Liver Cancer. Hepatocellular carcinoma is the sixth most common cancer worldwide in terms of numbers of cases. It is the third most common cause of death.

Liver CancerLiver Cancer

Hepatocellular carcinoma is the sixth most common cancer worldwide in Hepatocellular carcinoma is the sixth most common cancer worldwide in terms of numbers of cases. It is the third most common cause of death from terms of numbers of cases. It is the third most common cause of death from

cancer (third to lung and gastric cancer). cancer (third to lung and gastric cancer).


From: Global Cancer Statistics, 2002 -- Parkin et al_ 55 (2) 74 -- CA A Cancer Journal for Clinicians

The remaining malignant tumors are fibrolamellar carcinoma, intrahepatic cholangiocarcinoma (10% to 25% of liver cancers), cystadenocarcinoma,

angiosarcoma, hepatoblastoma, and undifferentiated embryonal sarcoma.

Worldwide, the major risk factors for liver cancer are infection with the hepatitis B and C viruses.

More than 75% of cases worldwide, and 85% of cases in developing countries, are caused by these two viruses.


From: Global Cancer Statistics, 2002 -- Parkin et al_ 55 (2) 74 -- CA A Cancer Journal for Clinicians

Frequency:

• 82% of cases (and deaths) are in developing countries (55% in China alone).

• The areas of high incidence are sub-Saharan Africa, eastern and southeastern Asia, and Melanesia.

• The incidence is low in developed areas, Latin America, and southcentral Asia.


• HCC is a malignant tumor of

hepatocellular origin.

• Grossly, HCC can undergo hemorrhage

and necrosis because of a lack of

fibrous stroma.

There are 3 growth patterns of HCC:

1.1. Solitary massSolitary mass - Often large

2.2. Multifocal or nodular patternMultifocal or nodular pattern -

Multiple nodules

3.3. DiffuseDiffuse - Multiple, small foci

scattered diffusely throughout the

liver

Liver CancerLiver CancerClinical presentation

variesvaries among high-incidence and low-incidence regions:

1.1. In high-incidence regionsIn high-incidence regions (ie, Asia, Africa), clinical

presentation of HCC tends to be aggressive and includes

bleeding, hepatic rupture, and hemoperitoneum.

In high-incidence regions of the world, the male-to-female ratio is approximately 8:1. In low-incidence regions, the male-to-female ratio is approximately 2:1.

In high-incidence regions of the world, patients present at age 30-50 years. In low-incidence regions, patients present at age 70-80 years.

(Patients with cirrhosis may present earlier)

2. 2. In low-incidence regionsIn low-incidence regions (ie, Western Hemisphere), clinical presentation of HCC

tends to be less aggressive and includes symptoms such as fever of unknown

origin, abdominal pain, malaise, weight loss, and hepatomegaly. Jaundice

is rare.

Liver CancerLiver CancerPreferred Examination:

Imaging studies are an important part of diagnosing Imaging studies are an important part of diagnosing HCCHCC, but which imaging , but which imaging procedure is used differs in the United States versus the rest of the world.procedure is used differs in the United States versus the rest of the world.

• Most studies screening for HCC have been performed outside the United States where ultrasound combined with AFP measurement achieves greater sensitivity and specificity than other methods.

• In contrast, in a recent study of United States patients with advanced cirrhosis, spiral CT was found to have an 88% sensitivity for detecting HCC, which was significantly better than the 59% sensitivity of abdominal US.

From: Hepatocellular carcinoma. A concise guide to its status and management Scott C. Ulmer, MD; POSTGRADUATE MEDICINE VOL 107 / NO 5 / 2000

• Fine-needle biopsy of the mass should always be considered when the diagnosis is unclear, but theoretically, it carries risks for percutaneous needle tract seeding of tumor and bleeding.

Radiologic evidence of Radiologic evidence of cirrhosiscirrhosis, , vascular invasionvascular invasion, or , or multifocal multifocal diseasedisease is is typical typical inin hepatocellular carcinoma hepatocellular carcinoma..

Liver CancerLiver CancerPreferred Examination:

Liver CancerLiver CancerUltrasound

• US appearance of HCC is variable.

• The quality of a US examination is operator dependent.


Liver US: large HCC with involvement of right hepatic vein

(white arrows: hepatic veins)

Vascular invasionVascular invasion


The 3-D US is useful in the demonstration of continuity of the intranodular vessels. This application provides better understanding of the hemodynamic vasculature in a tumor

Liver CancerLiver CancerCT Findings:

CT appearance of HCC varies depending on tumor size and the imaging phase.CT appearance of HCC varies depending on tumor size and the imaging phase.

1. Unenhanced CT typically reveals an iso-hypodense mass. If the mass is large, central areas of necrosis may be seen.

2. In the hepatic-arterial phase, lesions typically are hyperdense (relative to hepatic parenchyma) as a result of hepatic-arterial supply. Larger tumors may have necrotic central regions that typically are hypodense.

3. In the portal-venous phase, small lesions may be isodense or hypodense and difficult to see, since the remainder of the liver increases in attenuation. Larger lesions with necrotic regions remain hypodense.

4. In the delayed-postcontrast phase, small lesions may be inconspicuous on late phases. Delayed phase scans may show a tumor capsule, one of the more specific signs indicating HCC.


Micro - HCC

(a) precontrast CT scan demonstrates a hypoattenuating mass

(b) arterial-phase spiral CT scan showed the mass as a hypervascular area

(c) portal-phase CT scan demonstrate a hypoattenuating mass.


From: Discrimination of Small Hepatic Hemangiomas from Hypervascular Malignant Tumors … Tonsok Kim et al. Radiology. 2001;219:699-706

Small HCC, with a typical finding and washout.

Transverse hepatic arterial phase CT image of midliver. The mass enhances fairly

homogeneously but much less than the aorta.

Portal venous phase image at the same level. The mass is now hypoattenuating to

the liver and blood pool.


Unenhanced and contrast-enhanced axial scans:

In the unenhanced upper images a huge, mildly, inhomogenously attenuating mass can be seen in the right lobe of the liver, which enhances inhomogenously (in the lower two pictures).


Solitary HCC

(a) Transverse nonenhanced CT scan shows a large mass (arrows) in the left lobe that is hypoattenuating to the liver.

(b) Transverse CT scan obtained during the hepatic arterial phase after bolus injection of contrast material demonstrates heterogeneous enhancement of the tumor (arrows).

(c) Transverse CT scan obtained during the portal venous phase demonstrates the heterogeneous tumor and thrombosis of the left portal vein (arrow).

From: Hepatocellular Carcinoma in Noncirrhotic Liver: CT, Clinical, and Pathologic Findings in 39 U.S. Residents Giuseppe Brancatelli et al. Radiology 2002;222:89-94


From: Hepatocellular Carcinoma in Noncirrhotic Liver: CT, Clinical, and Pathologic Findings in 39 U.S. Residents Giuseppe Brancatelli et al. Radiology 2002;222:89-94

Multifocal HCC

(a) Transverse nonenhanced CT scan shows multiple, hyperattenuating lesions (solid arrows) with a central hypoattenuating, necrotic portion (open arrow), well seen in the largest lesion.

(b) Transverse CT scan obtained during the hepatic arterial phase after bolus injection of contrast material shows hyperattenuation of the lesions (arrows). The central portions remain hypoattenuating.

(c) Transverse CT scan obtained during the portal venous phase shows that the mass is isoattenuating to the liver parenchyma. Note the capsule (arrows) around the largest lesion.


MRIMRI is less sensitive than angiographically assisted helical CT in is less sensitive than angiographically assisted helical CT in diagnosing diagnosing HCCHCC and is currently used to further characterize the and is currently used to further characterize the

disease within a nodular liver.disease within a nodular liver.

MRI Findings:

• HCC on T1-weighted images may be isointense, hypointense, or

hyperintense relative to the liver.

• On T2-weighted images, HCC usually is hyperintense.

• Gadolinium-enhanced MRI typically demonstrates that HCCs enhance,

usually in the arterial phase and particularly if they are small.

• Pre- and postcontrast MRI has a 70-85% chance of detecting a solitary

mass of HCC.

Liver CancerLiver CancerMRI Findings:

MR imaging appearance of an HCC with a tumor capsule in a noncirrhotic liver.

(a) Axial fat-saturated T2-weighted fast SE image shows an HCC with predominantly high signal intensity (arrow). Owing to its fibrotic nature, the tumor capsule has low signal intensity on T2-weighted images and therefore is not visible.

(b) Axial gadolinium-enhanced 3D GRE image obtained during the arterial phase shows intense, nearly homogeneous enhancement of the lesion (arrow). This appearance may simulate FNH.

(c) Axial gadolinium-enhanced 3D GRE image obtained during the delayed phase shows enhancement of the tumor capsule surrounding the lesion (arrow), which demonstrates complete washout.

From: Focal Nodular Hyperplasia: Findings … Shahid M. et al. Radiographics. 2004;24:3-17


MR imaging appearance of an HCC with a central scar:

(a) Axial fat-saturated T2-weighted fast SE image shows a predominantly high-signal-intensity lesion with a low-signal-intensity central scar.

(b) Axial gadolinium-enhanced fat-saturated 2D T1-weighted GRE image obtained during the delayed phase shows washout of contrast material in most of the lesion and an enhanced tumor capsule. The central scar remains mainly unenhanced.

MRI Findings:

From: Focal Nodular Hyperplasia: Findings … Shahid M. et al. Radiographics. 2004;24:3-17

Liver CancerLiver CancerScreening for Liver TumorsScreening for Liver Tumors• SSerum alpha-fetoprotein (AFP)erum alpha-fetoprotein (AFP) levels are elevated in

many patients with HCC. However, AFP measurement is not an ideal test because it lacks both sensitivity and specificity.

• Real-time Real-time USUS is the most cost-effective modality for is the most cost-effective modality for evaluating patients with HCC.evaluating patients with HCC.

• Modifications in CT have increased its sensitivity in patients with HCC from 50% or 60% to more than 90%.

• In North America, screening for HCC in patients with In North America, screening for HCC in patients with HCV infection is widely accepted by hepatologists. HCV infection is widely accepted by hepatologists. In general, patients are screened by AFP In general, patients are screened by AFP measurements and measurements and USUS every 6 to 12 months.every 6 to 12 months.

• In patients with equivocal findings on CT, MRI is useful for its ability to accurately identify fatty infiltration and small HCCs

A) CT scan demonstrates no focal liver lesion.

B) Gadolinium DTPA-enhanced MRI reveals multiple focal enhancing liver lesions consistent with multifocal HCC (arrows).

Liver CancerLiver CancerCommon presenting symptoms and physical examination findings in hepatocellular carcinoma

Finding Average incidence (%)

Symptom

Abdominal pain 91

Abdominal swelling 43

Weight loss 35

Weakness 31

Feeling of fullness and anorexia 27

Vomiting 8

Jaundice 7

Physical examination

Hepatomegaly 89

Splenomegaly 65

Ascites 52

Jaundice 41

Fever 38

Hepatic bruit 28

From: Flickinger et al

Metastatic Liver TumorsMetastatic Liver Tumors


• The liver is the second most commonly involved organ by metastatic The liver is the second most commonly involved organ by metastatic disease, after the lymph nodes. disease, after the lymph nodes.

• In Europe and the United States, a focal liver lesion is more likely to represent a metastatic deposit than a primary malignancy.

• The liver may be the site of metastasis from virtually any primary malignant neoplasm, but the most common primary sites are the eye, colon, stomach, pancreas, breast, and lung.

• In children, the most common liver

metastases are from a neuroblastoma,

a Wilms tumor, or leukemia.


• Most liver metastases are multiple, involving both lobes in 77% patients, and only 10% are solitary.

• Multiple tumors often vary in size.

• Growing metastases compress adjacent liver parenchyma, causing atrophy and forming a connective tissue rim.

• Large metastases often outgrow their blood supply, causing hypoxia and necrosis at the center of the lesion.


CT is the examination of choice for evaluating liver metastases.CT is the examination of choice for evaluating liver metastases.

• Metastases may appear in a multitude of ways on CT scans.

• The majority of liver metastases are hypovascular (hypoattenuating) The majority of liver metastases are hypovascular (hypoattenuating) compared with surrounding parenchyma compared with surrounding parenchyma

Two rim enhancing metastases of lung cancer are present in the liver in contrast enhanced CT scan.

CT scan with contrast - metastases from a colonic adenocarcinoma.


CT examination: Unenhanced axial scans: Numerous, mostly round-shaped

hypodens lesions of different size are visible in both lobes of the liver.

CT examination: Postcontrast axial scans: The focal lesions are more prominent due

to contrast-enhancement of the normal parenchyma.

• During portal venous scanning, the attenuation of the normal liver parenchyma increases, revealing the relatively hypoattenuating metastases


• Hyperattenuating Hyperattenuating lesions due to lesions due to increased tumor increased tumor vascularity are vascularity are uncommon. uncommon.

• On arterial phase enhanced scans, these vascular metastases show homogenous enhancement compared with the surrounding liver

Arterial phase CT scan - metastases from a brest cancer


Hypervascular masses in patients with known hypervascular primary tumors Hypervascular masses in patients with known hypervascular primary tumors ((such such as renal cell carcinomas, pancreatic islet cell tumors, pheochromocytomas, as renal cell carcinomas, pancreatic islet cell tumors, pheochromocytomas, melanomas, and breast carcinomasmelanomas, and breast carcinomas)) should be regarded as metastasis until should be regarded as metastasis until

proven otherwise. proven otherwise.

48-year-old woman with hypervascular hepatic metastases (neuroendocrine primary tumor).

Arterial phase CT scan shows multiple hyperenhancing masses in liver.

From: CT of Focal Nodular Hyperplasia of the Liver Stephanie K et al. AJR 2000; 174:705-712


• The US appearance of liver

metastases is nonspecific. • However, the presence of

multiple hepatic nodules of

different sizes within the

liver is nearly always due to

metastases. • The echogenicity is

dependent on tumor

vascularity; the cellular

composition; the degree of

tissue invasion; and the

presence or absence of

necrosis, fibrosis and fatty

change.

Multiple metastases in the liver.

Ultrasound


Growing metastases compress adjacent liver parenchyma, causing atrophy and forming a connective tissue rim.


Large metastases often outgrow their blood supply, causing hypoxia and necrosis at the center of the lesion.


Approximately one half the patients with liver metastases have clinical signs of hepatomegaly or ascites


MRI Findings

• Liver metastases have a variety of appearances on MRI.

• Most liver tumors benign or malignant appear as hypointense lesions

on T1-weighted images and hyperintense lesions on T2-weighted

images.

(There are a few exceptions to this rule, for example, metastatic melanoma,

which exhibits high signal intensity on T1-weighted MRIs relative to the liver)

• Heavily T2-weighted images are useful in differentiating Heavily T2-weighted images are useful in differentiating

hemangiomas and cystshemangiomas and cysts because the signal intensity is higher in

these benign lesions as compared with liver metastases.


The patient has known colon carcinoma with liver metastases. T1 (left) and (right) T2 axial images of the liver.


From: Spectrum of MRI Appearances of Untreated Metastases of the Liver Ioana-Maria IM et al. AJR 2003; 181:809-817

Hypervascular metastases from carcinoid tumorcarcinoid tumor

• Axial T2-weighted image shows multiple areas of moderate hyperintensity.

• Unenhanced axial T1-weighted image shows corresponding areas of moderate hypointensityareas of moderate hypointensity (arrowheads).

• Axial T1-weighted image obtained 18 sec after initiation of IV contrast administration shows corresponding areas of intense, homogeneous, or peripheral ring enhancement of lesionsintense, homogeneous, or peripheral ring enhancement of lesions.

• Axial T1-weighted image obtained 90 sec after initiation of IV contrast administration shows peripheral washoutperipheral washout (arrow), a feature often apparent in hypervascular metastases.

18’’ 90’’


Morphologic characteristics on

T2-weighted images that suggest

metastatic liver disease include

the following: • heterogeneous signal intensity

with irregular and indistinct outer

margins• smooth or irregular central area of

high signal intensity with a

surrounding ring of signal intensity

lower than that of the central focus

but higher than that of the adjacent

normal liver.


Hypovascular metastasis from colon colon adenocarcinomaadenocarcinoma

• Axial T2-weighted image shows large lesion of heterogeneous signalheterogeneous signal intensity with central areas of marked hyperintensity.

• Unenhanced axial T1-weighted image shows lesion as area of moderate hypointensityarea of moderate hypointensity.

• Axial T1-weighted image obtained 18 and 90 sec after initiation of IV contrast administration shows thin peripheral ring peripheral ring enhancementenhancement

18’’ 90’’

From: Spectrum of MRI Appearances of Untreated Metastases of the Liver Ioana-Maria IM et al. AJR 2003; 181:809-817


Nuclear medicine techniquesNuclear medicine techniques

1.Hepatic arterial perfusion scintigraphy

(colorectal cancer)

2. Hepatic perfusion index

(occult or subclinical liver metastases)

3. 99mTc sulfur colloid scintigraphy

4. Somatostatin receptor analogue scintigraphy

GI carcinoids and other neuroendocrine tumors, insulinomas, glucagonomas, small-cell lung cancer, thyroid cancer

5. FDG PET

(colorectal cancer, GI carcinoids)

6. CEA immunoscintigraphy

(a variety of adenocarcinomas, such as colorectal cancer)


Esophageal cancer with extensive liver metastases and small peritoneal implants.

PET and PET/CT fusion images of patient with upper medialstinal esophageal cancer.

Liver Cancer. Hepatocellular carcinoma is the sixth most common cancer worldwide in terms of numbers of cases. It is the third most common cause of death.

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