rest are pigment stones composed predominantly
of bilirubin calcium salts
pigmented stones are more common in Asia and cholesterol stones are commonly caused by oral contraceptives, rapid weight loss, and diet.
Biliary pain
• Can be excruciating and constant or “colicky” (spasmodic)
• Result of the obstruction
• Larger calculi are less likely to enter the cystic or common ducts to produce obstruction, small stones or “gravel” are more dangerous
Cholesterol stones
- Pure cholesterol stones are pale yellow, round to ovoid, have a finely granular, hard external surface
- With increasing proportions of calcium carbonate, phosphates, and bilirubin, stones may be lamellated and gray‐white to black
• Surfaces of multiple stones may be rounded or faceted, because of tight
apposition
• Stones composed largely of cholesterol are radiolucent (However, sufficient calcium carbonate is found in 10% to 20% of cholesterol stones to render
them radiopaque)
Pigmented stones
- “Black” and “brown”
- Black pigment stones are found in sterile gallbladder bile
- Brown stones are found in infected intrahepatic or extrahepatic ducts
• Because of calcium carbonates and phosphates, approximately 50% to 75%
of black stones are radiopaque
• Brown stones, which contain calcium soaps, are radiolucent
Cholecystitis
• Inflammation of the gallbladder
• May be acute, chronic, or acute superimposed
on chronic
• Almost always occurs in association with
gallstones
• Cholecystitis is one of the most common
indications for abdominal surgery in the US
Acute Calculus Cholecystitis
An acute inflammation of the gallbladder, precipitated
90% of the time by obstruction of the neck or
cystic duct
• Primary complication of gallstones
• Chemical irritation and inflammation of the obstructed
gallbladder/ mucosal and mural inflammation
- Gallbladder impaired mobility (porcelain gallbladder)
- Distention and increased intraluminal pressure compromise blood flow to the mucosa
- Absence of bacterial infection – Only later in the course may bacterial contamination develop
Acute Acalculous Cholecystitis
• Thought to result from ischemia
• Cystic artery is an end artery (no collateral circulation)
• Occurs in patients who are hospitalized for
unrelated conditions
Risk factors: • Sepsis with hypotension and multisystem organ failure • Immunosuppression • Major trauma and burns • Diabetes mellitus • Infections
Liver Nodules and Tumors
Nodular Hyperplasias • Solitary or multiple hyperplastic liver nodules in the non cirrhotic liver • Focal nodular hyperplasia (FNH) • Nodular regenerative hyperplasia (NRH)
Benign neoplasms
• Cavernous Hemangioma
• Hepatic adenoma
Hepatocellular Carcinoma
Four major etiologic factors: • Chronic viral infection (HBV, HCV) • Chronic alcoholism • Non‐alcoholic steatohepatitis (NASH) • Food contaminants (primarily aflatoxins)
Could be
‐ Unifocal: usually one large mass
‐ Multifocal: widely distributed nodules of variable size
‐ Diffusely infiltrative cancer: sometimes entire liver
• Well differentiated or poor differentiated forms
• Repeated cycles of cell death and regeneration (eg.
Chronic hepatitis)
• Liver enlargement
• The diffusely infiltrative tumor may blend imperceptibly into a cirrhotic liver background
• Pale tumors with green hue
• Vascular invasion
• Portal vein or inferior vena cava involvement
• Intrahepatic metastases
• Satellite nodules (shown by molecular methods to be
derived from the parent tumor)
• Metastases outside the liver are primarily via
vascular routes (lung, late in disease)
• Lymph node metastases to the perihilar, peripancreatic, and para‐aortic nodes above and
below the diaphragm
Cholangiocarcinoma
Arising from bile ducts within and outside of the liver
• Risk factors
• Primary sclerosing cholangitis (PSC)
• HCV infection
• Previous exposure to Thorotrast (formerly used in
radiography of the biliary tract)
• In southeast Asia, chronic infection of the biliary tract by a liver fluke
Intrahepatic and extrahepatic forms of Cholangiocarcinoma
• Extrahepatic (80 to 90% of the tumors)
• Perihilar tumors (Klatskin tumors) located at the junction of the
right and left hepatic ducts forming the common hepatic duct
• Symptoms of biliary obstruction, cholangitis, and right upper
quadrant pain
• Small at time of diagnosis
• Intrahepatic
• Usually detected late in their course
• Obstruction of bile flow or a symptomatic liver mass
