Path: hepatic and biliary tumors

Question 1

Neoplasms and tumor-like lesions

Answer 1

• Benign: usually present as a mass in ASx individual w/ no prior liver disease
• Liver cell adenoma, focal nodular hyperplasia, cavernous hemangioma
• Malignant: hepatocellular CA, cholangioCA
• Mets
• Neoplasms of GB and extra hepatic bile ducts

Question 2

Liver cell adenoma 1

Answer 2

• Uncommon, usually single mass in a non-cirrhotic liver
• Association: OCPs (estrogen), androgens
• Hepatocyte responsible for metabolizing estrogen, and lots of estrogen somehow causes hepatocyte proliferation
• Almost all are in women (middle aged, on OCPs for several years)
• Labs are usually nl (never elevation of AFP, possible to see elevation of AST/ALT/AP)
• Pain can occur if adenoma outgrows its blood supply and undergoes necrosis

Question 3

Liver cell adenoma 2

Answer 3

• Gross: circumscribed yellow-brown mass, may have necrosis/hemorrhage
• Histo: composed of cytologically normal hepatocytes, only way to tell if its adenoma is that the sample was from a single mass (multiple masses in 20%)
• Liver cords are one or two cells thick, may have fatty change, and hepatocytes are slightly larger than nl liver cells
• Usually just stop OCP and mass begins to subside, but often are indications for removal due to fear of hemorrhage/necrosis
• Rarely malignant transformation to HCC occurs

Question 4

Focal nodular hyperplasia (FNH) 1

Answer 4

• Usually a single mass, found mostly in women (middle age), no risk of malignant transformation, usually conservative management
• Most are ASx, but some have RUQ pain
• Liver test usually nl (nl AFP), mass takes up technetium (adenomas do not)
• Pathogenesis: repeated thrombosis of hepatic arteries (intimal thickening) leads to ischemia of nearby cells, are resultant hyperplasia of other hepatocytes in compensation

Question 5

Focal nodular hyperplasia (FNH) 2

Answer 5

• Gross: light tan mass w/ central radiating fibrous septum
• Micro: fibrous structures radiating from abnormal portal tracts w/ variable lymphocytic infiltration, increased vascularity, and may have bile duct proliferation
• Hepatocytes are nl in size and cords 1-2 cells thick (is a polyclonal expansion: hyperplasia)

Question 6

Cavernous hemangioma

Answer 6

• Benign vascular lesions w/ communicating vascular spaces of variable size lined by endothelial cells
• Most frequently in middle age women, most pts are ASx
• Sx include abd swelling, RUQ pain/mass
• Micro: numerous congested vascular spaces, often quite large but variable in size
• Vascular spaces are lined by endothelial cells and separated by stroma of collagen
• Usually conservative management

Question 7

HCC 1

Answer 7

• Most common primary hepatic tumor in adults, composed of malignant hepatocytes that form thick (>3 cells thick) hepatic trabeculae
• Most often associated w/ underlying chronic liver disease e.g. cirrhosis (but 15% found in nl liver)
• Associated etiologies: CHB, CHC infections, alcoholic cirrhosis, hemochromatosis, toxins (aflatoxin from aspergillus), drugs (androgens, OCPs)
• CHB to HCC is different from CHC/alcholoic cirrhosis since a large amount of pts w/ HCC from CHB did not have cirrhosis (where as most pt w/ HCC from CHC/etoh go to cirrhosis first), thanks to HBV being a DNA virus (DNA planted in host genome)
• Clinical presentation of HCC: usually just epigastric discomfort/fullness, if pts have cirrhosis can have complications from that

Question 8

HCC 2

Answer 8

• Often pts w/ compensated cirrhosis who decompensated (recurring ascites/pain) will often have HCC
• Labs: AFP is most useful marker, will be constantly very high in HCC (>500)
• AFP also can be high in cirrhosis, but it fluctuates so may be >500 one day but then falls below 500 a few days later
• Steadily elevated or rising AFP in a cirrhotic pt indicated HCC
• AST/ALT have variable degrees of elevation
• HCC should be suspected in alcoholic cirrhosis who stopped drinking for a long period of time and suddenly develops liver failure

Question 9

Hereditary hemochromatosis and HCC

Answer 9

• Autosomal recessive mutations of HFE gene lead to hepcidin dysfxn (low hepcidin in presence of Fe overload) lead to Fe deposition in organs
• Liver cirrhosis occurs over time, and up to 1/3rd of them develop HCC
• Also damages pancreas (DM), heart (cardiomegaly and HF), joints (chondrocalcinosis and arthritis), skin (bronzing of skin)
• Only cure is phlebotomy, but once a pt is cirrhotic from HH it does not lower their risk for HCC

Question 10

Path of HCC

Answer 10

• Gross: usually a cirrhotic liver w/ areas of hemorrhage w/in large nodules, may see necrosis, often multifocal (multiple masses in cirrhosis-> HCC UPO)
• Micro: characteristic feature is thickened hepatic cords to >3 cells thick (usually 5-6)
• Hepatocytes large and hyper chromatic
• Variable trabecular networks, depending on degree of differentiation, and sinusoids lined by endothelial cells
• Trabecular subtype by far most common
• May be underlying fatty change, bile and mallory bodies may be seen, sometimes see formation of pseudo-glands
• Rx: surgical resection w/ chemoRx, Tx, poor outcome

Question 11

Fibrolamellar HCC

Answer 11

• Usually single mass and in non-cirrhotic livers, mean age is 23
• Sx: N/V, abd pain/distension
• Labs non-diagnostic, AFP usually not elevated
• Rx is resection, better prognosis than trabecular HCC
• Histo: fibrous bands of collagen btwn the thickened tumor cell cords, can see “pale body” inclusions (thought to be fibrinogen)

Question 12

CholangioCA

Answer 12

• An adenoCA that arises from intra and extra hepatic bile ducts
• Composed of glands or tubules growing w/in a moderate or abundant fibrous stroma
• Etiologies: fibrocystic disease, PSC, chronic UC, recurrent pyogenic cholangiohepatitis, infection/parasites, drugs/toxins
• Clinical: mostly middle-elderly men, abd pain, ascites/edema, jaundice, mass
• Labs: AP usually elevated, may have elevated bili
• Micro: variability in differentiation, but can see many large glands w/in a fibrous stroma, may see synthesis of mucin, can have perineural invasion
• Rx: only resection, bad prognosis

Question 13

Mets to liver

Answer 13

• Much more common than primary liver CA, usually from colon, lung, breast
• These lesions maintain the morphology of the primary neoplasm, are usually multifocal but can present as single mass (i.e. CRC)
• Often see tumor cells w/in portal tract or sinusoids
• See keratin pearls in squamous, dark melanin deposits in melanoma

Question 14

Gallbladder CA

Answer 14

• Usually female, older age, usually have stones
• In pts w/ cholelithiasis only those w/ calcified GB have high risk of GBCA, thus calcified GBs should be removed
• Clinically similar to cholelithiasis: RUQ pain, N/V, jaundice, anorexia, weight loss
• Labs: high bili and AP
• Rx is resection and chemoRx, decent prognosis
• Most common form is adenoCA

Question 15

CCA of extra hepatic bile ducts

Answer 15

• Cholelithiasis present in >20%, CCA usually silent until obstructive jaundice occurs, often have palpable GB and hepatomegaly
• Ampullary CA may present w/ hematemesis, melena, Fe def anemia
• May present w/ intermittent episodes of jaundice (sloughing of tumor)
• Most are adenoCA occurring in hepatic duct or CBD
• Rx is resection, poor prognosis