L29 hepatocellular carcinoma
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Transcript of L29 hepatocellular carcinoma
Hepatocellular Carcinoma
Lecture 27
HCCHepatoma
HCC,,,.2,28,28
Epidemiology• The fifth most common cancer worldwide and the
third most common cause of cancer mortality.• Because of its high fatality rates, the incidence
and mortality rates are almost equal..
HCC
About 82% of HCC cases occur in developing countries with high rates of chronic HBV infection (& HCV), such as in southeast Asian and African countries;
52% of all HCC cases occur in China.
• There is a clear predominance of males with a ratio of 2.4 : 1.
HCC
Risk factors The main risk factors for hepatocellular carcinoma
are;• Alcoholism• Hepatitis B• Hepatitis C (25% of causes globally)• Aflatoxin (Mycotoxin) B1 produced by Aspergillus
flavus• Cirrhosis of the liver• Hemochromatosis• Wilson's disease• Type 2 Diabetes (probably aided by obesity)HCC
• Alpha 1 antitrypsin deficiency• Chemical carcinogens: butter yellow,
nitrosamines• Prolonged immunosuppressive therapy• Other types of viral hepatitis• Tobacco smoking• Parasitic infestations: clonorchiasis,
schistosomiasis
HCC
HCC
Pathogenesis
• Hepatocellular carcinoma develops when
there is a mutation to the cellular machinery that causes the cell to replicate at a higher rate and/or results in the cell avoiding apoptosis.
HCC
UNCERTAIN
PathogenesisFour major etiologic factors associated with
HCC have been established:1. Chronic viral infection (HBV, HCV),2.Chronic alcoholism, 3.Food contaminants (primarily aflatoxins). 4.Non-alcoholic Steatohepatitis (NASH),
HCC
Other conditions include:
• Tyrosinemia, 40%• Glycogen storage disease, • Hereditary hemochromatosis,• Non-alcoholic fatty liver disease, and• α1-antitrypsin deficiency.
HCC
Many factors interact in the development of HCC, including:
• Genetic factors, • Age, • Gender, • Chemicals,• Hormones, and • Nutrition, HCC
Cirrhosis seems to be a prerequisite contributor to the emergence of HCC in Western countries.
HCC
Pathogenesis
• Repeated cycles of cell death and regeneration, in chronic hepatitis damage DNA repair mechanisms and eventually transform hepatocytes &
HCC develops.
HCC
Developing countries (endemic areas)
•Aflatoxin can bind covalently with cellular DNA and cause a specific mutation in p53.
HCC
HCC
HCC may appear grossly as (1) unifocal(2) multifocal, (3) diffusely infiltrative/spreading
cancer,
HCC
1.Unifocal tumorAKA Expanding type, most frequently, it forms a
single, yellow-brown, large mass, most often in the right lobe of the liver with central necrosis, hemorrhage and occasional bile-staining. It may be deceptively encapsulated.
HCC
2.Multifocal type• Less often, multifocal, multiple masses, 3-5 cm in
diameter, scattered throughout the liver are seen.
HCC
3. Infiltrating (Spreading) type
• Rarely, the HCC forms diffusely infiltrating tumor mass.
HCC
• All three patterns may cause liver enlargement, particularly the large unifocal and multinodular patterns.
• The diffusely infiltrative tumor may blend imperceptibly into a cirrhotic liver background.
HCC
HCC
HCC
Liver removed at autopsy showing a unifocal, massive neoplasm replacing most of the right hepatic lobe in a noncirrhotic liver;
HCC
• Lymph node metastases to the perihilar, peripancreatic, and para-aortic nodes above and below the diaphragm are found in fewer than half of HCCs that spread beyond the liver.
HCC
• HCC spreads extensively within the liver by obvious contiguous growth and by the development of satellite (outpost) nodules, which can be shown by molecular methods to be derived from the parent tumor.
HCC
•Metastasis outside the liver is primarily via vascular invasion, especially into the hepatic vein system, but hematogenous metastases, especially to the lung, tend to occur late in the disease.
HCC
• HCCs are usually PALER than the surrounding liver, and sometimes take on a GREEN hue when composed of well-differentiated hepatocytes
capable of secreting BILE.
HCC
HCC
• All patterns of HCCs have a strong propensity for
invasion of vascular structures. Extensive intrahepatic metastases ensue (develop), and occasionally, long, snakelike masses of tumor invade the portal vein (with occlusion of the portal circulation) or inferior vena cava, extending even into the right side of the
heart. HCC
• If HCC with venous invasion is identified in explanted livers at the time of liver transplantation, tumor recurrence is likely to occur in the transplanted donor liver.
HCC
• HCCs range from well-differentiated to highly anaplastic undifferentiated lesions.
I. In well-differentiated and moderately differentiated tumors, cells that are recognizable as hepatocytic in origin are disposed either in a trabecular pattern or in an acinar, pseudoglandular pattern.
HCC
Microscopy
• In the better differentiated variants,
globules of bile may be found within the cytoplasm of cells and in pseudocanliculi between cells.
HCC
Microscopy
• Acidophilic hyaline inclusions within the cytoplasm may be present, resembling Mallory bodies. There is surprisingly scant stroma in most HCCs,
explaining the soft consistency of these tumors.
HCC
II. In poorly differentiated forms, tumor cells can take on a pleomorphic appearance with numerous anaplastic
giant cells, can be small and completely undifferentiated, or may even resemble a spindle cell sarcoma.
HCC
Important diagnostic features are:
1.Histologic patterns2.Cytologic features
HCC
Histologic patterns
i) Trabecular or sinusoidal patterns- is the most common.
The trabecullae are made up of 2-8 cell wide layers of tumors cells separated by vascular spaces or sinusoids which are endothelium-lined.
HCC
Histologic Patterns• ii) Pseudo glandular or acinar
patterns is seen sometimes. The tumor cells are disposed around central cystic space formed by degeneration and breakdown in the trabeculae.
HCC
Histologic Patterns
• iii) Compact pattern resembles trabecular
pattern but the tumor cells form large solid masses with conspicuous sinusoids.
HCC
• iv) Scirrhous pattern is characterised by more abundant fibrous stroma.
HCC
2. Cytologic features:
• The typical cytologic features in the HCC consist of
cells resembling hepatocytes having
vesicular nuclei with prominent nucleoli.
HCC
• The cytoplasm is granular and eosinophilic but becomes increasingly basophilic with
increasing malignancy.
HCC
Aside from these features, a few others cytologic variants are:
• Pleomorphism, • Bizarre giant cell formation, • Spindle-shaped cells,• Tumor cells with clear cytoplasm, • Presence of bile within dilated canaliculi, and• Inracytoplasmic mallory’s hyline.
HCC
HCC
Microscopic view of a well-differentiated lesion; tumor cells are arranged in nests, sometimes with a central lumen. HCC
HCC
HCC
HCC
Fibrolamellar Carcinoma
• This variant constitutes 5% of HCCs. It occurs in young male and female adults (20 to 40 years of age) with equal incidence.
HCC
• Patients usually do not have underlying chronic liver diseases, and so the prognosis is better than the conventional HCC.
HCC
• The etiology of fibrolamellar carcinoma is unknown.
• It usually presents as • single large, hard “scirrhous” tumor with
fibrous bands coursing through it.
HCC
On microscopic examination it is composed of well-differentiated polygonal cells growing in nests or cords, and separated by parallel lamellae of dense collagen bundles. The tumor cells have abundant eosinophilic cytoplasm and prominent nucleoli .
HCC
Fibrolamellar carcinoma. A, Resected specimen showing a demarcated nodule in an otherwise normal liver
HCC
HCC
B, Microscopic view showing nests and cords of malignant-appearing hepatocytes separated
by dense bundles of collagen.
HCC
•Part II,• Lecture 28
HCC
Recap
• The main primary tumor is HCC• More common (82%) in Asia & Africa.• The main etiologic agents for HCC are
hepatitis B, C, alcoholic cirrhosis, hemochromatosis, and more rarely, tyrosinemia.
HCC
• In the western population about 90% of HCC develop in cirrhotic livers;
• In Asia almost 50% of cases develop in noncirrhotic livers.
HCC
• The chronic inflammation and cellular regeneration associated with viral hepatitis may be predisposing factors for development of carcinomas.
HCC
• Hepatocellular carcinomas may be unifocal or multifocal, tend to invade blood vessels, and recapitulate normal liver architecture to varying degrees.
HCC
Clinical Features
• The clinical manifestations of HCC are seldom characteristic and,
• in the Western population, often are masked by those related to the underlying cirrhosis or chronic hepatitis.
HCC
• In areas of high incidence such as tropical Africa, patients usually have no clinical history of liver disease, although cirrhosis may be detected at autopsy.
HCC
• In both populations most patients have• ill-defined upper abdominal pain,• malaise, • fatigue, • weight loss, and • sometimes awareness of an abdominal mass
or abdominal fullness.
HCC
• In many cases the enlarged liver can be felt on palpation, with sufficient
irregularity or nodularity to permit differentiation from cirrhosis.
HCC
• Jaundice,• fever, and • gastrointestinal or esophageal variceal
bleeding are inconstant findings.
HCC
Diagnosis Lab Study
• Elevated levels of serum α-fetoprotein are found in 50% of persons with HCC
HCC
• Recently, staining for Glypican-3 has
been used to distinguish early HCC from dysplastic nodules.
HCC
Imaging studies• Most valuable for detection of small tumors
are imaging studies:• Ultrasonography, • Hepatic angiography, • Computed tomography, and • Magnetic resonance imaging.
HCC
PrognosisOverall, death usually occurs from (1) cachexia, (2) gastrointestinal or esophageal variceal
bleeding, (3) liver failure with hepatic coma, or, rarely, (4) rupture of the tumor with fatal
hemorrhage.
HCC
• The 5-year survival of large
tumors is dismal, with the majority of patients dying within the first 2 years.
HCC
• With implementation of screening procedures and advances in imaging, the detection of HCCs less than 2 cm in diameter has increased in countries where such facilities are available. These small tumors can be removed surgically with good prognostic outcomes.
HCC
Treatment
• Radiofrequency ablation is used for local control of large tumors, and chemoembolization can also be used, according to a clinical algorithm that has been widely adopted.
HCC
• Recent findings show that the kinase
inhibitor sorafenib can prolong the life of individuals with advanced-stage HCC.
HCC
Primary billiary cirrhosisSecondary billiary cirrhosis
HCC
Primary Billiary Cirrhosis
• PBC is an inflammatory autoimmune disease mainly affecting the intrahepatic bile ducts. The primary feature of this disease is a nonsuppurative, inflammatory destruction of medium-sized intrahepatic bile ducts. It is accompanied by portal inflammation, scarring, and eventual development of cirrhosis and liver failure
HCC
Secondary billiary cirrhosis
• Secondary biliary cirrhosis is a condition resulting most often from uncorrected obstruction of the extrahepatic biliary tree.
HCC
HCC
HCC