Imaging features of benign and malignant liver tumors and cysts

Hemangioma

Hepatic hemangiomas are benign vascular tumors of the liver and have an estimated incidence of anywhere between 4% and 20%. ^, Most hemangiomas are found incidentally on imaging studies such as ultrasound and CT. The most typical forms of hemangioma are cavernous and flash-filling hemangiomas.

On US, hemangiomas are characteristically homogeneously hyperechoic, well-circumscribed masses with subtle posterior acoustic enhancement ( Fig. 14.1A ). A hyperechoic rim may also be seen in a portion of hemangiomas, particularly if the hemangioma was predominantly isoechoic to liver. Increased echogenicity is because of multiple vascular interfaces within hemangiomas. Although hemangiomas are vascular, flow is extremely slow, and usually no Doppler signal is evident. If a US shows a classic appearance of hemangioma and the patient has no risk factors, history of underlying liver disease (hepatitis, alcohol abuse, fatty liver, etc.), or malignancy, then no follow-up imaging needs to be performed. ^, It should be noted that those with a history of malignancy and at an increased risk for hepatocellular carcinoma (HCC) should be further evaluated upon the identification of an echogenic liver lesion. In a study of 1,982 patients with cirrhosis, US depicted hemangioma-like lesions in 44 patients; on follow-up, half of these proved to be HCCs, and half were hemangiomas.

Larger hemangiomas often lack characteristic features because of central fibrosis, necrosis, and myxomatous degeneration and can appear heterogeneously hyperechoic (see Fig. 14.1B ). When the background liver itself becomes hyperechoic as a result of steatosis, hemangiomas may appear hypoechoic to liver parenchyma. ^,

On CT, hemangiomas are typically hypoattenuating to surrounding liver on noncontrast imaging. In patients with hepatic steatosis, the liver is typically diffusely decreased in attenuation, thereby decreasing the conspicuity of hypoattenuating hemangiomas. However, fatty sparing around the rim of the hemangioma can occur, resulting in the presence of a hyperattenuating rim on noncontrast CT.

MRI is ideal for characterizing hemangiomas and is the preferred modality for characterization with a high sensitivity and specificity. On T2-weighted imaging, hemangiomas are T2 bright, nearly similar in intensity to cerebrospinal fluid (CSF). On diffusion-weighted imaging (DWI), hemangiomas appear hyperintense on low b -values and remain hyperintense at higher b -values, similar to malignant lesions. Nevertheless, they will also have high apparent diffusion coefficient (ADC) values, a phenomenon known as T2 shine-through. This can be useful when differentiating from metastases, which have lower ADC values.

The classical enhancement pattern of cavernous hemangiomas seen on multiphase contrast-enhanced imaging done on US, CT, and MRI is typically peripheral, nodular, discontinuous enhancement on arterial phase, with centripetal fill-in on portal venous phase and persistent homogenous enhancement on later postcontrast phases ( Fig. 14.2 ). The peripheral areas of enhancement follow the same attenuation or signal intensity of blood vessels (such as the hepatic artery or portal vein).

Caution must be used when assessing enhancement on MRI using a hepatocyte specific contrast agent such as gadoxetate disodium (Gd-EOB-DTPA). The overlapping extracellular phase and hepatobiliary excretion of this contrast may confound the typical hemangioma enhancement pattern and lead to the appearance of “pseudowashout” in the late dynamic phase. Because hemangiomas do not contain hepatocytes, they become gradually hypointense on the transitional and hepatobiliary phase. For this reason, we prefer not to use gadoxetate disodium as the contrast agent for initial liver lesion characterization and use a traditional extracellular fluid contrast (ECF) agent instead, such as one of the macrocyclic gadolinium agents (e.g., gadobenate dimeglumine, gadoterate meglumine, gadoteridol).

Flash-filling hemangiomas are often small lesions (under 1 cm in diameter) and appear as diffusely hypervascular, homogenous lesions. Homogenous enhancement is seen in the arterial phase, and enhancement density/intensity follows that of the aorta in subsequent phases.

Larger hemangiomas tend to follow the cavernous type enhancement pattern criteria, although giant hemangiomas (>6–10 cm) may also have variable signal intensity and a central scar. Giant hemangiomas often do not completely fill in with contrast on delayed phases.

Calcification in hemangiomas is rare and is reported in 10% to 20% of cases, although our own experience is much lower than 10%. Calcifications may correspond to phleboliths and are most easily detected on CT.

Sclerosed and sclerosing hemangiomas are a rare type of hemangioma where degeneration and intralesional fibrosis and hyalinization occurs ( Fig. 14.3 ). These hemangiomas do not exhibit typical appearances on MRI because of loss of normal vascular channels. Markedly sclerosed hemangiomas lack the classic T2 hyperintense signal on MRI and may even become isointense to the liver parenchyma. Commonly, they demonstrate little or minimal arterial-phase enhancement and show variable progressive enhancement in portal venous and delayed phases. Some sclerosed hemangiomas may not achieve any enhancement on any phase, particularly if the lesion shows marked sclerosis on histopathologic evaluation. Additional features that may be seen in sclerosed hemangiomas include capsular retraction and peritumoral arterial enhancement. Thus, sclerosed hemangioma are easily mistaken for metastatic disease in the liver and may require biopsy for definitive diagnosis.

Focal nodular hyperplasia

Focal nodular hyperplasia (FNH) is the second most common solid benign liver lesion after hemangioma. Pathologically, FNH contains all the elements of normal liver, may have a central fibrous scar, and is surrounded by hepatocytes and small bile ducts. FNH has been associated with oral contraceptive use, as well as chemotherapy in the pediatric age group, although the former association is not definitive.

On US, FNH has a smooth lobulated contour and variable echogenicity. A key to US diagnosis of FNH is the characteristic Doppler appearance of a central feeding artery with tortuous spoke-wheel vascularity. A recognized feature of FNH is the presence of a central scar, yet this is usually better depicted on CT, MRI, or CEUS.

On CT, FNH is isoattenuating or slightly hypoattenuating to adjacent liver on noncontrast imaging. If a central scar is present, it is hypointense on precontrast phase. Although described as a typical feature, a scar is usually only seen on CT in approximately 20% to 50% of cases. ^,

On MRI, most FNH are isointense to normal liver parenchyma and nearly invisible on T1- and T2-weighted images ( Fig. 14.4 ). Occasionally, some lesions may be mildly T1 hypointense or minimally T2 hyperintense. When discussing relative T1 and T2 signal, a normal background liver parenchyma is assumed. In a liver with iron deposition, which diffusely lowers the signal intensity of the liver parenchyma, T1 and T2 relative hyperintensity can be expected. A central scar can be seen more frequently on MRI and is hypointense on T1-weighted images and hyperintense on T2-weighted images (see Fig. 14.4 ).

After intravenous (IV) contrast administration, the typical enhancement pattern of FNH is diffuse homogenous hyperenhancement in the arterial phase, followed by fading to background hepatic attenuation/intensity by the portal venous phase (see Fig. 14.4 ). Fading to background hepatic parenchyma signal should be distinguished from “washout,” where a lesion becomes darker than background liver. When a central scar is present, it enhances on delayed phases, beginning at approximately 3 minutes when using ECF contrast agents. When a hepatocyte-specific contrast agent is used, lesional enhancement similar to or higher-than-normal to background hepatic parenchyma during the delayed hepatobiliary phase is expected in the majority of FNHs ( Fig. 14.5 ). Of note, with the use of a hepatobiliary-specific agent such as gadoxetate disodium, a central stellate scar, if present, does not progressively enhance on later dynamic phases and will appear relatively hypointense, reflecting the absence of hepatocytes and the presence of fibrous tissue within the scar.

Hepatocellular adenoma

Hepatocellular adenoma (HCA) is a benign hepatocellular tumor; however, unlike FNH, it is a true neoplastic lesion with associated complications, such as abdominal pain, bleeding, and, rarely, malignant degeneration. HCAs have been traditionally associated with oral contraceptive use in women of childbearing age or anabolic steroid use in men. More recently, metabolic syndrome associations such as diabetes mellitus and obesity have also been recognized as risk factors. Adenomas are usually solitary, with multiple lesions seen in less than 30% of cases. Adenomatosis has been a term typically reserved for the presence of greater than 10 adenomas, first described in 1985. However, adenomatosis does not refer to a particular type of adenoma, and it has become apparent that clinical features and histologic subtype are more important than the number of adenomas present.

Over the past decade, HCAs have been further characterized and subtyped by their specific morphologic and immunohistochemical phenotype, with the most recent classification in 2017 describing eight subtypes. Four additional subtypes were added to the already described hepatocyte nuclear factor (HNF)1α-inactivated HCA (H-HCA), inflammatory HCA (IHCA), β-catenin-activated HCA (β-HCA) and “unclassified” subtypes. The newly added subtypes were β-HCA exon 7/8, β-IHCA exon 3, β-IHCA exon 7/8, and sonic-hedgehog HCA (sh-HCA), some of which were previously lumped together in the “unclassified” section. When considering HCA diagnosis for a liver lesion on imaging, correlation with patient demographics is important because men with metabolic syndrome or anabolic steroid use and adenomas with β-catenin-activated mutations are at a much higher risk for malignant degeneration.

On US, HCAs have variable echogenicity but are often hyperechoic because of intratumoral fat content. Internal hemorrhage within adenomas may produce cystic areas. Vascular flow is usually detected on Doppler imaging; however, the pattern of flow is nonspecific and may be seen as exclusively intralesional or perilesional or both perilesional and intralesional flow. On CEUS, HCAs demonstrate homogenous arterial hyperenhancement, with rapid and complete, usually centripetal, filling. On later phases of imaging contrast enhancement, characteristics are heterogenous, with some lesions demonstrating washout and others remaining iso- or hyperenhanced. It should be noted that washout in portal or later phases on postcontrast imaging on CT or MRI is not a typical feature of adenoma. It has been postulated that washout demonstrated on CEUS is because the microbubbles remain intravascular compared with the ECF contrast agents, which may see diffusion across the vascular endothelium into the tumor interstitium.

The CT appearance of adenomas often overlaps with FNH and HCC. Adenomas tend to have similar attenuation to normal liver on unenhanced images. Larger adenomas, however, are more heterogenous in appearance than smaller lesions, depending on their predilection to hemorrhage and/or the presence of fat. The characteristic pattern of contrast enhancement is variable degrees of arterial hyperenhancement and fading or persistent enhancement in later phases, depending on the HCA subtype. For example, strong arterial hyperenhancement with persistent enhancement in portal venous and subsequent delayed sequences is more typical for inflammatory HCA ( Fig. 14.6 ).

MRI is preferred to CT for identification of intracellular fat and for better characterization of HCA. Furthermore, certain imaging features on MRI have been shown to be associated with different subtypes to date.

H-HCAs are more likely to have diffuse, homogenous intratumoral fat deposition compared with other subtypes ( Fig. 14.7 ). This can be demonstrated by diffuse signal drop-out on out-of-phase compared with in-phase T1-weighted imaging. They also typically enhance less avidly in the arterial phase and are heterogeneously low in signal in the delayed hepatobiliary phase.

A specific feature of I-HCAs is the presence of marked sinusoidal dilatation, which manifests as moderate diffuse intralesional hyperintensity or a rim of hyperintensity (known as the “atoll sign”) on T2-weighted images and corresponding arterial hyperenhancement with persistent delayed enhancement on postcontrast imaging. A “crescent sign” has also been recently proposed, which is similar to the atoll sign, but the rim of T2 hyperintensity and hyperenhancement is incomplete or crescent-shaped. Some I-HCAs may show focal or heterogenous fat deposition. I-HCAs also have a propensity for internal hemorrhage, which can manifest as T1 hyperintensity or hemosiderin deposition, as seen by signal drop-out on in-phase imaging. Intralesional hemorrhagic changes, however, are non-specific, with such changes also seen in other subtypes. For example sh-HCAs, which account for approximately 4% of HCAs, have also been noted to have a predilection to hemorrhage. β-HCAs have no specific differentiating characteristics. They tend to show moderate, often heterogenous arterial-phase enhancement, which may persist but is variable in the late dynamic and delayed phases. These lesions show diffuse glutamine synthetase expression from upregulation, although they may be heterogenous. This is in contradistinction to FNH, which show map-like glutamine synthetase expression distribution adjacent to hepatic veins. Unclassified HCAs have no specific genetic or histopathologic abnormalities. Similarly, no specific imaging features have been identified for these lesions.

Traditionally, HCAs are expected to be hypointense on the hepatobiliary phase when using hepatocyte-specific contrast agent, in contrast to FNHs, which retain the same contrast agent and appear iso- to hyperintense. Iso/hyperintense uptake by FNH has been shown to correlate to expression of hepatocyte proteins such as OATPB1/B3. Nevertheless, increasing studies have noted the retention of hepatocyte-specific contrast in a small proportion of adenomas, particularly the β-HCA subtype. This is thought to be explained by the expression of hepatocyte transport proteins such as OATPB1/B3 that can be seen in β-HCAs. The majority of adenomas do not display OATPB1/B3 expression, however, and the evaluation of hepatocyte-specific contrast uptake in a lesion remains helpful in the differentiation of FNH from adenoma, when an HCA has low signal in the delayed hepatobiliary phase. Care should also be taken in the interpretation of perceived retention of hepatocyte-specific contrast in some lesions, which may instead be explained by inherent hyperintensity on precontrast T1 imaging because of the presence of blood products or relative to underlying hepatic parenchymal steatosis.

Angiomyolipoma and other benign fat-containing hepatic tumors

Angiomyolipoma

Hepatic angiomyolipoma (HAML) is an uncommon tumor and is seen more frequently in women. HAML is generally considered a benign, solitary tumor made up of three elements: smooth muscle, thick-walled blood vessels, and mature adipose tissue. HAML imaging features may vary based on the relative proportions of the three elements within a lesion, which makes this lesion often challenging to diagnose on imaging. Although intralesional fat is typical in HAMLs, they can often show brisk, avidly enhancing soft tissue components with washout, which can overlap with other liver malignancies, such as HCC (see Chapter 89 ), and some lesions may present without detectable fat ( Fig. 14.8 ). Tortuous vessels and enlarged early draining veins to either portal veins or hepatic veins are features that have been associated with HAML. Intralesional hemorrhage may be seen in a small proportion of cases.

At US, HAMLs are typically well-demarcated, echogenic lesions, similar in appearance to hemangiomas. On CT, intralesional fat is evidenced by fat density tissue (< −20 HU). On MRI, the signal characteristics of macroscopic lipid follow that of subcutaneous fat and demonstrate signal drop out on T1-weighted and T2-weighted fat-saturated sequences. Microscopic fat can also be seen in HAML, seen as signal drop-out on out-of-phase compared with in-phase T1-weighted images.

Enhancement on multiphase CT and MRI is typically a heterogeneous pattern of hyperenhancement on arterial phase with washout on portal venous or delayed phase; however, gradual and prolonged enhancement may also be observed. Peripheral rim enhancement caused by peripheral tumor vessels may also be seen, a feature which the reader must be careful not to misdiagnose as a tumor capsule typically seen in a HCC. ^, On contrast-enhanced images using gadoxetic acid, HAMLs typically appear hypointense on delayed hepatobiliary phase. In summary, if a well-demarcated, hypervascular, macroscopic fat-containing tumor is seen with peripheral enhancement, if it has no tumor capsule, and if there are early draining veins, an angiomyolipoma should be considered, particularly in patients without cirrhosis.