tumors of the liver and intrahepatic bile ducts: radiologic–pathologic correlation

Tumors of the Liver andIntrahepatic Bile Ducts:RadiologicePathologicCorrelation
Rachel B. Lewis, MDa,b,c,*, Grant E. Lattin Jr, MDa,c,Hala R. Makhlouf, MD, PhDd, Angela D. Levy, MDe
KEYWORDS

� Liver � Hepatic neoplasms � Magnetic resonance imaging

Primary tumors of the liver canbebroadly classifiedpathologically based on their cell of origin.Epithelial tumors arise from hepatocytes or biliaryepithelium and include the benign neoplasms ortumor-like lesions focal nodular hyperplasia(FNH), hepatocellular adenoma (HCA), and biliarycystadenoma; in addition to the malignantneoplasms hepatocellular carcinoma (HCC), fibro-lamellar carcinoma, and intrahepatic cholangiocar-cinoma (ICC). Nonepithelial tumors consist oflymphoma and mesenchymal tumors, includingcavernous hemangioma, angiomyolipoma, solitaryfibrous tumor (SFT), angiosarcoma, and hepaticepithelioid hemangioendothelioma. Characteristicfindings onMR imaging canbe seen inmany cases.In this article we review the MR imaging appear-ance of these tumors with pathologic correlation.

The authors have nothing to disclose.The views expressed in this article are those of the authoposition of the Department of the Navy, Department ofa Department of Radiologic Pathology, Armed ForceWashington, DC 20306-6000, USAb Department of Radiology, National Naval Medical Cenc Department of Radiology and Nuclear Medicine, UnifoJones Bridge Road, Bethesda, MD 20814, USAd Division of Hepatic and Gastrointestinal Pathology, ArNW, Washington, DC 20306-6000, USAe Department of Radiology, Georgetown University HospUSA* Corresponding author. Department of Radiologic PathoStreet NW, Washington, DC 20306-6000.E-mail address: [email protected]

Magn Reson Imaging Clin N Am 18 (2010) 587–609doi:10.1016/j.mric.2010.08.0101064-9689/10/$ e see front matter. Published by Elsevier

BENIGN TUMORSEpithelial

Focal nodular hyperplasiaClinical and pathologic features

FNH is the second most common benign hepatictumor following hemangioma, accounting for 8%of primary hepatic tumors.1 It is classified asa regenerative lesion rather than a neoplasm. It isthought to represent a hyperplastic response toa congenital or acquired arterial malformation.FNH with histologic characteristics of both FNHand HCA and atypical pathologic and imagingcharacteristics for FNH, such as heterogeneityand lack of a central scar, were previously catego-rized as telangiectatic FNH. Because of recentmolecular evidence, they are now recognized asa subset of HCA.2

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Approximately 89% to 94% of FNH occur inwomen with a mean age at diagnosis of 38years.3,4 The majority of patients are asymptom-atic. In the remainder, abdominal pain andpalpable mass are the most common symptoms.Reports of hemorrhage or rupture of FNH areextremely rare.FNH are named for their nodular architecture,

subdivided by fibrous septa that coalesce intoa central or eccentric stellate scar. They are nonen-capsulated, but sharplymarginatedwith a lobulatedcontour. Prominent vessels cover their surface.Hemorrhage and necrosis are rare because theirgrowth is usually proportional to their vascularsupply.1 Their size ranges from 1 mm to 19 cm indiameter, with a mean of 5 cm.3 Approximately20% are multiple and there are reported associa-tions with other vascular malformations andneoplasms, including cavernous hemangiomas,which are present in 20% of patients with FNH.4

Microscopically, FNH consist of hyperplastichepatocytes that are arranged in two-cell thickhepatic plates separated by sinusoids containingendothelial cells and Kupffer cells. The fibroussepta contain numerous vessels, particularlythick-walled arteries with fibromuscular hyperplasiaand intimal fibrosis, in addition to an inflammatoryinfiltrate.5 Bile ductules are present at the junctionof the fibrous septa and hepatocytes; however,they do not connect to the intrahepatic bile ducts.

MR imaging features

The diagnosis of FNH can bemade with confidencewhen all typical MR imaging features are present onunenhanced and intravenous contrast-enhancedsequences (Fig. 1). These include isointensity or hy-pointensity on T1-weighted sequences (90% to100%of cases) and slight hyperintensity or isointen-sity on T2-weighted sequences (99% to 100% ofcases) with homogeneous signal intensity exceptfor a central scar.6e10 The scar is hyperintense onT2-weighted sequences because of the presenceof vascular channels, bile ductules, and myxoma-tous tissue.1 After the administration of intravenousgadolinium, FNH typically demonstrate moderate-to-strong homogeneous arterial enhancement,with slight hyperintensity or isointensity to back-ground liver in the portal venous and equilibriumphases (95% to 99% of cases).7,8 The central scardemonstrates initial relative hypointensity duringthe arterial phase of contrast enhancement, andsubsequent delayed enhancement from theprogressive accumulation of contrast within thefibrous tissue.1 Prominent peripheral draining veinsor a dominant draining vein may be observedsurrounding the lesion on equilibrium phase images(see Fig. 1D).

Atypical imaging features are found in 21% to57% of FNH.7,11,12 A central scar may not be visu-alized in up to 50% of cases, particularly in lesionsless than 3 cm in diameter.6,7 Rarely, the scar maydemonstrate low T2 signal intensity (1%) or lack ofenhancement (1% to 2%) simulating fibrolamellarcarcinoma.7,8,11 Other atypical features includehypoenhancement during any phase of contrast-enhanced imaging, heterogeneous signal intensityfrom hemorrhage, high T1 signal intensity fromsinusoidal dilatation or steatosis, and a peripheralpseudocapsule of low T1 and high T2 signal inten-sity from adjacent compressed liver.11

Liver-specific MR imaging contrast agents canbe helpful in the diagnosis of FNH. Superparamag-netic iron oxide (SPIO) particles taken up byKupffer cells lower the signal intensity of FNH onT2-weighted and T2*-weighted sequences,although usually to a slightly less extent thannormal liver, and improve visualization of thecentral scar.13 Hepatobiliary agents, such as man-gafodipir or delayed imaging with gadobenate di-meglumine, result in isointensity or hyperintensityon T1-weighted images because FNH containsfunctioning hepatocytes and biliary ductules (seeFig. 1E). In one study of gadobenate dimeglumine,97% of FNH were hyperintense or isointensecompared with 100% of HCA being hypointenseon a 1 to 3 hour delayed T1 sequence.8 The centralscar, hypointense during the hepatobiliary phase,was also better delineated.

Differential diagnosis

Focal hepatic lesions that may have a central scaror scar-like fibrosis include hemangioma, fibrola-mellar carcinoma and HCC. Giant hemangiomasmay contain focal fibrosis that simulates a centralscar (discussed below). This is usually larger andmore hyperintense on T2-weighted sequencescompared with the scar of FNH and the contrastenhancement pattern of hemangiomas is distinc-tive. The scar of fibrolamellar carcinoma containscalcification in 55% and is typically hypointenseon T2-weighted sequences. Both fibrolamellarcarcinoma and HCC tend to be more heteroge-neous than FNH because they commonly haveintratumoral hemorrhage and necrosis.Hypervascular liver lesions such as HCA and

HCCmay also be considered in the differential diag-nosis of FNH, particularly when a central scar is notvisualized. The distinction between these tumors isdiscussed in the following section on HCA.

Hepatocellular adenomaClinical and pathologic features

HCA is a rare benign neoplasm that most oftenarises in the setting of hormonal or metabolic

Fig. 1. Focal nodular hyperplasia. Fat-suppressed T1-weighted image (A) and T2-weighted image (B) shows a cir-cumscribed mass (arrows) isointense to normal liver with a low T1, high T2 signal intensity central scar (arrow-head). Fat-suppressed T1-weighted images (CeE) during the intravenous administration of gadobenatedimeglumine show homogeneous hyperintensity of the mass (arrows) during the arterial phase (C) with theexception of the hypointense central scar (arrowhead). During the equilibrium phase (D), the mass (arrows) is iso-intense to liver and there is delayed enhancement of the central scar (arrowhead). Prominent draining vessels arepresent around the periphery (curved arrows). (E) A three-hour delayed hepatobiliary phase image shows isoin-tensity of the mass (arrows) with a well-delineated central scar (arrowhead). (F) Photograph of the cut surface ofthe resected specimen reveals a nodular mass with a central stellate scar (arrowhead).

Tumors of the Liver and Intrahepatic Bile Ducts 589

stimulation. The most common cause is oralcontraceptives, with an annual incidence of 3 to4 per 100,000 in women on long-term contracep-tives, compared with 1 per million in women whohave not taken oral contraceptives or have takenthem for less than 2 years.14 Risk increases withthe duration of use and potency of oral contracep-tives and appears to be lower with second andthird generation lower dose formulations.15 Otherrisk factors for HCA include anabolic steroid use,pregnancy, gynecologic tumors, glycogen storage

diseases (particularly type Ia, von Gierke disease),and galactosemia. Sporadic cases have beenreported in men and women without any riskfactors, but are rare.

Similar to FNH, HCA are usually found in womenof childbearing age, with most in the third to fourthdecades of life. The majority of patients are symp-tomatic, complaining of acute, episodic, or chronicabdominal pain, or a palpable mass. Only 5% to10% of lesions are incidentally discovered.5

Twenty five percent present with tumor rupture

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and subcapsular or intraperitoneal hemorrhage,which occurs in lesions 5 cm or greater in diam-eter.16 Besides hemorrhage, the other mainworrisome complication of HCA is malignanttransformation to HCC, with a frequency of 4%to 9% in surgical series, found in lesions over4 cm in diameter.16,17

The majority, 70% to 80%, of HCAs are solitary.Multiple lesions are often seen with anabolicsteroid use and glycogen storage diseases. Anentity called liver adenomatosis has beendescribed consisting of greater than 10 adenomasin patients without hormonal risk factors orglycogen storage disease. However, this may notwarrant a separate classification, since many ofthe cases described have been in women on oralcontraceptives and other than the number oflesions, there is no difference in imaging orpathology.18e20

On sectioning, HCAs are typically well circum-scribed round or oval masses 5 to 15 cm in diam-eter with a variegated appearance from areas ofhemorrhage, necrosis, and infarction. They areusually unencapsulated, but a thin fibrous capsuleis sometimes present. Histologically, they are

Fig. 2. Hepatocellular adenoma. T1-weighted in-phase (A)sity in the mass (asterisk) in (B), compatible with steatosisrepresent subacute hemorrhage. (C) Photomicrograph (stain) of the corresponding specimen demonstrates tumor(right) with many tumor cells containing fat vacuoles.

composed of a trabecular pattern of normal ap-pearing hepatocytes that may have increasedcytoplasmic fat and glycogen. Thin-walled arteriessupply the parenchyma but without otherelements of portal triads including bile ducts orsignificant connective tissue support, which maypredispose to hemorrhage.2 Degenerativechanges are commonly seen on histology,including infarction, hemorrhage, peliosis, andsinusoidal dilatation.2

MR imaging features

The appearance of HCA on MR imaging is quitevariable, reflecting the various gross pathologicfeatures. Focal areas of high T1 signal are presentin 45% to 77%of HCAs, which correspond to stea-tosis, hemorrhage, or peliosis on pathologic corre-lation (Fig. 2).21e23 With steatosis, signal intensityloss on chemical shift imaging is seen. On T2-weighted sequences, 47% to 74% of HCAs arepredominantly hyperintense with only 4% to 10%hypointense.21e23 Heterogeneity is present on T1-or T2-weighted sequences in 51% to 94%, corre-lating pathologically with hemorrhagic necrosisand peliosis.21e23 A capsule is seen onMR imaging

and out-of-phase (B) images show loss of signal inten-. Areas of high signal intensity in both images (arrow)original magnification, �40; hematoxylin-eosin [H-E]cells (left) that are paler than the normal hepatocytes


in 17% to 31% of cases, which demonstrates lowT1 and variable T2 signal intensity.21,23

During the administration of intravenous gadoli-nium, 96% of HCAs demonstrate marked arterialenhancement (Fig. 3).8 Signal intensity in the portalvenous and equilibrium phases is more varied andHCAs may be hyperintense, isointense, or hypoin-tense although the majority of HCAs appear isoin-tense in the equilibrium phase.8 Contrastenhancement may be heterogeneous or homoge-neous. Kupffer cells are reduced in number andfunction so adenomas rarely show uptake ofSPIO particles.24


FNH, HCC, hypervascular metastases, as well asHCA should be considered in the differentialdiagnosis of hypervascular hepatic lesions. Ina study by Arrive and colleagues,21 88% ofadenomas had heterogeneous signal, T1 hyper-intensity or a peripheral rim, which distinguishthem from FNH. Conversely, the demonstrationof a central scar-like area of fibrosis is unusualin HCA. However, the MR imaging features ofFNH without a central scar are similar to homo-geneous HCA without hemorrhage, fat or

Fig. 3. Hepatocellular adenoma. (A) Fat-suppressed T2-wemass in the right lobe. Arterial phase (B) and two-hour deate dimeglumine show immediate heterogeneous hyperinatobiliary phase. (D) Photograph of the cut specimen demohemorrhage.

necrosis, particularly seen in smaller lesions.Delayed imaging with gadobenate dimegluminemay be helpful in these cases. Fibrolamellarcarcinoma is more common in men than HCAand may be distinguished by a central scar, lobu-lated margins, and malignant features. There istremendous overlap in the features of HCA andHCC. Biopsy is often performed for HCAs notrequiring surgical resection. MR elastography,which measures the stiffness of tissue, mayhelp differentiate benign tumors, including HCA,from malignant tumors since benign hepatictumors demonstrate lower shear stiffness, basedon preliminary results.25 Hypervascular metas-tases are usually multiple, markedly hyperintenseon T2-weighted sequences, and rarely contain fatand hemorrhage.

Biliary cystadenoma and cystadenocarcinomaClinical and pathologic features

Biliary cystadenomas are rare cystic neoplasms,accounting for less than 5% of intrahepatic cystsof bile duct origin in a surgical series.26 Otherbiliary derived cysts include simple hepatic cysts,polycystic liver disease, choledochal cysts, andbiliary hamartomata. Biliary cystadenocarcinomas

ighted image shows a heterogeneously hyperintenselayed (C) images after the administration of gadoben-tensity of the mass and hypointensity during the hep-nstrates a sharply marginated mass with focal areas of

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are the malignant counterpart of cystadenomas,and are discussed together with cystadenomasbecause of overlapping pathologic and imagingfeatures. Biliary cystadenomas are mostcommonly found in middle-aged women, with anaverage age of 38 to 45 years and female prepon-derance of 93% to 96%.27,28 Biliary cystadenocar-cinomas occur on average at a slightly older age,56 years, and are relatively more common in menthan women compared with cystadenomas (62%of cystadenocarcinomas are found in women).29

Clinical symptoms are nonspecific, includingabdominal pain and palpable mass. Jaundicecan be seen when there is biliary obstruction.The majority of biliary cystadenomas and cysta-

denocarcinomas are intrahepatic, but occur occa-sionally in the extrahepatic bile ducts andgallbladder.27e29 They are encapsulated, multiloc-ular cystic masses with a smooth outer contour.The cyst contents vary and may be clear,mucinous, bilious, hemorrhagic, or mixed fluid.27

Biliary cystadenocarcinomas are more likely thancystadenomas to demonstrate papillary excres-cences and polypoid masses in the cyst cavities.5

Benign columnar or cuboidal epithelial cells linethe cyst locules of cystadenomas. Similar benignappearing epithelium is found in addition tomalignant epithelial cells in over 90% of biliary cys-tadenocarcinomas, supporting the theory of

Fig. 4. Biliary cystadenoma. T1-weighted (A) and fat-suppmultiple septa dividing locules of low T1 and high T2enhanced fat-suppressed T1-weighted image shows enhaof the cut surface of the resected specimen shows a mult

a progression between the two.29 A layer ofmesenchymal tissue that resembles ovarianstroma usually surrounds the epithelium. Theovarian-like stroma is only seen in women, andmay confer a better prognosis in cases ofcystadenocarcinoma.27

MR imaging features

Cystadenomas and cystadenocarcinomas aremultilocular cystic masses on imaging (Fig. 4).MR imaging allows characterization of the cystcontents, although the signal varies with proteinconcentration and age of hemorrhage. In general,compared with muscle, mucinous fluid is isoin-tenseonT1-weighted sequencesandhyperintenseon T2-weighted sequences, serous fluid has lowT1and high T2 signal intensity, and hemorrhage canbe identified by high T1 signal intensity or fluid-fluid levels. A low T2 signal intensity outer capsulemay be seen, likely from hemorrhage within thewall.27,30 With contrast administration, there isenhancement of the cyst wall and septa. Althoughthe imaging findings overlap, the presence ofenhancing mural nodules is suggestive of biliarycystadenocarcinoma, and their absence favorsbiliary cystadenoma.27,30 No imaging finding corre-lates with the presence of ovarian-like stroma.27

Magnetic resonance cholangiopancreatography(MRCP) can help define the relationship of the cyst

ressed T2-weighted (B) images show a cystic mass withsignal intensity. (C) Intravenous gadolinium contrastncement of the cyst wall and septa. (D) Photographiloculated cystic mass.


to the bile ducts. Dilatation of the peripheral bileducts may be seen from obstruction. Rarely, biliarycystadenomas or cystadenocarcinomas maycommunicate with or prolapse into a bile duct.31


The differential diagnosis of a hepatic complexcystic mass is broad. Infectious causes, includingpyogenic abscess, amebic abscess, and hydatidcysts are a main consideration. Clinical and labo-ratory data, including amebic and echinococcalserologies, can help distinguish these. HelpfulMR imaging findings include low signal intensity,nonenhancing walls of the daughter cysts, or non-enhancing membranes within a hydatid cyst.Pyogenic and amebic abscesses are not encapsu-lated, have ill-defined enhancing margins, andoften have a rim of edema between central areasof necrosis and adjacent normal liver. Cystichepatic neoplasms, including mesenchymalhamartoma and undifferentiated embryonal cellsarcoma, are usually found in children. Cysticmetastases are oftenmultiple and there is a clinicalhistory of known primary. Hepatocellular carci-noma may have a cystic appearance when thereis significant necrosis after treatment.

Nonepithelial

Cavernous hemangiomaClinical and pathologic features

Cavernous hemangioma is the most commonbenign hepatic tumor with a reported prevalenceof 1% up to 20%.32,33 It can occur at any ageand demonstrates a female predominance, witha female-to-male ratio of 2:1 to 5:1.34 The vastmajority are incidentally found. Patients with largelesions may present with abdominal pain or symp-toms from mass effect on adjacent structures.Rare complications include intratumoral hemor-rhage, rupture with hemoperitoneum, and unusualhematologic manifestations such as erythrocyto-sis from secretion of erythropoietin andKasabach-Merritt syndrome, which consists ofa consumptive coagulopathy, thrombocytopenia,and hemolytic anemia.

Cavernous hemangiomas are well-circumscribedand vary from less than 1 cm to over 30 cm in size.5

Ten to twenty percent are multiple and there is a re-ported association with focal nodular hyperplasia.4

Microscopically, a honeycomb appearance isgenerated by numerous blood filled spaces, eachlined by a single layer of flat endothelial cells incontrast to hepatic peliosis, which is characterizedby blood-filled spaces without an endothelial lining.They can be quite heterogeneous, containing areasof recent or organized thrombus, fibrosis, and,rarely, calcification. Fibrosis is typically central but

can involve the entire lesion, referred to as a scle-rosed or hyalinized hemangioma.5

MR imaging features

On imaging, hepatic cavernous hemangiomashave smooth well-defined margins and are roundor lobular in shape. They are hypointense onT1-weighted sequences except for regions ofhyperintensity in the rare occasion of hemorrhage.Hemangiomas have high T2 signal intensity ap-proaching that of cerebrospinal fluid and showeven higher signal intensity on long TE T2-weighted sequences. They may not be completelyhomogeneous, with nodules or septa of low T2signal intensity in 80% of cases, corresponding tofibrosis on pathology.35 Additionally, many gianthemangiomas, variably defined as greater than 4cm up to greater than 12 cm in diameter, containa central cleft of cystic degeneration or liquefactionthat compared with the remainder of the lesion ishypointense on T1-weighted sequences andhyperintense on T2-weighted sequences (Fig. 5).36

During the administration of intravenous gadoli-nium contrast agents, a pattern of early peripheraldiscontinuous nodular enhancement with progres-sive centripetal complete or incomplete filling-inhas 84% sensitivity, 100% specificity, and 95%accuracy for the diagnosis of hemangioma.37 Thesignal intensity of the enhancing areas parallelsaortic enhancement (see Fig. 5B and C). Thefibrous septa and central clefts of large hemangi-omas do not enhance (see Fig. 5C). Anotherfrequent enhancement pattern is early homoge-neous hyperenhancement, which is often calledflash-filling. In a study of 154 hemangiomas bySemelka and colleagues,38 23% displayed thatpattern; all were less than 1.5 cm in diameter.

Completely sclerosed hemangiomas demon-strate extensive fibrosis, resulting in atypicalimaging findings. Volume loss from fibrosis maycause adjacent retraction of the hepatic capsule.39

T2 signal may be less hyperintense and there maybe a lack of early enhancement with delayed slightperipheral enhancement.34 Increased fibrosis withvolume loss and capsular retraction can also beseen in hemangiomas in the setting of progressivecirrhosis.40


There is no differential diagnosis for cavernoushemangiomas that demonstrate a classic patternof contrast enhancement. The imaging features oflesions with rapid homogeneous enhancementoverlap with other hypervascular liver tumors,including HCC, HCA, and hypervascular metas-tases. One helpful finding in differentiating a flash-filling hemangioma fromahypervascularmetastasis

Fig. 5. Giant cavernous hemangioma. (A) T2-weighted image shows a large hyperintense mass arising from theleft hepatic lobe with central stellate high T2 signal intensity (arrow). Intravenous gadolinium contrast-enhanced,fat-suppressed images show peripheral nodular discontinuous enhancement (arrowheads) in the portal venousphase (B) with progressive filling in on the delayed image (C). The central scar-like region (arrow) does notenhance. (D) Photograph of the cut surface of the resected specimen reveals spongy hemorrhagic tissue witha central myxoid area (arrow).

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is hyperintensity of a hemangioma on the delayedphase. Metastases often demonstrate heteroge-neous or peripheral washout.

AngiomyolipomaClinical and pathologic features

Angiomyolipoma is a benign tumor composed ofsmooth muscle, fat, and thick-walled bloodvessels. It rarely occurs in the liver, with over 200cases reported in medical literature.41 The averageage of presentation is 50 years (range 10 to 79) witha female predominance.42 The majority aresporadic, although 6% to 10% occur in patientswith tuberous sclerosis.42,43 Conversely, 13% ofpatients with tuberous sclerosis have hepaticangiomyolipomas, which are usually multiple andassociated with multiple bilateral renal angiomyoli-pomas.44 Patients either have nonspecific symp-toms such as abdominal discomfort or mass orthe lesion is an incidental finding, although intraper-itoneal rupture and malignant transformation rarelyoccur.45,46

Angiomyolipomas are well-circumscribed non-encapsulated round or ovoid masses that vary insize from less than 1 cm to 36 cm in diameter.42

The cut surface is yellow to tan in color and focalareas of hemorrhage or necrosis may be present.Microscopic findings are diverse since the relativeproportion of smooth muscle cells, mature adiposetissue, and blood vessels varies widely. The myoidcomponent usually predominates and consists ofspindle cells, epithelioid cells, and intermediateovoid or short spindle cells. The fat componentvaries from scattered cells involving less than 10%of the tumor in 30% of cases to greater than 70%in 10% of cases.43 The vascular componentincludes both a rich capillary network in additiontomultiple tortuous thick-walled vessels with occa-sional calcification.

MR imaging features

Hepatic angiomyolipomas demonstrate a spec-trum of appearances on MR imaging, reflectingtheir varied histologic composition. They may behyperintense, hypointense, or heterogeneous


with hyperintense and hypointense areas on T1-weighted sequences, depending on the amountand distribution of fat.46e49 Areas of macroscopicfat demonstrate peripheral low signal (etching arti-fact or India ink artifact) on out-of-phasesequences and diffusely decreased signal inten-sity with fat-suppression sequences (Fig. 6). Areasof microscopic fat demonstrate diffuse loss ofsignal on out of phase sequences.50 Fat signalintensity may not be present in lesions with mini-mal pathologic fat composition.51 On T2-weightedsequences, hepatic angiomyolipomas are homo-geneously or heterogeneously hyperintense. Withgadolinium, most hepatic angiomyolipomasdemonstrate hyperenhancement during the arte-rial phase and may be hyperintense, isointense,or hypointense during the portal venous and de-layed phases.46e48,51


HCA, HCC, myelolipoma, and fat-containingmetastases, such as liposarcoma and malignantteratoma, can contain fat and soft tissue compo-nents and their MR imaging appearance may bedifficult to distinguish from angiomyolipomas.

Fig. 6. Angiomyolipoma. (A) T1-weighted in-phase imagetense with a focus of high signal intensity (arrowhead). (Bfact of the areas of high signal intensity on the in-phase imPhotomicrograph (original magnification, �40; H-E stain)nents of smooth muscle cells, fat cells, and blood vessels.

Solitary fibrous tumorClinical and pathologic features

SFT is a rare hepatic neoplasm that is similar totumors arising in the pleura, mediastinum, andother sites. It occurs in adults, with a mean ageof 57 years and a 2:1 female-to-male ratio.52 Clin-ical presentation varies from asymptomatic toabdominal discomfort or fullness due to masseffect.53

SFT is typically a large well-circumscribed intra-hepatic or pedunculated firm mass with a nodularor smooth surface. When sectioned, these tumorsare gray to white in color with a whorled appear-ance and may contain central hemorrhage ornecrosis.5,52 Bundles of spindle cells with eithera haphazard arrangement or a storiform patternare present microscopically.5,52 The majority ofSFTs are benign in biologic behavior but malignanttransformation may occur. The true incidence ofmalignant transformation is not known owing tothe low number of reported tumors. With slightlygreater than 50 tumors appearing in the literatureto date, to the authors’ knowledge there is onlyone reported case of a primary hepatic SFT withdistant metastases.54

shows a heterogeneous mass that is primarily hypoin-) T1-weighted out-of-phase image shows etching arti-age (arrowhead) consistent with macroscopic fat. (C)

of the corresponding specimen demonstrates compo-

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MR imaging features

When evaluated by MR imaging, SFT of the liver ischaracteristically hypointense on T1-weightedsequences, variably hypointense or hyperintenseon T2-weighted sequences and demonstratesheterogeneous enhancement following the admin-istration of intravenous contrast.55,56 Contrastenhancement may be avid and progressive,increasing through the arterial and venous phasesresulting in increased enhancement in the delayedphase (Fig. 7).57 The marked enhancement ofsome tumors is thought to be due to prominentvascularity.57


The imaging findings of a large, solitary, well-demarcated, heterogeneous mass are largelynonspecific. Progressive delayed enhancementcan be seen with fibrotic lesions, including ICC,the sclerosing type of HCC and epithelioid heman-gioendothelioma in addition to SFT. Vascularlesions such as cavernous hemangioma and an-giosarcoma also demonstrate progressiveenhancement, although the typical early peripheraldiscontinuous nodular enhancement pattern ofa hemangioma distinguishes it from SFT.

Fig. 7. Solitary fibrous tumor. (A) T2-weighted image showsignal intensity centrally corresponding to regions of necsuppressed T1-weighted images show a multilobulated mphase (B) that increases centripetally in the portal venous

MALIGNANT TUMORSEpithelial

Hepatocellular carcinoma and precursor lesionsClinical and pathologic features

HCC is the most common primary liver malignancyin adults. It is the fifth most common cancer in theworld, although there is striking geographic varia-tion depending on the prevalence of major riskfactors. Hepatitis B virus infection and aflatoxinB1 contribute to the high incidence in Africa andparts of Asia, whereas hepatitis C virus infectionis the main risk factor in Japan.58 The incidenceof HCC in the United States has more thandoubled in the past two decades, primarily relatedto an epidemic of hepatitis C virus infection fromthe 1960s to the 1980s.59 Other predisposingfactors include cirrhosis of any cause, such asheavy alcohol consumption, hemachromatosis,hereditary tyrosinemia, and alpha-1-antitrypsindisease. Obesity and diabetes are also related toHCC through nonalcoholic fatty liver disease.Between 15% and 50% of patients in the UnitedStates have no known risk factor.59

The incidence of HCC increases with age, witha mean age of diagnosis of 65 years in the United

s a large heterogeneous mass with marked increasedrosis. Dynamic intravenous gadolinium-enhanced, fat-ass with avid peripheral enhancement in the arterialphase (C) and persists in the equilibrium phase (D).


States. In countries where hepatitis B virus isendemic, HCC occurs at an earlier age, oftenbefore 40.58 Three quarters of patients are male,which may relate to higher rates of known riskfactors and androgen receptors often present onthe tumors.5 Clinical symptoms vary widely. Mostpatients present with abdominal pain, weightloss, and hepatomegaly, often with a palpablemass. Decompensated cirrhosis may be the onlyindication of HCC, likely from neoplastic portal orhepatic vein thrombosis. Rarely, HCC can causeobstructive jaundice, spontaneous rupture withhemoperitoneum, or paraneoplastic syndromes,including hypertrophic osteoarthropathy. Serumalpha-fetoprotein is reportedly elevated in 70%to 90% of patients; however, it is usually normalor minimally elevated in patients with small HCCs(defined as >2 cm in diameter).5,60 The sensitivityand specificity of serum alpha-fetoprotein asa screening test vary widely depending on thecutoff value (<20 ng/mL is most commonly used)in addition to other factors, and higher qualitystudies are needed to determine its utility.61,62

HCC may arise from a single cell or group ofhepatocytes or may develop in a stepwise patternin cases of cirrhosis from a regenerative nodulethrough a spectrum of low-grade and high-gradedysplasticnodules.A regenerativenodule isa local-ized proliferation of hepatocytes and supportstroma with normal blood supply and no atypia.Low-grade and high-grade dysplastic nodulesdemonstrate increasing nuclear to cytoplasmicratios, nuclear atypia, distortion of the normal platearchitecture, and increasing arterial supply. Thesechanges are more advanced in well-differentiatedHCC,which are also associatedwithmitotic figuresand invasion of the stroma or portal tracts. Thereare several histologic growth patterns of HCC,

Fig. 8. Pathologic features of hepatocellular carcinoma. (Astain) of a bile producing, moderately differentiated hepa(B) Photograph of the cut surface of a hepatocellular carcappearance with areas of fat and hemorrhage.

with a trabecular pattern being most common(Fig. 8A). The fibrolamellar pattern, which hasabundant stroma, has distinct clinical and patho-logic features and is discussed separately.

A single mass with or without satellite nodules isthe most common gross appearance of HCC. Italso may arise as multiple discrete nodulesthroughout the liver or more rarely diffuse infiltra-tion. Large tumors are often heterogeneous anda mosaic appearance may be seen from areas ofsteatosis, hemorrhage, cholestasis, fibrosis, andnecrosis (see Fig. 8B). They are soft tumorsbecause of a lack of desmoplasia except for fibro-lamellar and rare scirrhous variants. A fibrouscapsule is common in lesions over 1.5 cm in diam-eter.60 Vascular invasion is found in close to threequarters, usually involving the portal or hepaticveins. Bile duct invasion is much more infrequent,seen in about 3%.5 Intrahepatic, lung, regionallymph nodes, bone, and adrenal gland are themost common sites of metastatic disease.

MR imaging features

MR imaging has the highest combination of sensi-tivity and specificity for HCC compared with otherimaging modalities, at 81% and 85%, respec-tively.61 However, sensitivity is less for smallertumors that may be similar in appearance tocirrhotic nodules. Regenerative nodules and low-grade dysplastic nodules demonstrate variableT1 signal intensity, low T2 signal intensity and areisointense or slightly hypointense with intravenousgadolinium enhancement. High-grade dysplasticnodules are usually less than 2 cm in diameterand can display slightly higher T2 signal intensityand arterial phase enhancement with portalvenous phase washout, similar to smallHCC.60,63 Small HCC are usually well

) Photomicrograph (original magnification, �200; H-Etocellular carcinoma with a trabecular growth pattern.inoma shows an encapsulated mass and a variegated

Lewis et al598

differentiated and demonstrate variable T1 signalintensity, slightly high T2 signal intensity, andhomogeneous intense arterial phase enhance-ment with portal venous phase washout.63 SmallHCC also may have a nodule-in-a-nodule appear-ance, indicating that it is arising within a largerregenerative or dysplastic nodule.The appearance of large HCCs is quite variable.

The most common pattern is hypointensity onT1-weighted sequences, hyperintensity onT2-weighted sequences and diffuse heteroge-neous immediate enhancement (Fig. 9).64 Hyper-intense T1 signal can be seen, from intratumoralfat, copper, or glycogen, and is more common inlow-grade tumors.65 A mosaic pattern of varyingsignal intensities on unenhanced and enhancedsequences is frequent, reflecting the heteroge-neous pathologic appearance. A tumor capsule,more common in larger tumors, usually demon-strates low T1 and T2 signal intensity and delayedenhancement. In capsules over 4 mm in thickness,inner low T2 and outer high T2 signal intensitylayers may be seen from layers of inner fibroustissue and outer compressed vessels and bileducts.65 Evidence of invasiveness is frequent inlarger tumors, including extracapsular extension,satellite nodules (Fig. 10), vascular invasion, andmetastatic disease. Tumor thrombus can bedistinguished from bland thrombus by expansion

Fig. 9. Small hepatocellular carcinoma. (A) T2-weighted(arrow). Dynamic intravenous gadolinium-enhanced, fat-hyperenhancement in the arterial phase (B) and central whead) in the portal venous phase (C) and equilibrium pha

of the lumen and contiguity to and similar imagingcharacteristics with the primary tumor, includingon T2, postcontrast and diffusion-weightedsequences.66,67

In addition to gadolinium chelates, several otherintravenous contrast agents have been studied inthe diagnosis of HCC. After the administration ofSPIO particles, HCC is typically hyperintense onT2- and T2*-weighted sequences although somewell-differentiated tumors may demonstrateuptake and be isointense or hypointense.63 Toimprove sensitivity, some investigators advocatea double-contrast protocol of SPIO particles anda gadolinium chelate because of their synergisticeffects.68 Combined extracellular and hepatocel-lular agents, including gadoxetic acid, may alsoimprove sensitivity.69 Larger prospective studiesare needed to determine the best screeningmethod.


In patients with cirrhosis, arterial enhancing lesionsare not uncommon and, in addition to HCC, theymay represent dysplastic nodules or transient arte-rial enhancement from arterioportal shunts or ob-structed distal parenchymal portal veins. In onestudy, 93% of arterial enhancing lesions less thanor equal to 2 cm in diameter and not seen on otherphasesof enhancement or unenhancedsequences

image shows a small predominantly isointense masssuppressed T1-weighted images show heterogeneousashout with peripheral capsular enhancement (arrow-se (D).

Fig. 10. Multifocal hepatocellular carcinoma. (A) T1-weighted in-phase image shows a heterogeneous mass con-taining areas of hyperintensity, isointensity, and hypointensity. (B) T1-weighted out-of-phase image showsmultiple areas of etching artifact from macroscopic fat (arrowheads). Intravenous gadolinium-enhanced, fat-sup-pressed T1-weighted images show heterogeneous enhancement of the dominant mass as well as multiple addi-tional hyperenhancing masses (arrows) in the arterial phase (C) with central washout and peripheral capsularenhancement in the portal venous phase (D).

Fig. 11. Fibrolamellar carcinoma. Masson trichromestain shows bands of blue staining fibrous lamellaein between sheets of rounded and polyhedral cellsthat are deeply eosinophilic staining.


were nonneoplastic.70 Confluent fibrosis canappear mass-like and have hyperintense T2 signalintensity, although it typically is wedge-shaped,demonstrates delayed enhancement, may beassociated with capsular retraction, and iscommonly centrally located, in the anterior andmedial segments of the liver.67

In patients without cirrhosis, the differentialdiagnosis of small HCCs includes other arterialenhancing masses such as flash-filling hemangi-omas, FNH, HCA, and hypervascular metastasis.The differential of a large, encapsulated, heteroge-neous mass includes HCC, HCA, SFT, and hepaticsarcomas.

Fibrolamellar carcinomaClinical and pathologic features

Fibrolamellar carcinoma is a distinct variant of HCCseen in youngpatientsusuallywithoutprevious liverdisease.71 It has an equal gender distribution witha mean age of presentation of 23 years.72 Present-ing symptoms range from abdominal pain, hepato-megaly, and palpable mass to, more rarely,gynecomastia or venous thrombosis.72 Serumalpha-fetoprotein levels are generally not elevatedin contrast to patients with HCC; however, mildelevation may occur in approximately 10% ofpatients.5

The gross appearance of fibrolamellar carci-noma is usually a nonencapsulated but well-demarcated solitary mass. Less frequent morpho-logic appearances include a mass with peripheralsatellite lesions, bilobedmass, or diffusemultifocaldisease.72 Two thirds occur in the left lobe.5 Fibro-lamellar carcinoma is characterized histologicallyby prominent fibrous lamellae (Fig. 11) supportinggroups of tumor cells that contain a coarse eosin-ophilic granular cytoplasm attributable to the

Lewis et al600

presence of abundant mitochondria.5 The fibroustissue may coalesce into a central scar, whichcommonly contains calcification.

MR imaging features

On MR imaging, fibrolamellar carcinoma is large,lobulated mass that is characteristically hypoin-tense to isointense and hyperintense to isointenseon T1- and T2-weighted sequences, respec-tively.72,73 A central scar usually demonstrateslow T1 and T2 signal intensity because of itsfibrous content. Calcification of the scar is betterevaluated by CT scan. Following the intravenousadministration of gadolinium, there is heteroge-neous enhancement in the arterial and portalvenous phases becoming more homogeneous inthe delayed phase (Fig. 12).72 The central scarmost commonly does not enhance and will appearmore conspicuous on the delayed phase. Rarely,high T2 signal and delayed enhancement can beseen in scars with increased vascularity.72


In a young adult patient without underlying hepaticdisease or other risk factors, the main differentialconsiderations for fibrolamellar carcinoma areFNH and HCA. FNH typically demonstrates homo-geneous enhancement apart from the central scarand the scar is hyperintense on T2-weighted

Fig. 12. Fibrolamellar carcinoma. (A) Fat-suppressed T2-whepatic lobe containing a hypointense central scar (enhanced, fat-suppressed T1-weighted images during artegeneous enhancement with progressive increased homogebivalved resected specimen shows a white fibrous central

sequences and usually smaller than that of fibrola-mellar carcinoma.73 HCA usually does not havea central scar and, unlike fibrolamellar carcinoma,often contains areas of high T1 signal intensity.

Intrahepatic cholangiocarcinomaClinical and pathologic features

Defined as an adenocarcinomaoriginating from theintrahepatic bile ducts, ICC is the second mostcommon primary liver malignancy. Risk factorsencompass the spectrum of biliary conditionsleading to chronic inflammation, including chronicparasitic infection, recurrent pyogenic cholangitis,hepatolithiasis, primary sclerosing cholangitis,and congenital anomalies, including choledochalcysts and Caroli disease. The most significantworldwide risk factors areparasitic infection and in-trahepatic stone formation.5 Clinical features ina series from the Atlas of Tumor Pathology5 (AFIP)showed a nearly 3:1 male-to-female ratio with pre-senting symptoms of upper abdominal pain andascites, weight loss, jaundice, weakness, andnausea and vomiting, in decreasing frequency.ICC is a nonencapsulated, firm or hard tumor

that varies from white to tan in color. Necrosis andhemorrhage rarely occur. The patterns of growthmay be characterized as mass-forming, periductalinfiltrating, or intraductal.74,75Microscopic features

eighted image shows an isointense mass in the leftarrow). Dynamic intravenous gadolinium contrast-rial (B) and equilibrium (C) phases show early hetero-neity (arrow). (D) Photograph of the cut surface of thescar arising within a solitary mass.


include cells that are arranged in tubules, nests,acini, or trabeculae, and may mimic adenocarci-nomas originating outside of the liver. Generally,ICC is well-differentiated and consists of cuboidalto columnar epithelium with moderate cytoplasmthat varies from clear to mildly granular and eosin-ophilic.5 It is hypovascular and may have a markedfibrous component.

MR imaging features

TheMR imaging features of ICC differ according toits pattern of growth. Mass-forming ICC is irregu-larly marginated and demonstrates hyperintenseT2 and hypointense T1 signal intensity. Followingthe administration of intravenous contrast, irreg-ular peripheral enhancement may be observedwith gradual centripetal filling that persists intothe delayed phase of imaging owing to the fibrouscomposition (Fig. 13).75 Encasement of hepaticvessels without thrombosis and hepatolithiasisare not uncommon findings.75 Transient hepaticintensity differences and capsular retraction mayalso be observed.74,76

Pure periductal infiltrating tumors are rare in ICCin contrast to hilar cholangiocarcinoma, but oftenare found in a combined pattern with the mass-forming variant.75 Periductal ICC grows along

Fig. 13. Intrahepatic cholangiocarcinoma. Dynamic intravT1-weighted images show peripheral enhancement in theenhancement and retention of contrast at 60 seconds (B) aresected gross specimen shows a white mass encompassin

a narrowed or dilated duct, causing peripheralductal dilatation.74,75 MRCP can be helpful in iden-tifying the ductal irregularity and dilatation.

The intraductal variant rarely occurs in the intra-hepatic ducts. It may appear on MR imaging asduct dilatation with or without a visible polypoidmass.74 T2 sequences are helpful in identifyingintraductal filling defects and associated ductaldilatation. Both periductal and intraductal en-hancement may be seen with each of theserespective growth patterns.


The differential diagnosis of hepatic masses andmass-like lesions with delayed phase enhance-ment includes scirrhous HCC, metastatic disease,immature abscess, confluent hepatic fibrosis, andSFT. Scirrhous HCC versus ICC is an importantpreoperative distinction due to differences insurgical management and prognosis. Both ofthese tumors demonstrate arterial phase periph-eral enhancement with progressive centripetalfilling. However, scirrhous HCC is usually homoge-neously hypointense on the hepatobiliary phaseimaging following the administration of gadoben-ate dimeglumine compared with ICC whichdemonstrates a peripheral washout pattern.77

enous gadolinium contrast-enhanced, fat-suppressedarterial phase (A) with gradually increasing centripetalnd 5 minutes (C) post injection. (D) Photograph of theg an intrahepatic vein.

Lewis et al602

Nonepithelial

AngiosarcomaClinical and pathologic features

Although the most common primary mesenchymalhepatic malignancy, angiosarcoma is rare. It isa high-grade vascular neoplasm of spindled orepithelioid endothelial cells. Early cases wereattributable to environmental exposures to vinylchloride, Thorotrast, arsenic, and anabolicsteroids, but they are now generally consideredto be idiopathic or secondary to cirrhosis.78 Thereis an association with hemochromatosis andneurofibromatosis type 1.79 The peak incidenceis in the sixth decade of life with a male predomi-nance.5 Clinical symptoms include hepatomegaly,ascites, jaundice, pain, and, rarely, an acuteabdomen with hemoperitoneum.Grossly, angiosarcoma is a grayish white tumor

mass or multiple nodules ranging in size from a fewmillimeters to several centimeters with hemor-rhagic foci and cavities of blood. There are fourmain morphologic patterns: multiple nodules,a dominant mass, a combination of a mass andnodules, or diffuse infiltration without definablemass.78 Microscopically, an aggressive pattern isobserved with endothelial cells growing alongsinusoids, portal venous branches, and terminalhepatic venules.5 Sinusoidal growth eventuallyresults in irregular cavity walls lined by tumor cellsfilled with blood, whereas invasion of the periph-eral portal and hepatic venous systems results inluminal obstruction leading to hemorrhage, infarc-tion, and necrosis.5

MR imaging features

Angiosarcoma is often hypointense on T1-weighted sequences and hyperintense onT2-weighted sequences, although areas of highT1 signal intensity and heterogeneous T2 signal

Fig. 14. Angiosarcoma. (A) T1-weighted image shows a hyintensity compatible with hemorrhage. (B) Fat-suppressedcentral higher signal intensity hemorrhage.

intensity or fluid levels may be present owing to in-tratumoral hemorrhage (Fig. 14).80 Rim enhance-ment is seen early following the administration ofintravenous contrast with delayed centripetalenhancement. Enhancement is heterogenous inthe arterial phase with progressive enhancementon the delayed phase that is frequently irregular,ring-shaped, or bizarre in morphology, and isdistinguishable from the more nodular peripheralenhancement of hemangiomas.78


Given that angiosarcoma can present as a domi-nant mass or multiple nodules, the differentialdiagnosis includes more common neoplasmssuch as metastatic disease and HCC. Persistentdelayed enhancement, intratumoral hemorrhageand the presence of splenic or pulmonary metas-tasis are findings suggestive of angiosarcoma.78

Hemangioma may be a consideration within thedifferential diagnosis as well. With only 10 to 20new cases of angiosarcoma diagnosed in theUnited States annually, hemangiomas are approx-imately 10,000 times more common than angio-sarcomas.79 Although angiosarcomas may rarelymimic hemangiomas, they usually appear moreheterogeneous and can be distinguished fromthe characteristic peripheral discontinuousnodular enhancement seen in hemangiomas.81

Mass-forming ICCsmay also mimic angiosarcomawith peripheral arterial phase enhancementand progressive centripetal filling. Bile duct dilata-tion, if present, favors cholangiocarcinoma.79

Epithelioid hemangioendotheliomaClinical and pathologic features

Epithelioid hemangioendothelioma is a rare low-grade malignant vascular tumor of endothelialorigin. It has a variable clinical course. There is

pointense mass containing a large area of high signalT2-weighted image shows a hyperintense mass with


an increased female to male incidence with 62%ofcases occurring in women within a series of 137tumors studied at the AFIP.82 Age range variedfrom 12 to 86 years of age with a mean of 47 yearsand highest incidence in the 30- to 40-year range.Clinical features vary from asymptomatic (42% ofcases in the AFIP series) to severe and includenausea, periodic vomiting, anorexia, weakness,jaundice, pain, and hepatosplenomegaly. Otherless common findings include hemoperitoneum,liver failure or a Budd-Chiarielike syndrome.5

The gross appearance of epithelioid heman-gioendothelioma is a tan to white tumor nodulewith firm consistency that may be hyperemic alongits margin. These nodules vary from several milli-meters to centimeters in size and may coalescein a subcapsular location with associated capsularretraction.83 Histologically, the nodules consist ofcentral relatively fibrous hypocellular stroma withmarginal active proliferation of epithelioid anddendritic cells.83 The nodules are ill-defined anddemonstrate multiacinar involvement, growingalong and invading sinusoids, portal venousbranches, and terminal hepatic venules.5

Fig. 15. Epithelioid hemangioendothelioma. (A) T1-weighlescent nodular masses, many with central low and periphimage shows central high and peripheral relatively lowerresected gross specimen shows multiple fibrotic masses an

MR imaging features

The characteristic imaging morphology ismultifocal nodules in a subcapsular distributionthat may coalesce, associated with capsularretraction or venous invasion. Epithelioid heman-gioendothelioma is hypointense on T1-weightedsequences and heterogeneously hyperintense onT2-weighted sequences. A pattern described asthe bright-dark ring sign consists of a peripheralrim of high T1 and low T2 signal intensity whichmay be from peripheral thrombosed vascularchannels (Fig. 15).84

Following the administration of intravenousgadolinium, a multilayered appearance may beseen with central hypointensity surrounded bya ring of increased enhancement and an outerhypointense rim.83 These alternating areas ofsignal intensity correlate with a hypocellularcentral stroma surrounded by hyperemic tissuesecondary to cell proliferation with a thin avascularrim due to sinusoid and small vessel invasion.83

The central fibrous portion demonstrates delayedenhancement.84 Well-defined peripheral tumorsthat have a portal or hepatic venous branch

ted image shows multiple subcapsular masses and coa-eral relatively higher signal intensity. (B) T2-weightedsignal intensity of the nodules. (C) Photograph of thed coalescent nodules with capsular hepatic retraction.

Fig. 16. Primary hepatic lymphoma, diffuse large B-cell type. T1-weighted (A) and T2-weighted (B) images showa large solitary mass that is T1 hypointense and heterogeneously hyperintense on the T2-weighted image. (C)Intravenous gadolinium contrast enhanced fat suppressed T1-weighted image shows peripheral rim enhance-ment and central hypointensity due to necrosis (arrow). (D) Photograph of the cut surface of the resected spec-imen shows a well-demarcated white-tan tumor with a central stellate necrotic area (arrow).

Lewis et al604

tapering or terminating at its periphery have beenobserved in epithelioid hemangioendothelioma,referred to as the lollipop sign.85


Epithelioid hemangioendothelioma may beconfused for metastatic disease, cholangiocarci-noma, angiosarcoma, sclerosing HCC, abscess,cirrhosis, or venoocclusive disease. Althoughmany of these diagnoses may show increasingenhancement through the delayed phase ofimaging, a multinodular morphology in a subcap-sular location with capsular retraction can help tonarrow the differential. Lesions in this distributionwith concentric rings of varying signal intensityfavors epithelioid hemangioendothelioma.

Primary hepatic lymphomaClinical and pathologic features

Primary hepatic lymphomadefined by its originwithinor confinement to the liver is a rare malignancy withsecondary involvement of the liver much morecommon. A higher incidence is seen in patients thatare immunocompromised, such as transplant recipi-ents and patients with increased exposure to virusessuch as Epstein Barr virus, HIV, or hepatitis viruses.86

Most patients are middle aged men with nonspecific

symptoms such as abdominal pain or discomfort,weight loss, fever, and hepatomegaly.87

Generally an aggressive disease, primaryhepatic lymphoma has been treated with varyingcombinations of surgery, radiotherapy, andchemotherapy. When resected, the gross spec-imen consists of bulky solitary or multiple nodulesthat are white to yellow in color. Depending on thecause, a variety of cell types such as small B-cell,large B-cell, and T-cell, in addition to virus-specificproliferative findings, may be present. The majorityare large B-cell lymphomas.5

MR imaging features

Primary hepatic lymphoma usually presents asa solitary mass compared with secondarylymphoma, which is more frequently diffuse ormultifocal.86 Other patterns include multifocalmasses or diffuse infiltration. It is usually hypoin-tense and hyperintense on T1- and T2-weightedsequences, respectively.88,89 However, slightlyincreased T1 signal intensity and low T2 signalintensity have also been reported.86,89 With admin-istration of gadolinium contrast agents, patchyenhancement in the arterial phasewith progressiveportal venous enhancement has been described.90

There may be prominent perilesional rim

Table 1Summary of MR imaging features of hepatic tumors

Precontrasta Postcontrast

Helpful FeaturesT1 T2 Arterial Portal Ve us or Delayed

Focal Nodular HyperplasiaCentral Scar

Iso to hypoHypo

Iso to hyperHyper

HyperHypo

Iso to hyp rHyper

Homogeneity except forcentral scar

Hepatocellular Adenoma Variable Iso to hyper Hyper Variable Often heterogeneous, mayhave hemorrhage, steatosis,capsule

Cavernous HemangiomaCentral Scar

HypoHypo

HyperHyper

Peripheral nodularHypo

Centripet l fillingHypo

Small may be flash-filling,enhancement parallelsblood pool

Angiomyolipoma Variable Hyper Hyper Variable Contains variable amountof fat

Solitary Fibrous Tumor Hypo Variable Heterogeneous Progressiv Large well-circumscribed mass

Hepatocellular CarcinomaCapsule

VariableHypo

HyperHypo

HyperHypo

HypoHyper

Small HCC may behomogeneous, larger HCCmay have a mosaic pattern,capsule, vascular invasion

Fibrolamellar CarcinomaCentral Scar

Hypo to isoHypo

Iso to hyperHypo

HeterogeneousHypo

Increasing y homogeneousHypo

Low signal scar on allsequences, no internal fat

IntrahepaticCholangiocarcinoma

Hypo Hyper Peripheral Gradual c ntripetal Biliary dilatation, capsularretraction

Angiosarcoma Hypo Hyper Rim, heterogeneous Irregular ntripetal Hemorrhage, splenicmetastasis

EpithelioidHemangioendothelioma

Hypo withhyper rim

Hyper withhypo rim

Concentric rings Delayed c ntral Subcapsular location, capsularretraction

Primary Hepatic Lymphoma Hypo Hyper Rim, heterogeneous Progressiv No specific features

Abbreviations: Hyper, hyperintense; Hypo, hypointense; Iso, isointense.a Signal intensity of lesion in comparison to liver parenchyma and signal intensity of scar in comparison to remain er of the lesion.

Tumors

oftheLive

randIntra

hepatic

Bile

Ducts

605

no

e

a

e

l

e

ce

e

e

d

Lewis et al606

enhancement, attributed to adjacent vasculitis.90

Central heterogeneous signal and enhancementmay also be present depending on the degree ofnecrosis, fibrosis, and vascularity (Fig. 16).89,90


Secondary hepatic lymphoma may be easier todiagnose than primary hepatic lymphoma givenevidence of extrahepatic nodal disease. The differ-ential diagnosis for primary hepatic lymphoma isquite broad, including other primary andsecondary hepatic malignancies, as well as infec-tious and inflammatory processes. As a result,biopsy is often required with immunohistochem-istry for diagnosis.

SUMMARY

Primary hepatic tumors demonstrate diverse clin-ical and pathologic features. When typical imagingfeatures are present (Table 1), the MR imagingappearance may be diagnostic, such as FNHand cavernous hemangioma, or suggestive of thediagnosis, such as biliary cystadenoma or cysta-denocarcinoma, angiomyolipoma, HCC in thebackground of cirrhosis, fibrolamellar carcinoma,ICC, or epithelioid hemangioendothelioma. Inmany cases, however, biopsy is required for diag-nosis and treatment planning. Newer MR imagingcontrast agents and techniques may prove tofurther narrow the imaging differential diagnosis.

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