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Mimics of Hepatic Neoplasms
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Mimics of Hepatic Neoplasms Rafel Tappouni MD, Michelle D. Sakala MD, Keyanoosh Hosseinzadeh MD
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S0037-198X(15)00041-3 http://dx.doi.org/10.1053/j.ro.2015.08.003 YSROE50518
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Seminar in Roentgenology
Cite this article as: Rafel Tappouni MD, Michelle D. Sakala MD, Keyanoosh Hosseinzadeh MD, Mimics of Hepatic Neoplasms, Seminar in Roentgenology, http://dx.doi.org/ 10.1053/j.ro.2015.08.003 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Mimics of Hepatic Neoplasms Rafel Tappouni MD, Michelle D Sakala MD, Keyanoosh Hosseinzadeh MD
Department of Radiology Wake Forest University School of Medicine One, Medical Center Blvd Winston-Salem, NC 27157 Tel: 336-716-2471 Fax: 336-716-0555 Contact: [email protected]
Abstract: Liver lesions are commonly encountered during surveillance imaging. These include a myriad of lesions ranging from neoplastic to nonneoplastic lesions. performed
by
Characterization of these lesions is usually
ultrasound
(US),
contrast
enhanced
computed
tomography (CECT) and magnetic resonance imaging (MRI). Many of the lesions have diagnostic features based on specific features related to lesion echogenicity, attenuation, intensity and enhancement. Making the correct diagnosis often depends on the pattern of enhancement of hepatic parenchyma, presence of systemic disease and presence of known malignancy and/or diffuse liver disease. Awareness of mimics of hepatic neoplasms that may have a similar enhancement pattern to neoplastic lesions is essential to avoid misdiagnosis and unnecessary biopsy. Familiarity with the pathophysiology, clinical history, and cross
sectional imaging appearance of the liver is crucial in distinguishing neoplastic from non-neoplastic conditions. This article describes liver lesions that can resemble benign or malignant liver neoplasms and highlights their specific findings that enable radiologists to make the accurate diagnosis. Introduction: The normal liver receives a dual blood supply from the hepatic artery and the portal vein, each supplying approximately 25% and 75% of blood volume respectively [1]. As a result, there is low enhancement of the normal liver parenchyma during the arterial phase as the contrast transported by the hepatic artery is diluted by a ratio of 4:1 by unopacified portal venous blood. Note that hepatic neoplasms are usually predominantly supplied by the hepatic artery. This distinction is the basis for the multiphase contrast enhanced liver protocol for computed tomography (CT) and MRI. It is important to realize that the arterial and portal venous supplies are not independent vascular channels; communications exist between the two via the hepatic sinusoids with blood flowing through the liver sinusoids and emptying into the central vein of each lobule. The central veins coalesce into hepatic veins, which drain into the inferior vena cava. When vascular
compromise occurs, the dual blood supply can change in the volume and direction of blood flow; when the portal venous flow decreases and/or reverses direction of flow, arterial flow increases to compensate.
Disruption to the inflow or outflow of blood to the liver may give rise to nonneoplastic hypervascular lesions, vascular shunts and perfusion abnormalities within the liver. In patients with diffuse liver disease, the background liver architecture is altered and the hepatic blood flow and drainage is disrupted. Therefore great attention should be taken when evaluating a focal lesion in the setting of diffuse liver disease to avoid misdiagnosing a vascular lesion as neoplastic. The distorted architecture of the hepatic parenchyma in cirrhosis is a predisposing condition to developing an arterioportal shunt. Focal non-neoplastic lesions in hepatic steatosis, iron overload and the combination of both can present a diagnostic dilemma. Pyogenic, fungal and parasitic infections in addition to inflammatory conditions can involve the liver. If there is a solid component from granulation or inflammatory tissue, these lesions can mimic metastatic disease.
In this review, we discuss the appearances of liver lesions that may mimic neoplasms in vascular and perfusion disorders, diffuse liver disease and infectious and inflammatory conditions.
Vascular and Perfusion Disorders: Arterioportal Shunts Arterioportal (AP) shunts result from the entry of blood from a high pressure arterial system to a low pressure portal venous system through an abnormal connection. This leads to an increase in the regional perfusion pressure resulting in local parenchymal perfusion abnormality [2]. AP shunts can be divided into spontaneous, posttraumatic and iatrogenic. Spontaneous AP shunts are common in the setting of cirrhosis. They are frequently peripheral, but can be central, and usually measure less than 2 cm in size (Fig 1). These lesions represent abnormal vascularity with no clinical significance or pathological alterations and can resolve on subsequent imaging [3-5]. They can be associated with focal lesions such as hepatocellular carcinomas and hemangiomas [6]. In comparison to AP shunts, which are spontaneous, AP fistulas are most commonly iatrogenic and represent connections between a high pressure hepatic artery and an
adjacent low pressure portal vein. They result from arterial injury from liver biopsy or biliary intervention [7] and may progress to hemodynamically significant fistulas requiring endovascular treatment.
Arterioportal shunts are usually subcapsular and do not exhibit mass effect on adjacent vessels and bile ducts. They are usually not seen on unenhanced CT as they are isoattenuating to the surrounding liver. At CT performed in the hepatic arterial phase (HAP), AP shunts typically appear as a peripherally located enhancing focus and are less commonly centrally located. On portal venous phase, (PVP) the shunt becomes isoattenuating compared to the background liver [8]. In some cases, early enhancement of a dilated peripheral branch of the portal vein occurs during the hepatic arterial phase, before opacification of the main portal vein (Fig 1) [9]. On MRI, these lesions are occult on unenhanced T1 and T2-weighted sequences and the enhancement pattern parallels that of the CT [10, 11]. AP shunts are typically not seen on US. AP fistulas are indistinguishable from AP shunts on imaging unless there is evidence of iatrogenic intervention such a gas filled biopsy tract.
In cirrhotic patients, AP shunts less than 2 cm are referred to as pseudolesions and can be difficult to distinguish from hepatocellular carcinoma. Distinguishing features of hepatocellular carcinoma include mass effect, washout on the PVP, and hypointensity in the hepatobiliary phase of MR images following administration of liver-specific contrast agents. However, if the pseudolesion is small and round, the specificity of these imaging features to differentiate AP shunts from well differentiated hepatocellular carcinoma is low [11]. The American Association for the study of Liver Diseases recommends imaging follow up for small indeterminate hypervascular lesions for assessment of imaging features and growth [12]. In cirrhotic patients, it is suggested that a six month follow up CT or MRI is the recommendation for small, indeterminate enhancing liver nodules [13].
Budd-Chiari Syndrome Budd-Chiari syndrome is the obstruction of hepatic venous outflow at the hepatic veins or hepatic inferior vena cava (IVC) level. The outflow obstruction leads to increased sinusoidal pressure and diminished portal venous flow. This results in centrilobular congestion followed by
hepatocellular necrosis and atrophy. It affects women more than men and can occur at any age.
It is classified into primary and secondary types. Primary causes include congenital webs and diaphragms in addition to injury and infection. The majority of secondary causes are thrombotic, most commonly secondary to a hypercoagulable state from contraceptive use, pregnancy, paroxysmal nocturnal hematuria, polycythemia, protein S and C deficiency, antithrombin III deficiency and factor V Leiden mutations. In these cases, the thrombus is usually in a major hepatic vein or hepatic IVC. Secondary causes include chemotherapy and radiation therapy, where the thrombus is in a central or in a sublobular vein. In addition, bone marrow transplantation can cause thrombosis of small centrilobular veins [14, 15]. Primary Budd-Chiari is more common in Asia, India, and Africa versus secondary causes being more common in western countries. The clinical presentation depends on the acuteness of the disease. The acute form has rapid onset of jaundice and ascites, whilst the subacute or chronic form is more gradual. The less common fulminant form has rapid progression over eight weeks from disease onset to hepatic encephalopathy.
During the acute stage, hepatocellular necrosis develops rapidly as collateral vessels have not yet developed. At unenhanced CT, the liver morphology is maintained but the liver is enlarged and diffusely hypodense secondary to edema. There is narrowing of the hepatic veins and IVC, which may appear hyperattenuating when a thrombus is present [16]. HAP shows decreased peripheral enhancement due to diminished perfusion caused by decreased portal perfusion from increased sinusoidal pressure. There is early enhancement of the caudate lobe and the central liver due to separate venous drainage. PVP may demonstrate a “flip-flop” pattern with hypoattenuation of the central liver due to washout and increased attenuation of the periphery of the liver due to contrast flow from capsular veins.
In the subacute or chronic phase, the peripheral areas are deprived of flow from the portal system and cannot regenerate. However, because of accessory venous drainage and preservation of the portal venous supply to the caudate lobe, the central region of the liver may undergo hypertrophy (Fig 2) [16, 17]. Portosystemic and intrahepatic collateral vessels are formed (Fig 2). These pathways include intrahepatic veno-
venous
comma-shaped
collaterals,
systemic
collaterals
in
the
subcutaneous tissues and capsular vein collaterals. Ascites (Fig 2) and splenomegaly are frequently seen. The chronic thrombus in the IVC can calcify and portal vein thrombus may form secondary to portal flow stagnation. On HAP, the liver demonstrates diffuse heterogeneous enhancement. Formation of macroregenerative nodules in the chronic phase is a response to decreased hepatic perfusion. This leads to atrophy with compensatory formation of regenerative nodules in those regions of the liver with preserved blood supply. These nodules are typically 0.5 to 4 cm in size and are not seen on unenhanced CT. They enhance homogeneously on HAP phase, although some show rim enhancement (Fig 3). On the PVP, the nodules remain hyperattenuating compared to the surrounding liver [15, 18]. On MRI, these nodules are isointense on T1-weighted images and the enhancement parallels that of CT. Pathologic examination of these nodules reveals benign hyperplastic hepatocytes fed by large arteries [17].
Grey scale US shows narrowing, non-visualization and/or thrombosis of the hepatic veins. Color Doppler US shows intrahepatic collaterals and
flat and/or reversed flow within the hepatic veins and IVC. The portal vein may demonstrate slow hepatofugal flow.
In contrast to macroregenerative nodules, hepatocellular carcinoma classically demonstrates washout in the portal venous phase. The formation of collateral vessels, hepatic vein narrowing, thrombosis and clinical
history
are
important
clues
to
help
differentiate
macroregenerative nodule from hepatocellular carcinoma. Caudate hypertrophy and transient attenuation differences should not be mistaken as a hepatic neoplasm, with the latter causing mass effect and vascular distortion.
Passive Hepatic Congestion Passive hepatic congestion is the stasis of blood in liver parenchyma due to cardiac disease causing impaired hepatic venous drainage. The decreased hepatic blood flow, elevated hepatic venous pressure, and diminished arterial oxygen content, if untreated, will lead to hepatocellular hypoxia and necrosis. The incidence of passive hepatic congestion is not known and there is no known age or sex predilection. Passive hepatic congestion is seen in congestive heart failure,
cardiomyopathy, pericardial effusion, constrictive pericarditis and tricuspid valvular disease. In early stages, the disease is subclinical and asymptomatic liver dysfunction is common. If untreated, patients can develop jaundice, hepatomegaly, fibrosis and cardiac cirrhosis [19]. The treatment goal is to reduce hepatic venous congestion and right-sided heart pressure.
On CT and MRI obtained in HAP, the retrograde flow of contrast material from the right atrium into the IVC leads to early enhancement of a dilated IVC and central hepatic veins (Fig 4). PVP shows delayed enhancement of the hepatic veins due to the stagnant venous outflow resulting from elevated central venous pressure (Fig 4). The hepatic parenchyma shows progressive enhancement, described as mottled or mosaic in appearance, with linear or curvilinear areas of decreased enhancement representing stagnant hepatic venous outflow (Fig 4). Other features include peripheral large patchy areas of decreased enhancement and perivascular lymphedema. The appearance is of low attenuation
linear
areas
surrounding
the
hepatic
IVC
[20].
Cardiomegaly, pleural effusions and ascites may be present. Pericardial calcification may be seen in the setting of constrictive pericarditis.
Uncorrected passive hepatic congestion can lead to cardiac cirrhosis, also known as congestive hepatopathy [21]. Ultrasound shows a dilated IVC and hepatic veins, hepatomegaly and ascites. Duplex Doppler US shows an extra retrograde wave at the end of diastole as the right atrium and ventricle fill passively via the superior vena cava and IVC during diastole [22].
Heterogeneous
enhancement
with
patchy
areas
of
decreased
enhancement can mimic liver masses. Clues to making the correct diagnosis of passive hepatic congestion are identification of dilated hepatic veins, retrograde flow from the right atrium and delayed mottled hepatic enhancement.
Hereditary Hemorrhagic Telangiectasia Hereditary Hemorrhagic Telangiectasia (HHT) is a multisystem autosomal-dominant vascular remodeling disease resulting in multiple telangiectasias and arteriovenous malformations. It primarily affects the skin, lungs, gastrointestinal tract, liver and central nervous system. Patients are usually adults and there is no sex predilection. The most common presentation is epistaxis and hemoptysis [23]. Hepatic
involvement is usually diagnosed 10-20 years after the appearance of telangiectasias [24, 25] and imaging findings often correlate poorly with symptoms [26, 27]. A third of patients have liver manifestations, although some report a higher incidence of up to 74% [25, 27].
Hepatic involvement is characterized by hyperdynamic circulation, which can result from shunting from hepatic artery to hepatic vein, hepatic artery to portal vein and portovenous and extrahepatic shunts. Liver involvement can result in portal hypertension, hepatic encephalopathy, ischemic cholangiopathy, hepatocellular necrosis and ultimately liver failure. The diagnosis of the hepatic involvement is based on clinical manifestations coupled with imaging findings.
Imaging features on CECT or MRI in HAP show dilation and tortuosity of the extra- and intrahepatic arterial branches with early opacification of portal or hepatic veins (Fig 5), indicating arterioportal or arteriovenous shunting respectively [24, 26, 27]. In addition, the arterial phase may show a mosaic pattern of enhancement with areas of transient hepatic attenuation difference that is indicative of AP shunts, pseudolesions such as telangiectasias and confluent vascular masses that can mimic
neoplasms. Dilated, tortuous hepatic arteries are often conspicuous and may
help
distinguish
HHT
from
passive
hepatic
congestion.
Telangiectasias are subcentimeter, usually non-spherical, hypervascular nodules that may coalesce into larger spherical confluent vascular masses (Fig 5). These confluent masses appear as large vascular pools with
early
and
persistent
enhancement
in
HAP.
Multiplanar
reformations and maximum-intensity projections may be helpful to detect small lesions, especially those adjacent to vessels [28]. PVP shows normal homogenous enhancement of the liver with enlargement of the hepatic veins and IVC. Unlike cavernous hemangiomas, telangiectasias and vascular masses associated with HHT will not show peripheral discontinuous nodular enhancement. Liver biopsy is not required for diagnosis or justified given the risk of bleeding.
Ultrasound Doppler shows vascular malformations as “color spots” [29]. The hepatic artery is often enlarged with aliasing on color Doppler US due to increased turbulence and flow velocity. Spectral Doppler may exhibit abnormally low-resistance arterial flow (Fig 5), arterialization of portal flow or reversal of portal flow depending on the size and severity
of the shunt [30]. Hepatic veins demonstrate a high amplitude waveform and loss of the triphasic waveform (Fig 5) [31]. Hepatic Infarction Hepatic infarction is coagulative necrosis from hepatocyte cell death form local ischemia involving more than one hepatic lobule. The local hepatic ischemia is usually caused by an obstruction to the blood supply to the area, most commonly due to thrombus. Liver infarcts have gross and microscopic appearances similar to ischemic infarcts in other organs [32]. Causes include: Iatrogenic such as hepatobiliary surgery and intrahepatic chemoembolization; traumatic such as laceration of portal vein and hepatic artery; transplant-related such as hepatic artery stenosis or thrombosis; and hypercoagulable states secondary to sickle cell anemia, vasculitis and infection [33].
Hepatic infarction is relatively rare because of the dual blood supply and extensive collateral pathways of the liver. However with the increasing rate of liver transplantation and vascular complications related to hepatobiliary surgery, there has been a significant increase in the detection of hepatic infarction [34]. Unenhanced CT shows peripheral
wedge-shaped,
rounded
or
irregularly
shaped
low
attenuation areas that parallel the bile ducts. Contrast enhanced CT obtained in the HAP and PVP shows sharply defined, poorly enhancing, conspicuous and peripheral wedge-shaped low-attenuation lesions extending to the liver surface. The shape of larger infarcts is typically geographic with straight borders. Wedge shaped infarcts are usually peripheral. In contrast, rounded infarcts are more central in location (Fig 6) [35]. The majority of hepatic infarcts do not enhance but can demonstrate decreased heterogeneous enhancement. The enhancing component represents non-displaced vessels or viable tissue within the infarcted area [35]. A surrounding rim composed of nonvascularized fibrous tissue may be present (Fig 6). Formation of gas within hepatic infarcts can be either infectious or sterile.
On MRI, hepatic infarcts appear hypointense on T1-weighted images and hyperintense on T2-weighted images (Fig 6) [36]. Contrastenhanced MRI parallels CT. Ultrasound can show an ill-defined heterogeneous peripheral hypoechoic area which is hypovascular or avascular, if completely necrotic. The infarcted area may become anechoic and cystic with distinct borders [37].
In the appropriate clinical setting, the diagnosis is established with ease; however, hepatic infarcts may mimic focal hepatic steatosis, abscess and neoplasm [33, 38]. The geographic segmental shape with straight borders and lack of enhancement of an infarct helps differentiate it from a neoplastic lesion. Focal hepatic steatosis occurs in characteristic areas, and the parenchymal enhancement in focal steatosis is maintained. A hepatic abscess has rim like peripheral enhancement and a nonenhancing central area [9]. Preservation of portal tracts within the infarct can help differentiate an infarct from a hypoattenuating mass in transplanted livers.
Diffuse Liver Related Disorders: Hemochromatosis Hemochromatosis is a disorder characterized by a progressive increase in body iron stores and iron deposition resulting in organ dysfunction. There is no gender predisposition and age of onset ranges from 30 to 60 years. In men, the diagnosis usually becomes evident in middle age whereas in women, clinical presentation is delayed to the post-menopausal period.
Hemochromatosis is
classified
into
primary
or
secondary
hemochromatosis. Primary hemochromatosis is an autosomal recessive genetic disease that leads to the increase of iron absorption secondary to alteration of the protein that is responsible for iron absorption. Secondary hemochromatosis is caused by parenteral iron infusion or multiple transfusions, increased iron absorption such as in cirrhosis and anemias related to ineffective erythropoiesis such as thalassemia and myelodysplastic syndrome.
On unenhanced CT, hemochromatosis shows homogenous increase in hepatic attenuation (75-130 HU) [39] making the hepatic and portal veins appear hypoattenuating compared to background liver. T1weighted gradient-echo in-phase and opposed-phase sequences show decreased liver signal on the in-phase compared to that of the opposed-phase sequences. Gradient-echo T2* weighting sequence shows decreased liver signal
compared
to
that
of
paraspinal
musculature.
Primary
hemochromatosis shows decreased signal intensity from iron deposition in the liver, heart and pancreas whereas in secondary hemochromatosis, the liver and spleen and bone marrow demonstrate decreased signal intensity [40].
The association between hepatic steatosis and hepatic iron deposition is a recognized finding [41] which can make the diagnosis challenging (Fig 7). The drop in signal intensity occurs on the out-of-phase images in steatosis versus drop in signal intensity on the in-phase images for hemochromatosis.
Although the diffuse form of steatosis and hemochromatosis is usually easily diagnosed, the nodular form gives rise to pseudonodules which can mimic true lesions. These pseudonodules may be areas of focal steatosis, focal fatty sparing or focal regions of iron overload (Fig 7). Careful attention should be made to the signal change on dual echo sequences, the pattern of enhancement and the lack of mass effect and vascular distortion. Compared to hepatocellular carcinoma, these pseudolesions have no expansive effect or vascular distortion, and their enhancement parallels that of the background liver [40].
Patients with
chronic
anemia
and
iron
overload
may have
extramedullary erythropoiesis in the hepatic parenchyma which can mimic a hepatic mass. The signal characteristics of hepatic
extramedullary
erythropoiesis
usually
parallels
that
of
the
extramedullary erythropoiesis in the paravertebral regions [42]. Atypical Hepatic Steatosis Hepatic steatosis is a common condition in adults with prevalence of 1530% [43, 44]. The prevalence is higher in obesity, diabetes and patients with high alcohol consumption and hyperlipidemia [45].
Atypical hepatic steatosis can have different patterns including focal, multifocal, perivascular and subcapsular. The focal pattern can be due to focal fatty infiltration or focal fatty sparing. Focal fatty infiltration occurs in certain locations within the liver that commonly include the area adjacent to the falciform ligament, ligamentum venosum, porta hepatis, gallbladder fossa and the subcapsular region. The location of focal fatty sparing is essentially the same as the focal fatty infiltration.
On CT and MRI, focal fat can be distinguished from a liver lesion because it is fat containing, occurs in a specific location, has no mass effect on the adjacent structures, has nondistorted vessels running through the area and has geographic margins [49]. On HAP or PVP, focal steatosis enhances similar to or less than that of background liver. Multifocal
fatty deposition is less common than the focal pattern and can involve atypical locations. The fatty foci may be round and can be seen in any location within the liver, mimicking a true focal lesion. Chemical shift gradient-echo MRI is often needed, especially in patients with known primary malignancy or cirrhosis, to differentiate intracellular lipid deposition from malignancy.
The perivascular pattern is characterized by a fat halo surrounding the portal veins, hepatic veins or both. CT shows uniformly sized, confluent low-attenuation halos surrounding the venous segments. If the vessel courses in the imaging plane, the halo appears as tram-like. If the vessel is perpendicular to the imaging plane, the vein appears as a central dot (Fig 8) [50]. MRI shows signal intensity loss on the opposed-phase sequence compared to the in-phase sequence (Fig 8).
Hepatic
metastases can be differentiated from perivascular steatosis because of lack of size uniformity and central dot pattern, in addition to heterogeneous enhancement. Confluent Hepatic Fibrosis Confluent hepatic fibrosis is a common finding in liver cirrhosis and can be focal or diffuse. It appears as a wedge-shaped mass in a subscapular
location radiating from the porta hepatis, with capsular retraction or focal flattening of the capsule. The most common location is the medial segment of the left lobe, anterior segment of the right lobe or both [34].
On unenhanced CT, confluent hepatic fibrosis appears as a peripheral hypoattenuating lesion with capsular retraction and volume loss. On the PVP it demonstrates mild enhancement and appears iso to hyperattenuating compared to background liver. On MRI, confluent fibrosis appears as low signal on T1-weighted images and high signal on T2-weighted images with progressive delayed enhancement on gadolinium-enhanced images (Fig 9) [52]. These features are not unique for confluent fibrosis and cannot differentiate from hepatocellular carcinoma;
studies
have
shown a
false-positive diagnosis
of
hepatocellular carcinoma on CT [53] and MRI [54] for lesions that subsequently prove to be focal confluent fibrosis. However, unlike infiltrative hepatocellular carcinoma, the geographic location and pattern of confluent fibrosis, vessel crowding and overlying capsular contraction can be helpful in making the diagnosis (Fig 9) [52].
Inflammatory and Infectious Lesions Hepatic candidiasis The manifestations of Candida infection range from local mucous membrane infection to widespread dissemination with multisystem organ failure. These infections can be acute or chronic and localized or systemic.
Invasive
systemic
candidiasis
is
a
well-recognized
complication of myelosuppressive treatment that usually manifests as generalized gastrointestinal symptoms, hepatomegaly and fever [55]. There has been a considerable rise in the incidence of systemic candidiasis over the past decades due to advances in cancer treatment [56]. The most common organs involved are the liver and spleen followed by the kidneys. Hepatic spread results from gastrointestinal colonization with secondary hematogenous seeding to the portal venous system and development of microabscesses, which carries a high morbidity and mortality.
On US, four patterns have been described that correlate with the stage of the disease. The most common is a uniform hypoechoic nodule. This is the least specific pattern and may mimic hepatic metastatic disease and lymphoma. The second is a central echogenic nidus with a
hypoechoic rim. This pattern is usually seen in early infection and is referred to as a "target" sign (Fig 10). The third is a central hypoechoic area of necrosis surrounded by an echogenic zone of inflammatory cells and a hypoechoic rim due to fibrosis. This pattern is typical of early disease and known as a “wheel within wheels" sign (Fig 10). The fourth pattern is usually seen at later stages of the infection and appears as an echogenic lesion with variable degrees of posterior acoustic shadowing indicating early disease resolution [57, 58].
On CECT, hepatic candidiasis appears as multiple round, discrete low attenuation liver lesions ranging from 2 to 20 mm in size. These usually enhance centrally after intravenous contrast, although peripheral or rim enhancement may occur (Fig 10) [59, 60]. The enhancing component is an inflammatory portion and the hypodense component contains fungi and necrosis. The "wheels within wheels" pattern is infrequently seen at CT, whereas the "target" pattern is only seen occasionally (Fig 10) [61].
MRI of the acute stage shows multiple rounded small T1-weighted hypointense and markedly T2-weighted hyperintense lesions without enhancement. In the subacute stage, the lesions appear hyperintense on
T1- and T2-weighted images, enhance with gadolinium and have a dark surrounding rim. The “wheels within wheels“ and “target” enhancement patterns can also be seen on MRI (Fig 10) and parallel that of CT. Chronic treated lesions can be irregular and can measure up to 3 cm. They appear as minimally hypointense on T1- weighted images, iso- to mildly hyperintense on T2-weighted images, hypointense on arterial phase and minimally hypointense on equilibrium phase images [62, 63].
Features that help differentiate hepatic fungal disease from metastatic disease include multiplicity, uniformity with small size, rounded outline, “target” or “wheels within wheels“ pattern of enhancement and splenic involvement. Clinical correlation is important as hepatic candidiasis most
commonly
occurs
in
hematological
malignancy
or
immunosuppressed patents, and antibiotic-resistant fever is a highly suggestive sign.
Intrahepatic Hydatid Cyst Hydatid disease is caused by the Echinococcus tapeworm. Patients are usually asymptomatic at early stages. The symptomatology depends on
the location and size of the cysts. When the Echinococcus embryo is ingested, it gets absorbed by the intestine and is transported to the liver by the portal vein. It is then filtered by the liver; however, any unfiltered embryos become hydatid cysts [64]. Abdominal pain, weight loss, and jaundice may develop when the liver is affected.
Histopathologically, the cyst is composed of three layers: the outer pericyst that corresponds with fibrotic liver tissue; the endocyst, an inner germinal layer; and the thin ectocyst, a translucent membrane. As the cyst matures, the endocyst invaginates leading to the development of daughter cysts in the periphery.
Hydatid cysts have variable features on US ranging from unlilocular, multilocular and solid appearing lesions. Delaminated endocysts can give rise to wavy bands referred to as the “water lily” sign. Unenhanced CT shows a well-defined complex hypoattenuating lesion with a wellformed wall. Coarse wall calcification is common, seen in 50% of cases. The hyperattenuating matrix, also referred to hydatid sand, is frequently seen filling the central portion of the lesion. Daughter cysts are seen in 75% of cases and appear as multiple hypoattenuating round
areas that are peripheral in location surrounding the hydatid sand (Fig 11) [65]. On MRI, the pericyst is seen as a hypointense rim on both T1and T2-weighted images due to its fibrous composition and calcifications. The matrix appears hypointense on T1- weighted images and markedly hyperintense on T2-weighted images. Daughter cysts appear as hypointense relative to the matrix on both T1- and T2weighted images [66].
The appearance of the well-formed wall with coarse calcification, the central matrix and peripheral daughter cysts produce pathognomonic features of a hepatic hydatid cyst. However, making the diagnosis can be challenging when the daughter cysts are absent, the central matrix is minimal and if there is no wall calcification. Patient history and laboratory findings are helpful in these cases to raise the possibility of hydatid disease.
Pyogenic Abscess Pyogenic liver abscesses may develop from a gastrointestinal source that spreads to the liver via the portal circulation, by direct spread from biliary infection and by arterial hematogenous seeding in the setting of
systemic infection. The most common organisms are gram-negative bacteria and Clostridium species, and more than 50% are polymicrobic [64].
Pyogenic abscesses are stratified according to size with microabscesses being less than 2 cm and macroabscesses being greater than 2 cm. Microabscesses can appear as multiple diffusely scattered lesions that appear similar to fungal microabscesses. Microabscesses can also be cluster-like and coalesce focally in an early stage of the evolution into a larger abscess.
Ultrasound of microabscesses shows hypoechoic nodules or ill-defined areas of distorted hepatic echogenicity with little through transmission. Large abscesses may be hypoechoic or hyperechoic with variable amounts of internal echoes. Gas within an abscess causes high-intensity linear echoes with acoustic shadowing, also referred as dirty shadowing.
Contrast enhanced CT of microabscesses show multiple small, welldefined hypoattenuating lesions with rim enhancement and perilesional
edema (Fig 12). Large abscesses may be unilocular, hypoattenuating and with well-defined smooth margins or complex with internal septa, multiple locules and irregular margins (Fig 12). Rim enhancement and the presence of gas are relatively common. The septal and rim enhancement of individual abscesses is an important finding that can help distinguish a liver abscess from a necrotic hepatic mass.
On MRI, pyogenic abscesses have variable signal intensity on T1- and T2-weighted images. MRI has increased sensitivity in detecting perilesional edema, which shows increased signal intensity on T2weighted images (Fig 12). This can be a helpful feature in making the diagnosis [64, 67]. DWI can be helpful in differentiating a hepatic abscess from metastases, necrotic masses and malignant lesions with rim enhancement. The center of the hepatic abscess is hyperintense on DWI and has low ADC values due to pus-containing inflammatory cells, bacteria and/or necrotic tissue. In comparison, a necrotic tumor is hypointense on DWI and has high ADC values due to low viscosity and cellularity. The rim of an abscess may also appear as hyperintense on DWI and have high ADC versus the rim of a necrotic tumor where the ADC values are low [68-70].
Sarcoidosis Sarcoidosis is a mutisystemic inflammatory disease of unknown origin characterized by the formation of non-caseating epithelioid granulomas with surrounding fibrosis in the periportal regions and portal tracts. It affects young and middle-aged patients, with a higher prevalence in women than men. The most common manifestation of hepatic sarcoidosis is diffuse infiltration of noncaseating epithelioid granulomas in the liver [36]. The liver and spleen are the most frequently involved abdominal viscera with granulomata noted in 40-70% of patients [72]. The most common abdominal features include hepatosplenomegaly, abdominal adenopathy and focal liver and splenic nodules (Fig 13).
On US, lesions are hypoechoic relative to the background liver and there is hepatomegaly with increased liver echogenicity. On CECT, the liver nodules are hypoattenuating ranging in size between 5 to 20 mm and become more confluent with increasing size, corresponding to coalescing granulomas (Fig 13). On MRI, nodules are hypointense on T2-weighted images and hypoenhancing relative to background liver on early phase contrast images [36, 72]. Chest findings include bilateral
symmetric hilar adenopathy and subpleural peribronchovascular pulmonary micronodules (Fig 13).
Clinical history, small size of hepatic nodules, hepatomegaly, splenic nodules, adenopathy, pulmonary involvement and decrease in size of liver lesions after steroid treatment can help diagnose hepatic sarcoidosis and differentiate these lesions from metastases. Lymphoma can mimic hepatic sarcoidosis. However, lymphoma typically presents with larger retroperitoneal adenopathy and confluent adenopathy in the small bowel mesentery with vascular encasement. Radiation Fibrosis Radiation fibrosis of the liver occurs when the radiation portal field includes the liver. The acute phase manifests 4 to 8 weeks after radiation exposure and the majority of patients recover completely in 3 to 5 months. A minority progresses towards a chronic stage, with liver fibrosis and tissue retraction.
On unenhanced CT, there is a well-demarcated hypoattenuating area in a non-anatomic distribution that does not following anatomic liver segments. These areas have a straight line, referred to as the “straight
border” sign. In the acute phase these areas do not enhance, but in the chronic fibrotic phase there is prominent enhancement (Fig 14). On MR, acute changes show high signal on T2-weighted images and low signal on T1-weighted images. Chronic changes include mildly elevated signal on T2-weighted images with increased enhancement on arterial phase imaging that persists in the delayed phase. History of prior radiation, the “straight border” sign and the fibrotic changes are helpful clues in diagnosing radiation fibrosis [73].
Conclusion: Non-neoplastic conditions in the liver may exhibit features that mimic malignant lesions. To avoid the potential pitfall in misdiagnosis, the radiologist should be familiar with the vascular supply and drainage of the normal and diseased liver and the imaging appearance of diffuse, infectious and fibrotic liver diseases. Knowledge of the imaging in correlation with clinical history should prompt a correct diagnosis and avoid unnecessary and potentially harmful invasive liver biopsy and surgery.
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Images and Legends
Figure 1: Spontaneous AP shunt in a patient with cirrhosis and ascites: A) and B) Axial HAP CECT at two non-contiguous levels reveals the right hepatic artery (arrowhead) supplying a well-defined oval vascular shunt (asterisk) with early enhancement of a dilated right portal vein (arrow).
Figure 2: Subacute Budd-Chiari Syndrome: A) Axial, PVP CECT reveals thrombosed right (R), middle (M), and left (L) hepatic veins. Note right pleural effusion. B) Axial, PVP CECT at a lower level reveals a patent accessory hepatic vein (arrow), abdominal wall venous collaterals (arrowheads), and central enhancement and hypertrophy of the liver with sparing of the periphery and left lateral segment. Note perihepatic ascites.
Figure 3: Macroregenerative nodules (MRN) in chronic Budd-Chiari Syndrome: A) Axial HAP CECT demonstrates multiple homogenous and ring
enhancing
heterogeneously
lesions enhancing
(arrowheads) parenchyma,
in
a
with
background attenuated
of and
chronically thrombosed hepatic caval confluence (arrow). Note TIPS (double arrow). B) Sectioned liver reveals innumerable MRN (arrowheads).
Figure 4: Passive hepatic congestion: A) Axial HAP CE CT reveals mottled central hepatic enhancement with retrograde enhancement of dilated right (R), middle (M), left (L) hepatic veins and the IVC (asterisk). B) PVP demonstrates mottled enhancement pattern with progressive
hepatic
parenchymal
enhancement
and
delayed
enhancement of hepatic veins (R, M, and L) at the caval confluence due to stagnant venous outflow (asterisk).
Figure 5: Hereditary Hemorrhagic Telangiectasia: A) Coronal MPR and B) axial HAP CECT reveal tortuous and dilated intrahepatic arterial branches (arrows in A) with early opacification of right (R), middle (M), left (L) hepatic veins from arteriovenous shunts. Note innumerable telangiectasias (arrowheads). C) Color Doppler US of an enlarged hepatic artery (8 mm) reveals a high amplitude low resistance waveform. D) Color Doppler US of the left hepatic vein reveals a high amplitude waveform with loss of the normal triphasic waveform.
Figure 6: Hepatic infarction in fulminant hepatitis: A) Axial, HAP CECT reveals multiple well-defined, rounded central and geographic subcapsular hypoattenuating mass-like lesions (arrows). B) Coronal T2weighted MRI reveals rounded subcapsular hyperintense lesions corresponding to edema (arrows). C) Axial, HAP contrast-enhanced 3D gradient echo MRI at the same level as (A) reveals predominantly necrotic hepatic lesions with rim enhancement (arrows).
Figure 7: Primary hemochromatosis, hepatic steatosis and cirrhosis with nodular siderosis: A) Screening US of the right lobe demonstrates two hypoechoic lesions in a cirrhotic liver with a background of diffusely increased echogenicity consistent with steatosis. B) Axial, HAP CECT reveals a hypervascular left hepatic lobe lesion (arrow) in a cirrhotic liver, concerning for hepatocellular carcinoma. C) Axial inphase and D) opposed-phase MRI show diffuse signal loss of hepatic parenchyma on the opposed-phase in keeping with steatosis. The left hepatic lobe lesion is not visualized on the opposed-phase image (circle), but numerous siderotic nodules are present on the in-phase including the left lobe lesion (arrow) that corresponded to lesions detected on US.
Figure 8: Perivascular fat deposition in a patient with breast cancer: A) Axial,
PVP
CECT
demonstrates
innumerable
subcentimeter
hypoattenuating nodules, some of which have a central hyperdense focus (arrows), concerning for metastases. B) Axial In-phase and C) opposed-phase MRI show multifocal nodular steatosis corresponding to CT lesions (arrows). D) Axial, PVP contrast-enhanced 3D gradient echo MRI reveals perivascular distribution of these nodules with a halo of fat surrounding hepatic and portal veins (arrows).
Figure 9: Confluent fibrosis in cirrhosis: A) Axial arterial and B) delayed contrast-enhanced 3D gradient echo MRI demonstrate a geographic or wedge-shaped hypointense area radiating from the portal hilum (asterisk in A) with progressive enhancement (asterisk in B), which contacts and retracts the liver capsule (arrowheads), causing volume loss. C) Axial T2-weighted image reveals an ill-defined hyperintensity corresponding to the edema within the fibrotic zone (asterisk).
\
Figure 10: Examples of hepatic microabscesses in patients with leukemia: A) Ultrasound demonstrates the “wheels within wheels” appearance (arrow) with a peripheral hypoechoic zone (fibrosis), inner echogenic zone (inflammatory cells) and central hypoechoic zone (pus, necrosis). A hypoechoic lesion (fibrosis) with hyperechoic center (inflammatory cells) termed as a “target” lesion (arrowhead) is present. B) and C) PVP CECT reveals hypoattenuating lesions with both “wheels within wheels” (arrow) and “target” (arrowhead) appearance. D) Pre and E) post contrast enhanced 2D gradient echo MRI reveal minimally hypointense lesions on the pre contrast image (D) that develop a “wheels within wheels” (arrow) and “target” (arrowhead) appearance on the post contrast image (E). The background hepatic siderosis increases the lesion to background contrast.
Figure 11: Hydatid cyst of liver: Axial unenhanced CT shows a rounded cyst with multiple daughter vesicles (arrows) with the typical peripheral location in a mother cyst and capsular retraction (arrowheads). A hydatid matrix with solid appearance in seen filling the central cavity (asterisk).
Figure 12: Pyogenic abscess secondary to appendicitis: A) Axial, T2weighted MRI reveals a large cluster of thick-walled hepatic abscesses with internal septa and perilesional hyperintense edema (asterisks). B) Axial, PVP CECT at the same level reveals wall enhancement of individual abscesses (arrowheads) and perilesional edema (asterisks). Note incompletely visualized drainage catheter.
Figure 13: Sarcoidosis of liver: A) Axial, PVP CECT demonstrates multiple hypoattenuating lesions (arrowheads) in an enlarged liver. B) and C) Axial CT of the chest (mediastinal and lung windows) show mediastinal and bilateral symmetric lymphadenopathy (white arrows in B) and subpleural peribronchovascular pulmonary micronodules in the right lung (black arrows in C). D) Hepatosplenic sarcoidosis: Axial CECT demonstrates innumerable hypoattenuating lesions within the liver and spleen.
Figure 14: Chronic radiation fibrosis in a patient with pancreatic carcinoma, 12 months after receiving external bean radiation: A) Axial, PVP CECT shows the “straight border “sign (arrowheads) of enhancing
fibrosis, flanked by hypoattenuating parenchyma (asterisks). B) Axial opposed and C) in-phase gradient-echo MRI demonstrates signal loss of the hepatic parenchyma (asterisks in B) that flanks the chronic fibrosis (arrowheads). D) Radiation planning CT demarcating the radiation portal corresponding to the fibrotic changes.
Mimics of Hepatic Neoplasms Rafel Tappouni MD, Michelle D. Sakala MD, Keyanoosh Hosseinzadeh MD
www.elsevier.com/locate/enganabound
PII: DOI: Reference:
S0037-198X(15)00041-3 http://dx.doi.org/10.1053/j.ro.2015.08.003 YSROE50518
To appear in:
Seminar in Roentgenology
Cite this article as: Rafel Tappouni MD, Michelle D. Sakala MD, Keyanoosh Hosseinzadeh MD, Mimics of Hepatic Neoplasms, Seminar in Roentgenology, http://dx.doi.org/ 10.1053/j.ro.2015.08.003 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Mimics of Hepatic Neoplasms Rafel Tappouni MD, Michelle D Sakala MD, Keyanoosh Hosseinzadeh MD
Department of Radiology Wake Forest University School of Medicine One, Medical Center Blvd Winston-Salem, NC 27157 Tel: 336-716-2471 Fax: 336-716-0555 Contact: [email protected]
Abstract: Liver lesions are commonly encountered during surveillance imaging. These include a myriad of lesions ranging from neoplastic to nonneoplastic lesions. performed
by
Characterization of these lesions is usually
ultrasound
(US),
contrast
enhanced
computed
tomography (CECT) and magnetic resonance imaging (MRI). Many of the lesions have diagnostic features based on specific features related to lesion echogenicity, attenuation, intensity and enhancement. Making the correct diagnosis often depends on the pattern of enhancement of hepatic parenchyma, presence of systemic disease and presence of known malignancy and/or diffuse liver disease. Awareness of mimics of hepatic neoplasms that may have a similar enhancement pattern to neoplastic lesions is essential to avoid misdiagnosis and unnecessary biopsy. Familiarity with the pathophysiology, clinical history, and cross
sectional imaging appearance of the liver is crucial in distinguishing neoplastic from non-neoplastic conditions. This article describes liver lesions that can resemble benign or malignant liver neoplasms and highlights their specific findings that enable radiologists to make the accurate diagnosis. Introduction: The normal liver receives a dual blood supply from the hepatic artery and the portal vein, each supplying approximately 25% and 75% of blood volume respectively [1]. As a result, there is low enhancement of the normal liver parenchyma during the arterial phase as the contrast transported by the hepatic artery is diluted by a ratio of 4:1 by unopacified portal venous blood. Note that hepatic neoplasms are usually predominantly supplied by the hepatic artery. This distinction is the basis for the multiphase contrast enhanced liver protocol for computed tomography (CT) and MRI. It is important to realize that the arterial and portal venous supplies are not independent vascular channels; communications exist between the two via the hepatic sinusoids with blood flowing through the liver sinusoids and emptying into the central vein of each lobule. The central veins coalesce into hepatic veins, which drain into the inferior vena cava. When vascular
compromise occurs, the dual blood supply can change in the volume and direction of blood flow; when the portal venous flow decreases and/or reverses direction of flow, arterial flow increases to compensate.
Disruption to the inflow or outflow of blood to the liver may give rise to nonneoplastic hypervascular lesions, vascular shunts and perfusion abnormalities within the liver. In patients with diffuse liver disease, the background liver architecture is altered and the hepatic blood flow and drainage is disrupted. Therefore great attention should be taken when evaluating a focal lesion in the setting of diffuse liver disease to avoid misdiagnosing a vascular lesion as neoplastic. The distorted architecture of the hepatic parenchyma in cirrhosis is a predisposing condition to developing an arterioportal shunt. Focal non-neoplastic lesions in hepatic steatosis, iron overload and the combination of both can present a diagnostic dilemma. Pyogenic, fungal and parasitic infections in addition to inflammatory conditions can involve the liver. If there is a solid component from granulation or inflammatory tissue, these lesions can mimic metastatic disease.
In this review, we discuss the appearances of liver lesions that may mimic neoplasms in vascular and perfusion disorders, diffuse liver disease and infectious and inflammatory conditions.
Vascular and Perfusion Disorders: Arterioportal Shunts Arterioportal (AP) shunts result from the entry of blood from a high pressure arterial system to a low pressure portal venous system through an abnormal connection. This leads to an increase in the regional perfusion pressure resulting in local parenchymal perfusion abnormality [2]. AP shunts can be divided into spontaneous, posttraumatic and iatrogenic. Spontaneous AP shunts are common in the setting of cirrhosis. They are frequently peripheral, but can be central, and usually measure less than 2 cm in size (Fig 1). These lesions represent abnormal vascularity with no clinical significance or pathological alterations and can resolve on subsequent imaging [3-5]. They can be associated with focal lesions such as hepatocellular carcinomas and hemangiomas [6]. In comparison to AP shunts, which are spontaneous, AP fistulas are most commonly iatrogenic and represent connections between a high pressure hepatic artery and an
adjacent low pressure portal vein. They result from arterial injury from liver biopsy or biliary intervention [7] and may progress to hemodynamically significant fistulas requiring endovascular treatment.
Arterioportal shunts are usually subcapsular and do not exhibit mass effect on adjacent vessels and bile ducts. They are usually not seen on unenhanced CT as they are isoattenuating to the surrounding liver. At CT performed in the hepatic arterial phase (HAP), AP shunts typically appear as a peripherally located enhancing focus and are less commonly centrally located. On portal venous phase, (PVP) the shunt becomes isoattenuating compared to the background liver [8]. In some cases, early enhancement of a dilated peripheral branch of the portal vein occurs during the hepatic arterial phase, before opacification of the main portal vein (Fig 1) [9]. On MRI, these lesions are occult on unenhanced T1 and T2-weighted sequences and the enhancement pattern parallels that of the CT [10, 11]. AP shunts are typically not seen on US. AP fistulas are indistinguishable from AP shunts on imaging unless there is evidence of iatrogenic intervention such a gas filled biopsy tract.
In cirrhotic patients, AP shunts less than 2 cm are referred to as pseudolesions and can be difficult to distinguish from hepatocellular carcinoma. Distinguishing features of hepatocellular carcinoma include mass effect, washout on the PVP, and hypointensity in the hepatobiliary phase of MR images following administration of liver-specific contrast agents. However, if the pseudolesion is small and round, the specificity of these imaging features to differentiate AP shunts from well differentiated hepatocellular carcinoma is low [11]. The American Association for the study of Liver Diseases recommends imaging follow up for small indeterminate hypervascular lesions for assessment of imaging features and growth [12]. In cirrhotic patients, it is suggested that a six month follow up CT or MRI is the recommendation for small, indeterminate enhancing liver nodules [13].
Budd-Chiari Syndrome Budd-Chiari syndrome is the obstruction of hepatic venous outflow at the hepatic veins or hepatic inferior vena cava (IVC) level. The outflow obstruction leads to increased sinusoidal pressure and diminished portal venous flow. This results in centrilobular congestion followed by
hepatocellular necrosis and atrophy. It affects women more than men and can occur at any age.
It is classified into primary and secondary types. Primary causes include congenital webs and diaphragms in addition to injury and infection. The majority of secondary causes are thrombotic, most commonly secondary to a hypercoagulable state from contraceptive use, pregnancy, paroxysmal nocturnal hematuria, polycythemia, protein S and C deficiency, antithrombin III deficiency and factor V Leiden mutations. In these cases, the thrombus is usually in a major hepatic vein or hepatic IVC. Secondary causes include chemotherapy and radiation therapy, where the thrombus is in a central or in a sublobular vein. In addition, bone marrow transplantation can cause thrombosis of small centrilobular veins [14, 15]. Primary Budd-Chiari is more common in Asia, India, and Africa versus secondary causes being more common in western countries. The clinical presentation depends on the acuteness of the disease. The acute form has rapid onset of jaundice and ascites, whilst the subacute or chronic form is more gradual. The less common fulminant form has rapid progression over eight weeks from disease onset to hepatic encephalopathy.
During the acute stage, hepatocellular necrosis develops rapidly as collateral vessels have not yet developed. At unenhanced CT, the liver morphology is maintained but the liver is enlarged and diffusely hypodense secondary to edema. There is narrowing of the hepatic veins and IVC, which may appear hyperattenuating when a thrombus is present [16]. HAP shows decreased peripheral enhancement due to diminished perfusion caused by decreased portal perfusion from increased sinusoidal pressure. There is early enhancement of the caudate lobe and the central liver due to separate venous drainage. PVP may demonstrate a “flip-flop” pattern with hypoattenuation of the central liver due to washout and increased attenuation of the periphery of the liver due to contrast flow from capsular veins.
In the subacute or chronic phase, the peripheral areas are deprived of flow from the portal system and cannot regenerate. However, because of accessory venous drainage and preservation of the portal venous supply to the caudate lobe, the central region of the liver may undergo hypertrophy (Fig 2) [16, 17]. Portosystemic and intrahepatic collateral vessels are formed (Fig 2). These pathways include intrahepatic veno-
venous
comma-shaped
collaterals,
systemic
collaterals
in
the
subcutaneous tissues and capsular vein collaterals. Ascites (Fig 2) and splenomegaly are frequently seen. The chronic thrombus in the IVC can calcify and portal vein thrombus may form secondary to portal flow stagnation. On HAP, the liver demonstrates diffuse heterogeneous enhancement. Formation of macroregenerative nodules in the chronic phase is a response to decreased hepatic perfusion. This leads to atrophy with compensatory formation of regenerative nodules in those regions of the liver with preserved blood supply. These nodules are typically 0.5 to 4 cm in size and are not seen on unenhanced CT. They enhance homogeneously on HAP phase, although some show rim enhancement (Fig 3). On the PVP, the nodules remain hyperattenuating compared to the surrounding liver [15, 18]. On MRI, these nodules are isointense on T1-weighted images and the enhancement parallels that of CT. Pathologic examination of these nodules reveals benign hyperplastic hepatocytes fed by large arteries [17].
Grey scale US shows narrowing, non-visualization and/or thrombosis of the hepatic veins. Color Doppler US shows intrahepatic collaterals and
flat and/or reversed flow within the hepatic veins and IVC. The portal vein may demonstrate slow hepatofugal flow.
In contrast to macroregenerative nodules, hepatocellular carcinoma classically demonstrates washout in the portal venous phase. The formation of collateral vessels, hepatic vein narrowing, thrombosis and clinical
history
are
important
clues
to
help
differentiate
macroregenerative nodule from hepatocellular carcinoma. Caudate hypertrophy and transient attenuation differences should not be mistaken as a hepatic neoplasm, with the latter causing mass effect and vascular distortion.
Passive Hepatic Congestion Passive hepatic congestion is the stasis of blood in liver parenchyma due to cardiac disease causing impaired hepatic venous drainage. The decreased hepatic blood flow, elevated hepatic venous pressure, and diminished arterial oxygen content, if untreated, will lead to hepatocellular hypoxia and necrosis. The incidence of passive hepatic congestion is not known and there is no known age or sex predilection. Passive hepatic congestion is seen in congestive heart failure,
cardiomyopathy, pericardial effusion, constrictive pericarditis and tricuspid valvular disease. In early stages, the disease is subclinical and asymptomatic liver dysfunction is common. If untreated, patients can develop jaundice, hepatomegaly, fibrosis and cardiac cirrhosis [19]. The treatment goal is to reduce hepatic venous congestion and right-sided heart pressure.
On CT and MRI obtained in HAP, the retrograde flow of contrast material from the right atrium into the IVC leads to early enhancement of a dilated IVC and central hepatic veins (Fig 4). PVP shows delayed enhancement of the hepatic veins due to the stagnant venous outflow resulting from elevated central venous pressure (Fig 4). The hepatic parenchyma shows progressive enhancement, described as mottled or mosaic in appearance, with linear or curvilinear areas of decreased enhancement representing stagnant hepatic venous outflow (Fig 4). Other features include peripheral large patchy areas of decreased enhancement and perivascular lymphedema. The appearance is of low attenuation
linear
areas
surrounding
the
hepatic
IVC
[20].
Cardiomegaly, pleural effusions and ascites may be present. Pericardial calcification may be seen in the setting of constrictive pericarditis.
Uncorrected passive hepatic congestion can lead to cardiac cirrhosis, also known as congestive hepatopathy [21]. Ultrasound shows a dilated IVC and hepatic veins, hepatomegaly and ascites. Duplex Doppler US shows an extra retrograde wave at the end of diastole as the right atrium and ventricle fill passively via the superior vena cava and IVC during diastole [22].
Heterogeneous
enhancement
with
patchy
areas
of
decreased
enhancement can mimic liver masses. Clues to making the correct diagnosis of passive hepatic congestion are identification of dilated hepatic veins, retrograde flow from the right atrium and delayed mottled hepatic enhancement.
Hereditary Hemorrhagic Telangiectasia Hereditary Hemorrhagic Telangiectasia (HHT) is a multisystem autosomal-dominant vascular remodeling disease resulting in multiple telangiectasias and arteriovenous malformations. It primarily affects the skin, lungs, gastrointestinal tract, liver and central nervous system. Patients are usually adults and there is no sex predilection. The most common presentation is epistaxis and hemoptysis [23]. Hepatic
involvement is usually diagnosed 10-20 years after the appearance of telangiectasias [24, 25] and imaging findings often correlate poorly with symptoms [26, 27]. A third of patients have liver manifestations, although some report a higher incidence of up to 74% [25, 27].
Hepatic involvement is characterized by hyperdynamic circulation, which can result from shunting from hepatic artery to hepatic vein, hepatic artery to portal vein and portovenous and extrahepatic shunts. Liver involvement can result in portal hypertension, hepatic encephalopathy, ischemic cholangiopathy, hepatocellular necrosis and ultimately liver failure. The diagnosis of the hepatic involvement is based on clinical manifestations coupled with imaging findings.
Imaging features on CECT or MRI in HAP show dilation and tortuosity of the extra- and intrahepatic arterial branches with early opacification of portal or hepatic veins (Fig 5), indicating arterioportal or arteriovenous shunting respectively [24, 26, 27]. In addition, the arterial phase may show a mosaic pattern of enhancement with areas of transient hepatic attenuation difference that is indicative of AP shunts, pseudolesions such as telangiectasias and confluent vascular masses that can mimic
neoplasms. Dilated, tortuous hepatic arteries are often conspicuous and may
help
distinguish
HHT
from
passive
hepatic
congestion.
Telangiectasias are subcentimeter, usually non-spherical, hypervascular nodules that may coalesce into larger spherical confluent vascular masses (Fig 5). These confluent masses appear as large vascular pools with
early
and
persistent
enhancement
in
HAP.
Multiplanar
reformations and maximum-intensity projections may be helpful to detect small lesions, especially those adjacent to vessels [28]. PVP shows normal homogenous enhancement of the liver with enlargement of the hepatic veins and IVC. Unlike cavernous hemangiomas, telangiectasias and vascular masses associated with HHT will not show peripheral discontinuous nodular enhancement. Liver biopsy is not required for diagnosis or justified given the risk of bleeding.
Ultrasound Doppler shows vascular malformations as “color spots” [29]. The hepatic artery is often enlarged with aliasing on color Doppler US due to increased turbulence and flow velocity. Spectral Doppler may exhibit abnormally low-resistance arterial flow (Fig 5), arterialization of portal flow or reversal of portal flow depending on the size and severity
of the shunt [30]. Hepatic veins demonstrate a high amplitude waveform and loss of the triphasic waveform (Fig 5) [31]. Hepatic Infarction Hepatic infarction is coagulative necrosis from hepatocyte cell death form local ischemia involving more than one hepatic lobule. The local hepatic ischemia is usually caused by an obstruction to the blood supply to the area, most commonly due to thrombus. Liver infarcts have gross and microscopic appearances similar to ischemic infarcts in other organs [32]. Causes include: Iatrogenic such as hepatobiliary surgery and intrahepatic chemoembolization; traumatic such as laceration of portal vein and hepatic artery; transplant-related such as hepatic artery stenosis or thrombosis; and hypercoagulable states secondary to sickle cell anemia, vasculitis and infection [33].
Hepatic infarction is relatively rare because of the dual blood supply and extensive collateral pathways of the liver. However with the increasing rate of liver transplantation and vascular complications related to hepatobiliary surgery, there has been a significant increase in the detection of hepatic infarction [34]. Unenhanced CT shows peripheral
wedge-shaped,
rounded
or
irregularly
shaped
low
attenuation areas that parallel the bile ducts. Contrast enhanced CT obtained in the HAP and PVP shows sharply defined, poorly enhancing, conspicuous and peripheral wedge-shaped low-attenuation lesions extending to the liver surface. The shape of larger infarcts is typically geographic with straight borders. Wedge shaped infarcts are usually peripheral. In contrast, rounded infarcts are more central in location (Fig 6) [35]. The majority of hepatic infarcts do not enhance but can demonstrate decreased heterogeneous enhancement. The enhancing component represents non-displaced vessels or viable tissue within the infarcted area [35]. A surrounding rim composed of nonvascularized fibrous tissue may be present (Fig 6). Formation of gas within hepatic infarcts can be either infectious or sterile.
On MRI, hepatic infarcts appear hypointense on T1-weighted images and hyperintense on T2-weighted images (Fig 6) [36]. Contrastenhanced MRI parallels CT. Ultrasound can show an ill-defined heterogeneous peripheral hypoechoic area which is hypovascular or avascular, if completely necrotic. The infarcted area may become anechoic and cystic with distinct borders [37].
In the appropriate clinical setting, the diagnosis is established with ease; however, hepatic infarcts may mimic focal hepatic steatosis, abscess and neoplasm [33, 38]. The geographic segmental shape with straight borders and lack of enhancement of an infarct helps differentiate it from a neoplastic lesion. Focal hepatic steatosis occurs in characteristic areas, and the parenchymal enhancement in focal steatosis is maintained. A hepatic abscess has rim like peripheral enhancement and a nonenhancing central area [9]. Preservation of portal tracts within the infarct can help differentiate an infarct from a hypoattenuating mass in transplanted livers.
Diffuse Liver Related Disorders: Hemochromatosis Hemochromatosis is a disorder characterized by a progressive increase in body iron stores and iron deposition resulting in organ dysfunction. There is no gender predisposition and age of onset ranges from 30 to 60 years. In men, the diagnosis usually becomes evident in middle age whereas in women, clinical presentation is delayed to the post-menopausal period.
Hemochromatosis is
classified
into
primary
or
secondary
hemochromatosis. Primary hemochromatosis is an autosomal recessive genetic disease that leads to the increase of iron absorption secondary to alteration of the protein that is responsible for iron absorption. Secondary hemochromatosis is caused by parenteral iron infusion or multiple transfusions, increased iron absorption such as in cirrhosis and anemias related to ineffective erythropoiesis such as thalassemia and myelodysplastic syndrome.
On unenhanced CT, hemochromatosis shows homogenous increase in hepatic attenuation (75-130 HU) [39] making the hepatic and portal veins appear hypoattenuating compared to background liver. T1weighted gradient-echo in-phase and opposed-phase sequences show decreased liver signal on the in-phase compared to that of the opposed-phase sequences. Gradient-echo T2* weighting sequence shows decreased liver signal
compared
to
that
of
paraspinal
musculature.
Primary
hemochromatosis shows decreased signal intensity from iron deposition in the liver, heart and pancreas whereas in secondary hemochromatosis, the liver and spleen and bone marrow demonstrate decreased signal intensity [40].
The association between hepatic steatosis and hepatic iron deposition is a recognized finding [41] which can make the diagnosis challenging (Fig 7). The drop in signal intensity occurs on the out-of-phase images in steatosis versus drop in signal intensity on the in-phase images for hemochromatosis.
Although the diffuse form of steatosis and hemochromatosis is usually easily diagnosed, the nodular form gives rise to pseudonodules which can mimic true lesions. These pseudonodules may be areas of focal steatosis, focal fatty sparing or focal regions of iron overload (Fig 7). Careful attention should be made to the signal change on dual echo sequences, the pattern of enhancement and the lack of mass effect and vascular distortion. Compared to hepatocellular carcinoma, these pseudolesions have no expansive effect or vascular distortion, and their enhancement parallels that of the background liver [40].
Patients with
chronic
anemia
and
iron
overload
may have
extramedullary erythropoiesis in the hepatic parenchyma which can mimic a hepatic mass. The signal characteristics of hepatic
extramedullary
erythropoiesis
usually
parallels
that
of
the
extramedullary erythropoiesis in the paravertebral regions [42]. Atypical Hepatic Steatosis Hepatic steatosis is a common condition in adults with prevalence of 1530% [43, 44]. The prevalence is higher in obesity, diabetes and patients with high alcohol consumption and hyperlipidemia [45].
Atypical hepatic steatosis can have different patterns including focal, multifocal, perivascular and subcapsular. The focal pattern can be due to focal fatty infiltration or focal fatty sparing. Focal fatty infiltration occurs in certain locations within the liver that commonly include the area adjacent to the falciform ligament, ligamentum venosum, porta hepatis, gallbladder fossa and the subcapsular region. The location of focal fatty sparing is essentially the same as the focal fatty infiltration.
On CT and MRI, focal fat can be distinguished from a liver lesion because it is fat containing, occurs in a specific location, has no mass effect on the adjacent structures, has nondistorted vessels running through the area and has geographic margins [49]. On HAP or PVP, focal steatosis enhances similar to or less than that of background liver. Multifocal
fatty deposition is less common than the focal pattern and can involve atypical locations. The fatty foci may be round and can be seen in any location within the liver, mimicking a true focal lesion. Chemical shift gradient-echo MRI is often needed, especially in patients with known primary malignancy or cirrhosis, to differentiate intracellular lipid deposition from malignancy.
The perivascular pattern is characterized by a fat halo surrounding the portal veins, hepatic veins or both. CT shows uniformly sized, confluent low-attenuation halos surrounding the venous segments. If the vessel courses in the imaging plane, the halo appears as tram-like. If the vessel is perpendicular to the imaging plane, the vein appears as a central dot (Fig 8) [50]. MRI shows signal intensity loss on the opposed-phase sequence compared to the in-phase sequence (Fig 8).
Hepatic
metastases can be differentiated from perivascular steatosis because of lack of size uniformity and central dot pattern, in addition to heterogeneous enhancement. Confluent Hepatic Fibrosis Confluent hepatic fibrosis is a common finding in liver cirrhosis and can be focal or diffuse. It appears as a wedge-shaped mass in a subscapular
location radiating from the porta hepatis, with capsular retraction or focal flattening of the capsule. The most common location is the medial segment of the left lobe, anterior segment of the right lobe or both [34].
On unenhanced CT, confluent hepatic fibrosis appears as a peripheral hypoattenuating lesion with capsular retraction and volume loss. On the PVP it demonstrates mild enhancement and appears iso to hyperattenuating compared to background liver. On MRI, confluent fibrosis appears as low signal on T1-weighted images and high signal on T2-weighted images with progressive delayed enhancement on gadolinium-enhanced images (Fig 9) [52]. These features are not unique for confluent fibrosis and cannot differentiate from hepatocellular carcinoma;
studies
have
shown a
false-positive diagnosis
of
hepatocellular carcinoma on CT [53] and MRI [54] for lesions that subsequently prove to be focal confluent fibrosis. However, unlike infiltrative hepatocellular carcinoma, the geographic location and pattern of confluent fibrosis, vessel crowding and overlying capsular contraction can be helpful in making the diagnosis (Fig 9) [52].
Inflammatory and Infectious Lesions Hepatic candidiasis The manifestations of Candida infection range from local mucous membrane infection to widespread dissemination with multisystem organ failure. These infections can be acute or chronic and localized or systemic.
Invasive
systemic
candidiasis
is
a
well-recognized
complication of myelosuppressive treatment that usually manifests as generalized gastrointestinal symptoms, hepatomegaly and fever [55]. There has been a considerable rise in the incidence of systemic candidiasis over the past decades due to advances in cancer treatment [56]. The most common organs involved are the liver and spleen followed by the kidneys. Hepatic spread results from gastrointestinal colonization with secondary hematogenous seeding to the portal venous system and development of microabscesses, which carries a high morbidity and mortality.
On US, four patterns have been described that correlate with the stage of the disease. The most common is a uniform hypoechoic nodule. This is the least specific pattern and may mimic hepatic metastatic disease and lymphoma. The second is a central echogenic nidus with a
hypoechoic rim. This pattern is usually seen in early infection and is referred to as a "target" sign (Fig 10). The third is a central hypoechoic area of necrosis surrounded by an echogenic zone of inflammatory cells and a hypoechoic rim due to fibrosis. This pattern is typical of early disease and known as a “wheel within wheels" sign (Fig 10). The fourth pattern is usually seen at later stages of the infection and appears as an echogenic lesion with variable degrees of posterior acoustic shadowing indicating early disease resolution [57, 58].
On CECT, hepatic candidiasis appears as multiple round, discrete low attenuation liver lesions ranging from 2 to 20 mm in size. These usually enhance centrally after intravenous contrast, although peripheral or rim enhancement may occur (Fig 10) [59, 60]. The enhancing component is an inflammatory portion and the hypodense component contains fungi and necrosis. The "wheels within wheels" pattern is infrequently seen at CT, whereas the "target" pattern is only seen occasionally (Fig 10) [61].
MRI of the acute stage shows multiple rounded small T1-weighted hypointense and markedly T2-weighted hyperintense lesions without enhancement. In the subacute stage, the lesions appear hyperintense on
T1- and T2-weighted images, enhance with gadolinium and have a dark surrounding rim. The “wheels within wheels“ and “target” enhancement patterns can also be seen on MRI (Fig 10) and parallel that of CT. Chronic treated lesions can be irregular and can measure up to 3 cm. They appear as minimally hypointense on T1- weighted images, iso- to mildly hyperintense on T2-weighted images, hypointense on arterial phase and minimally hypointense on equilibrium phase images [62, 63].
Features that help differentiate hepatic fungal disease from metastatic disease include multiplicity, uniformity with small size, rounded outline, “target” or “wheels within wheels“ pattern of enhancement and splenic involvement. Clinical correlation is important as hepatic candidiasis most
commonly
occurs
in
hematological
malignancy
or
immunosuppressed patents, and antibiotic-resistant fever is a highly suggestive sign.
Intrahepatic Hydatid Cyst Hydatid disease is caused by the Echinococcus tapeworm. Patients are usually asymptomatic at early stages. The symptomatology depends on
the location and size of the cysts. When the Echinococcus embryo is ingested, it gets absorbed by the intestine and is transported to the liver by the portal vein. It is then filtered by the liver; however, any unfiltered embryos become hydatid cysts [64]. Abdominal pain, weight loss, and jaundice may develop when the liver is affected.
Histopathologically, the cyst is composed of three layers: the outer pericyst that corresponds with fibrotic liver tissue; the endocyst, an inner germinal layer; and the thin ectocyst, a translucent membrane. As the cyst matures, the endocyst invaginates leading to the development of daughter cysts in the periphery.
Hydatid cysts have variable features on US ranging from unlilocular, multilocular and solid appearing lesions. Delaminated endocysts can give rise to wavy bands referred to as the “water lily” sign. Unenhanced CT shows a well-defined complex hypoattenuating lesion with a wellformed wall. Coarse wall calcification is common, seen in 50% of cases. The hyperattenuating matrix, also referred to hydatid sand, is frequently seen filling the central portion of the lesion. Daughter cysts are seen in 75% of cases and appear as multiple hypoattenuating round
areas that are peripheral in location surrounding the hydatid sand (Fig 11) [65]. On MRI, the pericyst is seen as a hypointense rim on both T1and T2-weighted images due to its fibrous composition and calcifications. The matrix appears hypointense on T1- weighted images and markedly hyperintense on T2-weighted images. Daughter cysts appear as hypointense relative to the matrix on both T1- and T2weighted images [66].
The appearance of the well-formed wall with coarse calcification, the central matrix and peripheral daughter cysts produce pathognomonic features of a hepatic hydatid cyst. However, making the diagnosis can be challenging when the daughter cysts are absent, the central matrix is minimal and if there is no wall calcification. Patient history and laboratory findings are helpful in these cases to raise the possibility of hydatid disease.
Pyogenic Abscess Pyogenic liver abscesses may develop from a gastrointestinal source that spreads to the liver via the portal circulation, by direct spread from biliary infection and by arterial hematogenous seeding in the setting of
systemic infection. The most common organisms are gram-negative bacteria and Clostridium species, and more than 50% are polymicrobic [64].
Pyogenic abscesses are stratified according to size with microabscesses being less than 2 cm and macroabscesses being greater than 2 cm. Microabscesses can appear as multiple diffusely scattered lesions that appear similar to fungal microabscesses. Microabscesses can also be cluster-like and coalesce focally in an early stage of the evolution into a larger abscess.
Ultrasound of microabscesses shows hypoechoic nodules or ill-defined areas of distorted hepatic echogenicity with little through transmission. Large abscesses may be hypoechoic or hyperechoic with variable amounts of internal echoes. Gas within an abscess causes high-intensity linear echoes with acoustic shadowing, also referred as dirty shadowing.
Contrast enhanced CT of microabscesses show multiple small, welldefined hypoattenuating lesions with rim enhancement and perilesional
edema (Fig 12). Large abscesses may be unilocular, hypoattenuating and with well-defined smooth margins or complex with internal septa, multiple locules and irregular margins (Fig 12). Rim enhancement and the presence of gas are relatively common. The septal and rim enhancement of individual abscesses is an important finding that can help distinguish a liver abscess from a necrotic hepatic mass.
On MRI, pyogenic abscesses have variable signal intensity on T1- and T2-weighted images. MRI has increased sensitivity in detecting perilesional edema, which shows increased signal intensity on T2weighted images (Fig 12). This can be a helpful feature in making the diagnosis [64, 67]. DWI can be helpful in differentiating a hepatic abscess from metastases, necrotic masses and malignant lesions with rim enhancement. The center of the hepatic abscess is hyperintense on DWI and has low ADC values due to pus-containing inflammatory cells, bacteria and/or necrotic tissue. In comparison, a necrotic tumor is hypointense on DWI and has high ADC values due to low viscosity and cellularity. The rim of an abscess may also appear as hyperintense on DWI and have high ADC versus the rim of a necrotic tumor where the ADC values are low [68-70].
Sarcoidosis Sarcoidosis is a mutisystemic inflammatory disease of unknown origin characterized by the formation of non-caseating epithelioid granulomas with surrounding fibrosis in the periportal regions and portal tracts. It affects young and middle-aged patients, with a higher prevalence in women than men. The most common manifestation of hepatic sarcoidosis is diffuse infiltration of noncaseating epithelioid granulomas in the liver [36]. The liver and spleen are the most frequently involved abdominal viscera with granulomata noted in 40-70% of patients [72]. The most common abdominal features include hepatosplenomegaly, abdominal adenopathy and focal liver and splenic nodules (Fig 13).
On US, lesions are hypoechoic relative to the background liver and there is hepatomegaly with increased liver echogenicity. On CECT, the liver nodules are hypoattenuating ranging in size between 5 to 20 mm and become more confluent with increasing size, corresponding to coalescing granulomas (Fig 13). On MRI, nodules are hypointense on T2-weighted images and hypoenhancing relative to background liver on early phase contrast images [36, 72]. Chest findings include bilateral
symmetric hilar adenopathy and subpleural peribronchovascular pulmonary micronodules (Fig 13).
Clinical history, small size of hepatic nodules, hepatomegaly, splenic nodules, adenopathy, pulmonary involvement and decrease in size of liver lesions after steroid treatment can help diagnose hepatic sarcoidosis and differentiate these lesions from metastases. Lymphoma can mimic hepatic sarcoidosis. However, lymphoma typically presents with larger retroperitoneal adenopathy and confluent adenopathy in the small bowel mesentery with vascular encasement. Radiation Fibrosis Radiation fibrosis of the liver occurs when the radiation portal field includes the liver. The acute phase manifests 4 to 8 weeks after radiation exposure and the majority of patients recover completely in 3 to 5 months. A minority progresses towards a chronic stage, with liver fibrosis and tissue retraction.
On unenhanced CT, there is a well-demarcated hypoattenuating area in a non-anatomic distribution that does not following anatomic liver segments. These areas have a straight line, referred to as the “straight
border” sign. In the acute phase these areas do not enhance, but in the chronic fibrotic phase there is prominent enhancement (Fig 14). On MR, acute changes show high signal on T2-weighted images and low signal on T1-weighted images. Chronic changes include mildly elevated signal on T2-weighted images with increased enhancement on arterial phase imaging that persists in the delayed phase. History of prior radiation, the “straight border” sign and the fibrotic changes are helpful clues in diagnosing radiation fibrosis [73].
Conclusion: Non-neoplastic conditions in the liver may exhibit features that mimic malignant lesions. To avoid the potential pitfall in misdiagnosis, the radiologist should be familiar with the vascular supply and drainage of the normal and diseased liver and the imaging appearance of diffuse, infectious and fibrotic liver diseases. Knowledge of the imaging in correlation with clinical history should prompt a correct diagnosis and avoid unnecessary and potentially harmful invasive liver biopsy and surgery.
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Images and Legends
Figure 1: Spontaneous AP shunt in a patient with cirrhosis and ascites: A) and B) Axial HAP CECT at two non-contiguous levels reveals the right hepatic artery (arrowhead) supplying a well-defined oval vascular shunt (asterisk) with early enhancement of a dilated right portal vein (arrow).
Figure 2: Subacute Budd-Chiari Syndrome: A) Axial, PVP CECT reveals thrombosed right (R), middle (M), and left (L) hepatic veins. Note right pleural effusion. B) Axial, PVP CECT at a lower level reveals a patent accessory hepatic vein (arrow), abdominal wall venous collaterals (arrowheads), and central enhancement and hypertrophy of the liver with sparing of the periphery and left lateral segment. Note perihepatic ascites.
Figure 3: Macroregenerative nodules (MRN) in chronic Budd-Chiari Syndrome: A) Axial HAP CECT demonstrates multiple homogenous and ring
enhancing
heterogeneously
lesions enhancing
(arrowheads) parenchyma,
in
a
with
background attenuated
of and
chronically thrombosed hepatic caval confluence (arrow). Note TIPS (double arrow). B) Sectioned liver reveals innumerable MRN (arrowheads).
Figure 4: Passive hepatic congestion: A) Axial HAP CE CT reveals mottled central hepatic enhancement with retrograde enhancement of dilated right (R), middle (M), left (L) hepatic veins and the IVC (asterisk). B) PVP demonstrates mottled enhancement pattern with progressive
hepatic
parenchymal
enhancement
and
delayed
enhancement of hepatic veins (R, M, and L) at the caval confluence due to stagnant venous outflow (asterisk).
Figure 5: Hereditary Hemorrhagic Telangiectasia: A) Coronal MPR and B) axial HAP CECT reveal tortuous and dilated intrahepatic arterial branches (arrows in A) with early opacification of right (R), middle (M), left (L) hepatic veins from arteriovenous shunts. Note innumerable telangiectasias (arrowheads). C) Color Doppler US of an enlarged hepatic artery (8 mm) reveals a high amplitude low resistance waveform. D) Color Doppler US of the left hepatic vein reveals a high amplitude waveform with loss of the normal triphasic waveform.
Figure 6: Hepatic infarction in fulminant hepatitis: A) Axial, HAP CECT reveals multiple well-defined, rounded central and geographic subcapsular hypoattenuating mass-like lesions (arrows). B) Coronal T2weighted MRI reveals rounded subcapsular hyperintense lesions corresponding to edema (arrows). C) Axial, HAP contrast-enhanced 3D gradient echo MRI at the same level as (A) reveals predominantly necrotic hepatic lesions with rim enhancement (arrows).
Figure 7: Primary hemochromatosis, hepatic steatosis and cirrhosis with nodular siderosis: A) Screening US of the right lobe demonstrates two hypoechoic lesions in a cirrhotic liver with a background of diffusely increased echogenicity consistent with steatosis. B) Axial, HAP CECT reveals a hypervascular left hepatic lobe lesion (arrow) in a cirrhotic liver, concerning for hepatocellular carcinoma. C) Axial inphase and D) opposed-phase MRI show diffuse signal loss of hepatic parenchyma on the opposed-phase in keeping with steatosis. The left hepatic lobe lesion is not visualized on the opposed-phase image (circle), but numerous siderotic nodules are present on the in-phase including the left lobe lesion (arrow) that corresponded to lesions detected on US.
Figure 8: Perivascular fat deposition in a patient with breast cancer: A) Axial,
PVP
CECT
demonstrates
innumerable
subcentimeter
hypoattenuating nodules, some of which have a central hyperdense focus (arrows), concerning for metastases. B) Axial In-phase and C) opposed-phase MRI show multifocal nodular steatosis corresponding to CT lesions (arrows). D) Axial, PVP contrast-enhanced 3D gradient echo MRI reveals perivascular distribution of these nodules with a halo of fat surrounding hepatic and portal veins (arrows).
Figure 9: Confluent fibrosis in cirrhosis: A) Axial arterial and B) delayed contrast-enhanced 3D gradient echo MRI demonstrate a geographic or wedge-shaped hypointense area radiating from the portal hilum (asterisk in A) with progressive enhancement (asterisk in B), which contacts and retracts the liver capsule (arrowheads), causing volume loss. C) Axial T2-weighted image reveals an ill-defined hyperintensity corresponding to the edema within the fibrotic zone (asterisk).
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Figure 10: Examples of hepatic microabscesses in patients with leukemia: A) Ultrasound demonstrates the “wheels within wheels” appearance (arrow) with a peripheral hypoechoic zone (fibrosis), inner echogenic zone (inflammatory cells) and central hypoechoic zone (pus, necrosis). A hypoechoic lesion (fibrosis) with hyperechoic center (inflammatory cells) termed as a “target” lesion (arrowhead) is present. B) and C) PVP CECT reveals hypoattenuating lesions with both “wheels within wheels” (arrow) and “target” (arrowhead) appearance. D) Pre and E) post contrast enhanced 2D gradient echo MRI reveal minimally hypointense lesions on the pre contrast image (D) that develop a “wheels within wheels” (arrow) and “target” (arrowhead) appearance on the post contrast image (E). The background hepatic siderosis increases the lesion to background contrast.
Figure 11: Hydatid cyst of liver: Axial unenhanced CT shows a rounded cyst with multiple daughter vesicles (arrows) with the typical peripheral location in a mother cyst and capsular retraction (arrowheads). A hydatid matrix with solid appearance in seen filling the central cavity (asterisk).
Figure 12: Pyogenic abscess secondary to appendicitis: A) Axial, T2weighted MRI reveals a large cluster of thick-walled hepatic abscesses with internal septa and perilesional hyperintense edema (asterisks). B) Axial, PVP CECT at the same level reveals wall enhancement of individual abscesses (arrowheads) and perilesional edema (asterisks). Note incompletely visualized drainage catheter.
Figure 13: Sarcoidosis of liver: A) Axial, PVP CECT demonstrates multiple hypoattenuating lesions (arrowheads) in an enlarged liver. B) and C) Axial CT of the chest (mediastinal and lung windows) show mediastinal and bilateral symmetric lymphadenopathy (white arrows in B) and subpleural peribronchovascular pulmonary micronodules in the right lung (black arrows in C). D) Hepatosplenic sarcoidosis: Axial CECT demonstrates innumerable hypoattenuating lesions within the liver and spleen.
Figure 14: Chronic radiation fibrosis in a patient with pancreatic carcinoma, 12 months after receiving external bean radiation: A) Axial, PVP CECT shows the “straight border “sign (arrowheads) of enhancing
fibrosis, flanked by hypoattenuating parenchyma (asterisks). B) Axial opposed and C) in-phase gradient-echo MRI demonstrates signal loss of the hepatic parenchyma (asterisks in B) that flanks the chronic fibrosis (arrowheads). D) Radiation planning CT demarcating the radiation portal corresponding to the fibrotic changes.