Hepatic Tumors Flashcards
HCC
HCC is the most common primary malignant tumor of the liver.
It is the fifth most common cancer in men and the eighth most common in women, and it ranks fourth in annual cancer mortality rates
HCC
Male predominance is, however, more obvious in populations at high risk for the tumor (mean male-to-female ratio, 3.7:1) than in those at low or intermediate risk (2.4:1)
HBV
HBV DNA is integrated into cellular DNA in approximately 90% of HBV-related HCCs.1
Risk Factors for HCC
MAJOR RISK FACTORS
Chronic HBV infection Chronic HCV infection Cirrhosis
NAFLD
OTHER LIVER CONDITIONS
α1-Antitrypsin deficiency Hemochromatosis Membranous obstruction of the inferior vena cava Type 1 and type 2 glycogen storage disease Type 1 hereditary tyrosinemia Wilson disease
INHERITED CONDITIONS NOT ASSOCIATED WITH LIVER DISEASE
Ataxia-telangiectasia
Hypercitrullinemia
OTHER FACTORS
Cigarette smoking
Diabetes mellitus
Dietary exposure to aflatoxin B1 Oral contraceptive steroid use
HCC
Possible direct carcinogenic effects include cis-activation of cellular genes as a result of viral integration, changes in the DNA sequences flanking the integrated viral DNA, transcriptional activation of remote cellular genes by HBV-encoded proteins (particularly the X protein), and effects resulting from viral mutations.
The REACH-B (Risk Estimation for Hepatocellular Carcinoma
in Chronic Hepatitis B) score provides a
simple-to-use tool for
risk estimation for HCC among individuals with chronic HBV
infection and includes gender, age, serum ALT level, hepatitis B e antigen status, and serum HBV DNA level.
HCV
In Japan, Italy, and Spain, HCV is the single most common etiologic factor for HCC, and in other industrialized countries, HCV infection, often in combination with alcohol abuse, has emerged as a major cause of the malignancy.
HCV
Almost all HCV-induced HCCs arise in cirrhotic livers, and most of the exceptions are in livers with chronic hepatitis and fibrosis.
Cirrhosis
Risk factors for HCC included
obesity, a low platelet count, and the presence of antibody to hepatitis B core antigen
Aflatoxin B1
Dietary exposure to aflatoxin B1, derived from the fungi Aspergillus flavus and Aspergillus parasiticus, is an important risk factor for HCC in parts of Africa and Asia
Other
Malignant transformation has been attributed to the cirrhosis but may also result from oxidant stress secondary to the accumulation of copper in the liver.
HCC also may develop in patients with other inherited metabolic disorders that are complicated by cirrhosis,
such as α1-antitrypsin deficiency and type 1 hereditary tyrosinemia, and in patients with certain inherited diseases in the absence of cirrhosis—for example, type 1 glycogen storage disease
Key Molecular Pathways Involved in Hepatocarcinogenesis
Angiogenic signaling Epigenetic promoter methylation and histone acetylation Growth factor-stimulated receptor tyrosine kinase JAK/STAT signaling PI3-kinase/AKT/mTOR p53 and cell cycle regulation Ubiquitin-proteasome Wnt/β-catenin
Paraneoplastic Manifestations Associated with HCC
Carcinoid syndrome Hypercalcemia Hypertension Hypertrophic osteoarthropathy Hypoglycemia Neuropathy Osteoporosis Polycythemia (erythrocytosis) Polymyositis Porphyria Sexual changes—isosexual precocity, gynecomastia, feminization Thyrotoxicosis Thrombophlebitis migrans Watery diarrhea syndrome
Diagnosis of HCC
The gold standard for the diagnosis of HCC is pathology.
Dysplastic nodules and even regenerative cirrhotic nodules can be seen on imaging studies and are potentially confused with HCC.
Serum Tumor Markers
Serum tumor markers generally are not diagnostic for HCC by themselves but can be used in conjunction with imaging findings to diagnose HCC.
Additionally, they may raise the suspicion of HCC and lead to more sensitive and serial imaging of the liver.
Conventional liver biochemical tests do not distinguish HCC from other hepatic mass lesions or cirrhosis.
AFP
AFP is an α1-globulin normally present in high concentrations in fetal serum but in only minute amounts thereafter.
____can potentially be used for the diagnosis of HCC, surveillance, and prognostication.
Measurement of AFP
can be considered diagnostic for HCC in an appropriate clinical context.
Although there is no specific diagnostic cutoff, values above 400 ng/mL in association with a liver mass can be considered diagnostic in most cases.
Clearly, markedly elevated AFP levels (>10,000 ng/mL to > 1,000,000 ng/mL)
serum AFP levels appear to have some prognostic utility,
particularly with regard to LT, for which levels above 1000 ng/mL have been associated with poorer outcomes and higher rates of tumor recurrence.
False-positive AFP results (for HCC)
also may occur in patients with tumors of endodermal origin, non-seminomatous germ cell tumors, pregnancy, and regenerating livers in the set- ting of ALF.
Fucosylated AFP
AFP is heterogeneous in structure. Its microheterogeneity results from differences in the oligosaccharide side chain and accounts for the differential affinity of the glycoprotein for lectins.
Des-γ-Carboxy Prothrombin
Serum concentrations of des-γ-carboxy prothrombin (DCP) (also known as prothrombin produced by vitamin K absence or antagonist II) are raised in most patients with HCC.
DCP is an abnormal prothrombin that is thought to result from a defect in the post-translational carboxylation of the prothrombin precursor in malignant cells
Imaging
The diagnosis of HCC generally requires imaging evidence of a focal lesion in the liver, although large infiltrating lesions can also be diagnostic.
Arterial hyperenhancement, particularly seen on dynamic contrast imaging of the liver, is observed because the blood supply of HCC comes from newly formed abnormal arteries (neoangiogenesis).
as a nodule transforms from low- to high-grade dysplasia and then to HCC, the primary blood supply shifts from portal to arterial;
new abnormal arterial branches produce characteristic findings on dynamic contrast imaging of the liver and subsequent hypoenhancement in the portal venous and delayed phases (“washout”)
HCC
European and American liver societies recommend
noninvasive diagnosis of HCC can be made in a nodule greater than 1 cm in diameter that demonstrates arterial hyperenhancement and portal venous or delayed washout.
The LI-RAD categories
assist the clinician in assessing the risk that a nodule is HCC, with LI-RAD 3 being intermediate risk, LI-RAD 4 probable HCC, and LI-RAD 5 definite HCC.
smaller tumors (<5 cm) are most often hypoechoic
and may demonstrate a thin peripheral fibrous capsule.
Small HCCs can also be uniformly hyperechoic and therefore indistinguishable from focal fat or a hemangioma
Multiphase (also called dynamic) multidetector CT
is the most popular imaging technique for the diagnosis of HCC
The classic and most diagnostic pattern for HCC is a combination of hyperenhancement in the arterial phase (with the uninvolved liver lacking enhancement), loss of central nodule enhancement compared with the enhancing uninvolved liver (washout), and capsular enhancement in the portal-venous and delayed phases
HCC
Guidelines recommend biopsy of lesions
larger than 1 cm and serial imaging for lesions smaller than 1 cm that do not have characteristic arterial enhancement and washout
Dynamic CT
is also useful for detecting invasion into the portal or hepatic veins and identifying the location and number of tumors; these findings are critical for planning treatment
Dynamic MRI using gadolinium contrast agents (extracellular)
provides another way of distinguishing HCC from normal liver
tissue.
HCC may take 1 of 3 forms:
nodular, massive, or diffusely infiltrating.
The nodular variety of HCC
is most common and usually coexists with cirrhosis.
It is characterized by numerous round or irregular nodules of various sizes scattered throughout the liver;
some of the nodules are confluent.
