quiz 5- liver tumors, GB, pancreas Flashcards
• What is biliary atresia? 2 types?
o Aka extrahepatic ductopenia and progressive obliterative cholangiopathy.
o Congenital: common bile duct blocked or absent. 1/10-15,000 (?? 1/300 in US); some die in hours-days
o Acquired: usu AI, a principal form of chronic liver transplant rejection
• What are ssx of congenital biliary atresia? Dx? Tx?
o initial sxs mb indistinguishable from neonatal jaundice
o Prolonged jaundice resistant to photo therapy
o progressive cholestasis: pruritus, fat-sol vit def, malabsorption →cirrhosis, portal HTN
o 1-6 wks: clay colored stools, dark urine, swollen abd, enlarged, hardened
o liver enzymes grossly markedly elevated
o hyperbilirubinemia is conjugated, doesn’t cause kernicterus
o dx: US
o tx: Kasai procedure (anastomosis), liver transplant (need by age 3); un tx → liver failure
• what causes biliary atresia? Pathogenesis?
o Unknown cause (both congenital and acquired?); congenital: part/all of bile duct missing
o Mb damage dt immune response: Reovirus 3, congenital CMV, EBV, AI, malformation
o → bile trapped in liver (can’t get to intestine) = biliary stasis
o → Proliferation of small bile ductules → fibrosis → cirrhosis
• What are Choledochal cysts? Morbidities?
o congenital cystic dilatations of bile ducts
o Often jxn bw common bile duct and pancreatic duct (empties into CBD > 1 cm proximal to ampulla)
o Western: 1/10^5- 2x10^6; Japan (asia): 1/1,000
o Children: pancreatitis, cholangitis, histo hepatocellular damage
o Adults: hepatic abscesses, cirrhosis, portal HTN, recurrent pancreatitis, cholelithiasis
o Cholangiocarcinoma, 9-28%, mb dt susceptibility to bile as carcinogen
• How are choledochal cysts dx? Sxs?
o most dx as kids (60-70% w sxs)
o Infants: jaundice and clay colored stools → workup for biliary atresia; palpable mass in the RUQ, HM
o Kids: intermittent biliary obstruction (RUQ mass, jaundice), recurrent bouts of pancreatitis (↑ amylase, lipase)
o Adults: 1+ severe complications; vague RUQ pn (mc); jaundice, cholangitis
o Triad (only 10-20%): mass, abd pn, jaundice
• What is pathophysiology of choledochal cyst?
o Abn union, pancreatic secretions reflux into CBD, enzymes activated
o → damage, weaken bile duct wall
o Defects in epithelialization and recanalization
o → formation of a choledochal cyst
• What are classes of choledochal cysts?
o I-V
o I: mc, 80-90%; saccular dilatations of CBD, segment r entire duct
o I and IV have subclasses: IA, IB, IC, IVA, IVB
• What is cholelithiasis?
o crystalline mass formed within gallbladder, made of bile components
o may pass distally into other parts of biliary tract: cystic duct, CBD, pancreatic duct, ampulla of Vater
• what are risk factors for gallstones?
o female, overweight, age near or > 40
o ↑ in N and S American Indians, Hispanics, N Euro
o ↓ melatonin, which inhibits cholesterol secretion from GB, ↑ conversion of cholesterol to bile, antioxidant
o Polyfactorial: inherited body chemistry, body wt, GBmotility, diet (↓fiber, ↑chol, ↑starch), rapid wt loss, constipation, fewer meals, less fish, ↓folate, Mg, Ca, vit C
o PPIs ↓ GB fxn
o mb ↓ risk: wine and whole-grain bread
• what are some risks of having gallstones?
o In ampulla of Vater: obstruct exocrine pancreas → pancreatitis
o In GB: acute cholecystitis
• What is acute cholecystitis?
o Bile retained in GB; Usu caused by cholelithiasis, esp cystic duct block
o 2nd infx: intestinal microorganisms, E coli, Klebsiella, Pseudomonas, Bacteroides fragilis, Enterococcus.
o GB wall inflamed; severe: → necrosis and rupture
o spreads to outer covering, irritates surrounding structures, diaphragm, bowel
• what are ssx of cholecystitis?
o RUQ pn (biliary colic), initially intermittent (mb referred, R scapula)→constant, severe pain o pain after fatty meals o ↓ fever, diarrhea, N/V o GB mb tender and distended o ↑AST,ALT, WBC
• What is acalculous cholecystitis?
o Less common, w/o stones
o mb no stones in debilitated trauma patients, CAD, immunosuppressed
o obstructing tumors or inadequate blood supply
o also anorexia nervosa: lack of stimulation of GB → bile stasis
o can progress more rapidly to gangrene and sepsis
• What is gross and microappearance of acute cholecystitis?
o US: 1.9 cm stone; thickening of GB wall consistent w chronic cholelithiasis
o Micro: extensive ulceration of mucosa, hemorrhage, edema, dense transmural infiltrate of Ns and mononuclear inflam cells
• What are the types of gallstones?
o On basis of composition
o Cholesterol: light yellow to dark green/brown; oval 2-3 cm in length, tiny dark central spot. At least 80% cholesterol by weight (too much), and not enough bile salts; > 80% in US
o Pigment: mc in developing world; ↑ w hemolytic anemia, cirrhosis, biliary tract infxs; small, dark, bilirubin and calcium salts; < 20% cholesterol; st xray
o Mixed stones: 20–80% chol; calcium (seen on xray) carbonate, palmitate phosphate, bilirubin, other bile pigments
• What are the size and consistency variations of gallstones?
o grain of sand to golf ball
o single large stone or many smaller ones
o Pseudoliths: aka sludge, thick, alone or w fully formed gallstones; presentation like lith
o composition affected by age, diet and ethnicity
• What are the risk factors for forming gallstones?
o Older: time-dependent process
o Female (3:1)- estrogen induces changes in lipid metabolism and GB function; ↑ risk preg, multiparous, OCPs, hormone tx
o Race and ethnicity- > 75% American Indian F > 40
o Genetics
o Obesity- alterations in lipid metabolism, ↑cholesterol synthesis dt ↑ activity of hydroxy-methyl-glutaryl- CoA (HMG CoA) reductase
o Crohn’s: ↓ ileal resorption of bile salts
o Total parenteral nutrition: → stasis and distension
o Rapid weight loss: 30-40% gastric bypass; removal of GB prophylactically
o ability of GB to effectively empty; presence of additional proteins and salts in the bile
• how does bacterial infx contribute to gallstones?
o Bile is normally sterile
o Infx: bacteria hydrolyze conjugated bilirubin → ↑unconjugated bilirubin → precipitation of calcium bilirubinate crystals
o Bacteria also hydrolyze lecithin to release fatty acids, may bind calcium and precipitate
o Claylike, “brown pigment stones”
o often form in bile ducts
• how do cholesterol stones form?
o Liver cells secrete cholesterol into bile w phospholipid (lecithin) in form of small spherical membranous, “unilamellar vesicles”, and bile salts (detergents)
o In GB: Bile salts dissolve unilamellar vesicles → soluble aggregates, “mixed micelles”
o Compared w vesicles (hold 1 molecule of cholesterol for every molecule of lecithin), mixed micelles have lower carrying capacity for cholesterol (about 1 for every 3 lecithin)
o → bile supersaturated w cholesterol, and cholesterol monohydrate crystals may form
• What are the main factors that determine whether cholesterol gallstones will form are?
o 1) the amount of cholesterol secreted by liver cells, relative to lecithin and bile salts
o 2) the degree of concentration and extent of stasis of bile in the gallbladder.
• What are bilirubin stones?
o Most bilirubin in bile is glucuronide conjugates, water soluble and stable,
o Some is unconjugated, like fatty acids, phosphate, carbonate, and other anions, tends to form insoluble precipitates with calcium
o Hemolysis/cirrhosis: ↑ unconj bili → stones
o Jet black color= black pigment stones (10-20% in US)
• What is cholesterolosis?
o abnormal deposition of cholesterol and TG filled M0s in GB lamina propria
o → bulge and lift the superficial epithelium overlying them.
o St assoc w chronic cholecystitis
o Mb localized or extensive and diffuse
o “strawberry gallbladder“= w diffuse mucosal involvement; hundreds of tiny (1mm or less) bright yellow dots (cholesterol); mucosa is red
o Asx, no clinical sig
o St find w chronic cholecystitis, cholelithiasis, but nor causative
o Both the pathogenesis and epidemiology is unknown
• What is chronic cholecystitis?
o pathogenesis not well understood.
o Mb hx repeated attacks of acute cholecystitis
o Bacteria in GB in 1/3 – ¼ cases
o F 30-50 (like acute)
o Usu assoc w cholelithiasis
o Asx, or like acute w chronic dz, biliary colic, fistula formation, GB hydrops, perforation
o Predisposes to GB CA
• What is gross appearance of chronic cholecystitis? Micro?
o GB mb enlarged, normal or shrunken
o GB wall is thickened, mucosal lining lost normal velvety, granular appearance; shaggy, roughened mucosal surface
o Fibrosis, necrosis, ulceration
o Outpouchings of mucosa thru muscle of GB wall (Rokitansky - Aschoff Sinuses)
o Micro: chronic inflam cells (M0s, Ls, plasma cels); surface epithelium lose normal delicate papillary appearance, fibrosis, chronic inflammation in the lamina propria; Rokitansky-Aschoff sinuses (pockets) in muscularis
• What is Porcelain gall bladder?
o calcification of GB dt persistent inflammation dt gallstones, exact cause not clear
o GB= porcelain-like vessel, dt fibrosis and calcification
o a morphological variant of chronic cholecystitis.
o Usu overweight F, ~40
o Tx: surgical removal (but if CA, fear of causing seeding)
o ↑ risk GB CA
• What is Choledocholithiasis?
o gall stone that has passed into CBD
o Obstruct bile flow → abd pn, jaundice
o Stagnant bile often becomes infected → ductal system into the liver →ascending cholangitis (emergency)
o If Obstruct pancreatic duct in ampulla of Vater → activate pancreatic digestive enzymes → acute pancreatitis
• What is MRCP? ERCP?
o MRCP: Magnetic resonance cholangiopancreatography;To visualize biliary and pancreatic ducts in non-surgical manner; see if gallstones are lodged in any of the ducts surrounding GB
o ERCP: Endoscopic retrograde cholangiopancreatography, for x-ray; combo endoscopy and fluoroscopy to dx biliary or pancreatic ductal do; see inside of stomach and duodenum, inject dyes into biliary ducts and pancreas; dx gallstones, inflammatory strictures, leaks from trauma and surgery, CA; dx or tx uses; Endoscopic sphincterotomy (both of the biliary and the pancreatic sphincters); Removal of stones; Insertion of stents, dilate strictures
• What is ascending/acute cholangitis? Ssx?
o Life-threatening, medical emergency
o infx of bile duct, usu dt bacteria ascending at jxn w duodenum
o esp if bile duct is already partially obstructed by gallstones (70-90%)/stricture
o ssx: jaundice, fever, abd pain, rigors, malaise; sever: ↓BP, shock; elderly mb atypical
o charcot’s triad: abd pn, jaundice, fever (20-70%)
o reynold’s pentad: Charcot + mental confusion, septic shock
• what is tx for acute cholangitis? Px? Micro?
o Tx: initial IV fluids/abx, tx underlying problem
o Px: Risk death, dt irreversible shock, multiple organ failure (dt severe infx); Mort rate 10-30%
o Micro: mb secondary sclerosing cholangitis, looks just like PSC (onion-skin)
• What is GB CA? incidence? Types?
o Aggressive; Strong assoc w gallstone dz, but w gall stones adenocarcinoma is rare
o 6,000 new cases of GB adenocarcinoma in US per yr (relatively uncommon)
o M:F 4:1 (2:1), avg 70 (50-60); N Indian, ppl of Americas
o Most are well differentiated adenocarcinomas
o Others: papillary adenocarcinoma, poorly differentiated adenocarcinoma, well differentiated adenocarcinoma w squamous metaplasia
• What are ssx of GB CA? tx?
o Early: asx, unless in head of pancreas → compresses CBD; mb mimic stones
o Sx: severe RUQ pn, wt loss, loss appetite, jaundice, palpable mass, vomit dt obstruction
o Often mets by time of dx
o Tx: cholecystectomy, part of liver, assoc LNs
• What is gross appearance of GB CA?
o firm, tan, flat tumor, in part of mucosa
o thickened wall indicates transmural spread of tumor
o mb exophytic, growing fungating mass into cavity of GB
• what is micro appearance of GB CA? grades?
o micro adeno: tubular glands like colonic adenocarcinoma; Goblet cell variant
o Papillary adenocarcinoma (grade 1)
o Well-differentiated tubular adenocarcinoma (grade 1)
o Moderately differentiated tubular adenocarcinoma (grade 2)
o Poorly differentiated tubular adenocarcinoma (grade 3)
• what are risk factors for GB CA?
o obesity
o chronic cholecystitis and cholelithiasis
o Various single nucleotide polymorphisms (SNPs)
o UC, (+/- PSC), choledochal cyst, parasites, gallstones
• What are markers for GB CA?
o FU-MK-1 (MK-1 antigen)
o 79% of samples
• Describe normal pancreas anatomy:
o Location: Retroperitoneal, near celiac plexus. head surrounded by duodenum, tail near hilum of spleen.
o 15 cm long, 100 grams
o Gross: head, body, tail; pink/tan, visible lobules; normally surrounded by mass of adipose
o Micro: 2 types of tissue, exocrine and endocrine
o Exocrine: many glands/acini, spherical collections of pyramidal cells, basally situated, round nucleus, abundant strongly basophilic cytoplasm. tips of cells project into central lumen, drained by fine ducts → pancreatic duct, smaller lined by cuboidal cells, larger by taller, more columnar cells
o Endocrine: 1 million clusters of cells = islets of Langerhans, equally distributed throughout exocrine pancreas; surrounded by network of fine capillaries. Each islet composed of many cell types, most beta (insulin), Alpha -glucagon. Also delta cells, PP cells, D1 and D2 cells, enterochromaffin cells
• Who gets acute pancreatitis? Complications? Tx?
o M ( < 40) > F; MC obese
o F: usu related to gallstones
o M: usu alcohol-induced
o 10-15% mortality; 30% if more severe
o Possible complications: abscesses, drained percuneously (F=M); Non-infected pseudocysts resolve spontaneously in ~50%
o Necrosis: needs surgery
o Mild: tx w IV fluids, analgesics
o Sever: aggressive fluid tx, abx, tube feedings
o CT and US in aspiration of pseudocysts, suspected pancreatic abscesses
• Gross appearance of acute pancreatitis. Micro:
o Firm, markedly edematous, multiple foci of hemorrhage, yellow white fat necrosis
o Extensive necrosis → loss of the normal lobular surface markings, soft to touch, grossly hemorrhagic
o Saponification: chelation of calcium salts w fatty acids liberated by pancreatic enzymes
o Hemorrhage dt digestion of vessel walls by pancreatic enzymes
o Micro: Necrotic debris and dense neutrophilic infiltrate. Necrotic changes (fatty infiltration w ghost-like cell outlines, notable hemorrhage)
• What are acute and chronic pancreatitis? Ssx?
o 80% all pancreatitis cases dt alcohol (#1 chronic) + gallstones (#1 acute)
o Acute: begin suddenly, last few days
o Chronic: many years
o severe upper abd pain, may radiate to back, N/V worse w eating; ARDS, DIC, shock
o PE: mb fever, ↑BP dt pain, ↓BO dt dehydration, bleeding; ↑ HR, RR; tender abd, ↓ BS (reflex bowel paralysis). Guarding, rebound tenderness;
o Classic (actually rare): Grey-Turner sign or Cullen sign, characteristic
• What are ssx w chronic pancreatitis? Assoc risks?
o Unexplained wt loss dt ↓ pancreatic enzyme production and secretion
o Comp: DM, ↑ risk pancreatic CA
• What causes acute pancreatitis?
o Etio: infx, ischemia, drugs; alcohol, gallstones (#1); peptic ulcer, vascular thrombosis
o Drugs: AIDS drugs didanosine, Pentamidine; anticonvulsant Valproic acid; chemo drugs L-asparaginase, Azathioprine; Exogenous estrogen dt ↑TGs; statin drugs; diabetes drug Sitagliptin
o Pathogenesis: Acinar cells release enzymes → proteolysis, lipolysis, hemorrhage of pancreas. dt duct obstruction → secondary acinar cell injury, direct acinar cell toxicity, or deranged intracellular transport
o → ↑serum pancreatic enzymes, amylase and lipase
• What are general causes of pancraetitis?
o Inherited: activate trypsinogen in pancreas →auto-digestion
o trauma, steroids, mumps, AI, scorpions, ↑ blood Ca, ↑ TGs, hypothermia
o risk w ERCP
o pregnancy, dt ↑ TGs, gallstones
o DM II (3x risk)
o Less common: pancreatic CA, pancreatic duct stones, pancreatic vasculitis, porphyria (acute intermittent and erythropoietic protoporphyria)
• Gross appearance of chronic pancreatitis? Histo?
o Gross: shrunken and fibrotic. main duct dilated, filled w calcified secretions
o Micro: enzymic fat necrosis, hemorrhage, inflammatory infiltrate, vessels w necrotic walls
• What are complications of pancreatitis?
o Pseudocyst: peri-pancreatic fluid collection w ↑pancreatic enzymes within a defined fibrous wall, w/o epithelial lining
o Pancreatic abscess: pseudocysts that become infected; pus, necrosis, liquefaction
o Infected necrosis w/o abscess
• What are pancreatic pseudocysts?
o =fibrinous encapsulation of a collections of pancreatic fluid
o Acute pancreatitis → damage pancreatic parenchyma and ductal system → necrosis superimposed on chronic inflammation
o → leak pancreatic enzymes, buildup of fluid w enzymes, and hemolyzed blood and necrotic debris
o → pancreas encapsulates the fluid in fibrous capsule = psuedocyst because it has no epithelial lining
o May → abscess, but not requirement
o Can adhere to other organs, visceral linings, etc (ex: spleen)
o Assoc w alcohol, gallstones, other causes of pancreatitis
• Gross pancreatic pseudocysts? Micro?
o G: Usu unifocal intra- or peri-pancreatic cyst w pus and old blood. Pancreatic wall very dense; psuedocyst or cysts may communicate with pancreatic duct system
o M: no epithelial lining, contains cholesterol clefts, blood both fresh and clotted, hemosiderin laden M0s
• What are pancreatic abscesses?
o Late presentation of acute necrotizing pancreatitis (4 wks post acute, 3-5% ppl w recurrent acute); found on CT, MRI, US
o Mc assoc w infx pancreatic pseudocysts; Often dt colonic bacteria translocation, E. coli, Klebsiella pneumoniae, Enterococcus faecalis, Staph aureus, Pseudomonas aeruginosa, Proteus mirabilis, other Streptococcus, or Candida
o Mb dt fibrous wall formation around fluid collections from penetrating peptic ulcers, gall stones, alcohol, blunt trauma
o Complication: rupture; ~20% mortality if acute pancreatitis superimposed on pre-existing pancreatic abscess
• What are the tumors of the pancreas?
o Benign: pseudopapillary tumor, serous cystadenoma, mucinous cystadenoma
o Malig: pancreatic adenocarcinoma, mucinous cystadenocarcinoma
o Exocrine: solid or cystic
o Endocrine: non-functional and functional
o Cystic: serous cystic, mucinous cystic, intraductal papillary mucinous, solid pseudopapillary
• What are mucinous cystic neoplasms of the pancreas?
o Benign, borderline, malig (transform in untx); based on histo; MC cystic tumor of pancreas; 50% of all cystic tumors o Women (80-95%), 40s-50s; compress organs → wt loss, sense of fullness o columnar, mucin-producing epithelium, supported by ovarian-type stroma
• what is a Solid pseudopapillary tumor?
o Aka: solid-cystic, papillary-cystic, solid and papillary (epithelial) neoplasm.
o Rare, benign, usu young women; good px
o Any part of pancreas
o round, well-demarcated, 2–17 cm (avg 8), hemorrhage; thick, fibrous capsule surrounding a solitary, solid to cystic mass
o micro: sheets of cells, uniform nuclei, eosinophilic or clear cyto, PAS (+) eosinophilic cytop inclusions (mb like panc endocrine tumor); necrosis, cell death away from blood vessels →pseudo-papillae (cystic areas bw tumor cells); finger-like projections
• what is serous cystadenoma?
o 2nd MC cystic tumor of pancreas; usu benign; malignant transformation rare (serous cystadenocarcinoma)
o Slow-growing, but mb large, press organs → abd distension, pn
o honeycombed appearance, also seen on CT (dx)
o micro: cysts which lined by ciliated cuboidal epithelium
o assoc w von Hippel-Lindau syndrome.
o tx: surgery only if sxs; usu as if no other lesions (w/o VHL)
• what is von Hippel-Lindau syndrome?
o rare, AD, asx
o cysts often develop in pancreas, liver, kidney
o pancreatic: uncommon, usu Simple benign cysts and cystadenomas
o rare: Extrahepatic biliary obstruction 2nd to pancreatic cysts
o hemangioblastomas in organs: cerebellum, spinal cord, kidney, retina
o café au lait spots and port-wine stains
o other CAs: renal angiomas, renal cell carcinoma (clear cell variety), pheochromocytoma
o ear involvement: endolymphatic sac tumors, epididymal cystadenomas
• pt w vHL?
o 37 yo F, 2 mo hx generalized pruritus
o admitted for biliary drainage
o dx vHL syndrome 10 yrs earlier, w retinal hemangiomas and pancreatic and renal cysts
o Surgical removal pancreatic cyst 10 yrs ago dt abd
o FHx retinal angiomas in siblings
• What is pancreatic adenocarcinoma?
o Aka pancreatic ductal adenocarcinoma,
o MC pancreatic CA; 90-95% of all malig pancreatic tumors.
o From exocrine pancreas: pancreatic ducts (99%) or from acinar cells (1%)
o Rare: from islet cells = neuroendocrine tumors
o 2nd MC cause death of all GI CAs; 4th MC cause death worldwide
o “silent killer”: asx early, later sxs nonspecific, dx late
• What are ssx of pancreatic adenocarcinoma?
o upper abd pn, radiates to back (body or tail)
o loss appetite, N/V, sig wt loss
o painless jaundice if in head (75%), obstructs CBD thru pancreas; pruritis
o pale-colored stool and steatorrhea
o st Trousseau sign: spontaneous blood clots in portal vessels, deep veins of extremities, or superficial veins anywhere
o may develop DM, ↑ glucose
o Clinical depression
• How does pancreatic CA metastasize? Px?
o first to regional LNs, later liver, st lungs; st bone or brain
o 1yr survival: 25%; 5 yr 6%
o Avg: 10 mos local, 6 mos mets
o Some die in weeks of dx
• What is histo for pancreatic adenocarcinoma?
o Mod-poor differentiated glandular structures
o similar to hepatobiliary cancers (cholangiocarcinoma) and some stomach cancers
o Thus, can’t be certain its primary
• What are 3 precancerous lesions that can lead to pancreatic CA?
o Pancreatic intraepithelial neoplasia (PIN): microscopic
o intraductal papillary mucinous and mucinous cystic neoplasms (both macroscopic); cellular origin debated
• 2nd mc type of exocrine pancreatic CA?
o Mucinous
o Slightly better px than pancreatic adenocarcinoma.
• What are the tumors of the liver? Benign and malignant?
o Most dt metastasis: G (colon, MC), breast, ovarian, lung, renal, prostate
o B: hemangioma, adenoma
o M: hepatocellular carcinoma, cholangiocarcinoma
• What are hepatic hamangiomas? Cavernous?
o MC liver tumor, 7-8% autopsies
o C: blood filled dilated vessels, like the ones on skin
o Usu asx, unless liver is traumatized (bx)
• What are hepatic adenomas? 2 types?
o Benign, often asx
o Very rarely, can develop from another cell line that has arisen within a hepatic adenoma
o Hepatocyte (MC)
o Bile duct
• What are features of hepatocyte adenomas?
o young women, mb dt OCPs (regress after stop)
o may get large (25-30 cm) in prego dt ↑E → rupture, hemorrhage, peritonitis
o ddx= HCC
o gross: can be anywhere, often under capsule, well-demarcated from rest of parenchyma; pale, yellow-brown (fatty change), bile stain
o micro: normal looking hepatocytes arranged in sheets and cords (slightly small, ↑N:C, less eosinophilic)
o usu no Typical portal tracts and central veins, cells not arranged in a typical lobular pattern, but significant vascular supply
• What are features of bile duct adenomas?
o less common
o may look more like hamartomas
o usu small (1 cm max)
o micro: slit-like to circular spaces lined by epithelium (looks like normal bile duct epi)
• what are 2 main types of primary liver carcinoma? Rare?
o HCC: MC, aka hepatoma; from hepatocytes; mc visceral tumor worldwide
o Cholangiocarcinoma: from bile duct epithelium
o Rare: mixed tumors, sarcoma, hepatoblastoma
• What causes HCC?
o Common: chronic hepatitis B infx (esp where its endemic, like China)
o HBV at birth: 200x risk
o chronic hep C more common in US, 25% worldwide
o Risks vary by country
o alcoholic: MC cause cirrhosis/HCC in US
o Both HBV and HCV: ↑ risk HCC
o Others: Aflatoxin, Hemochromatosis, Wilson’s dz
o Hyperinsulinemia/DM II (↑ w time uncontrolled)
• What is epidemiology of HCC?
o M»F (8:1, behaviors)
o fibrolamellar subtype: M=F
o US: ↑ in Asians/Islander → Native Americans, Hispanics, blacks, whites
o Worldwide: mc cancer in many countries (dt HBV, HCV cirrhosis)
• What is gross and micro appearance of HCC? Serum?
o Gross: 3 main forms; greenish-yellow hue dt bile leakage; well-demarcated
o 1) unifocal, large mass
o 2) multifocal, smaller satellite nodules
o 3) diffusely iunfiltrative
o Micro: fibrosis (blue color change) =cirrhosis; lose architecture, nuclear atypia; cells look like hepatocyte origin; normal cords or pseudo-glandular; become more anaplastic
• What is pathogenesis of HCC?
o Esp in chronic infxs 2nd to HBV/ HCV by repeated immune attack liver cells (infx or bystanders)
o → mistakes in repair →Mutation → replicate fast, avoid apoptosis
o HCV → cirrhosis
o HBV and alcoholism: can skip cirrhosis, directly cause HCC
• What are ssx of HC? Labs?
o Non-specific: RUQ pn, ↓ appetite, wt loss, fatigue
o Bruising, jaundice
o Fatal, unless early dx, tumor surgically resected
o Labs: ↑ serum alpha-fetoprotein, ↑ALP (block biliary tract)
• How is HCC metastatic?
o invades vasculature
o common: snake-like masses invade portal vein or IVC
• what is cholangiocarcinoma? classes?
o Rare, < 10% of all primary liver malignancies
o Extrahepatic and intrahepatic ( → hilar, peripheral)
o Hilar: discrete mass
o Peripheral: MC, in interlobular ducts at braches in portal triads; single or multiple
• What are risks for cholangiocarcinoma? Tumor markers?
o chronic inflammation/injury of biliary epithelium
o CA 19-9 and CA-50 usu (+) in cholangiocarcinoma (neg in HCC)
• What are hepatic angiosarcomas?
o (Angiosarcoma = endothelial tumor; in skin, soft tissue organs such as the breast, heart)
o rare
o after exposures: arsenic (pesticides) and polyvinyl chloride (plastics industry)
• what are ssx of metastases to liver?
o Mb Numerous mass lesions of variable size.
o mb central necrosis
o mb ↑ ALP
o usu no hyperbilirubinema (not all bile ducts obstructed)
o transaminases usu not ↑
o MC: primary colon adenocarcinoma
