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liver CA path
GI
42
Medical
Graduate
09/15/2010

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Term
what is focal nodular hyperplasia? how does it appear?
Definition
a subcapsular grayish white mass often consisting of fibrosis in the center w/broad strands radiating in a *stellate formation* (can help differentiate it from CA). focal nodular hyperplasia may be pedunculated.
Term
what characterizes incidence of focal nodular hyperplasia?
Definition
focal nodular hyperplasia is *usually asymptomatic, often found as an incidental finding. it is more common in females >40 yrs and found typically to be solitary, though *occasionally focal nodular hyperplasia can be multicentric (this indicates other possible vascular malformations/CA in the body, esp the brain)
Term
are all components of the liver lobule present with focal nodular hyperplasia?
Definition
yes
Term
how does focal nodular hyperplasia affect hepatocytes?
Definition
some *hepatocytes may increase in glycogen and fat* - this may be what gives it the change in appearance from reddish-brown to yellowish-orange
Term
what characterizes the fibrosis seen in focal nodular hyperplasia?
Definition
there may be acute/chronic inflammation present, it *may represent a cirrhosis-like regenerative response following a localized liver injury* as the fibrous septa divide the lesion into lobules resembling cirrhosis (*but cirrhosis is more generalized).
Term
is there a genetic component to focal nodular hyperplasia?
Definition
yes there is an associated presence of the ras oncogene product p21
Term
what is a general difference between focal nodular hyperplasia and liver cell adenoma?
Definition
focal nodular hyperplasia is more of a reactive change and liver cell adenoma is more of a neoplastic change
Term
what are some associations with liver cell adenoma?
Definition
liver cell adenoma generally affects more women (> 30) and there is a *strong association with oral contraceptive use. there are also associations with some *glycogen storage diseases and *anabolic steroid use.
Term
how do liver cell adenomas present?
Definition
liver cell adenomas are *often symptomatic and can lead to life-threatening hemoperioneum
Term
how do liver cell adenomas appear?
Definition
they can be multiple, but usually solitary. they usually have a *well-defined capsule which is *sharply demarcated from surrounding liver tissue by color change. there is *no central scar. *hepatocytes are well-differentiated and contain *eosinophilic cytoplasm - however there are no portal triad, central veins or connections to the biliary system (haphazard arrangement)*. liver cell adenomas can mimic a well differentiated liver cell CA.
Term
what kinds of hormone receptors are found in liver cell adenomas?
Definition
estrogen/progesterone receptors in 75% of cases, androgen receptors in 20%
Term
what is the malignant potential for liver cell adenomas and focal nodular hyperplasia?
Definition
very low
Term
between liver cell adenomas and focal nodular hyperplasia, which is more vascular? which has more potential for necrosis?
Definition
liver cell adenomas: more necrosis
focal nodular hyperplasia: more vascularity
Term
what characterizes incidence of liver cell CA/hepatocellular CA?
Definition
liver cell CA is relatively rare in the US, more common in africa/southeast asia. generally *males over 50 w/cirrhosis are affected. incidence is increasing due to the increase of incidence of hep C
Term
how do pts with liver cell CA present?
Definition
abdominal pain, ascites, and hepatomegaly - and if tumor invades the common bile duct, jaundice may be present. *serum elevation of AFP (alpha fetoprotein) is seen in many cases
Term
what are some of the common risk factors for liver cell CA?
Definition
hep B/C, cirrhosis (if pre-existing, and liver CA occurs - worse prognosis), liver cell dysplasia, adenomatous dysplasia, thorium dioxide exposure, anabolic steroid use, OCP and other progestational agents, alpha1 antitrypsin deficiency (esp the PIZ variant), tyrpsinemia (a chronic form of inborn metabolism error), ataxia-telangiectasia (congenital immune deficiency), and aflatoxins (metabolic products of aspergillus-contaminated food)
Term
what are the gross features of liver cell CA?
Definition
liver cell CA may present as multiple nodules (mimics metastasized CA - typical outcome of cirrhotic livers), a single mass, diffuse liver involvement, or a large mass replacing the majority of the liver, there *may be a capsule, tumor size varies, and portal vein thrombosis is found in many advanced cases (liver cell CA is one of the CAs that can spread hematogenously rather than through lymph).
Term
what is seen in liver cell CA, that is not seen in focal nodular hyperplasia or liver cell adenomas?
Definition
necrosis and hemorrhage. heterogeneous cut surface.
Term
what are the histologic features of liver cell CA?
Definition
trabecular/solid/tubular growth patterns - the thicker the trabeculae, (the more likely that lesion is CA). there may be a great range of differentiation among tumor cells, those poorly differentiated show great pleomorphism w/bizarre mitotic figures and giant tumor cells. well differentiated tumors may be difficult to distinguish from benign lesions. there may be mallory bodies, globules containing AFP/alpha1-antitrypsin, Cu, bile pigment (golden-brown), and there may be focal neuroendocrine differentiation. tumor islands may also form, which break off from hepatocytes and consist of high N/C ratio, large nuclei & nucleoli
Term
what are some of the genetic associations w/liver cell CA?
Definition
aflatoxin can bind to DNA and mutate p53, viral hepatitis may disrupt the cellular genome, there may be point mutations in KRAS, p53, c-MYC expression, and TGF alpha and there may be activation of WNT or AKT pathways.
Term
what are the different kinds of liver cell CA?
Definition
clear cell, sclerosing, small cell, lymphoepithelioma, sarcomatoid, mixed hepatocarcinom-cholangiocarcinoma, and fibrolamellar
Term
what characterizes the clear cell type of liver cell CA?
Definition
these make up about 9% of liver cell CA, high association with female pts and *cirrhosis. the *cytoplasm is clear due to glycogen and fat.
Term
what characterizes the sclerosing type of liver cell CA?
Definition
sclerosing liver cell CA often *follows therapy, may be *associated w/PTH-like protein and feels hard upon palpation
Term
what characterizes the small cell type of liver cell CA?
Definition
small cell liver cell CA consists of small cells growing in *broad nests. they are positive for *low molecular wt keratin and positive for *AFP
Term
what characterizes the lymphoepithelioma type of liver cell CA?
Definition
the lymphoepithelioma type of liver cell CA resembles the *nasopharyngeal lesion and is **related to EBV**
Term
what characterizes the sarcomatoid type of liver cell CA?
Definition
the sarcomatoid type of liver cell CA contains *spindle cells or *multinucleated cells. they may also contain *osteoclast-like giant cells, bone, cartilage and skeletal muscle*
Term
what characterizes the mixed hepatocarcinoma-cholangiocarcinoma type of liver cell CA?
Definition
the mixed hepatocarcinoma-cholangiocarcinoma type of liver cell CA has dual differentiation into liver cell and bile duct lines, which occurs at both the morphologic and immunohistochemical level. there are *ductular formations lined by tumor cells resembling hepatocytes rather than bile duct cells.
Term
what characterizes the fibrolamellar type of liver cell CA? (*know this*)
Definition
the fibrolamellar type of liver cell CA is seen mostly in *young pts, is *not associated with cirrhosis, and has a *generally favorable prognosis
Term
how does fibrolamellar type of liver cell CA present histologically?
Definition
there is fibrosis seen arranged in lamellar (layer-like) fashion around neoplastic hepatocytes (similar but *not cirrhosis). the tumor cells are *polygonal and have *eosinophilic cytoplasm (not the typical rectangular/square shape of most hepatocytes). collagen I, III, and V are most prominent and there are *abundant mitochondria (add to eosinophilia).
Term
what characterizes the spread of liver cell CA?
Definition
liver cell CA often spreads through the *portal venous system. metastasis may also occur in the pulmonary arterial tree of the lungs, in the hepatic vein, in the inferior vena cava and the right atrium. lymph node and diaphragm involvement may also occur.
Term
what factors are involved in liver cell CA prognosis?
Definition
stage (how far it has spread), size (smaller the tumors, the better the prognosis), encapsulation (capsule = better), number of tumors (single mass = better), portal vein involvement (worse), increased pleomorphism/mitotic figures (worse), cirrhosis (worse), high AFP levels (worse), and c-myc amplification (worse)
Term
what characterizes incidence of hepatoblastoma?
Definition
hepatoblastoma is less common than liver cell CA, seen mostly in infants and associated with a variety of congenital anomalies (such as virilization from ectopic sex hormone) - there is *no relationship with cirrhosis, however serum AFP is often elevated.*
Term
how do hepatoblastomas appear grossly/histologically?
Definition
grossly: solid, well-circumscribed and usually initially solitary then multiple later. heterogenous cut surface w/possible bone, cartilage, epithelial etc elements along w/hemorrhage/necrosis. histologically: *immature hepatocyte (hepatoBLASTOMA) elements and *foci of extramedullary hematopoiesis (nucleated RBCs in the liver).
Term
what are the 2 types of hepatoblastoma?
Definition
*mixed epithelial & mesenchymal type: contain a stromal component which may develop to bone/cartilage. *epithelial type: composed of polygonal fetal cells/smaller embryonal cells.
Term
what are genetic associations for hepatoblastomas?
Definition
frequent activation of the **WNT/beta-catenin signaling pathway. chromosomal abnormalities such as **FOXG1 (regulator of TGF-beta). some association w/FAP
Term
what is the most common benign tumor of the liver?
Definition
hemangiomas, which are well-circumscribed, spongy red purple lesions - most of which are cavernous type w/dilated vascular spaces. rarely, spontaneous bleeding can occur - leading to thrombocytopenic purpura (often found incidentally)
Term
what characterizes an angiosarcoma as found in the liver?
Definition
angiosarcomas are characterized by *free anastomosing vascular channels w/marked variation in their degree of differentiation - vascular channels may still be visible or completely obliterated (*look more solid than spongy). if the lesion is poorly differentiated, it may resemble a variety of other tumors and *may not resemble a vascular lesion. it may be identified by *factor VIII related antigen and other endothelial markers*.
Term
what are the risk factors for angiosarcoma of the liver?
Definition
cirrhosis (macronodular, associated with hemochromatosis), vinyl chloride exposure (component of many plastics such as water pipes, & building materials, generally produces multicentric, hemorrhagic, necrotic areas, usually fatal), thorium dioxide exposure (old contrast medium, may be combined with liver cell cancer or cholangiocarcinoma), and arsenic exposure (in fowler's solution)
Term
how does angiosarcoma appear histologically?
Definition
spindle-like cells, vague vascular lumen formation, dense areas of tumor infiltration, anaplastic
Term
what are the majority of malignant liver tumors?
Definition
metastatic from the bowel, lung, breast, pancreas, kidney, and stomach
Term
how might tumors from the gallbladder, extrahepatic bile ducts and pancreas spread to the liver?
Definition
direct expansion
Term
how do metastatic tumors in the liver appear?
Definition
usually multiple, they can be large, the capsule may be raised by these discrete masses, and some may have central necrosis w/umbilication (dimple in middle) in larger lesions, esp those tumors arising from large bowl CA where mucin production is abundant
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