Imaging Pearls ❯ Liver ❯ Hepatoma
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- “HCC is the most common primary liver malignancy worldwide.It is one of few malignancies in which specific imaging findings alone, without tissue diagnosis, is considered adequate to proceed with further clinical management, including locoregional therapy, surgical resection, and/or liver transplantation.Thus, accurate diagnosis is critical so as to not inappropriately treat patients. This requires synthesis of several key imaging features. Unfortunately, definitive diagnosis of HCC can occasionally be a diagnostic dilemma owing to the occasional overlap of HCC imaging features with additional hepatic lesions such as dysplastic nodules, benign neoplasms, or other malignant neoplasms (which require a different treatment approach).”
Imaging and Management of Liver Cancer
Abdullah O.Alenezi et al.
Seminars in Ultrasound, CT and MRI
Volume 41, Issue 2, April 2020, Pages 122-138 - The Surveillance, Epidemiology, and End Results (SEER) Data for Hepatoma
- The Surveillance, Epidemiology, and End Results (SEER) Data for Hepatoma
- The Surveillance, Epidemiology, and End Results (SEER) Data for Hepatoma
- The Surveillance, Epidemiology, and End Results (SEER) Data for Hepatoma
- The Surveillance, Epidemiology, and End Results (SEER) Data for Hepatoma
- The Surveillance, Epidemiology, and End Results (SEER) Data for Hepatoma
- The Surveillance, Epidemiology, and End Results (SEER) Data for Hepatoma
- “Major risk factors for development of HCC include hepatitis B or cirrhosis caused by chronic hepatitis C infection, excess alcohol intake, and certain metabolic diseases. The result of these risk factors is either repeated incidence or sustained hepatic parenchymal inflammation, which results in progressive fibrosis and cirrhosis. Eventually, via a step-wise progression, there is a transformation from preneoplastic lesions (low-grade dysplastic nodule, high-grade dysplastic nodule) to HCC (well-differentiated HCC, moderately differentiated HCC and finally, an advanced, poorly differentiated HCC).”
Imaging and Management of Liver Cancer
Abdullah O.Alenezi et al.
Seminars in Ultrasound, CT and MRI
Volume 41, Issue 2, April 2020, Pages 122-138 - "For imaging diagnosis of HCC, regardless of imaging used, the late arterial phase images are the most critical; an ideal late arterial phase image depicts both hepatic artery and early portal vein contrast opacification, without opacification of the hepatic veins. Arterial phase images acquired too early or too late result in inadequate tumoral enhancement; thus, the major imaging feature (APHE), which is required for imaging diagnosis of HCC, will not be detected.”
Imaging and Management of Liver Cancer
Abdullah O.Alenezi et al.
Seminars in Ultrasound, CT and MRI
Volume 41, Issue 2, April 2020, Pages 122-138 
Hepatic nodules with arterial phase hyperenhancement and washout on enhanced computed tomography/magnetic resonance imaging: how to avoid pitfalls
Mimi Tang et al.
Abdominal Radiology https://doi.org/10.1007/s00261-020-02560-0- “HCC is the most common primary malignant tumors of the liver and typically arises in liver cirrhosis. Nevertheless, approximately 20% of HCCs can arise in patients without cirrhosis. There are many causes that can induce the development of HCC, such as hepatitis B virus infection, exposure to Aflatoxin B1, inherited diseases (hemochromatosis, alpha1-antitrypsin deficiency, type I glycogen storage disease, porphyria), metabolic syndrome, non-alcoholic fatty liver disease including non-alcoholic steatohepatitis (NASH), use of anabolic steroids and hepatocellular adenoma.”
Imaging of primary malignant tumors in non-cirrhotic liver
G.Mamone et al.
Diagn Interv Imaging 2020 Feb 3;S2211-5684 - "HCC in non-cirrhotic liver often presents as a large solitary mass or dominant mass with peripheral satellite lesions, likely due to the absence of surveillance. Peripheral satellite lesions were present in 24% of patients in the study by Fisher et al. For the same reason, extrahepatic spread of disease, including metastases, is more frequently found in non-cirrhotic patients compared to patients with cirrhosis (20.5% vs. 6.5%, respectively). HCC in non-cirrhotic liver can invade the portal vein or hepatic veins in 15% of patients . Abdominal lymphadenopathy can be found in approximately 20% of non-cirrhotic patients with HCC.”
Imaging of primary malignant tumors in non-cirrhotic liver
G.Mamone et al.
Diagn Interv Imaging 2020 Feb 3;S2211-5684 - "Fibrolamellar HCC is an uncommon variant of non-cirrhotic HCC (approximately 5%) and occurs in non-cirrhotic liver of young patients between the 2nd and 3rd decades of life. It is more prevalent in Europe and North America compared to Asia and Africa and it accounts for 0.5 to 1% of all cases of liver cancer. Unlike conventional HCC, fibrolamellar HCC has a less aggressive biologic behavior and better prognosis. Tumor markers such as alpha fetoprotein are not elevated in fibrolamellar HCC. Surgical resection is the best therapeutic option and the 5-year survival rate after resection is better than that of conventional HCC.”
Imaging of primary malignant tumors in non-cirrhotic liver
G.Mamone et al.
Diagn Interv Imaging 2020 Feb 3;S2211-5684 - “On imaging, fibrolamellar HCC appears as a large solitary mass, sometimes multifocal, with sharp and lobulated margins. A central scar is detected in 71–73% of fibrolamellar HCC, often stellate and with radial septae. Calcifications can be found in 67–68% of tumors and may be punctate, nodular or stellate, often involving the central scar. Large areas of hemorrhage are uncommon and fat is usually absent.”
Imaging of primary malignant tumors in non-cirrhotic liver
G.Mamone et al.
Diagn Interv Imaging 2020 Feb 3;S2211-5684 - "On dynamic contrast-enhanced CT and MRI, fibrolamellar HCC shows heterogeneous hypervascularity during the arterial phase, and iso-hypoattenuation/iso-hypointensity during portal and delayed phases. The central scar is usually hypoattenuating/hypointense during arterial and portal venous phases. Late enhancement of the central scar may be present in 12% of fibrolamellar HCC, in relation to fibrous nature.”
Imaging of primary malignant tumors in non-cirrhotic liver
G.Mamone et al.
Diagn Interv Imaging 2020 Feb 3;S2211-5684 - “The main differential diagnosis includes FNH, hepatic adenoma and common HCC. However, FNH demonstrates homogeneous arterial enhancement and adenoma often contains areas of hemorrhage or fat, which are usually absent in fibrolamellar HCC. Furthermore, calcifications are rare in FNH and adenoma, the scar in FNH is usually smaller and hyperintense on T2-weighted images and FNH is typically iso-hyperintense on MRI obtained with a hepato-specific contrasts agent. Finally, 65% of fibrolamellar HCC are associated with lymph node metastasis and peritoneal carcinosis is not rare at the time of diagnosis.”
Imaging of primary malignant tumors in non-cirrhotic liver
G.Mamone et al.
Diagn Interv Imaging 2020 Feb 3;S2211-5684 - “Here, the role of imaging is to differentiate HCC from several non- malignant cirrhosis-associated nodules (e.g., regenerative, low and high-grade dysplastic nodules), benign lesions or pseudo lesions that may be encountered in the cirrhotic liver (e.g., hemangiomas, focal or confluent fibrosis, transient per- fusion disorders), as well as other malignant lesions such as intrahepatic cholangiocarcinoma (ICC). Like most other solid tumors, HCC presents with variable imaging features corresponding to a wide spectrum of pathological and biological characteristics.”
Hepatocellular Carcinoma: Current Imaging Modalities for Diagnosis and Prognosis
Maxime Ronot - Yvonne Purcell - Valérie Vilgrain
Digestive Diseases and Sciences (2019) 64:934–950 - "Early HCC can be considered the equivalent of “carcinoma in situ” or “micro-invasive carcinoma” and therefore a transitional tumor between preneoplastic lesions and overt or advanced HCC. Compared to overt HCC, early HCCs are usually smaller (< 1.5 cm), vaguely nodular with ill-defined margins, and lack a peripheral capsule. They correspond to well-differentiated lesions.”
Hepatocellular Carcinoma: Current Imaging Modalities for Diagnosis and Prognosis
Maxime Ronot - Yvonne Purcell - Valérie Vilgrain
Digestive Diseases and Sciences (2019) 64:934–950 - “As previously stated, the hallmarks of HCC are the association of non-rim arterial phase hyperenhancement and washout on the portal venous and/or delayed phases. Historically, arterial phase hyperenhancement corresponds to the first imaging feature described in HCC. However, it is not specific alone and may also be observed in benign lesions, focal perfusion disorders, arterio-portal shunts, non-HCC malignancies such as intrahepatic cholangiocarcinoma, and more rarely in other cirrhosis-associated nodules such as high-grade dysplastic nodules. Therefore, washout has been used to increase the specificity of the diagnosis of HCC on imaging.”
Hepatocellular Carcinoma: Current Imaging Modalities for Diagnosis and Prognosis
Maxime Ronot - Yvonne Purcell - Valérie Vilgrain
Digestive Diseases and Sciences (2019) 64:934–950 - "It is important to note that around 40% of HCCs lack arterial phase enhancement. These mainly correspond to early HCCs or poorly differentiated infiltrative HCCs. Moreover, 40–60% of small HCCs do not exhibit washout during the venous phases. Arterial phase hyperenhancement must not be predominantly peripheral (hence the term “non-rim”) because this appearance favors the diagnosis of other malignancies such as cholangiocarcinoma.”
Hepatocellular Carcinoma: Current Imaging Modalities for Diagnosis and Prognosis
Maxime Ronot - Yvonne Purcell - Valérie Vilgrain
Digestive Diseases and Sciences (2019) 64:934–950 - "The capsule corresponds to a peripheral rim of hyperenhancement during the portal venous or delayed phase . Studies of resected HCCs have shown that the image of capsule on CT or MRI is correlated with the presence of a tumor capsule at pathology. However, the presence of a capsule at imaging may also correspond to a “pseudocapsule” including mixed fibrous tissue and dilated sinusoids. Nevertheless, a capsule image has been shown to be an important predictor of HCC. The added value of this finding is weak because most encapsulated HCCs have the typical hallmarks.”
Hepatocellular Carcinoma: Current Imaging Modalities for Diagnosis and Prognosis
Maxime Ronot - Yvonne Purcell - Valérie Vilgrain
Digestive Diseases and Sciences (2019) 64:934–950 - Detection of Hepatoma In The Cirrhotic Liver
- CT
- MR
- Ultrasound
- Artificial Intelligence (AI) - Purpose: To assess guideline compliance and quality of hepatocellular carcinoma, (HCC) diagnostic imaging within com- munity hospitals (CH) and their Tertiary referral center (TRC) in a moderately high incidence region.
Conclusions: Community hospital HCC diagnostic scans significantly lag in critical quality parameters of tumor enhancement, arterial phase timing, perceived image quality, and LI-RADS CT technique compliance compared to a TRC.
Diagnostic imaging of hepatocellular carcinoma at community hospitals and their tertiary referral center in the era of LI‐RADS: a quality assessment study
Andrew Chan et al.
Abdominal Radiology (2019) 44:4028–4036 - “In conclusion, this study found that a substantial proportion of CH CT scans did not comply with LI-RADS imaging technique recommendations. We recommend that a major systematic effort be initiated in jurisdictions with moderate and high incidence of HCC to translate LI-RADS’ technique-related guidelines into community practice.”
Diagnostic imaging of hepatocellular carcinoma at community hospitals and their tertiary referral center in the era of LI‐RADS: a quality assessment study
Andrew Chan et al.
Abdominal Radiology (2019) 44:4028–4036 - “In the United States, the incidence of HCC has increased since the 1980s. HCC detection at an early stage through surveillance and curative therapy has considerably improved the 5-year survival. Therefore, medical societies advocate systematic screening and surveillance of target populations at par- ticularly high risk for developing HCC to facilitate early- stage detection.”
Epidemiology of hepatocellular carcinoma: target population for surveillance and diagnosis
An Tang et al.
Abdom Radiol (2018) 43:13–25 - "Major risk factors for HCC include cirrhosis, chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV), alcoholic fatty liver disease, and non-alcoholic fatty liver disease (NAFLD). Additional risk factors for HCC include aflatoxin, family history and genetic factors, obesity, diabetes, smoking, and coinfection with human immunodeficiency virus (HIV).”
Epidemiology of hepatocellular carcinoma: target population for surveillance and diagnosis
An Tang et al.
Abdom Radiol (2018) 43:13–25 - "HCC is a common cancer and second leading cause of cancer mortality worldwide. The geographic distribution of HCC reflects the distribution of HBV and HCV, which currently are the two major etiologic risk factors worldwide. Regardless of the underlying etiology, hepa- tocarcinogenesis generally takes decades of repetitive liver injury. Cirrhosis is a marker of cumulative liver damage, and its presence places patients at high risk for HCC development.”
Epidemiology of hepatocellular carcinoma: target population for surveillance and diagnosis
An Tang et al.
Abdom Radiol (2018) 43:13–25 - Risk factors for HCC
- cirrhosis
- chronic infection with hepatitis B virus (HBV)
- hepatitis C virus (HCV)
- excess alcohol consumption
- non-alcoholic fatty liver disease
- family history of HCC
- obesity
- type 2 diabetes mellitus
- smoking
- “Hepatocellular carcinoma (HCC) constitutes over 90% of all primary hepatic malignancies, with approximately 80% a complication of hepatitis B and C infection. Additional risk factors include alcoholic and nonalcoholic fatty liver disease, smoking, α-1 antitrypsin deficiency, hemochromatosis, and environmental and dietary factors.”
Liver Calcifications and Calcified Liver Masses: Pattern Recognition Approach on CT Madhavi Patnana et al AJR 2018; 211:76–86 - “The frequency of HCC varies geographically. High-frequency areas in the world are sub-Saharan Africa, China, Hong Kong, and Taiwan. Low-frequency areas include North and South America, Australia, parts of the Middle East, and most of Europe. In the United States, the frequency has been increasing over the past 20 years and is postulated to be associated with chronic hepatitis C infection.”
Liver Calcifications and Calcified Liver Masses: Pattern Recognition Approach on CT Madhavi Patnana et al AJR 2018; 211:76–86 - “Evaluation for HCC is optimally detected with a dynamic multiphase contrast-enhanced imaging study (CT or MRI) to assess the pattern of vascularity. Most HCCs develop in the presence of cirrhosis but can also occur without cirrhosis. HCC has various presentations, including a single mass (most common), multifocal masses, or a diffusely infiltrative tumor. The classic imaging pattern of solitary or multifocal HCC on CT or MRI (with extracellular contrast agents) is late arterial hypervascularity with portal venous phase or late washout and an enhancing peripheral capsule.”
Liver Calcifications and Calcified Liver Masses: Pattern Recognition Approach on CT Madhavi Patnana et al AJR 2018; 211:76–86 - “Vascular invasion can be seen, particularly involving the portal vein more frequently than the hepatic veins, and appears as an intraluminal tumor growth . These tumors also have hemorrhagic areas and necrosis and can develop dystrophic calcification, although it is rare. Calcification is more common after liver-directed therapy.”
Liver Calcifications and Calcified Liver Masses: Pattern Recognition Approach on CT Madhavi Patnana et al AJR 2018; 211:76–86 - “The fibrolamellar variant of HCC is much less common and has different imaging characteristics compared with HCC. This tumor tends to occur in a younger population (5–35 years old) and affects both male and female patients equally. There is no connection with chronic viral hepatitis or cirrhosis. It has a better prognosis compared with HCC.”
Liver Calcifications and Calcified Liver Masses: Pattern Recognition Approach on CT Madhavi Patnana et al AJR 2018; 211:76–86 - “Nodal metastatic disease is common (50–65%) and most frequently occurs in the hepatoduodenal ligament, retroperitoneum, pelvis, and mediastinum. Distant metastatic disease occurs in approximately 20–30% of cases, with the most common sites being in the lung, peritoneum, and adrenal glands.”
Liver Calcifications and Calcified Liver Masses: Pattern Recognition Approach on CT Madhavi Patnana et al AJR 2018; 211:76–86
- Primary Liver Tumors: Facts
- Hepatoma: Frequency
- Hepatoma: SEER Data
- Hepatoma: SEER Data
- Hepatoma: Facts
- “Recurrence of HCC reduces survival rates in patients treated with surgery, and one of the most relevant risk factors for tumour recurrence is microvascular invasion (mVI). The identification of mVI on preoperative examinations could improve surgical planning's and techniques so as to reduce the risk of tumour recurrence. During our study, we have revised 101 CT examinations of the liver performed on patients diagnosed with solitary HCC who had surgical treatment and pathological analysis of the specimens for mVI in order to detect CT signs which could be reliable in mVI prediction. On CT examinations, the tumours were evaluated for margins, capsule, size, contrast enhancement, halo sign and Thad. From our statistical analysis, we found out that irregularity in tumour margins and defects in peritumoural capsule are the most significant characteristics predicting mVI in HCC. Every report on CT examinations performed on surgical candidate patients should include suggestions about mVI probability in order to tailor procedures, reduce tumour recurrence risk and improve survival rates.”
Vascular microinvasion from hepatocellular carcinoma: CT findings and pathologic correlation for the best therapeutic strategies. Reginelli A et al. Med Oncol. 2017 May;34(5):93 - “Recurrence of HCC reduces survival rates in patients treated with surgery, and one of the most relevant risk factors for tumour recurrence is microvascular invasion (mVI). The identification of mVI on preoperative examinations could improve surgical planning's and techniques so as to reduce the risk of tumour recurrence. During our study, we have revised 101 CT examinations of the liver performed on patients diagnosed with solitary HCC who had surgical treatment and pathological analysis of the specimens for mVI in order to detect CT signs which could be reliable in mVI prediction. On CT examinations, the tumours were evaluated for margins, capsule, size, contrast enhancement, halo sign and Thad. From our statistical analysis, we found out that irregularity in tumour margins and defects in peritumoural capsule are the most significant characteristics predicting mVI in HCC.”
Vascular microinvasion from hepatocellular carcinoma: CT findings and pathologic correlation for the best therapeutic strategies. Reginelli A et al. Med Oncol. 2017 May;34(5):93
- Hepatocellular Carcinoma: Facts
- 3rd leading cause of death worldwide
- Strong male predilection
- Risk factors:
- Hepatitis B and C
- Cirrhosis
- Fatty liver
- Management options
- Surgery, chemoembolization, transplant - HCC – Criteria for Liver Transplant
Milan Criteria
- Single lesion ? 5 cm
- 3 lesions smaller than 3 cm
- No vascular invasion
- No metastatic disease outside of the liver
UCSF Criteria
- Single lesion ? 6.5 cm
- 3 lesions smaller than 4.5 cm
- No vascular invasion
- No metastatic disease outside of the liver - Fibrolamellar HCC
- Young patients without cirrhosis
- Theoretically less aggressive
- Large, aggressive looking (lobulated)
- Hypervascular with delayed washout
- Encapsulated
- Central scar – Ca++
- Adenopathy common
- “Hepatocellular adenomas are relatively rare, benign liver tumors usually occurring in young women (mean age 35 years) and are often associated with the use of oral contraceptives. Spontaneous bleeding of hepatocellular ade- noma may give rise to serious complications, especially when rupture into the abdomen has occurred.”
A Bleeding Liver Tumor
van Gulik TM
Dig Surg 2002;19:106–108 - “Bevacizumab when combined with chemotherapy exerts significant activity against many solid tumors through tumor angiogenesis inhibition; however, it can induce severe side effects. We report the rare case of a 27-year-old premenopausal woman with locally advanced breast cancer that was marked by rapid tumor necrosis followed by massive hemorrhage shortly after bevacizumab and paclitaxel administration.”
Rapid tumor necrosis and massive hemorrhage induced by bevacizumab and paclitaxel combination therapy in a case of advanced breast cancer.
Onco Targets Ther. 2013 Oct 7;6:1393-8
Ono M et al. - “Spontaneous rupture of hepatocellular carcinoma (HCC) is a life-threatening presentation, with an incidence of <3% of HCC patients in Western countries. The reported overall mortality is < or =50% in Asian countries, where the incidence is 12% to 14%.”
Spontaneous rupture of hepatocellular carcinoma: a Western experience.
Am J Surg. 2009 Feb;197(2):164-7.
Battula N et al.
- Hepatocellular Carcinoma
- 3rd leading cause of death worldwide
- Strong male predilection
- Risk factors:
- Hepatitis B and C
- Cirrhosis
- Fatty liver
- Management options
- Surgery, chemoembolization, transplant
- Hepatoma: Facts
- Commonly develops in the setting of chronic liver disease especially in patients with Hepatitis B and C
- The median survival following diagnosis is 8-20 months
- Clinical presentation includes cirrhotic patients who develop decompensation including ascites, encephalopathy, jaundice or variceal bleeding
- Patients may also present with abdominal pain, weight loss or a palpable mass
- Cirrhosis: Common Causes
- Alcohol abuse (the most common cause in the United States)
- Autoimmune diseases of the liver
- Hepatitis B or C virus infection
- Inflammation of the liver that is long-term (chronic)
- Iron overload in the body (hemachromatosis) - “Each year 50000 to 1 million individuals are diagnosed with hepatocellular carcinoma (HCC) worldwide. Incidence rates demonstrate dramatic geographic variability, ranging from<5 new cases per 100000 persons per year in developed western countries to>100 per 100000 persons per year in parts of south-east Asia and sub-Saharan Africa. Although the United States is among regions of low incidence, a 70% increase in HCC has been observed over the past two decades, apparently related to the emergence of chronic hepatitis C.”
Diagnosis of Hepatocellular Carcinoma
Bialecki ES, Di Bisceglie AM
HPB 2005;7(1):26-34 - “Brancatelli etal. describe hepatic lesions which can mimic HCC on CT imaging including regenerating nodules, hemangiomas, focal fat, dysplastic nodules, and peliosis. The accuracy increases with greater imaging speed, which allows faster administration of contrast media, thereby dramatically improving contrast enhancement . The added speed and flexibility of multidetector CT (MDCT) allows high quality, thin-section imaging with three-dimensional capabilities .”
Diagnosis of Hepatocellular Carcinoma
Bialecki ES, Di Bisceglie AM
HPB 2005;7(1):26-34
- Hepatocellular Carcinoma
1. 3rd leading cause of death worldwide
2. Strong male predilection
3. Risk factors:
- Hepatitis B and C
- Cirrhosis
- Fatty liver
4. Management options
- Surgery, chemoembolization, transplant - Hepatocellular Carcinoma
1. Overall MDCT sensitivity for HCC is 90%+
2. Sensitivity 60% for lesions < 2 cm
- False positives increase for small lesions
3. Three patterns:
- Solitary
- Multifocal
- Diffuse - Hepatocellular Carcinoma
1. Hypervascular in the arterial phase
- Homogeneous for lesions < 3 cm
2. Washout in the venous or delayed phase
3. Encapsulated, with enhancement of capsule on delayed images
4. Can have a central scar
5. Fat
6. Hemorrhage - LIRADS
Liver Imaging Reporting and Data System
- LIRADS 1: Definitely Benign
- LIRADS 2: Probably Benign
- LIRADS 3: Intermediate Probability for HCC
- LIRADS 4: Probably HCC
- LIRADS V: Definitely HCC - Fibrolamellar HCC
1. Young patients without cirrhosis
2. Theoretically less aggressive
3. Large, aggressive looking (lobulated)
4. Hypervascular with delayed washout
- Encapsulated
- Central scar – Ca++
5. Adenopathy common - Solid Malignant Masses
1. Metastases
- Hypovascular
- Hypervascular
2. Cholangiocarcinoma
3. Lymphoma
4. Hepatic Sarcoma
5. Epithelioid Hemangioendothelioma
"MDCT has reasonable sensitivity in the detection of hepatocellular carcinoma in patients with cirrhosis who undergo liver transplantation. Attention should be paid, however, to avoiding overestimation of the extent of disease."
Role of MDCT in the Diagnosis of Hepatocellular Carcinoma in Patients with Cirrhosis Undergoing Orthotopic Liver Transplantation
Ronzoni A et al
AJR 2007;189;792-798"The more accurate and detailed pretreatment evaluation of HCC progression using a unified CTA system contributed to the improvement of survival of patients with HCC."
Impact of a Unified CT Angiography System on Outcome of Patients with Hepatocellular Carcinoma
Toyoda H et al.
AJR 2009; 192:766-774"The more accurate and detailed pretreatment evaluation of HCC progression using a unified CTA system contributed to the improvement of survival of patients with HCC. In addition it contributed to the improved efficacy of TACE with an increased survival rate."
Impact of a Unified CT Angiography System on Outcome of Patients with Hepatocellular Carcinoma
Toyoda H et al.
AJR 2009; 192:766-774