Approach to the adult patient with an incidental solid liver lesion

INTRODUCTION — Liver lesions may be detected on imaging studies performed for an unrelated reason (ie, incidental liver lesion). The approach in this topic applies to liver lesions found incidentally in adult patients without signs or symptoms (eg, right upper quadrant pain) attributable to the lesion and without risk factors for hepatic malignancy. Separate strategies and individual adjustments are needed for high-risk populations including patients with any of the following risk factors [1]:

●Cirrhosis

●Chronic hepatitis B virus infection without cirrhosis

●History of malignancy with propensity to metastasize to the liver

The approach to patients with suspected hepatocellular carcinoma (HCC) and indications for HCC surveillance are discussed separately. (See "Clinical features and diagnosis of hepatocellular carcinoma" and "Surveillance for hepatocellular carcinoma in adults".)

The approach to patients with a liver lesion that is predominantly cystic is presented separately. (See "Diagnosis and management of cystic lesions of the liver".)

The evaluation and management of patients with liver abscess is discussed separately. (See "Pyogenic liver abscess" and "Extraintestinal Entamoeba histolytica amebiasis".)

PREVALENCE — Technologic advances in imaging such as computed tomography (CT) and magnetic resonance imaging and their widespread use have led to detection of many incidental findings [2]. For example, in a study including over 17,000 individuals who underwent screening chest CT, the prevalence rate of incidental hepatobiliary findings was 6 percent [3].

DIFFERENTIAL DIAGNOSIS — The etiology of incidental liver lesions can be categorized as benign or malignant. While most incidental lesions occur as a focal finding, multiple lesions may be seen in some patients (eg, those with more than one hepatic hemangioma).

Benign lesions — Benign liver lesions that may be found incidentally include [4] (see 'Lesion characteristics' below):

●Hepatic hemangioma – Hepatic hemangiomas (also referred to as cavernous hemangiomas because of the cavernous vascular space seen histologically) are the most common benign liver lesion. Hepatic hemangioma can be diagnosed at any age; however, the majority of lesions (up to 80 percent) are diagnosed in patients who are between the ages of 30 and 50 years. In adults, hemangiomas occur more frequently in females with a ratio of approximately 3:1 [5,6]. The lesion is most often solitary but multiple hemangiomas may be present. Most patients with hepatic hemangioma are asymptomatic and have an excellent prognosis. (See "Hepatic hemangioma".)

●Focal nodular hyperplasia – Focal nodular hyperplasia (FNH) is a benign liver lesion that is composed of a proliferation of hyperplastic hepatocytes surrounding a central stellate scar. Typically, FNH is a solitary lesion that is more commonly seen in women [7-9].

There is increasing recognition of FNH among patients undergoing abdominal imaging for other reasons. In a large observational series including patients referred for ultrasound or contrast-enhanced computed tomography (CT), the prevalence of FNH was 0.2 percent and 1.6 percent, respectively [10,11]. (See "Focal nodular hyperplasia".)

●Hepatocellular adenoma – Hepatocellular adenoma (HCA) (also termed hepatic adenoma) is an uncommon solid, benign liver lesion that develops in an otherwise normal-appearing liver. Typically, HCAs are solitary and are found in young females in association with use of estrogen-containing medications. In addition, patients with glycogen storage disease or metabolic syndrome are at higher risk for developing HCA (image 1). (See "Hepatocellular adenoma".)

●Regenerative nodules – Regenerative nodules develop in response to liver injury and are comprised of a proliferation of hepatocytes and surrounding stroma. They are typically seen in the setting of cirrhosis [12,13].

Malignant lesions — Malignant liver lesions that may be found incidentally include [4]:

●Hepatocellular carcinoma – Hepatocellular carcinoma is a primary tumor of the liver that develops in the setting of chronic liver disease, particularly in patients with cirrhosis of any cause or chronic hepatitis B virus infection (image 2). (See "Epidemiology and risk factors for hepatocellular carcinoma".)

The diagnosis of HCC can be made with dynamic contrast enhanced CT or MRI tailored for liver lesion evaluation in patients at risk for HCC. (See "Clinical features and diagnosis of hepatocellular carcinoma".)

●Cholangiocarcinoma – Cholangiocarcinomas (bile duct cancers) arise from the epithelial cells of the intrahepatic ducts and extrahepatic bile ducts, and may be found incidentally during the early stage of disease. A number of risk factors for cholangiocarcinoma have been recognized. In the United States and Europe, the main risk factors are primary sclerosing cholangitis and fibropolycystic liver disease (eg, choledochal cysts), while hepatolithiasis (also called recurrent pyogenic cholangitis) is commonly associated with cholangiocarcinoma in Asia. (See "Epidemiology, risk factors, anatomy, and pathology of cholangiocarcinoma".)

●Metastatic disease – The liver is a common site for metastasis from solid tumors, and patients with a history of malignancy are at higher risk for metastatic disease [14]. (See "Potentially resectable colorectal cancer liver metastases: Integration of surgery and chemotherapy".)

DIAGNOSTIC APPROACH

Factors that guide decision-making

Assess risk factors for liver malignancy — As a first step, it is important to confirm that the patient does not have risk factors for hepatocellular carcinoma (eg, cirrhosis, chronic hepatitis B infection) or for liver metastases (eg, history of extrahepatic malignancy) (algorithm 1). The diagnostic evaluation for patients who are at risk for developing a malignant liver lesion is discussed separately. (See "Clinical features and diagnosis of hepatocellular carcinoma".)

The clinical features and diagnosis of cirrhosis are presented separately. (See "Cirrhosis in adults: Etiologies, clinical manifestations, and diagnosis".)

Lesion characteristics — For patients without risk factors for a malignant hepatic lesion, the initial diagnostic evaluation is primarily based on the imaging appearance of the incidental lesion. Some liver lesions (eg, hepatic hemangioma <3 cm) can be diagnosed based on noncontrast ultrasound if imaging criteria are met, while other lesions require further diagnostic evaluation based on lesion characteristics (eg, lesion size, margins). (See "Hepatic hemangioma", section on 'Diagnostic approach'.)

The following lesion characteristics guide further imaging selection and management [1]:

●Size – Most incidental liver lesions <1 cm are benign, while some small lesions may be difficult to definitively characterize by imaging methods [15,16]. Most lesions ≥1 cm can be diagnosed either by further imaging (eg, MRI tailored for liver lesion evaluation) and/or histology.

●Margin – Benign lesions typically have smooth margins.

●Enhancement pattern on contrast enhanced imaging –Most liver lesions have characteristic enhancement features (table 1):

•Hepatic hemangioma – Hepatic hemangioma typically demonstrates peripheral nodular enhancement in the early phase, followed by a centripetal pattern or "filling in" during the late phase (image 3). Peripheral nodular or globular enhancement representing venous lakes is seen in most hemangiomas >4 cm in size [17]. (See "Hepatic hemangioma", section on 'Imaging'.)

•Hepatocellular adenoma – On contrast-enhanced computed tomography (CT), hepatocellular adenoma may show peripheral enhancement that reflects the large subcapsular feeding vessels with a centripetal pattern of enhancement [18]. (See "Hepatocellular adenoma", section on 'Imaging studies'.)

•Focal nodular hyperplasia – Administration of a liver specific gadolinium-based magnetic resonance contrast agent produces rapid enhancement of focal nodular hyperplasia due to its arterial blood supply, resulting in a hyperintense lesion on early films. On delayed images, it becomes more isointense with respect to normal liver. The central scar enhances on delayed imaging as contrast gradually diffuses into the fibrous center of the mass (image 4 and image 5) [19,20]. (See "Focal nodular hyperplasia", section on 'Imaging'.)

•Hepatocellular carcinoma – Hepatocellular carcinoma (HCC) typically demonstrates a non-rim arterial phase hyperenhancement relative to the liver parenchyma (table 2). (See "Clinical features and diagnosis of hepatocellular carcinoma", section on 'Imaging'.)

•Intrahepatic cholangiocarcinoma – On cross-sectional imaging following contrast administration, there is peripheral (rim) enhancement throughout both arterial and venous phases. (See "Clinical manifestations and diagnosis of cholangiocarcinoma", section on 'Imaging studies'.)

•Liver metastases – The enhancement pattern of liver metastases varies depending on the primary malignancy. For example, metastatic liver lesions from the colon, stomach, and pancreas usually show lower attenuation (ie, are darker) in contrast to the brighter surrounding liver parenchyma on multiphasic CT of the liver (image 6) [21]. Hypervascular metastases, such as those from neuroendocrine tumors, renal cell carcinoma, breast carcinoma, melanoma, and thyroid carcinoma, appear as rapidly enhancing lesions visible on the arterial phase of enhancement. (See "Metastatic well-differentiated gastroenteropancreatic neuroendocrine tumors: Presentation, prognosis, imaging, and biochemical monitoring", section on 'Imaging'.)

●Growth pattern (if available) – For patients who have previous imaging available for comparison, absence of lesion growth over a one year time period suggests that the lesion is more likely to be benign [22].

Initial evaluation — For most patients with incidental liver lesions of uncertain etiology, the initial work up includes liver imaging (eg, contrast-enhanced, multiphasic, cross-sectional imaging [eg, magnetic resonance imaging (MRI)]) and identifying possible risk factors (eg, oral contraceptive use) [1]. If imaging fails to make the diagnosis, subsequent options include imaging surveillance or histologic evaluation (eg, biopsy or surgical resection).

For example, for female patients with suspected hepatocellular adenoma based on noncontrast ultrasound, the diagnosis is made with contrast-enhanced, cross-sectional imaging using MRI. (See "Hepatocellular adenoma", section on 'Diagnostic approach'.)

Is additional imaging warranted? — For patients with incidental lesions but without risk factors for liver malignancy, the need for additional imaging depends on whether the lesion can be diagnosed based on the initial study. For example, the diagnosis of hepatic hemangioma can be made with noncontrast ultrasound if the following criteria are met (see "Hepatic hemangioma", section on 'Diagnostic approach'):

●Typical features are present (ie, homogenous, hyperechoic, well-delineated margin)

●Lesion size is <3 cm

●Patient has no history of cirrhosis or extrahepatic malignancy

For lesions with a suspected diagnosis based on initial imaging study, further imaging is warranted to confirm the diagnosis. For example, if the diagnosis of hepatocellular adenoma is suspected based on ultrasound, the diagnosis can be made with a multiphase, contrast-enhanced MRI study.

Selecting an imaging modality — Diagnostic imaging of solid liver lesions of uncertain etiology typically starts with contrast-enhanced, multiphasic, cross-sectional imaging. We typically use MRI; however, CT scan is an alternative if MRI is contraindicated or not available. (See "Patient evaluation for metallic or electrical implants, devices, or foreign bodies before magnetic resonance imaging".) If the diagnosis remains uncertain after further imaging and the results will affect patient management, obtaining tissue for histologic examination (via biopsy or surgical resection) or surveillance imaging may be required. (See 'Subsequent evaluation' below.)

Typical imaging characteristics of solid liver lesions on noncontrast ultrasound, contrast-enhanced CT and MRI are listed here (table 1).

Specific imaging modalities

Magnetic resonance imaging (MRI) — MRI with multiphase enhancement of the liver can be performed using a gadolinium-based contrast agent (GBCA), while lesion intensity on T1- and T2-weighted images helps identify specific lesions [23]. While GBCA is well tolerated in most patients, it is associated with a small risk for nephrogenic systemic fibrosis or acute adverse reaction. These issues, along with patient evaluation before gadolinium administration, are discussed separately. (See "Patient evaluation before gadolinium contrast administration for magnetic resonance imaging".)

Specific GBCAs for liver lesion examination include:

●Gadoxetate disodium – Gadoxetate disodium, an MRI contrast agent that is slightly different from other gadolinium contrast, is typically used in this setting [24]. Gadoxetate is primarily taken up intracellularly by the hepatocytes and excreted in bile whereas other gadolinium contrast agents remain primarily extracellular and are excreted by the kidneys. This pharmacologic difference slightly alters the requirements for post-contrast imaging with gadoxetate. In addition to the image sets usually acquired for dynamic contrast administration, a hepatobiliary phase image set (usually 10 to 30 minutes after injection) is required. (See "Principles of magnetic resonance imaging".)

Thus, liver lesions that contain hepatocytes with an intact biliary excretion mechanism will take up this contrast agent and be easily distinguished from lesions that do not. Such lesions (eg, focal nodular hyperplasia (image 7)), are typically benign and usually appear at least isointense to the liver parenchyma on delayed (two to three hours) post-contrast sequences.

Lesion characteristics (eg, vascularity) that are visible on post-contrast, delayed images have contributed to imaging diagnostic accuracy. A study of 108 patients with confirmed focal nodular hyperplasia or hepatocellular adenoma (HCA) found that overall the sensitivity and specificity for contrast-enhanced MRI in differentiating focal nodular hyperplasia from HCA were 97 and 100 percent, respectively [25].

●Gadolinium ethoxybenzyl-diethylenetriamine pentaacetic acid – Gadolinium ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) is another GBCA that is taken up by hepatocytes and can be used to evaluate solid liver lesions [26]. Gd-EOB-DTPA is water-soluble, so it can be administered as a bolus injection. It can evaluate the enhancement characteristics and vascularity of liver lesions with a single-contrast injection. One area in which it has been used is the detection of hepatic metastases. Because metastatic lesions are not comprised of functional hepatocytes, they do not take up contrast and can be differentiated from the surrounding liver parenchyma [27,28].

Computed tomography (CT) — Multiphase, contrast-enhanced CT (non-contrast, arterial, and portal venous phases) findings that help differentiate among lesions include the lesions' patterns of vascular enhancement and washout after contrast administration, the number of lesions, and associated findings in the liver [1]. For example, an enhancing solitary mass in a cirrhotic-appearing liver with portal vein thrombosis, ascites, and splenomegaly is suggestive of hepatocellular carcinoma, while a small peripheral-enhancing lesion in an asymptomatic female with an otherwise normal-appearing liver is suggestive of hepatic hemangioma (table 1). (See "Hepatic hemangioma".)

While CT is widely available, it exposes patients to radiation, and this is discussed in more detail separately. (See "Radiation-related risks of imaging".)

Ultrasonography — Ultrasound is commonly performed as a noncontrast, transabdominal examination, but it can also be performed with contrast enhancement or intraoperatively:

●Noncontrast ultrasound – Characteristics on noncontrast ultrasound that may help with the diagnosis of a solid liver lesion include the lesion's echogenicity, the characteristics of the lesion's margins, the presence or absence of through-transmission, and findings on Doppler imaging [29]. Visualization may be difficult with lesions under the right hemidiaphragm, if there is overlying bowel gas, or in patients with obesity.

●Contrast-enhanced ultrasound – Contrast-enhanced ultrasonography (CEUS) (where available) can be used to evaluate incidental liver lesions. Studies looking at CEUS for the characterization of focal liver lesions have estimated that CEUS has a sensitivity of approximately 95 percent and a specificity of approximately 94 percent for diagnosing malignancy [30-34].

Ultrasound contrast agents modify the basic physical interactions between ultrasound waves and body tissues and amplify the signal produced by flowing blood. These agents may be useful for detecting subtle flow abnormalities and for distinguishing areas of abnormal flow relative to normal background parenchymal perfusion. As a result, they may improve the characterization of liver lesions compared with noncontrast ultrasound. Contrast-enhanced ultrasonography has been used increasingly in some countries as a primary imaging modality for evaluation of patients with a liver lesion, and this is discussed in more detail separately. (See "Contrast-enhanced ultrasound for the evaluation of liver lesions".)

●Intraoperative ultrasonography – Intraoperative ultrasonography (during which the transducer is placed directly upon the liver surface) is the most sensitive imaging technique for diagnosing liver metastases [35]. As with other hepatic masses, intraoperative ultrasonography can be helpful in delineating the extent of disease and vascular landmarks during hepatic resection [36]. (See "Open hepatic resection techniques", section on 'Staging laparoscopy and use of ultrasound'.)

Subsequent evaluation — If the etiology of the liver lesion is uncertain after obtaining contrast-enhanced, cross-sectional imaging, options include imaging-guided biopsy, surgical resection, or surveillance imaging.

Biopsy — If the diagnosis is uncertain after obtaining contrast-enhanced, cross-sectional imaging, an imaging-guided biopsy can be performed if the results are likely to affect the patient's management [37-41]. However, a number of controversial issues surround the role of biopsy in this setting. First, it is often nondiagnostic when used to evaluate some types of liver lesions such as hepatocellular adenomas and focal nodular hyperplasia. Second, it is associated with some degree of risk, including bleeding and seeding of neoplastic cells [42]. For example, a biopsy is generally not performed in patients with suspected hepatocellular adenoma because of risk of hemorrhage, and this is discussed separately. (See "Hepatocellular adenoma", section on 'Diagnostic approach'.)

The use of liver biopsy for patients with suspected hepatocellular carcinoma is discussed separately. (See "Clinical features and diagnosis of hepatocellular carcinoma", section on 'Liver biopsy'.)

Surgical resection — Surgical resection is rarely necessary for the establishing the diagnosis of an incidental solid liver lesion but may be performed for lesions of uncertain etiology that become symptomatic. If the diagnosis of HCC is suspected despite the absence of risk factors such as cirrhosis, surgical resection with histologic confirmation may be pursued if HCC cannot be excluded based on imaging. (See "Surgical resection of hepatocellular carcinoma".)

Surveillance imaging — For incidental lesions that cannot be characterized with cross-sectional, contrast-enhanced imaging but are not amenable to biopsy (eg, lesions <1 cm in size), surveillance imaging may be performed to detect lesion growth, changes in lesion appearance, and development of new lesions. Surveillance intervals are individualized depending on the suspected diagnosis and patient risk factors (eg, oral contraceptives) and generally range from 6 to 12 months.

Surveillance imaging for patients at risk for HCC is discussed separately. (See "Clinical features and diagnosis of hepatocellular carcinoma", section on 'Diagnostic approach' and "Surveillance for hepatocellular carcinoma in adults".)

SPECIAL POPULATIONS

Patients with extrahepatic malignancy — Metastases to the liver are a potential cause of solid liver lesions in patients with a history of extrahepatic malignancy. In such patients, the evaluation begins with a search for metastatic disease in other organs. This typically involves computed tomography of the abdomen and pelvis as well as chest imaging. The presence of lesions in multiple organs supports a diagnosis of metastatic disease. The specific staging evaluation will depend on the primary malignancy.

Image-guided liver biopsy is often useful to confirm the diagnosis of metastatic disease [43]. However, histologic confirmation is not always essential if reasonable certainty can be achieved with imaging studies, or in settings in which there would be little benefit to the patient to confirm the diagnosis.

However, patients with extrahepatic malignancies may also have incidental liver lesions, so if the evaluation for metastatic disease suggests the lesion is not metastatic in origin, additional evaluation may be required (eg, surveillance imaging, particularly for lesions <1 cm in size). (See 'Surveillance imaging' above.)

Patients with cirrhosis — Patients with cirrhosis and some patients with chronic liver disease (eg, chronic hepatitis B virus infection) are at risk for developing hepatocellular carcinoma, and the approach to evaluating such patients is discussed separately. (See "Surveillance for hepatocellular carcinoma in adults" and "Clinical features and diagnosis of hepatocellular carcinoma".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Focal liver lesions".)

SUMMARY AND RECOMMENDATIONS

●Background – Incidental liver lesions may be detected on imaging studies performed for an unrelated reason in adult patients without signs or symptoms (eg, right upper quadrant pain) attributable to the lesion. (See 'Introduction' above.)

The etiology of incidental liver lesions can be categorized as benign (eg, hepatic hemangioma, focal nodular hyperplasia) or malignant (eg, hepatocellular carcinoma). While most incidental lesions occur as a focal finding, multiple lesions may be seen in some patients (eg, those with more than one hepatic hemangioma). (See 'Differential diagnosis' above.)

●Diagnostic approach – As a first step in the diagnostic evaluation of an incidental liver lesion, it is important to confirm that the patient does not have risk factors for hepatocellular carcinoma (eg, cirrhosis, chronic hepatitis B virus infection) or for liver metastases (eg, history of extrahepatic malignancy) (algorithm 1). The diagnostic evaluation for patients who are at risk for developing a malignant liver lesion is discussed separately. (See "Clinical features and diagnosis of hepatocellular carcinoma".)

For patients without risk factors for a malignant liver lesion, the initial diagnostic evaluation is primarily based on the imaging appearance of the incidental lesion. Lesion characteristics that guide further management include lesion size, appearance (eg, margin), enhancement pattern, and growth pattern. (See 'Lesion characteristics' above.)

•Diagnostic imaging – Diagnostic imaging of solid liver lesions of uncertain etiology typically starts with contrast-enhanced, multiphasic, cross-sectional imaging. We typically use magnetic resonance imaging (MRI); however, computed tomography (CT) scan is an alternative if MRI is contraindicated or not available. (See "Patient evaluation for metallic or electrical implants, devices, or foreign bodies before magnetic resonance imaging" and 'Selecting an imaging modality' above.)

MRI with multiphase enhancement of the liver can be performed using a gadolinium-based contrast agent (GBCA). (See 'Magnetic resonance imaging (MRI)' above.)

While GBCA is well tolerated in most patients, it is associated with a small risk for nephrogenic systemic fibrosis or acute adverse reaction. These issues, along with patient evaluation before gadolinium administration, are discussed separately. (See "Patient evaluation before gadolinium contrast administration for magnetic resonance imaging".)

•Subsequent testing – If the etiology of an incidental liver lesion is uncertain after obtaining contrast-enhanced cross-sectional imaging, subsequent options include imaging-guided biopsy, surgical resection, or surveillance imaging. (See 'Subsequent evaluation' above.)

●Patients with extrahepatic malignancy – For patients with a history of extrahepatic malignancy, liver metastases are a potential cause of solid liver lesions. In such patients, the evaluation begins with a search for metastatic disease in other organs (eg, CT of the abdomen and pelvis as well as chest imaging). The presence of lesions in multiple organs supports a diagnosis of metastatic disease, and the specific staging evaluation will depend on the primary malignancy. (See 'Patients with extrahepatic malignancy' above.)