Hepatic Incidentalomas Richard M. Gore, MD*, Geraldine M. Newmark, MD, Kiran H. Thakrar, MD, Uday K. Mehta, MD, Jonathan W. Berlin, MD Recent advances in multidetector computed tomography (MDCT), magnetic resonance (MR) imaging, and ultrasonography have led to the detection of incidental hepatic lesions in both the oncology and nononcology patient population that in the past remained undiscovered. These in- cidentalomas are unexpected, asymptomatic abnormalities that are discovered serendipitously while searching for other pathology. 1–18 Such inci- dental hepatic lesions have created a management dilemma for both clinicians and radiologists, particularly in the oncology patient in whom any mass, clinical or subclinical, warrants further eval- uation. Strategies for optimizing patient manage- ment of these lesions are only beginning to emerge in terms of deciding which of these inci- dentalomas can be ignored, which can simply be monitored over time, and which require more aggressive workup. Subjecting the patient to unnecessary testing and treatment carries its own set of risks that can result in an injurious and expensive cascade of imaging and intervention. Preoperative fine- needle aspiration may minimize diagnostic error but is associated with a nontrivial morbidity of 0.5% and mortality of 0.05%. 19 The exhaustive evaluation performed in some patients reflects the unwillingness of many physicians to accept uncertainty even in the case of a very rare diagnosis. This unwillingness is in part driven by a paucity of data on the topic, the lack of clear-cut algorithms with regard to diagnostic and treatment strategies, fear of potential malpractice liability, and/or the anxiety of the patient. In this review, guidelines concerning the approach to some of the more common hepatic incidentalomas are presented. CYSTIC (ULTRASONOGRAPHY AND MDCT), HYPOINTENSE (T1-WEIGHTED MR IMAGING), AND HYPERINTENSE (T2-WEIGHTED) HEPATIC INCIDENTALOMAS Hepatic lesions that are cystic on ultrasonography on MDCT, hypointense on T1-weighted MR imaging, and hyperintense on T2-weighted MR imaging are commonly found incidentally. Their differential diagnosis is extensive and they are usually benign in patients with no history of malig- nancy, hepatic dysfunction, or hepatic risk factors. These lesions are listed in Box 1 and are dis- cussed more fully in this section. Hepatic Cysts Simple hepatic cysts are single, unilocular cysts that lined by a single layer of cuboidal bile duct epithelium. The walls of these cysts are composed of a thin layer of fibrous tissue adjacent to normal hepatic parenchyma. These cysts are considered to be congenital and developmental in origin, although they are typically discovered incidentally in the fifth through seventh decades of life. 20–22 The incidence of simple hepatic cysts ranges up to 14% in autopsy series, 17% in CT series, and 20% in surgery series. 23,24 The vast majority of cysts are found incidentally and do not require Department of Radiology, North Shore University Health System, Pritzker School of Medicine, University of Chicago, 2650 Ridge Avenue, Evanston, IL, USA * Corresponding author. Department of Radiology, Evanston Hospital, 2650 Ridge Avenue, Evanston, IL 60201. E-mail address: [email protected]KEYWORDS Incidentaloma Hepatic cyst Bile duct hamartoma Hepatic hemangioma Focal nodular hyperplasia Hepatic adenoma Liver metastases Liver CT Radiol Clin N Am 49 (2011) 291–322 doi:10.1016/j.rcl.2010.10.004 0033-8389/11/$ – see front matter Ó 2011 Elsevier Inc. All rights reserved. radiologic.theclinics.com
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HepaticIncidentalomas
Richard M. Gore, MD*, Geraldine M. Newmark, MD,Kiran H. Thakrar, MD, Uday K. Mehta, MD,Jonathan W. Berlin, MD
Recent advances in multidetector computedtomography (MDCT), magnetic resonance (MR)imaging, and ultrasonography have led to thedetection of incidental hepatic lesions in both theoncology and nononcology patient populationthat in the past remained undiscovered. These in-cidentalomas are unexpected, asymptomaticabnormalities that are discovered serendipitouslywhile searching for other pathology.1–18 Such inci-dental hepatic lesions have created amanagementdilemma for both clinicians and radiologists,particularly in the oncology patient in whom anymass, clinical or subclinical, warrants further eval-uation. Strategies for optimizing patient manage-ment of these lesions are only beginning toemerge in terms of deciding which of these inci-dentalomas can be ignored, which can simply bemonitored over time, and which require moreaggressive workup.
Subjecting the patient to unnecessary testingand treatment carries its own set of risks thatcan result in an injurious and expensive cascadeof imaging and intervention. Preoperative fine-needle aspiration may minimize diagnostic errorbut is associated with a nontrivial morbidity of0.5% and mortality of 0.05%.19 The exhaustiveevaluation performed in some patients reflectsthe unwillingness of many physicians to acceptuncertainty even in the case of a very rarediagnosis. This unwillingness is in part driven bya paucity of data on the topic, the lack ofclear-cut algorithms with regard to diagnosticand treatment strategies, fear of potential
Department of Radiology, North Shore University HealtChicago, 2650 Ridge Avenue, Evanston, IL, USA* Corresponding author. Department of Radiology, EvansE-mail address: [email protected]
Radiol Clin N Am 49 (2011) 291–322doi:10.1016/j.rcl.2010.10.0040033-8389/11/$ – see front matter � 2011 Elsevier Inc. All
c
malpractice liability, and/or the anxiety of thepatient. In this review, guidelines concerning theapproach to some of the more common hepaticincidentalomas are presented.
CYSTIC (ULTRASONOGRAPHY AND MDCT),HYPOINTENSE (T1-WEIGHTED MRIMAGING), AND HYPERINTENSE(T2-WEIGHTED) HEPATIC INCIDENTALOMAS
Hepatic lesions that are cystic on ultrasonographyon MDCT, hypointense on T1-weighted MRimaging, and hyperintense on T2-weighted MRimaging are commonly found incidentally. Theirdifferential diagnosis is extensive and they areusually benign in patients with no history of malig-nancy, hepatic dysfunction, or hepatic risk factors.These lesions are listed in Box 1 and are dis-cussed more fully in this section.
Hepatic Cysts
Simple hepatic cysts are single, unilocular cyststhat lined by a single layer of cuboidal bile ductepithelium. The walls of these cysts are composedof a thin layer of fibrous tissue adjacent to normalhepatic parenchyma. These cysts are consideredto be congenital and developmental in origin,although they are typically discovered incidentallyin the fifth through seventh decades of life.20–22
The incidence of simple hepatic cysts ranges upto 14% in autopsy series, 17% in CT series, and20% in surgery series.23,24 The vast majority ofcysts are found incidentally and do not require
h System, Pritzker School of Medicine, University of
ton Hospital, 2650 Ridge Avenue, Evanston, IL 60201.
any treatment or further evaluation. If sufficientlylarge, they can stretch Glisson’s capsule leadingto pain, cause biliary obstruction, or be compli-cated by hemorrhage or infection.20–22
Sonographically (Fig. 1A), simple hepatic cystspresent as anechoic masses with smooth borders,nondetectable walls, no septations, no mural cal-cification, and posterior acoustic enhancement.25
On CT (see Fig. 1B), uncomplicated hepaticcysts manifest as well-defined, water-attenuated(<20 HU) intrahepatic masses, with smooth, thinwalls, no internal structure, and no enhancementfollowing contrast administration. The attenuationvalues of small hepatic cysts can be influencedby partial volume averaging, pixel size, matrixsize, kilovoltage and milliamperage of the x-raybeam, slice thickness, reconstruction algorithm,patient diameter, and pseudoenhancement. Allthese factors can influence the attenuation of thecyst contents. Hemorrhage and infection canalso lead to increased density of hepaticcysts.20,23,24
On MR (see Fig. 1C), cysts are usually oval-shaped, homogeneous, well-defined lesions thatare sharply marginated with normal liver. Cystshave low signal intensity on T1-weighted imagesand high signal intensity on T2-weighted images;they do not show enhancement following contrastadministration. Hemorrhage and infection canincrease the signal intensity of cysts on T1-weighted images and can lead to inhomogeneityof the lesion.26
The differential diagnosis of a hepatic cystincludes cystic metastases from cystic primarytumors (ie, ovarian and cystic pancreatic
primaries) and solid tumors that can producecystic metastases (ie, gastrointestinal stromaltumor and endometrial carcinoma). Pyogenic andamebic abscesses typically show mural enhance-ment but can mimic cysts particularly when theyare small. Cystic biliary neoplasms such as biliarycystadenoma or cystadenocarcinoma are usuallylarge lesions with internal septations, mural nodu-larity, and a thicker wall.27
Bile Duct Hamartomas
Bile duct hamartomas (BDHs), also known asbiliary microhamartomas or von Meyenburgcomplexes, are a focal disorderly collection ofbile ducts that results from failure of involution ofembryonic bile ducts. BDHs are composed of oneor more dilated duct-like structures lined by biliaryepithelium and accompanied by a variable amountof fibrous stroma. With extreme dilatation BDHscan be visible on cross-sectional imaging. BDHsrange in size from 1 to 5 mm, and there can be50,000 to 100,000 BDHs in a normal liver.21 BDHsare found in 0.69% to 5.6% of individuals atautopsy.21 BDHs as a rule are asymptomaticlesions found incidentally. Their major clinicalsignificance is the fact that they may be misdiag-nosed as multiple liver metastases or micro-abscesses.28
Virtually all persons with adult polycystic liverdisease (APLD) have multiple BDHs and 11% ofpatients with multiple BDHs have APLD.20,21 It ispostulated that the larger cysts of APLD resultfrom gradual dilatation of the hamartomas.On cross-sectional imaging, BDHs are typically
multiple round or irregular focal lesions of nearlyuniform size (up to 15 mm) scattered throughoutthe liver.Sonographically, BDHs have been described as
either hypoechoic or anechoic small nodules withdistal acoustic enhancement. However, hypere-choic biliary hamartomas or a combination ofhypo- and hyperechoic lesions has also beenreported. Small hyperechoic cystic lesions withcomet-tail echoes may also be seen.25–29
BDHs manifest on CT (Fig. 2A, B) as multiple,widely scattered, small (<1.5 cm), low-attenuation lesions, which do not demonstratediscernible contrast enhancement.24,30,31
BDHs are hypointense on T1-weighted MRimages (Fig. 3A) and hyperintense at T2-weighted images. If the TE (echo time) isincreased at T2-weighted imaging, the signalintensity of these lesions increases further andapproaches that of cerebrospinal fluid (seeFig. 3B, C). BDHs do not usually show contrastenhancement on CT or MR imaging, although
Fig. 1. Simple hepatic cysts: imaging findings. (A) Oblique right upper quadrant sonogram shows multiple well-marginated, thin-walled, anechoic hepatic cysts with increased through transmission of sound. (B) Axial contrast-enhanced CT scan shows large, bilateral, nonenhancing water density hepatic cysts. (C) Coronal T2-weighted MRimage in a patient with adult polycystic liver and renal disease shows multiple well-marginated, hyperintensehepatic cysts with thin walls. Note the absence of mural thickening or nodularity.
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a peripheral enhancing rim has been describedon early and late postgadolinium images. Histo-pathologically, this rim enhancement correlateswith compressed liver parenchyma surroundingthe lesions.32–34
lesions are usually more heterogeneous in size andin attenuation or signal intensity. Unlike BDHs,hepatic cysts are rarely as uniformly small ornumerous, whereas the cysts in APLD are usuallylarger and more numerous.35–37
Polycystic Liver Disease
Patients with APLD are usually discovered inci-dentally at the time of radiologic examination.Approximately 70% of patients with APLD willalso have polycystic kidney disease. Pathologi-cally, these cysts are identical to simple cysts orBDHs.21
On cross-sectional imaging, APLD lesions aretypically cystic and show no contrast enhance-ment. The lesions are well marginated andanechoic, and show increased through-transmission sonographically.25 These cysts havewater density on CT unless complicated by infec-tion or hemorrhage. Mural calcification can occa-sionally be seen.20,27 At MR imaging, cysts show
very low signal intensity on T1-weighted imagesand high signal intensity on T2-weighted images(see Fig. 1C). Higher signal intensity may bepresent on T1-weighted images as a result ofhemorrhage or infection.26,30
Biliary Cystadenoma and Adenocarcinoma
Biliary cystadenomas and cystadenocarcinomasare rare cystic neoplasms lined by mucin-secreting columnar epithelium that are histologi-cally and radiographically similar to cystadenomasand cystadenocarcinomas of the ovary andpancreas.22 Biliary cystadenomas are usuallyseen in middle-aged women who may presentwith abdominal pain, distention, and occasionallyjaundice.20,25 When small, they may be seen inci-dentally and mimic benign hepatic cystic disease.Sonographically, cystic biliary neoplasms are
hypoechoic, and may have septations and a vari-able degree of mural thickening or nodularity.20,25
On MDCT these lesions have low attenuation,
Hepatic Incidentalomas 295
and a unilocular or multilocular cystic appearanceon CT (Fig. 4).27
Irregular papillary growths and mural nodulesalong the internal septa and wall are seen in cysta-denomas and cystadenocarcinomas, althoughpapillary excrescences and solid portions aremore common in the latter. Cystadenomas occa-sionally have fine septal calcifications whereascystadenocarcinomas may have thick, coarse,mural, and septal calcifications. The differentialdiagnosis of these lesions includes hepatic cysts,hydatid cysts, liver abscesses, cystic metastases,hematoma, cystic sarcomas, and choledochalcysts.20,22,27
Focal Hepatic Steatosis
Hepatic fatty metamorphosis or steatosis is themetabolic complication of a variety of toxic,ischemic, and infectious insults to the liver. It is themost common abnormality seen on liver biopsy ofalcoholic patients and is observed in up to 50% ofpatients with diabetes. With the current obesityepidemic in the United States, hepatic steatosisis becoming increasingly common.38
When fatty infiltration is diffuse or lobar,segmental, or wedge shaped, differentiation fromother focal hepatic disease is straightforward. Inthese cases the region of fat has a straight-linemargin with normal parenchyma, typically extend-ing to the liver capsule without associated bulgingof the hepatic contour to suggest an underlyingmass.39,40
When steatosis is nodular or focal, differentia-tion from metastatic disease and other massescan be problematic on CT.41 Absolute CT attenua-tion values are unreliable indicators because fatty
Fig. 4. Biliary cystadenomas and cystadenocarcinomassimulating multiple hepatic cysts: CT findings.Multiple hypodense lesions are identified within theliver are seen on this contrast-enhanced scan. One ofthe cystic lesions shows mural calcifications (arrow).
infiltration does not produce a fat-density lesion;rather, the steatosis merely diminishes the densityof the region to lower than that of normal liverparenchyma.42 There are several features thatare helpful in this differentiation: focal fat doesnot cause local contour abnormalities; portal andhepatic venous branches course normally throughthe fatty areas; and these lesions may improve ina matter of days.39
The 2 most common areas of focal fatty infiltra-tion and focal sparing in an otherwise normal ordiffusely fatty liver are surrounding the gallbladderfossa and adjacent to the falciform ligament insegments II, III, and IV (Figs. 5–7). In the gall-bladder fossa (Fig. 8), direct vascular communica-tions to the portal system through aberrant gastricvenous flow or accessory cystic veins permitperfusion of this portion of the liver by systemicblood flow rather than by splanchnic venous bloodfrom the portal veins. The liver adjacent to thefalciform ligament has also been shown to haveaberrant direct venous flow. Consequently, a thirdblood supply to these areas may help spare themthe adverse effects of toxic agents enteringthrough the portal circulation. This variant vascularblood supply is also key in the development ofregions of transient hepatic attenuation differ-ences (THADs) on CT and transient hepatic inten-sity differences (THIDs) on MR imaging (see laterdiscussion).43
On hepatic arterial phase (HAP) imaging, a hypo-vascular region is often seen in segment IV (Fig. 9)adjacent to the falciform ligament, which on portalvenous phase (PVP) or delayed images becomesisodense with the liver. This appearance mayresult from the aberrant venous blood flow orfrom the fact that this region is a watershed areaof hepatic arterial and portal venous bloodflow.39,43
Sonographically, fat is hyperechoic due to anincreased number of echogenic foci resultingfrom the proliferation of fat-nonfat interfaces.Four patterns of focal fatty hepatic infiltrationhave been described: hyperechoic nodule,multiple confluent hyperechogenic lesions, hypo-echoic skip nodules, and irregular hyperechoicand hypoechoic areas. Focal areas of hepaticparenchyma may occasionally be spared fromthe fatty metamorphosis and appear as an ovoid,spherical, or sheet-like hypoechoic mass in anotherwise echogenic liver. Its characteristic loca-tion, the lack of mass effect on surroundingvessels, and a straight-line interface betweennormal and fatty parenchyma are useful differen-tiating signs.25,39
Hepatic hemangiomas (HH), which are typicallyhyperechoic compared with normal hepatic
Fig. 5. Focal hepatic steatosis: CT-sonographic findings. (A) Transverse sonogram of the left lobe of the liverdemonstrates a well-marginated, hyperechoic mass (arrow) in the medial segment of the left lobe adjacent tothe falciform ligament. (B) Corresponding contrast-enhanced CT scan shows a hypodense “lesion” (arrow). (C)Coronal CT scan in a different patient shows focal fat (arrow) in the lateral segment of the left lobe.
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parenchyma, may appear hypoechoic whencompared with adjacent liver parenchyma inpatients with a diffusely fatty liver, and MR or CTmay be needed for differentiation.44 Focal fattyinfiltration in an otherwise normal-appearing liveron ultrasonography may also produce a hypere-choic space-occupying mass. An angular or inter-digitating geometric margin is also characteristicof focal fat.45
MR imaging is particularly effective in evaluatingthe liver in patients with diffuse and focal steatosis.Proton chemical shift imaging, also termedopposed-phase gradient echo imaging, is a highlyaccurate technique in differentiating fatty meta-morphosis from neoplasm. This technique exploitsthe difference in precession frequency between fatand water protons (3.37 ppm). On opposed-phaseimages, the fat signal is subtracted from the watersignal whereas on in-phase images, the fat andwater signals are combined. Lesions containingfat will therefore show a loss of signal intensity
on the opposed-phase images when comparedwith the in-phase sequences.46
Fat Abutting the Intrahepatic Portionof the Inferior Vena Cava
A commonly seen, an incidental anatomic variantthat simulates a mass is a focal collection of fatlocated medial to the intrahepatic portion of theinferior vena cava (IVC) at or above the level ofconfluence of the hepatic veins and the IVC. Thisfat is contiguous to the fat around the subdiaph-ragmatic portion of the esophagus. The fat collec-tions have a characteristic location, orientation,size, shape, and density on CT (Fig. 10). Thepresence of this fat is not related to obesity butis found more commonly in patients with cirrhosisreflecting altered hepatic morphology. These fatcollections should not be confused with hepaticfatty tumors such as lipoma, angiomyolipoma, orhepatic neoplasms, which often contain fat such
Fig. 6. Focal hepatic steatosis: MR features. (A) Contrast-enhanced T1-weighted image reveals a hypointenselesion (arrow) adjacent to the falciform ligament in the medial segment of the left lobe. (B) In-phase image showsthat this lesion has mild hyperintensity (arrow). (C) Opposed-phase image shows that this region (arrow) losessignificant signal intensity, indicating that this represents a focal area of fat deposition.
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as adenomas (HA) and hepatocellular carcinomas(HCC).47–51
Hepatic Lipomas
Benign hepatic tumors composed of fat cellsinclude lipoma, hibernoma, and combined tumorssuch as myelolipoma (fat and hematopoietictissue), angiomyolipoma (fat and blood vessels),and angiomyelolipoma.21
Fig. 7. Focal sparing in an otherwise fatty liver: CT findinfocal sparing from fatty infiltration in the medial and lateformatted image in the same patient shows sparing of fatgallbladder fossa (arrows).
Sonographically these lesions are highly echo-genic and may be indistinguishable from HH.45
On CT, these fatty tumors appear as well-definedmasses with attenuation values in the range offat (Fig. 11). Lipomas show high signal intensityon T1-weighted sequences and low signal inten-sity with fat-suppressed techniques. Lipomasshow negligible enhancement following theadministration of contrast material. Angiomyolipo-mas may not have a predominantly lipid content,
gs. (A) Coronal reformatted image of the liver showsral segments of the left lobe (arrows). (B) Coronal re-deposition in the hepatic parenchyma adjacent to the
Fig. 8. Parabiliary venous system. These veins drain the gallbladder, stomach, and pancreatic head, and mayconnect to the main portal vein or drain directly into liver parenchyma (black arrows). These vessels are respon-sible for the presence of fatty deposition, fatty sparing, and THIDs (transient hepatic intensity differences) andTHADs (transient hepatic attenuation differences) adjacent to the gallbladder fossa. (From Desser TS. Under-standing transient hepatic attenuation differences. Semin Ultrasound CT MR 2009;30:408–17, Figure 4; withpermission.)
Fig. 9. The paraumbilical venous system. This system connects abdominal and chest wall vasculature to the infe-rior vena cava via collateral pathways that traverse the liver along its embryologic mesenteries (falciform liga-ment). These vessels account for the presence of fatty deposition, fatty sparing, and THIDs and THADsadjacent to the falciform ligament. (From Desser TS. Understanding transient hepatic attenuation differences.Semin Ultrasound CT MR 2009;30:408–17, Figure 3; with permission.)
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Box 2Flash-filling hepatic lesions
Hemangiomas
Focal nodular hyperplasia
THIDs
THADs
Adenomas
Nodular regenerative hyperplasia
Hypervascular metastases
Hepatocellular carcinoma
Fibrolamellar carcinoma
Arteriovenous malformations
Peliosis
Arterioportal shunts
Arteriovenous shunts
Portovenous shunts
Fig. 10. Fat adjacent to the inferior vena cava simu-lating a caval tumor. Contrast-enhanced CT scanshows a fat density “mass” abutting the anterioraspect of the inferior vena cava (arrow). This variantis more commonly seen in patients with cirrhosiscaused by the changes in hepatic morphology thataccompany this disease.
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and have a more complex pattern on MR that maybe difficult to differentiate from HCC.26,39
HYPERVASCULAR FLASH-FILLINGINCIDENTALOMAS
Small hypervascular, flash-filling hepatic defectsare commonly found incidentally on MDCT. Thedifferential diagnosis of these lesions is extensiveand most are usually benign in patients with nohistory of malignancy, hepatic dysfunction, orhepatic risk factors. These lesions are listed inBox 2 and discussed more fully in this section.Their imaging features are described in Table 1.
Fig. 11. Hepatic lipoma. Contrast-enhanced CT showsa well-marginated fat density (�58 HU) mass (arrow)in the right lobe of the liver.
Hepatic Hemangiomas
HHs are the most common benign tumor of theliver, with a reported incidence ranging from 1%to 20%.21,52–54 These lesions are most commonlyseen in women with a female/male ratio of 5:1.21 Inmost cases, HHs are found incidentally on cross-sectional imaging examinations performed forsymptoms and signs unrelated to this lesion.Most patients with HHs are asymptomatic andrequire no treatment. Clinical examination andlaboratory tests are typically normal.52,54
HHs are composed of dilated endothelial-linedvascular channels, infiltrated by varying degreesof fibrous stroma. On cut sections, they appearspongy and are filled with dark venous blood.HHs are composed of varying-sized vascularchannels, lined by a flattened endothelium under-lined by a basement membrane, and separatedby strands of fibrous stroma of various thick-nesses. The vascular lumina are empty or blood-filled. Thrombi are frequent. According to theclassic description, the interface between HHand the surrounding liver is well circumscribedand demarcated. However, there is generallyno fibrous capsule and occasionally vascularchannels may extend into the adjacent liverparenchyma.20,21
There are several variant types of HHs seen oncross-sectional imaging including: small (<2 cm)“flash-filling” lesions, which tend to enhancehomogenously during the HAP; giant HHs (variablydefined as >4–10 cm in diameter) with central non-enhancing scars; atypical centrifugally filling HHs;
Table 1Imaging features of hypervascular flash-filling hepatic incidentalomas
Diagnosis HAP PVP Delayed MR Imaging Scar Hints
Small hemangioma<2 cm
HypervascularTHID or THAD
HYPER; followsblood pool
HYPER; followsblood pool
T2 HYPER;light bulb
Flash fill; follows blood poolCommon in young women
Large hemangioma2–10 cm
Nodular peripheraldiscontinuousenhancement
THID or THAD
Centripetalenhancement
Progressivefill-in
T2 HYPER;light bulb
FNH Hyper HYPER to ISO ISO T1 ISOT2 ISO
Progressiveenhancement
T2 HYPER
May contain fatStealth lesionsMay only see on HAP
Adenomas Hypervascular Variable Variable Signal drop-outopposed phase
May contain fatMay have hemorrhage;hyperdense NCCT
NRH Hypervascular HYPER to ISO ISO T1 ISOT2 ISO
If present similarto FNH
Found in liver with alteredvenous system
HCC Hyperneovascularity Variable Hypo-washout T2 hyperintenseSimilar to spleen
May contain fatMay contain hemorrhageOften invades portal andhepatic veins
FLC Heterogeneouslyhypervascular
Heterogeneous Variable TI HYPO to ISOT2 HYPER
T1 HYPOT2 HYPOCalcifications
No fatHeterogeneousenhancement
Calcification of central scar
Hypervascularmetastases
HypervascularMay see rimor target sign
THID or THAD
ISO or HYPO ISO or HYPOPeripheralwashout
T2 HYPERSimilar to spleen
Arterioportalshunts
AVM
Hypervascular ISO ISO ISO on T1 and T2 Usually nonsphericalMay regress spontaneously
From Kamaya A, Maturen KE, Tye GA, et al. Hypervascular liver lesions. Semin Ultrasound CT MR 2009;30:387–407; with permission.
Gore
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Hepatic Incidentalomas 301
and hyalinized HHs (also called sclerosed or scle-rosing HHs), which may show little enhancementor delayed peripheral enhancement.20,53
Most HHs are discovered sonographically(Fig. 12) during right upper quadrant ultrasonog-raphy performed to rule out cholelithiasis. Theselesions typically are well circumscribed and hyper-echoic to normal hepatic parenchyma. In thesetting of hepatic steatosis or cirrhosis, however,they may appear hypoechoic. Although this lesionis hyperechoic, in many cases HHs will exhibitposterior acoustic enhancement because thedilated, fluid-filled sacs of blood do not attenuatesound. An atypical but not uncommonsonographicappearance of HHs is a lesion with an echogenicrim with an internal hypoechoic pattern.25
HHs only rarely demonstrate internal flow onDoppler interrogation, due to the multidirectional-ity and slow velocity of flow. Though not currentlyapproved for clinical use in the United States,contrast-enhanced sonography plays an impor-tant role in confirming the nature of HHs in Europeand Asia. Both a flash-filling and nodular, periph-eral, centripetal pattern of enhancement can beseen, identical to the patterns identified oncontrast-enhanced MDCT and MR imaging.55–57
On unenhanced CT scans, HHs have low atten-uation compared with adjacent normal hepaticparenchyma, and when small may be impossibleto differentiate from cysts. The classic enhance-ment pattern of HHs on HAP imaging is highlycharacteristic: peripheral, nodular, discontinuousenhancement isodense with the aorta, withprogressive centripetal fill-in on subsequent
Fig. 12. Hepatic hemangiomas: sonographic features. (A)genic hepatic lesions (arrows). (B) Sagittal sonogram shenhancement (arrows), a sonographic hallmark of hepatic
phases. On PVP images, the lesions may becomeuniformly hyperenhancing compared with thenormal parenchyma, which generally persists intodelayed phases. Histologic correlation indicatesthat smaller vascular spaces enhance morequickly, and the spectrum, from HAP hyperattenu-ating nodules to gradually enhancing “puddles,”reflects the variety of internal architecture ofHHs.20,53,58
Small lesions (Fig. 13) often enhance uniformlyproducing a so-called flash-filling appearance,whereas large lesions (6–10 cm) often showcentral regions that do not exhibit contrastenhancement. HHs can also cause arterioportalshunting, which can simulate metastatic disease.It is important to image HHs over multiple phasesto identify the characteristic pattern ofenhancement.20,45,53
On MR, HHs typically have moderately lowsignal intensity on T1-weighted images anddemonstrate marked hyperintensity on T2-weighted images, which may contain regions oflow signal intensity corresponding with zones offibrosis. HHs maintain high signal intensity onlonger TE (>120 milliseconds), T2-weighted sequ-ences. The majority of small (<1.5 cm) lesionsshow uniform flash filling. Medium-sized lesions(1.5–5 cm) show peripheral nodular enhancementprogressing centripetally to uniform enhancement(Fig. 14). Most large lesions (>5 cm) exhibit periph-eral nodular enhancement while the central portionremains hypointense.26,45,59,60
Small HHs often show robust, uniform, flashfilling (Fig. 15) and may be difficult to differentiate
Axial sonogram shows 3 well-marginated, very echo-ows a well-marginated mass (calipers) with acoustichemangiomas.
Fig. 13. Flash-filling hemangioma: CT features. Axial (A and B) contrast-enhanced CT images show a robustlyenhancing hepatic mass (white arrow) associated with a prominent THAD (black arrows).
Fig. 14. Hepatic hemangioma: classic MR imaging features. (A) There is a large subcapsular hepatic mass (arrow)that shows peripheral nodular enhancement on this sagittal contrast-enhanced image. (B) Delayed sagittal imageshows centripetal “filling in” of this mass, with the enhanced portions of the mass remaining isodense with theblood pool. Note the central scar (arrow) does not enhance.
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Fig. 15. Flash-filling hemangioma: MR imaging features. (A) Axial T2-weighted image shows a homogeneous,hyperintense hepatic lesion (arrow). (B) T1-weighted contrast-enhanced axial image demonstrates robust, homo-geneous enhancement of this mass (arrow).
Fig. 16. Focal nodular hyperplasia: sonographicfeatures. Color Doppler sonography shows increasedblood flow and a spoke-wheel pattern of bloodvessels radiating peripherally from a central feedingartery. Note the dilated feeding artery.
Hepatic Incidentalomas 303
from other HAP enhancing neoplasms, such asHCC or hypervascular metastases. Distinguishingfeatures, however, can be found on PVP and de-layed images. Hypervascular neoplasms oftenshow washout, whereas HHs show persistentenhancement.
Focal Nodular Hyperplasia
Focal nodular hyperplasia (FNH) is the secondmost common benign hepatic neoplasm, consti-tuting 8% of primary hepatic tumors with anestimated prevalence of 0.9% and an 8:1 female-to-male predominance. These lesions are typicallyfound incidentally at cross-sectional imaging, atelective surgery, or at autopsy. FNHs are mostfrequently found in women during the third to fifthdecade of life. Although these lesions tend tooccur in the same population as hepaticadenomas (HA), the pathogenesis of FNH is notbelieved to be related to oral contraceptive use,although hormonal contraceptives can havea trophic effect. In 80% to 85% of cases, FNHpresents as a solitary lesion, most often less than5 cm in size.20,21,60
FNH is defined microscopically as a tumor likecondition characterized by a central fibrous scarwith surrounding nodules of hyperplastic hepato-cytes and small bile ductules. There is intensebile duct proliferation with a surrounding inflam-matory infiltrate. Kupffer cells are invariablypresent. The nodules lack normal central veinsand portal tracts. The bile ductules seen in thecentral scar do not connect to the biliary tract.Blood vessels course through the tumor and aremost abundant in the fibrous scar.20,21,60
Grossly, FNH is a well-circumscribed solitary(95%) lesion that is typically located on the surfaceof the liver. On cut section, the majority of thesetumors have an obvious central scar. Although
the margin is sharp, there is no capsule. Hemor-rhage and necrosis are rare, and most tumorsare less than 5 cm in size. FNH is believed to bea hyperplastic response to increased arterial flowin the setting of a vascular malformation, eithercongenital or acquired.20,21,60–62
Sonographically, FNH is usually nearly isoechoicand less commonly hypoechoic, with the normalliver parenchyma. Its contours are typically lobu-lated and a hypoechoic halo may occasionally beseen, producing a pseudocapsule appearance. Acentral stellate scar may be identified as a mildlyhyperechoic structure in 20%of cases, particularlyif the lesion is large.
On color Doppler sonography (Fig. 16), FNHshows increased blood flow, and a pattern ofblood vessels radiating peripherally from a centralfeeding artery with a characteristic spoke-wheelpattern. Spectral Doppler analysis typically revealsa pulsatile, low-resistance waveform; occasion-ally, large peripheral draining veins may be seen.Contrast-enhanced ultrasonography demonstrates
Fig. 17. Focal nodular hyperplasia: CT findings. Coronal (A) and axial (B) images performed during a pulmonaryembolism study show a large incidental hypervascular hepatic mass with a central scar. Note the hypertrophiedfeeding artery and early draining vein (black arrow). The white arrow indicates the central scar.
Fig. 18. Focal nodular hyperplasia: central scar on MRimaging. Axial unenhanced T2-weighted image showsa hyperintense central scar (arrow), a diagnosticfinding in this lesion. (From Ros PR, Erturk SM. Benigntumors of the liver. In: Gore RM, Levine MS, editors.Textbook of gastrointestinal radiology. 3rd edition.Philadelphia: Saunders; 2008. p. 1603, Figure 88–13A;with permission.)
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early HAP enhancement with a centrifugal fillingpattern, with the lesion becoming hyperechoicduring the late HAP and slightly hyperechoic orisoechoic on the PVP and delayed phases.25,63
On nonenhanced CT scans, FNH usuallyappears as a homogeneous hypo- or isodensemass. In one-third of cases, a low-density centralscar is visualized. During the HAP, FNH showsintense enhancement and the central scar remainshypodense (Fig. 17). During PVP, the difference inattenuation between FNH and normal liverpromptly diminishes so that the tumor may beslightly hyperdense or isodense, with a hypo- orisodense central scar. On delayed imaging thelesion is isodense, but the central scar typicallybecomes hyperdense.20,53,64
Calcifications in the central scar are exceedinglyrare and if present, fibrolamellar carcinoma (FLC)should be strongly considered. Thoughnonspecific,the central scar is a helpful distinguishing feature ofFNH but is only seen in 32% to 60% of lesions.65–67
FNHcanbeconfidently diagnosedwhen a homoge-neously and robustly enhancing, noncalcified massis seen during HAP imaging that gradually becomesisodense on delayed images accompanied bya central scar, which slowly accretes contrastmedia. This classic appearance is most reliable inlesions larger than 3 cm.68–72
MR imaging has a higher sensitivity (70%) andspecificity (98%) than MDCT and ultrasonographyfor the characterization of FNH.73 On nonen-hanced studies, FNH is often difficult to distinguishfrom normal surrounding liver parenchyma, as thistumor is isointense on T1-weighted images, andbecomes slightly hyperintense to isointense onT2-weighted images. As with CT, the mass is char-acteristically homogeneous. The central scar is
hypointense on T1-weighted images andmarkedlyhyperintense on T2-weighted images (Fig. 18), thelatter being a distinguishing feature. MR visualizesthe central scar in 78% of lesions.74–76
FNH enhances robustly and homogeneouslyduring the HAP, with the exception of the late-enhancing central scar (Fig. 19). On both PVPand delayed imaging, the mass again becomesisointense or slightly hyperintense to thesurrounding liver, with delayed enhancement ofthe central scar.74–76
The accurate diagnosis of FNHs is importantbecause they are benign lesions with no risk of
Fig. 19. Focal nodular hyperplasia: MR imaging features. (A) Arterial-phase axial T1-weighted image showsa robustly enhancing hepatic mass with the exception of the central scar (arrow). (B) Hepatic venous-phase axialT1-weighted image shows delayed enhancement of the central scar (arrow) while the remainder of the lesion isnearly isointense with normal hepatic parenchyma.
Fig. 20. Hepatic adenoma: sonographic findings.Sagittal sonogram reveals a nonspecific appearingechogenic mass (calipers) with a hypoechoic regioncentrally corresponding to an area of hemorrhage.
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malignant degeneration, rupture, or hemorrhage.Several typical imaging characteristics of FNHcan permit a confident diagnosis, including lesionhomogeneity, delayed enhancement of a centralscar, marked T2 hyperintensity of the centralscar, homogeneous HAP enhancement, and thelack of a capsule. Although none of these featuresare specific when seen alone, the combination ofseveral of them is suggestive.20,53,64
Hepatic Adenomas
Hepatocellular adenomas (HA) are rare, histologi-cally benign neoplasms that have a small risk formalignant transformation into HCC, as well asa propensity for hemorrhage and rupture. Themajority of these lesions occur in young womentaking oral contraceptives. The estimated annualincidence in individuals with no history of oralcontraceptive use is 1 in 1 million, which increasesto 30 to 40 in 1 million with prolonged oral contra-ceptive use.22 The risk of developing HAs isrelated to the both the duration of use and doseof hormones. The decline in the overall amountof hormones found in oral contraceptives hasbeen paralleled by a decreased incidence of thistumor. These lesions regress when oral contra-ceptives are discontinued.22
Patients using estrogen- or androgen-containingmedications are also at increased risk for HA devel-opment. Other populations noted to have anincreased incidence of HAs include individualswith type I glycogen storage disease. In thesepatients, hepatic adenomas tend tobemultiple.20,22
The classic clinical presentation of HAs is that ofa spontaneous hemorrhage or rupture causingacute abdominal pain; however, most of thetumors are asymptomatic and found incidentally.In 70% to 80% of cases, HAs present as solitary
lesions ranging in size from less than 1 cm to15 cm. On gross pathology, adenomas are well-circumscribed, pale-yellow tumors that usuallydo not have a capsule. Histologically, they arecomposed of sheets of cells resembling normalhepatocytes containing abundant glycogen andlipid. Prominent arteries and draining veins areseen; however, the tumor lacks portal tracts andterminal hepatic veins. Kupffer cells are presentin up to 20% of cases. Fatty hepatocytes arefrequently present.21,22
The imaging features of HAs depend on theamount of lipid, hemorrhage, or fibrosis withinthe tumor, and the status of the surroundinghepatic parenchyma.
The sonographic findings (Fig. 20) are usuallyvariable and nonspecific, but HAs typically
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manifest as a large hyperechoic lesion with centralanechoic areas, corresponding to zones of internalhemorrhage. If the adenoma has undergone signif-icant necrosis and hemorrhage, the ultrasono-graphic appearance is that of a complex masswith large cystic components. Color Doppler eval-uation can be helpful, demonstrating peripheraland intratumoral vessels showing a flat continuousDoppler waveform in contrast to the usual pulsatilewaveform of FNH and HCC.25,77,78
Fig. 21. Hepatic adenoma: CT and MR imaging featureshepatic mass (black arrows) with focal areas of fat. Thienhancement on hepatic arterial phase image (B) that shIn-phase (D) and opposed-phase (E) MR images reveal dro(white arrow).
On unenhanced CT (Fig. 21A), uncomplicatedHAs are isodense or hypodense to the surroundingliver. Hyperdense areas corresponding to hemor-rhage can be noted as well. Low-density regionsmay correspond to regions of intratumoral fat.Following contrast administration, CT (see
Fig. 21B, C) shows homogeneous enhancementon HAP imaging in 81% to 90% of cases, particu-larly if the lesions are small (<3 cm). The enhance-ment is moderate and remains less than that of the
. (A) Axial unenhanced CT scan shows a low-densitys lesion exhibits moderate, inhomogeneous contrastows gradual washout on delayed phase (C) CT image.p-out of signal intensity by the fat within this tumor
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arterial vasculature. It is less impressive and moreheterogeneous than seen in FNH. On PVP and de-layed imaging, the lesion is nearly isodense to thesurrounding liver. Due to the presence of necrosis,fat, and hemorrhage, some 25% of lesions willhave a more heterogeneous appearance. Fat hasbeen identified in 7% of lesions and calcificationsare present in 5% to 15%. Larger lesions tend tobe more heterogeneous than smaller lesions, andthe CT appearance is nonspecific.53,79
HAs do not have a central scar, a point useful indistinguishing the lesion from FNH, which tends tooccur in the same patient population. In the back-ground of hepatic steatosis, HAs typically are hy-perdense on all phases.78,79
By virtue of its ability to depict internal lipidcontent (see Fig. 21D, E) and hemorrhage within- and opposed-phase sequences and superiorcontrast resolution, MR imaging can often bettercharacterize HAs.26
HAs can be isointense on T1-weightedsequences or may be hyperintense due to fatcontent. HAs are quite variable in T2 signal inten-sity and often show signal dropout on opposed-phase imaging (Fig. 22). Following gadoliniumadministration, there is faint enhancement duringthe HAP only, with an isointense appearance ondelayed imaging. A peripheral rim can be seen inup to one-third of lesions, representing the variablypresent fibrous capsule. Unlike FNH lesions, HAsdo not take up superparamagnetic iron oxideparticles because they lack Kupffer cells. Similarly,there is no significant uptake of hepatocellular-specific contrast agents by HAs. Scintigraphic
Fig. 22. Intralesional fat and hemorrhage in a patient wimage shows a large low-signal mass that contains regionsrhage (arrow). (B) Opposed-phase axial MR image demonssity due intratumoral fat. The hemorrhagic mass also show
studies are not particularly useful for HA character-ization, as they do not demonstrate uptake oneither Tc-99m sulfur colloid scans or iminodiaceticacid studies.80,81
Although benign, HAs are important to accu-rately diagnose, because 10% of patients willpresent acutely due to adenoma rupture andsubsequent hemoperitoneum. Furthermore, thereis a risk of malignant degeneration in up to 10%of tumors. Both of these risks are morepronounced with larger lesions. For these reasons,HAs are typically surgically resected. Although thecharacteristics of the mass on CT and/or MR canoften result in a confident diagnosis, there is stilloccasional overlap between the appearance ofan adenoma and that of FNH, which also occursin young women. Brancatelli and colleagues81
have noted that in these cases, the most usefuldistinguishing features are the presence orabsence of a central scar as well as the signalcharacteristics on MR indicating the presence orabsence of fat and the degree of lesion heteroge-neity. Furthermore, a well-differentiated HCC canhave many of the same imaging features as thoseof an HA and in these cases, clinical correlationwith other features, such as the presence ofcirrhosis and the patient’s serum a-fetoprotein,may be helpful in narrowing the differentialdiagnosis.81
Nodular Regenerative Hyperplasia
Nodular regenerative hyperplasia (NRH) is definedas a diffuse nodularity of the liver produced by
ith multiple hepatic adenomas. (A) In-phase axial MRof high signal intensity, indicating intralesional hemor-trates additional lesions (arrows) with low signal inten-s loss of signal intensity, indicating the presence of fat.
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many regenerative nodules that are not associatedwith fibrosis.20,39,82 NRH grossly is characterizedby the presence of multiple bulging subcapsularnodules that on cut surface appear as discrete,round, flat nodules that resemble diffuse involve-ment with metastatic carcinoma. These nodulesvary in size from a few millimeters to several centi-meters and are diffusely scattered. Microscopi-cally, the nodules are composed of cellsresembling normal hepatocytes, and no fibrosisis noted; this is an important difference betweenNRH and regenerating nodules of cirrhosis.21,39,82
NRH is rare, although some autopsy series haveshown a prevalence as high as 0.6%.21 NRH isassociated with various systemic disease anddrugs that are also associated with the Budd-Chiari syndrome: polycythemia vera, chronicmyelogenous leukemia, myeloid metaplasia,Hodgkin disease and non-Hodgkin lymphoma,chronic lymphocytic leukemia, rheumatoidarthritis, Felty syndrome, polyarteritis nodosa,scleroderma, systemic lupus erythematosis,steroids, and antineoplastic medications.21,39,82
The sonographic appearance of NRH is variable,ranging from normal to a liver with multiple focalnodules that vary in echogenicity. Central hemor-rhage with a large nodule may occur and producea complex mass.25,83 The CT appearance of NRHis also variable. On unenhanced scans, theselesions are usually hypodense but when hemor-rhagic, they may produce a complex mass withvariable density. On contrast-enhanced scans,HAP imaging shows hypervascular lesions(Fig. 23) that may become almost imperceptibleduring the PVP. On unenhanced MR imaging,NRH lesions are usually isointense to normal
Fig. 23. Nodular regenerative hyperplasia in patientwith Budd-Chiari syndrome: imaging features. Axialcontrast enhance CT scan shows multiple hyperen-hancing hepatic masses. (Case Courtesy of Michael P.Federle, MD and Richard L. Baron, MD.)
liver on T2-weighted images and contain fociof high signal on T1-weighted scans. As on CT,these lesions often show robust contrastenhancement.84
Hepatocellular Carcinoma
HCC is the third leading cause of cancer-relateddeath worldwide, and risk factors include hepatitisB carrier state, chronic hepatitis C virus infection,hemochromatosis, exposure to aflatoxins, andcirrhosis from any cause. Nonalcoholic steatohe-patitis is a recently recognized risk factor that, inview of the obesity epidemic in the United States,has the potential to make this disorder a major riskfactor for HCC. There are significant geographicfactors in HCC incidence, reflecting the heteroge-neous distribution of its main etiologic factors.Usually the diagnosis is made in symptomaticpatients, in patients with known cirrhosis, or inthose undergoing screening and surveillanceexaminations.21,85–89
In cirrhotic patients it is important to distinguishearly small HCCs from macroregenerative nodulesand dysplastic nodules, as well as atypical heman-giomas and metastases.HCC has a varied, nonspecific appearance on
ultrasonography. Small HCCs (<3 cm) often appearhypoechoic (Fig. 24) but may be hyperechoic,
Fig. 24. Hepatocellular carcinoma: sonographicfeatures. Sonogram demonstrates a hypoechoic masswith a peripheral halo sign (arrow). (From Ros PR,Erturk SM. Malignant tumors of the liver. In: GoreRM, Levine MS, editors. Textbook of gastrointestinalradiology. 3rd edition. Philadelphia: Saunders; 2008,p. 1627, Figure 89–4E; with permission.)
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particularly if there is fatty change or marked sinu-soidal dilatation. Tumors larger than 3 cm moreoften have a mosaic or mixed pattern. The capsuleof encapsulated HCCs may appear as a thin, hy-poechoic band.21,85,90–92
On unenhanced CT scans, HCCs may presentas hypodense lesions, due to necrosis and/or thepresence of fat. Because these neoplasms derivethe majority of their blood supply from the hepaticartery, they demonstrate robust enhancementduring the HAP and are relatively hypodense onthe delayed-phase images (Fig. 25). The tumorhas a variable appearance on PVP images,including isodense with the remainder of the liver.The capsule appears either isodense or hypo-dense relative to the liver during the HAP andenhances on delayed CT images.85,93–96
HCC has a variable appearance on MR imaging.It shows intermediate to high signal intensity onT2-weighted images, similar in intensity to thespleen, and variable intensity on T1-weightedimages, depending on the presence of internalfibrosis, fatty change, and the dominant histologicpattern.26,53,97,98
As with CT, HCC shows robust enhancementduring the HAP phase. These vascular lesionsoften show contrast washout to a greater degreethan the adjacent hepatic parenchyma (Fig. 26).The washout phenomenon can help differentiateHCCs from other hypervascular lesions.53,85
When well differentiated, HCCs may not behypervascular on HAP images. However, if awell-defined capsule and internal washout aredemonstrated on delayed-phase images, the
Fig. 25. Hepatocellular carcinoma: CT findings. (A) Axial CThepatic arterial phase demonstrates a small flash-filling mThis mass becomes hypodense (arrow) on portal venous p
diagnosis can be suggested. Larger lesions oftenhave areas of neovascularity and central areas ofnecrosis if they outgrow their blood supply.HCCs may occasionally contain areas of fat andmay spontaneously bleed, especially whenexophytic.53
Fibrolamellar Carcinoma
Fibrolamellar carcinoma (FLC) is a slow-growinghepatic neoplasm that arises in a normal liver.FLC is composed of neoplastic hepatocytes sepa-rated into cords by lamellar fibrous strands. Themost common variant of FLC shows areas ofglandular-type differentiation with mucin produc-tion. FLC does not commonly cause elevation ofa-fetoprotein, and no reliable serum tumormarkers have been identified.22 This tumor usuallyoccurs in adolescents and adults younger than 40years without predisposing risk factors. Whensymptomatic, patients may present with pain, ma-laise, weight loss, and occasionally jaundice.20
At presentation, FLC is generally a large, solitarymass, usually 5 to 20 cm in size, with well-definedand lobulated margins. Small peripheral satellitelesions may, on occasion, be present. FLCs oftenhave an irregular central scar (seen in 20%–71% ofpatients) and coarse calcifications within thecentral scar (seen in 35%–68% of patients).99,100
Sonographically, FLCs usually present asa large, well-defined, lobulated mass with mixedechogenicity. A central scar may be visualized asa central area of hyperechogenicity.25,99,100
scan obtained from a patient with cirrhosis during theass (arrow) in the medial segment of the left lobe. (B)hase images.
Fig. 26. Hepatocellular carcinoma: MR findings. Axial enhanced scans show a robustly enhancing tumor (arrow)duringthearterial phase (A),whichdemonstrateswashoutwith ringenhancementontheportal venousphase image(arrow) (B). (From Ros PR, Erturk SM. Malignant tumors of the liver. In: Gore RM, Levine MS, editors. Textbook ofgastrointestinal radiology. 3rd edition. Philadelphia: Saunders; 2008. p. 1631, Figures 89–9 E and F; with permission.)
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On unenhanced CT scans, FLC appears asa hypodense mass with a well-defined contour.Stellate calcifications may be found within thecentral scar (Fig. 27A). On contrast-enhancedCT, FLCs are typically heterogeneously hyper-vascular with avidly enhancing tumor vessels.Enhancement on PVP and delayed-phase
Fig. 27. Fibrolamellar carcinoma: imaging findings. (A) Enhenhancing lesion in the left lobe of the liver. Notice the caT1-weighted MR scan in the same patient shows an inhocontrast administration, this mass (large arrow) shows roband an enhancing peritoneal metastasis (small arrow).
images is variable, which reflects washout ofthe contrast from more vascular areas of thetumor together with delayed enhancementof the fibrous lamellae. The central scar is gener-ally low on both pre- and postcontrast CT butmay show delayed enhancement, simulatingFNH.85,101,102
anced CT scan shows a robustly but inhomogeneouslylcification of the central scar (arrow). (B) Unenhancedmogeneous, low signal-intensity mass. (C) Followingust enhancement except for the scar. There is ascites
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On MR imaging (see Fig. 27B, C), FLCs aregenerally hypo- to isointense relative to normalhepatic parenchyma on T1-weighted images,and slightly hyperintense on T2-weightedsequences. Because of its purely fibrous nature,the central scar is hypointense on T1- and T2-weighted images, a differentiating feature fromFNH. In addition, the central scar shows minimalor no enhancement. Hypointense septa radiatingtoward the tumor periphery may be better appreci-ated on MR imaging than on CT. FLCs have nodetectable intrinsic fat.26,53,103
The major differential diagnosis of FLC is FNHbecause both occur in the same age group. Differ-entiating features include: the central scar of FNHis hyperintense on T2-weighted images; FNH onlyrarely calcifies (<1.5% of cases compared with upto 55% of FLCs); and FNH is usually asymptomaticwhereas patients with FLC typically present withsymptoms.53
Hypervascular Metastases
Metastases are the most common malignant livertumors, and occur 20 times more frequently thanprimary hepatic neoplasms. The liver is secondonly to regional lymph nodes as a site of meta-static disease, and approximately 25% to 50%of all patients who die of cancer have liver metas-tases at autopsy.22,104 Except for infiltrativetumors such as lymphoma, most metastasesmanifest as multiple discrete lesions. The imagingappearance of metastases can vary greatlydepending on differences or blood supply, hemor-rhage, cellular differentiation, fibrosis, andnecrosis.
Fig. 28. Hypervascular liver metastases: CT features. (A) Amasses (arrows). These lesions show prompt washout duri
Most liver metastases are hypovascular, and asa result are hypointense on MR imaging and hypo-dense on CT as compared with normal liver paren-chyma during the PVP. Colon, lung, breast, andgastric cancers are the most common causes ofhypovascular liver metastases. These metastasesare best visualized during the PVP and typicallyshowing perilesional enhancement or a targetappearance. If the lesions do not show thisappearance, small hypodense or hypointensemetastases may be difficult to differentiate froma host of benign hepatic lesions describedearlier.53,105
Hypervascular metastases enhance earlier andare most conspicuous on the HAP. In addition,they demonstrate variable degrees of washouton delayed images. The most common causes ofhypervascular hepatic metastases include neuro-endocrine tumors (eg, carcinoid, pheochromocy-toma, and islet cell tumors), renal cell carcinoma,melanoma, choriocarcinoma, and thyroid carci-noma. Breast carcinoma and, rarely, pancreaticadenocarcinoma can also cause hypervascularmetastases.53,105
Hypervascular metastases smaller than 1.5 cmcan be difficult to distinguish from flash-fillingHHs, because both can display rapid enhance-ment during HAP contrast-enhanced CT and MRimaging (Figs. 28 and 29) and increased T2 signalintensity on MR imaging. On PVP or delayed-phase imaging, however, they do have a distinctlydifferent appearance. HHs retain their contrastmaterial and appear enhanced during the PVP,whereas hypervascular metastases tend to washout. Another potential distinguishing feature is
Fig. 29. Hypervascular metastases: MR features.Multiple enhancing hepatic masses are identified onthis contrast-enhanced axial MR scan in a patientwith metastatic renal cell carcinoma.
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the “peripheral washout” sign, a specific butinsensitive sign for malignancy that favors thediagnosis of metastasis or HCC over HH. Malig-nant lesions often show peripheral washout ofcontrast on delayed contrast-enhanced images,and a target appearance, with the rim appearinghypointense relative to the center. This targetappearance has been reported to be highlyspecific for hypervascular metastasis (100% spec-ificity) and is frequently observed in hypervascularmetastases from neuroendocrine and carcinoidtumors.105,106
Intrahepatic parenchymal perfusion disorderssuch as THIDs and THADs are epiphenomena ofalterations of the dual vascular supply of the liverseen on MR and CT, respectively. There isa compensatory relationship between hepaticarterial and portal venous blood supply so thatarterial flow increases when portal blood flowdecreases. This situation is made possible bycommunication among the main vessels, sinu-soids, and peribiliary venules that dilate inresponse to autonomic nervous activity andhumoral factors activated by hepatic demand foroxygen and metabolites. THADs and THIDs areareas of parenchymal enhancement on CT andMR visible during the HAP following the intrave-nous administration of contrast material. These“lesions” are an increasingly common cause ofhepatic incidentalomas, and can be classified bymorphology, etiology, and pathogenesis.43,107–128
THADs and THIDs associated with a truehepatic massMalignant and benign (Fig. 30) hepatic massesproduce 2morphologic types of THIDs and THADsvia 4 major pathophysiologic mechanisms: directsiphoning effect of the mass (lobar multisegmentalshape), or indirectly by means of portal hypoperfu-sion (sectorial shape) due to portal branchcompression or infiltration, by thrombus resultingin a portal branch blockade, or by flow diversioncaused by an arterioportal shunt.43,107–111,113–128
Lobar multisegmental THADs and THIDs occurwhen a benign hypervascular lesion or an abscessinduces an increase in the primary arterial inflow,which leads to surrounding parenchymal perfu-sion, the so-called siphoning effect. These THADsand THIDs do not assume a triangular shape, buta straight border may be present between the arte-rial phenomenon and the “normal” adjacentparenchyma.43,107–111,113–128
Sectorial THADs and THIDs follow hepaticvessel dichotomy and appear as triangular areasthat result from the strict relationship betweenthe portal hypoperfused area and the arterial reac-tion. These lesions can be seen in benign andmalignant tumors as well as abscesses causedby the spread of inflammatory mediators. TheTHADs and THIDs can be wedge- or fan-shapedin this instance.43,107–111,113–128
THADs and THIDs not associated with a masslesionTHIDs and THADs can be seen in the absence ofa focal lesion as a result of 3 mechanisms: portalhypoperfusion due to portal branch compressionor thrombosis (Fig. 31); flow diversion by arterio-portal shunts or by an anomalous blood supply;or inflammation or obstruction of the bile ductsor gallbladder.43,107–111,113–128
Sectorial THADs and THIDs are usually causedby portal hypoperfusion caused by portal vein orhepatic vein thrombosis, long-standing biliaryobstruction, or an arterioportal shunt that may becongenital, traumatic, or caused by cirrhosis.These THADs and THIDs can have a globularshape, especially when they are adjacent to Glis-son’s capsule.43,107–111,113–128
Polymorphous THADs and THIDs have 4 majorcauses: external compression by a rib or subcap-sular fluid collection; anomalous blood supplyfrom atypical arteries, collateral venous vessels,or accessory veins, especially in segment IV ofthe liver; inflammation of adjacent organs suchas cholecystitis and pancreatitis that spreadinflammatory mediators and reduce portal inflowdue to interstitial edema; and posttraumatic,
Fig. 30. THADs and THIDs associated with a benign mass: imaging features. Axial (A) and coronal (B) scans showa large hemangioma (H) in the lateral segment of the left lobe, causing a large THAD in the medial segment(arrows). Early (C) and late (D) phase MR images show a THID (H) on the early-phase images and resolution onthe delayed scan, which also shows filling in of the hemangioma (H).
In patients with obstruction of the superior venacava, the medial segment of the left lobe (segmentIV) of the liver will often show hyperenhancement(Fig. 32) due to collateral veins. The internalmammary vein connects to the left portal vein viathe paraumbilical vein. Diffuse THADs and THIDscan be seen in right-sided heart failure, the
Fig. 31. THID associated with portal vein thrombosis. (A) Ethe ascending portion of the left portal vein producing a TArrow indicates thrombus.
Budd-Chiari syndrome, and biliary obstruction,leading to abnormal attenuation and signal inten-sity adjacent to the portal triads.43,107–111,113–128
Hepatic arteriovenous malformation (AVM) iscongenital abnormality of blood vessels that
arly-phase contrast-enhanced MR image shows clot inHID (arrows). On delayed images (B) the THID resolves.
Fig. 32. THAD caused by superior vena cava obstruction by metastatic lung cancer. (A) Axial CT scan shows flash-filling lesions (arrows) along the anterior aspect of the medial segment of the left hepatic lobe. (B) Axial contrast-enhanced chest CT scan shows tumor (T) obstructing the superior vena cava (arrow).
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results in the shunting of blood through directcommunications between the arterial venouschannels. These vascular anomalies contain noabnormal tissue between the anomalousvessels.22,59,129,130
Sonographically, hepatic AVMs appear asa cluster of enlarged, tortuous vessels confinedto one lobe of the liver with increased venous pul-satility, decreased resistive indices, arterializationof portal flow, reversal of portal flow, and/or alias-ing on color Doppler imaging due increased turbu-lence and flow velocity. The hepatic artery isfrequently enlarged.59,129,130
AVMs show intense homogeneous enhance-ment on CT (Fig. 33) and MR during the HAPand early PVP images.Three types of intrahepatic vascular shunting
may occur: arterial to portal venous, arterial tohepatic venous, and portal to hepatic venous.Abnormal vascular connections between thehepatic arterial system and portal venous systemcan arise within hypervascular masses (eg, HCC,metastases), in the cirrhotic liver, secondary to
Fig. 33. Arteriovenous malformation: CT features. (A) Co(large arrow) in the left lobe of the liver and an incidental ccaudal to (A) shows a tortuous feeding artery (arrow). (Ca
trauma (eg, biopsy), or rarely through rupture ofhepatic artery aneurysms into the adjacent portalvein. The common pathophysiology of all arterio-portal shunting involves the entry of arterial bloodat systolic pressures into the low-pressure portalvenous system; subsequently, localized reversalof portal flow occurs and local parenchyma is sub-jected to increased perfusion pressure. Alteredand arterial dominant vascular supply to the local-ized parenchymamay cause a THAD, a THID, and/or focal fatty infiltration or sparing in a fatty liver,when small, intrahepatic vascular malformationsmay manifest as “color spots” on Dopplersonography.59,129,130
INCIDENTALOMAS IN SPECIFIC PATIENTCOHORTSHepatic Incidentalomas in the OncologyPatient
When evaluating a small hepatic mass in theoncology patient, 2 important facts must beconsidered. First, at postmortem examination,
ntrast-enhanced CT scan shows a hypervascular lesionystic pancreatic lesion (small arrow). (B) Scan obtainedse Courtesy of Elliot K. Fishman, MD.)
Fig. 34. Hemangioma in a fatty liver: CT findings. Asmall hyperdense lesion (arrow) is identified in theright lobe, which is isodense with the blood pool.
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benign hepatic lesions are detected in up to 52%ofthe general population.20,22 Second, the liver is themost common site of extranodal metastases, seenin up to 36% of patients.22 Small hepatic massesare commonly encountered in both populations oncross-sectional imaging. Hepatic cysts includingBDHs and HHs are present in nearly 40% ofpatients.22 When less than 1.5 cm in size, theselesions can be difficult to characterize and differen-tiate from metastatic disease.131–135 Severalstudies have specifically addressed this issue.
Jones and colleagues136 found at least onehepatic lesion 1.5 cm or smaller in 17% of allpatients in a retrospective study performed onnonhelical CT scanners. In patients with a knownmalignancy, 51% were benign, 26% were malig-nant, and 23% were indeterminate. The likelihoodof malignancy was 5%with 1 lesion, 19%with 2 to4 lesions, and 74% with 5 or more lesions. Ina second study of 2978 patients with cancer,Schwartz and colleagues137 found small (�1.0 cm)lesions in 12.7% of patients, of which 80.2%were benign, 11.6% were malignant, and 8.2%were indeterminate.
Studies performed with helical scanners havealso found the majority of small, low-attenuatinglesions within the liver in the oncology patient tobe benign. In a review of 1133 patients with colo-rectal and gastric cancer, Jang and colleagues138
found small (�1.5 cm) hypoattenuating lesions in25.5% of cases. Some 94% of lesions that weresmooth and low density (�20 HU) proved to bebenign. In a study of 941 women with breastcancer, Khalil and coworkers139 found 1 or moresmall, hypoattenuating lesion in 29.4%. In 92.7%of patients these lesions showed no change, in4.2% they disappeared, and in 3.1% they becamelarger. The investigators concluded that findinga small, hypodense lesion in the liver with no defi-nite metastases was a benign finding. Krakora andcolleagues,140 in a study of 153 patients withbreast cancer, discovered small hypoattenuatinghepatic lesions in 35%, noting that the presenceof these small lesions without definite hepaticmetastases did not contribute an increased riskof developing subsequent hepatic metastases.
The imaging findings and differential diagnosisof hypervascular metastases are described in anearlier section.
Fig. 35. Flash-filling incidentaloma in a patient withcirrhosis: MR findings. Contrast-enhanced axial scanshows a wedge-shaped hyperenhancing area (arrow)in the right lobe. Subsequent evaluation showed nounderlying mass.
Hepatic Incidentalomas in the Patient withDiffuse Hepatic Steatosis
Severe hepatic steatosis may alter the apparentenhancement pattern of focal hepatic lesions. Evenhypovascular tumors such as metastases canshow relatively high attenuation onCTand simulate
HHswithapersistentcontrastenhancementpattern.On unenhanced scans, the density of an HH mayappear hyperattenuating, though not greater thanthat of blood vessels (Fig. 34). HHs may also beaccompanied by a focal spared zone as seen inmalignanttumorsinfattyliver.Thisfindingcancreateconfusion sonographically, with a hypoechoic halosurroundingtheHHsimulatingthatseeninmalignanttumors rather than the usual hyperechoic rimsurrounding the HH. This unusual finding oftenmakes subsequent CT or MR imaging necessary.HHs in fatty liver can produce a peculiar halo on CTor MR imaging as well, but in most cases accuratediagnosis can be made without difficulty becauseof the characteristic dynamic enhancement patternofHHs.
Focal hepatic steatosis is a common pseudotu-mor detected on ultrasonography, MDCT, and MR
Gore et al316
imaging that can be problematic in the oncologypatient. On MDCT, focal fat appears as an areaof decreased attenuation that does not causemass effect and through which blood vesselsnormally course. If the diagnosis is uncertain,steatosis can be confirmed with in-phase andopposed-phase MR imaging, which is described
Incidental LivDetected
0.5–1.5<0.5 cm
High riskcLow or Average riska,b
Benign, no further follow up
Follow-upd
Low attenuation, benign imaging
featurese
Benign,no furtherfollow upf
Any risk levela,b,c
Lows
imag
Any risk levela,b,c
Follow-upd
Low attenuation, benign imaging featurese
Low attenuimagi
Benigno furfollow
HighAverage riskbLow riska
Benign,no further follow-upf
Follow-upd Evaluateg Biopsyprefe
Fig. 36. Algorithmfor theevaluationof thehepatic incidenold), with no known malignancy, hepatic dysfunction, hepathe liver. b Average-risk individuals: patient >40 years oldhepatic malignant risk factors or symptoms attributable tonancy with a propensity to metastasize to the liver, cirrhosinclude hepatitis, chronic active hepatitis, sclerosing cholansiderosis, oral contraceptive use, and anabolic steroid use.more frequent follow-up in some situations, for example,e Benign imaging features: typical hemangioma (see belowup to about 20 HU, no enhancement. May have sharp, bcyst, hemangioma, hamartoma, von Meyenburg complex (ill-defined margins, enhancement (more than about 20 Hmultiphasic MR imaging. h Hemangioma features: nodularsive enlargement of enhancing foci on subsequent phases.robustly enhancing lesion in average-risk, young patient: hence (THAD) flowartifact, and in average-risk, older patientnoses: adenoma, AVM, nodular regenerative hyperplasiaespecially if larger than 4 cm and subcapsular. j Hepatocellucell, neuroendocrine, carcinoid, renal cell carcinoma, melanatic lesions. (From Berland LL, Silverman SG, Gore RM, et alpaper of the ACR Incidental Finding Committee. J Am Coll
below. These pseudotumors are described morefully in an earlier section.
Hepatic Incidentalomas in the Patientwith Cirrhosis
Small, peripheral, THIDs (Fig. 35) and THADs arecommonly seen in the cirrhotic liver. These lesions
er Mass on CT
cm >1.5 cm
attenuation, uspicious ing featuresg
Flash filling(robustly enhancing)
High riskcLow or average riska,b
Follow-upd
ation, suspicious ng featuresf
Flash filling (robustly enhancing)
Evaluategn, ther uph,i
riskc
Benign, evaluate if
possible FNH, adenomah,i
, core rred Follow-upd, evaluateg
or biopsy, core preferred
Benign diagnostic imaging featuresh,i
No benign diagnosticimaging featuresj
taloma. a Low-risk individuals: youngpatient (�40yearstic malignant risk factors, or symptoms attributable to, with no known malignancy, hepatic dysfunction, orthe liver. c High risk individuals: known primary malig-is, and/or other hepatic risk factors. Hepatic risk factorsgitis, primary biliary cirrhosis, hemochromatosis, hemo-d Follow-up CT or MR imaging in 6 months. May needa cirrhotic patient who is a liver transplant candidate.), sharply marginated, homogeneous low attenuationut irregular shape. f Benign low-attenuation masses:bile duct hamartomas). g Suspicious imaging features:U), heterogeneous, enlargement. To evaluate, preferdiscontinuous peripheral enhancement with progres-Nodule isodense with vessels, not parenchyma. i Smallemangioma, FNH, transient hepatic attenuation differ-: hemangioma, THAD flowartifact.Other possible diag-. Differentiation of FNH from adenoma is important,lar or commonmetastatic enhancing malignancy: isletoma, choriocarcinoma, sarcoma, breast, some pancre-
. Managing incidental findings on abdominal CT: whiteRadiol 2010;7:754–73; with permission.)
Hepatic Incidentalomas 317
probably arise from portal hypoperfusion in thecontext of portal hypertension and even occlusion,permitting focal arterial dominance and resulting ina hypervascular imaging appearance. Theselesions are not true masses but rather representfoci of abnormal vascularity; they have no clinicalsignificance except as a marker for underlyinghepatocellular disease, but may simulate HCCand other hepatic tumors.140,141
During the HAP of enhancement on CT and MRimaging, peripheral subcentimeter nodular orirregular hypervascular foci denote the actual siteof vascular connection. HAP images sometimesdepict early intravascular enhancement of theassociated portal vein branch. During the PVP,the hypervascular nodule becomes much lessconspicuous or entirely undetectable. On follow-up imaging months to years later, most nontumo-rous arterioportal shunts in chronic liver diseasedisappear or spontaneously regress. The en-hancement patterns in MR imaging are almostperfectly analogous to CT, but the lesions are notvisible on precontrast T1- and T2-weightedimaging. The tiny foci of AP shunting in cirrhosisare not usually visible sonographically due to thehyperechogenicity and scarring of the liver.Indeed, most hypervascular lesions in cirrhosisexclusively depicted on the HAP imaging on CTand MR imaging are pseudolesions or benignlesions particularly if they are small, wedge-shaped, and subcapsular in location.141,142 Never-theless, a high index of suspicion must bemaintained in any cirrhotic patient with any focalhepatic lesion.
SUMMARY AND RECOMMENDATIONS
Ultimately the following 3 questions need to beanswered in patients with incidental hepaticmasses: (1) does the hepatic incidentaloma putthe patient at risk for an adverse outcome? (2)can primary or metastatic malignancy be accu-rately and confidently differentiated from a benignincidentaloma? and (3) if a lesion is benign, might itstill require surgical intervention, such as resectinga HA to prevent rupture?
The American College of Radiology has createda series of guidelines for the management of inci-dentally discovered hepatic masses discoveredon cross-sectional imaging.143 These guidelinesare depicted in Fig. 36 and are discussed here.
Managing incidental liver lesions depends onthe probable importance of the mass. Importanceis assessed based on the appearance of the massand the level of risk that each patient has for devel-oping significant liver masses, realizing that impor-tant liver masses are not limited to malignancies.
Patient risk for important hepatic masses is strati-fied as follows:
1. Low-risk individuals: Young patients (�40 yearsold), with no malignancy, hepatic dysfunction,hepatic malignant risk factors, or symptomsrelated to the liver
2. Average risk individuals: Patients older than 40years, with no known malignancy, hepaticdysfunction, hepatic malignant risk factors, orsymptoms related to the liver
3. High-risk individuals: Patients with a knownprimary malignancy with a propensity to metas-tasize to the liver, cirrhosis, and/or otherhepatic risk factor. Hepatic risk factors includecirrhosis, hepatitis, chronic active hepatitis,sclerosing cholangitis, hemosiderosis, hepaticdysfunction, and long-term anabolic steroid ororal contraceptive use.
Using these guidelines, the vast majority of inci-dental lesions can be correctly characterized.
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