Liver Tumors and Lesions

Question 1

Hemangioma

Answer 1

• Most common benign liver tumor (1-2% US pop)
• Male = female; all ages
• Found incidentally
• Gross - small red/blue cystic lesion; often sub-capular (on liver edge); can become fibrotic (white)
• Histo - blood-filled vascular cavity (RBCs coalesce together) lined w/ benign flat endothelium, varying amounts of fibrotic stroma (trichrome stain)
• Tx - resect only if causing pain

Question 2

Focal Nodular Hyperplasia

Answer 2

• Common in young women (oral contraceptives?)
• Usually found incidentally
• Mimics tumor
• Due to vascular problem that pre-disposes to formation
• Gross - solitary “central stellate scar” w/ normal liver surrounding it (or staghorn)
• Histo - central scar contains thick-walled arteries, lymphocytes, proliferating bile ductules
  
  • Do reticullin stain for type III collagen - normal
• Tx - resect only if causing pain

Question 3

Hepatocellula Adenoma (3 molecular targets)

Answer 3

• Young women on oral contraceptives & rarely in men taking anabolic steroids
• Often present w/ acute ab pain (bleeding into tumor tissue) or life threatening ab hemorrhage (tumor ruptures –> bleeding into ab)
• Molecular Targets
  
  • HNF1A mutation - transcription factor (benign, more fatty tumor)
  • Beta-catenin mutation - regulates transcription (higher likelihood of HCC)
  • gp130 mutation - co-receptor for IL-6 (associated w/ intense inflammation)
• Gross - solitary w. hemorrhage; surrounded by normal liver
• Histo - plump hepatocytes, few/no mitoses (not mitotically active), large thick-walled arteries, dilated veins, no evidence of portal tracts
  
  • Do reticullin stain for collagen III - normal hepatic plates
• Tx - resected b/c HCC and hemorrhage risks

Question 4

Von Meyenburg Complex (aka biliary microhamartoma)

Answer 4

• May be confused w/ metastasis (so send for testing)
• Developmental anomaly (hamartoma - normal tissue elements growing in disorderly manner)
• Usually found incidentally in surgery
• Gross - small, solitary, very white (from fibrous stroma)
• Histo - small ducts, fibrous stroma (trichrome stain), benign cuboidal epithelium
• If multiple … think about Polycystic Kidney Disease (PKD1 mutations)
• Tx unnecessary

Question 5

HCC (3 molecular targets)

Answer 5

• Associations - Hep B, Hep C, aflatoxin (fungal toxin), cirrhosis (any cause)
• Molecular Targets
  
  • TERT (telomerase rev transcriptase), beta catenin, p53
• 2nd leading cause of cancer death worldwide (lower incidence in US but inc b/c Hep C and fatty liver disease)
• Presentation - wt loss, RUQ ain
• Screening - CT for those w/ NASH and Hep B/C; 50% have alpha-fetoprotein (AFP)
• Tx - refractory to conventional tx; only hope is resection if small or liver transplant (but remaining liver still infected and at risk)
  
  • Sorafenib - inhibits MAPK path; stablizes disease for few mo NOT CURE
• Prognosis - death < 1 yr
• Gross - solitary, multi-nodular OR diffuse infiltrate; bulging white or green (bile) tissue; surrounding liver is cirrhotic
  
  • Often invades portal vein - see tumor thrombus
• Histo - huge cells but still hexagonal, huge nuclei (inc nucleus:cyto); mitotically active; aberrant arteries in middle of tumor; angiolymphatic invasion; can produce bile; THICK plates
  
  • Reticullin stain for collagen III shows no reticullin stain in tumor - thick plates

Question 6

4 HCC Associations

Answer 6

• Hep B - HBx protein that inactivates p53 tumor suppressor gene
• Aflatoxin - often in food grains; specific codon 249 point mutation in p53
• Hep C - core protein is oncogenic
• Cirrhosis - b/c hepatocyte proliferation promotes mutations and HCC

Question 7

Cholangiocarcinoma

Answer 7

• Arises from intrahepatic bile ducts up to portal tracts
• Inc incidence in SE Asia (liver fluke infestation) but rare in US
• Other causes - hepatoliths, congenital anomalies, primary sclerosing cholangitis, cirrhosis, Hep B, Hep C
• Mutations - RAS or in iso-citrate dehydrogenase (IDH1/IDH2)
• Presentation - present late w/ ab pain and wt loss so poor prognosis; mets to lymph and lungs
• Gross - white solitary mass w/ normal liver surrounding
• Histo - adenomcarcinoma w/ desmoplasia (fibrosis on trichrome)

Question 8

Extra-Hepatic Bile Duct Cancer

Answer 8

• Klatskin Tumor - name if at hilus of bile ducts
• RARE
• Associated w/ congenital anomalies and primary sclerosing cholangitis (so greater in males)
• Presentation - painless obstructuve jaundice and pruritus
• Tx - resection difficult / minimal improvement in survival
• Gross - in duct (nodular) or infiltrative around duct
• Histo - usually adenocarcinoma; often around nerves (perineural)

Question 9

Carcinoma of Gall bladder

Answer 9

• More common than bile duct cancer
• Female > Male; later in life
• Associated w/ gall stones, typhoid infection and primary
  sclerosing cholangitis
• Presentation - present late w/ jaundice and ab pain (may be found incidentally on gall bladder removal)
• Poor outcome (most die w/in 1 yr)
• Gross - infiltrative (thick wall of gall bladder) OR fungating (friable mass in gall bladder lumen)
• Histo - adenomcarcinoma that invades into muscle

Question 10

Where are liver mets commonly from?

Answer 10

Colorectal and lung