Cross-sectional imaging can be useful in the diagnosis of biliary tract and primary liver tumors. Hepatobiliary tumors are diverse in growth patterns, histologic types and tumor location. A fundamental understanding of the imaging features of hepatobiliary tumors is critical for diagnosis, staging and treatment. Knowledge about various manifestations and mimickers of biliary and primary liver tumors is essential for tumor diagnosis and suitable management. Magnetic resonance imaging and computed tomography technology continues to rapidly evolve and these tools not only aid in evaluation and treatment, but also can potentially define response to therapy and overall patient prognosis.
Key points
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Knowledge of the diverse manifestations and mimickers of biliary tract and primary liver tumors is essential for diagnosis and management.
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CT and MR imaging are essential in characterizing biliary tract and primary liver tumors, as well as defining potential involvement of surrounding structures.
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Volumetric functional MRI may be used to assess early response of biliary and primary liver tumors following intra-arterial therapy.
Introduction
Noninvasive imaging plays a critical role in the diagnosis, staging, and treatment of patients with biliary tract and primary liver tumors. In addition, imaging provides important information to assess tumor resectability as well as patient prognosis. Noninvasive imaging modalities, such as ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI), are the most common modalities used to image hepatobiliary diseases.
Imaging: Tumor Detection
Because biliary tract and primary liver tumors can vary significantly in location, growth pattern, and histologic subtype, these tumors can have a wide spectrum of radiologic appearances. Noninvasive cross-sectional imaging is critical to characterize biliary tract and primary liver tumors, as well as define their location to critical adjacent structures. Knowledge of the radiologic manifestations of the various possible biliary and primary liver tumors, as well as potential mimickers, is important in the accurate diagnosis and management of these tumors.
Imaging: Tumor Staging
Although US is sometimes the primary modality used in the evaluation of biliary tract and primary liver tumors, the accuracy of US varies according to the equipment and experience of the operator. Although the sensitivity of color Doppler US for portal vein occlusion is 100% and for portal vein infiltration is 83% with 100% specificity, US is less accurate in the estimation of tumor spread and the determination of tumor resectability compared with CT or MRI. CT and MRI have the advantage of 2- and 3-dimensional visualization, which is particularly useful to define vascular involvement, tumor extent, and spread to adjacent structures. Given that this information is crucial for tumor staging and treatment planning, CT or MRI is the preferred imaging modality for patients with suspected biliary or primary liver tumors.
Imaging: Treatment Response Assessment
CT and MRI are commonly used to evaluate treatment response among patients with biliary tract and primary liver tumors. Treatment response after locoregional therapies remains challenging given the limitations of using current available criteria for tumor assessment and treatment response, such as Response Evaluation Criteria in Solid Tumors (RECIST) and Modified RECIST (mRECIST). Alternative methods such as functional CT and MRI have been proposed. Contrast-enhanced CT can provide an estimation of perfusion (blood flow) and tumoral angiogenesis. In addition to perfusion, treatment response assessed by functional MRI with volumetric enhancement and apparent diffusion coefficient (ADC) are promising tools for early tumor assessment and patient prognosis.
Introduction
Noninvasive imaging plays a critical role in the diagnosis, staging, and treatment of patients with biliary tract and primary liver tumors. In addition, imaging provides important information to assess tumor resectability as well as patient prognosis. Noninvasive imaging modalities, such as ultrasonography (US), computed tomography (CT), and magnetic resonance imaging (MRI), are the most common modalities used to image hepatobiliary diseases.
Imaging: Tumor Detection
Because biliary tract and primary liver tumors can vary significantly in location, growth pattern, and histologic subtype, these tumors can have a wide spectrum of radiologic appearances. Noninvasive cross-sectional imaging is critical to characterize biliary tract and primary liver tumors, as well as define their location to critical adjacent structures. Knowledge of the radiologic manifestations of the various possible biliary and primary liver tumors, as well as potential mimickers, is important in the accurate diagnosis and management of these tumors.
Imaging: Tumor Staging
Although US is sometimes the primary modality used in the evaluation of biliary tract and primary liver tumors, the accuracy of US varies according to the equipment and experience of the operator. Although the sensitivity of color Doppler US for portal vein occlusion is 100% and for portal vein infiltration is 83% with 100% specificity, US is less accurate in the estimation of tumor spread and the determination of tumor resectability compared with CT or MRI. CT and MRI have the advantage of 2- and 3-dimensional visualization, which is particularly useful to define vascular involvement, tumor extent, and spread to adjacent structures. Given that this information is crucial for tumor staging and treatment planning, CT or MRI is the preferred imaging modality for patients with suspected biliary or primary liver tumors.
Imaging: Treatment Response Assessment
CT and MRI are commonly used to evaluate treatment response among patients with biliary tract and primary liver tumors. Treatment response after locoregional therapies remains challenging given the limitations of using current available criteria for tumor assessment and treatment response, such as Response Evaluation Criteria in Solid Tumors (RECIST) and Modified RECIST (mRECIST). Alternative methods such as functional CT and MRI have been proposed. Contrast-enhanced CT can provide an estimation of perfusion (blood flow) and tumoral angiogenesis. In addition to perfusion, treatment response assessed by functional MRI with volumetric enhancement and apparent diffusion coefficient (ADC) are promising tools for early tumor assessment and patient prognosis.
Hepatocellular carcinoma
Hepatocellular carcinoma (HCC) is the most common primary liver neoplasm. The incidence of HCC is increasing, and the disease most commonly afflicts patients with viral hepatitis, chronic liver disease, and cirrhosis. The appearance of HCC on US can be variable; an HCC mass may appear hypoechoic, mixed, or echogenic. Most small HCCs are hypoechoic to isoechoic with a peripheral hypoechoic halo, which corresponds to a fibrous capsule ( Fig. 1 ). Contrast-enhanced US with microbubbles often demonstrates tumor vascularization in the arterial phase and washout in the portal phase. Contrast-enhanced US may also have a role in assessing response after treatment.
HCC typically presents as an arterial enhancing lesion of CT or MRI. The HCC most commonly shows increased perfusion in the arterial phase, with higher perfusion reported in well-differentiated tumors. On CT and MRI most small HCC will enhance after contrast administration and display a “washout” of contrast material during the portal-venous phase ( Fig. 2 ). Features of HCC on MRI can vary as lesions may appear hypointense, isointense, or hyperintense compared with the normal liver parenchyma ( Fig. 3 ). Part of the reason for the varied appearance of the HCC lesion on MRI can be due to different signal intensity related to the underlying cirrhotic liver parenchyma.
Most HCC patients are not eligible for curative treatment because of advanced disease or poor liver function. These patients often receive intra-arterial therapy such as transarterial chemoembolization (TACE) or Yyttrium-90 therapy to treat the HCC and delay tumor progression. Recent studies have shown decreased vascularization of the index HCC after TACE therapy, yet higher flow values on any remaining viable tumor. In the assessment of tumor response to therapy, the use of size or enhancement criteria in the axial plane using RECIST, mRECIST, and European Association for the Study of the Liver (EASL) may not accurately represent the true amount of viable tumor using a single slice ( Fig. 4 ). Therefore, new techniques for diagnostic criteria combining anatomic and functional imaging techniques are needed.
CT is limited in the evaluation of lipiodol-containing TACE whereby high lipiodol density interferes with response assessment. On the other hand, the high concentration of lipiodol does not affect the signal intensity on fat-saturated T1-weighted MRI ( Fig. 5 ). Specifically, diffusion-weighted imaging provides indirect assessment of tissue properties, such as cellularity, perfusion, and cellular necrosis, giving a qualitative and quantitative analysis by ADC maps of the HCC ( Fig. 6 ). Studies have shown that diffusion-weighted imaging can improve the detection of HCC in cirrhotic livers. In addition, there is significant correlation between histologic grade and ADC values. Another study suggested that volumetric increase in ADC and decrease in venous enhancement after TACE can provide early response to therapy.
Fibrolamellar Carcinoma
Fibrolamellar carcinoma (FLC) is an HCC variant that occurs in young adults most commonly without elevated α-fetoprotein level or underlying hepatic liver disease. In fact, 85% of patients are less than 35 years of age. Clinical manifestations may include gynecomastia, jaundice, venous compression, or thrombosis that are frequently associated with abdominal pain or an abdominal mass.
FLC often appears as a large circumscribed nonencapsulated mass with a coalescent fibrous scar in up to 60% to 70% of cases. Other FLC presentations include satellite lesions, a bilobulated mass, or multiple masses.
US can demonstrate a solitary circumscribed mass with heterogeneous echotexture that is predominantly isoechoic to the liver parenchyma. The central scar is hyperechoic and may contain calcifications depicted as shadowing echoes.
CT shows similar findings with FLC appearing as a hypoattenuating density compared with the surrounding liver. After contrast administration, the tumor is hyperdense compared with the adjacent liver in the arterial phase with variable density in the portal venous phase. The central scar is hypodense compared with the rest of the tumor. On MRI, FLC appears as a mass that is T1-weighted hypointense to isointense and T2-weighted hyperintense to isointense with a central fibrotic scar that is T1-hypointense and T2-hypointense. Unlike focal nodular hyperplasia the central fibrous scar in FLC does not enhance after contrast administration ( Fig. 7 ).
Lymphoma of the liver
Primary lymphoma of the liver is extremely rare and usually manifests as a solitary focal mass; however, primary hepatic lymphoma can also present as multiple liver lesions or a diffuse process infiltrating the entire liver. On imaging, the differential diagnosis of primary lymphoma versus metastatic disease can be challenging.
On US primary hepatic lymphoma is generally hypoechoic relative to the normal liver. CT shows low-attenuation foci compared with the normal liver parenchyma with variable enhancement after contrast administration. MRI demonstrates T1-weighted hypointense foci that are hyperintense on T2-weighted images. However, the appearance of primary lymphoma on MRI varies and may be isointense on T1-weighted images. OnT2-weighted images the tumor can be hyperintense, hypointense, or isointense to normal liver.
Cholangiocarcinoma
Cholangiocarcinomas originate from the biliary epithelium within either the liver or the extrahepatic biliary tree. Cholangiocarcinoma is often a firm hypovascular tumor due to its fibrous stroma, and most commonly histologically is an adenocarcinoma with desmoplasia. Risk factors associated with cholangiocarcinoma are infection with liver flukes and hepatolithiases, which are endemic in certain geographic areas. The most common risk factors for cholangiocarcinoma include primary sclerosing cholangitis, hepatic cirrhosis, chronic hepatitis C, hepatitis B, Epstein-Barr virus infection, alcoholic liver disease, chronic inflammatory bowel disease, and diabetes. Nitrosamine compounds associated with parasitic infections act as cofactors owing to a carcinogenic effect on the proliferation of epithelial cells of the bile ducts.
Imaging patterns and the radiologic manifestations of cholangiocarcinoma are diverse because tumors vary in location, growth pattern, and histologic type. US may be the initial imaging modality used in patients with an elevated bilirubin level. US imaging of cholangiocarcinoma is often limited and typically only is helpful in detecting the level of obstruction. US is particularly limited in tumor staging. Doppler US may be helpful in differentiating vessels from dilated ducts. In contrast, CT has become the diagnostic test of choice for detailed evaluation and staging of cholangiocarcinoma in many centers. CT can provide information about local disease and metastatic spread to lymph nodes and distant organs. In other centers, MRI is the preferred imaging modality of choice for cholangiocarcinoma. On MRI, cholangiocarcinoma shows variable intensities depending on the amount of mucinous material, fibrous tissue, hemorrhage, and necrosis within the tumor. Diffusion-weighted imaging improves the diagnostic yield of MRI and may be useful in assessing early response to treatment. Magnetic resonance cholangiopancreatography (MRCP) has an added value in the evaluation of cholangiocarcinoma. Specifically, MRCP can help delineate the biliary tree and gallbladder with comparable diagnostic accuracy to endoscopic retrograde cholangiopancreatography. Accuracy of MRCP in localizing the site of obstruction has been reported to be 100%, with 95% accuracy in determining the cause of biliary obstruction. In general, cholangiocarcinoma is classified as either intrahepatic or extrahepatic in location.
Intrahepatic Cholangiocarcinoma
Intrahepatic cholangiocarcinoma (ICC) is the second most common primary malignancy of the liver. Based on growth pattern and tumor morphology, ICC has been classified into 3 subgroups: mass forming, intraductal growth pattern, and periductal infiltrating type (PIT).
US is often the initial imaging modality for evaluation of biliary dilatation and can reveal a mass when ICC is present.
On unenhanced CT, ICCs are noted to hypoattenuating or isoattenuating lesions. After contrast administration, most cholangiocarcinomas remain hypoattenuating during arterial and portal venous phase and show enhancement during delayed phases.
Contrast-enhanced MRI depicts early rim enhancement and persistent delayed enhancement of the tumor. These characteristic findings reflect the fibrous content within the tumor. Gadoxetic acid–enhanced images in the hepatobiliary phase depict the tumor as a hypointense lesion without liver-specific contrast uptake.
Mass forming type
Mass forming type (MFT) of ICC typically presents as a homogenous mass with irregular, well-defined margins often associated with dilatation of the biliary tree in the periphery. On US, MFT appears as hyperechoic (>3 cm), hypoechoic, isoechoic (<3 cm), or of mixed echogenicity. By CT, MFT ICC appears homogeneous in attenuation, with irregular peripheral enhancement that gradually becomes centripetal in pattern. On MRI MFT demonstrates irregular margins with variable high signal intensity on T2-weighted images and low signal intensity on T1-weighted images. Postcontrast images show an irregular peripheral enhancement with concentric filling, and significant central enhancement can be seen on delayed phase (20 minutes) MRI. Associated MFT findings are capsular retraction, satellite nodules, hepatolithiasis, and vascular encasement without gross tumor thrombus formation.
PIT
PIT ICC presents as a growth along a dilated or narrowed bile duct without mass formation. PIT can also present as an elongated or branchlike abnormality. On imaging, it is crucial to differentiate benign from malignant strictures, and the presence of an irregular margin, asymmetric narrowing, lymph node enlargement, enhancing ducts, or periductal soft tissue lesions should raise suspicion for a malignant stricture.
By US PIT appears as a small solitary masslike lesion or may be seen as diffuse bile duct thickening with or without obliteration of the bile duct lumen. Occasionally PIT may cause a diffusely abnormal liver echotexture that sometimes mimics HCC or metastases. On CT and MRI, PIT presents as diffuse periductal thickening and increased enhancement because of tumor infiltration with abnormal dilated or irregular narrow duct and peripheral ductal dilatation ( Fig. 8 ).
