Fat-containing Lesions of the Liver: Radiologic-Pathologic Correlation1

EDUCATION EXHIBIT 321

Fat-containing Lesionsof the Liver: Radiologic-Pathologic Correlation1

ONLINE-ONLYCME

See www.rsna.org/education/rg_cme.html.

LEARNINGOBJECTIVESAfter reading thisarticle and takingthe test, the reader

will be able to:

� List the wide spec-trum of fat-contain-ing lesions of theliver.

� Identify the imag-ing features of fat-containing liver le-sions and the cor-responding grosspathologic and histo-logic appearances.

� Describe the pat-terns of fatty changewithin hepatic neo-plasms, a finding thatmay be helpful indifferential diagnosis.

Srinivasa R. Prasad, MD ● Hanlin Wang, MD, PhD ● Humberto Rosas,MD ● Christine O. Menias, MD ● Vamsi R. Narra, MD ● William D.Middleton, MD ● Jay P. Heiken, MD

Fat-containing tumors of the liver are a heterogeneous group of tumorswith characteristic histologic features, variable biologic profiles, andvariable imaging findings. Benign liver lesions that contain fat includefocal or geographic fatty change (steatosis), pseudolesions due to post-operative packing material (omentum), adenoma, focal nodular hyper-plasia, lipoma, angiomyolipoma, cystic teratoma, hepatic adrenal resttumor, pseudolipoma of the Glisson capsule, and xanthomatous le-sions in Langerhans cell histiocytosis. Malignant liver lesions that cancontain fat include hepatocellular carcinoma, primary and metastaticliposarcoma, and hepatic metastases. Identification of fat within a liverlesion can be critical in characterization of the lesion. The imagingcharacteristics of a lesion coupled with the pattern of intratumoral fattychange are helpful in narrowing the differential diagnosis. Although thepresence of fat can be demonstrated with computed tomography orultrasound, magnetic resonance imaging is the most specific imagingtechnique for demonstration of both microscopic and macroscopic fat.©RSNA, 2005

Abbreviations: GRE � gradient echo, HCC � hepatocellular carcinoma

RadioGraphics 2005; 25:321–331 ● Published online 10.1148/rg.252045083 ● Content Codes:

1From the Department of Radiology, University of Texas Health Science Center at San Antonio (S.R.P.); the Department of Pathology and Immunol-ogy, Washington University, St Louis, Mo (H.W.); and the Department of Radiology, Mallinckrodt Institute of Radiology, 510 S Kingshighway Blvd,Ninth Floor, St Louis, MO 63110 (H.R., C.O.M., V.R.N., W.D.M., J.P.H.). Presented as an education exhibit at the 2002 RSNA Scientific Assem-bly. Received April 20, 2004; revision requested June 7; revision received and accepted June 30. All authors have no financial relationships to disclose.Address correspondence to J.P.H. (e-mail: [email protected]).

©RSNA, 2005

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IntroductionA variety of liver lesions ranging from benign enti-ties to malignant neoplasms may contain fat. Thebenign lesions include focal or geographic fattychange (steatosis), hepatocellular adenoma, focalnodular hyperplasia, lipoma, angiomyolipoma,teratoma, hepatic adrenal rest tumor, pseudo-lipoma of the Glisson capsule, and xanthomatouslesions in Langerhans cell histiocytosis. Malig-nant tumors that can contain fat primarily includehepatocellular carcinoma and primary and meta-static liposarcoma. This article reviews the spec-trum of focal fat-containing lesions in the liver,focusing on the imaging characteristics andpathologic correlation (Tables 1, 2).

Imaging Tech-niques and Characteristics

Fat has a characteristic appearance with each ofthe major cross-sectional imaging modalities. Itusually appears hyperechoic at ultrasound (US),

although fat in some regions may appear hypo-echoic (1). Fat attenuates sound more than theadjacent liver parenchyma, so partial acousticshadowing may occur deep to fatty tumors. Sincethe speed of sound is less in fat than in other softtissues, speed propagation artifacts and refractionartifacts can occur with fatty tumors (2). Fat is oflow attenuation compared with normal liver pa-renchyma at computed tomography (CT), with arange of �10 to �100 HU, and high in signalintensity on T1-weighted magnetic resonance(MR) images (3).

In addition, several MR imaging sequences aidin the detection of fat, including fat suppressionsequences and chemical shift imaging with op-posed-phase gradient-echo (GRE) sequences (4).The absence of a 180° refocusing radiofrequencypulse in GRE sequences results in the temporalcycling of lipid and water proton signals in andout of phase with respect to each other (4). At 1.5T, lipid and water protons precess in phase ap-proximately every 4.2 msec. During in-phase im-aging, the lipid and water signals are additive.Imaging during intermediate echo times of ap-proximately 2.1 msec and 6.3 msec, when lipid

Table 1Liver Lesions Containing Macroscopic Fat

Type ofLesion Lesions Containing Only Fat

Lesions Containing Fatand Soft Tissue

Benign Lipoma AdenomaXanthoma (Langerhans cell histiocytosis) Hepatic adrenal rest tumorPostoperative packing material Angiomyolipoma

(omentum) TeratomaMalignant Primary liposarcoma Hepatocellular carcinoma

Metastatic liposarcoma MetastasesPrimary liposarcomaMetastatic liposarcoma

Table 2Liver Lesions Containing Intracellular Lipid

Type ofLesion Lesions Containing Only Fat

Lesions Containing Fatand Soft Tissue

Benign Focal steatosis Focal nodular hyperplasiaMultifocal nodular steatosis AngiomyolipomaAdenoma

Malignant . . . Hepatocellular carcinoma

322 March-April 2005 RG f Volume 25 ● Number 2

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and water protons are out of phase, leads to phasecancellation effect at a voxel level, resulting in lossof signal in voxels with fat and water. Thus, ap-propriate selection of echo time can be used toobtain images with differing relative contributionsof fat and water signals. For example, images ob-tained with an out-of-phase echo time demon-strate a conspicuous drop in signal intensity intissues containing equimolar amounts of waterand lipid, compared with the signal intensity onequivalent in-phase images. The out-of-phaseGRE sequence is a useful technique for diagnosisof both diffuse and focal hepatic steatosis.

Benign Fat-containing Liver Lesions

Hepatic SteatosisHepatic steatosis can be either diffuse or focal.Focal steatosis is often easily recognized on thebasis of the typical periligamentous or periportallocation, the distribution of the lesions, and thepresence of nondistorted, traversing blood vessels(Figs 1, 2). However, patchy focal fat depositionor sparing may be mistaken for an infiltrative neo-plasm (5) (Fig 3). Multifocal nodular steatosis

Figures 1–3. (1) Focal hepatic steatosis. Axial US scan of the liver shows an ovoid, uni-formly hyperechoic focus (arrow), a finding consistent with focal fat. (2) Focal hepatic ste-atosis. (a) Axial in-phase T1-weighted MR image shows peripheral high-signal-intensity foci(arrow). (b) Axial opposed-phase T1-weighted MR image shows a uniform decrease in thesignal intensity of the foci (arrow). (3) Axial US scan shows patchy, diffuse hepatic steatosis(arrow), which simulates an infiltrative tumor.

RG f Volume 25 ● Number 2 Prasad et al 323

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(MNS) can simulate metastatic disease at US,CT, and MR imaging (6) (Fig 4). The combina-tion of in-phase and opposed-phase GRE imagingallows reliable differentiation of MNS from meta-static disease.

Fatty Pseudolesions of theLiver: Postoperative ChangesOmentum is often used as a packing material inhepatobiliary surgeries. It is important to recog-nize the imaging appearance of fatty omentum inpostoperative patients (Fig 5).

AdenomaHepatic adenoma is a benign, encapsulated neo-plasm that shows a propensity to frequent hemor-rhage and rare malignant change (Fig 6c). It mostcommonly occurs in young women taking oralcontraceptives. Other risk factors include type Iglycogen storage disease and use of anabolic ste-roids. Histologically, a hepatocellular adenomaconsists of normal-appearing hepatocytes ar-ranged in sheets and cords instead of the usuallobular architecture (Fig 6d). The presence ofdilated sinusoids with scanty connective tissuesupport that are fed by prominent arteries predis-poses to hemorrhage (7). The adenoma cells maybe filled with glycogen and fat (Fig 6d). Intra-

and intercellular lipid uncommonly manifests asmacroscopic fat deposits within the tumor (Fig7). In a series of hepatocellular adenomas imagedwith CT, lipid deposition was seen in only 7% oflesions (8). In contrast, 35%–77% of adenomasdemonstrate steatosis at chemical shift MR imag-ing (9,10) (Fig 6a, 6b). These findings correlatewith the variable lipid content of adenomas andthe superior contrast resolution and tissue distinc-tion of MR imaging compared with CT.

Figure 4. Multinodular hepatic steatosis. (a) Axial in-phase T1-weighted GRE imageshows subtle hyperintense foci (arrow). (b) Axial out-of-phase T1-weighted GRE imageshows uniform signal loss in the foci (arrows).

Figure 5. Contrast-enhanced CT scan shows afatty hepatic pseudomass due to omental packing(arrow). Such a pseudomass is a common post-operative finding.


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Figures 6, 7. Hepatic adenoma. (6a) Axial in-phaseT1-weighted GRE image shows a large, hypointensemass in the right hepatic lobe (arrow). (6b) Axial out-of-phase T1-weighted GRE image shows a homoge-neous decrease in the signal intensity of the adenoma(arrow). (6c) Photograph of the gross pathologic speci-men shows areas of hemorrhage (arrow). (6d) Pho-tomicrograph (original magnification, �200; hema-toxylin-eosin stain) shows intracytoplasmic fat vacuoles(arrow) within adenoma cells. (7) Nonenhanced CTscan of a patient with multiple adenomas shows macro-scopic fat deposition (arrow).


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Focal Nodular HyperplasiaFocal nodular hyperplasia (FNH) is the secondmost common benign hepatic lesion followinghemangioma. It occurs predominantly in youngasymptomatic women and is often discoveredincidentally. Histologically, FNH consistsof hepatocyte nodules that are circumscribedby fibrous septa containing bile ducts andmononuclear inflammatory cells (Fig 8c). In con-tradistinction to adenomas, which hemorrhageand have malignant potential, FNH exhibits be-nign behavior.

At US, FNH is typically isoechoic to liver pa-renchyma. Color and power Doppler US oftenshow a characteristic “spoke-wheel” pattern ofinternal vascularity (11). At CT and MR imaging,FNH demonstrates brisk, intense, homogeneouscontrast enhancement with rapid contrast mate-rial washout (Fig 8a). A central scar that is brighton T2-weighted images and shows delayed con-trast enhancement is a characteristic feature.

The presence of fat in FNH is extremely rareand is usually patchy in distribution (12) (Fig 8b,8c). Intratumoral steatosis may or may not beassociated with diffuse hepatic steatosis. Eisen-berg et al (13) proposed that intratumoral steato-sis might result either from ischemia possiblyfrom tumoral compression of adjacent liver or

from as yet unknown tumor-related by-products.Intratumoral steatosis is better demonstrated atMR imaging (14).

Figure 8. Focal nodular hyperplasia. (a) Axialarterial phase T1-weighted MR image shows a lobu-lated, well-circumscribed tumor with intense anduniform enhancement (arrow). (b) Axial opposed-phase T1-weighted GRE image shows a patchy pe-ripheral focus of low signal intensity (arrow), whichrepresents a focal fat deposit. (c) Photomicrograph(original magnification, �200; hematoxylin-eosinstain) shows intracellular fat vacuoles (arrow).

Figure 9. Axial US scan shows uniformly hyper-echoic lesions (arrow), which represent hepatic lipo-mas.


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LipomaHepatic lipomas are extremely uncommon (15).Histologically, these lesions consist of mature adi-pose tissue. Lipomas have characteristic findingsat imaging. At US, they appear as well-circum-scribed, uniformly hyperechoic lesions (Fig 9). AtCT and MR imaging, lipomas demonstrate pa-thognomonic characteristics of a fatty lesion.

AngiomyolipomaAngiomyolipoma (AML) is a benign, unencapsu-lated mesenchymal tumor that is composed ofvarying proportions of three elements: smoothmuscle cells, thick-walled blood vessels, and ma-ture adipose tissue (Fig 10b, 10c). AML occursmore commonly in the kidneys; hepatic involve-ment is rare. In contrast to renal AML, which isassociated with tuberous sclerosis in 20% of pa-tients, hepatic AML is associated with tuberoussclerosis in only 6% (16). AML can be histologi-cally classified on the basis of fat content intomixed, lipomatous (�70% fat), myomatous(�10% fat), and angiomatous types (17).

US, CT, and MR imaging typically demon-strate the fat component and prominent centralvessels. At US, AML may be highly echogenicand is then indistinguishable from a hemangioma.When present, sound attenuation, speed propaga-tion artifact, and refraction artifact allow distinc-tion of AML from other echogenic tumors, espe-cially hemangiomas (2). At CT, AML has beenreported to consist of two parts: a peripheral an-giomyomatous component with soft-tissue at-tenuation and a fatty component with an attenua-tion value less than �20 HU (18) (Fig 10a). MRimaging characteristics vary depending on theproportion of intratumoral fat (19). Frequently,AML has a high fat content, with high signal in-tensity on T1-weighted images and a significantdrop in signal intensity on fat-suppressed images.

AML demonstrates early intense contrast en-hancement that peaks later than that of a hepato-cellular carcinoma (HCC) (18). Dynamic con-trast-enhanced CT or MR images obtained dur-ing the early phase of enhancement may be usefulin discriminating between AML and fat-contain-ing HCC. The fatty areas of AMLs are well vas-cularized and enhance early, whereas steatoticfoci in HCC are relatively avascular and have lesscontrast enhancement (19). However, unlike re-nal AML, 50% of hepatic AMLs lack consider-able fat content (17). Because of this variable fatcontent, it is difficult to accurately distinguishAML from other hepatic tumors.

Figure 10. Hepatic angiomyolipoma. (a) Con-trast-enhanced CT scan shows a well-circumscribed,heterogeneous tumor of the right lobe with foci of fat(arrow). (b) Photograph of the gross specimenshows that the tumor is large and lobulated with ar-eas containing fat (arrow). (c) Photomicrograph(original magnification, �200; hematoxylin-eosinstain) shows proliferating smooth muscle (arrow),vessels, and adipose tissue (arrowheads).


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Cystic TeratomaTrue liver cystic teratomas are extremely rare,with only a few isolated case reports in the radiol-ogy literature (20,21). Most so-called “hepaticteratomas” represent either intraperitoneal or ret-roperitoneal teratomas that have invaded theliver. Teratomas are benign, encapsulated tumorsthat arise from pluripotential cells. They fre-quently have components derived from all threegerm layers, that is, ectoderm, endoderm, andmesoderm (22). The cystic mass frequently con-tains fat, hair, proteinaceous debris, and calcifica-tion. Imaging features reflect tissue heterogeneity(Fig 11b, 11c). The finding of a mass containingfat, fluid, and calcification is virtually diagnosticof a teratoma (Fig 11a) (22).

Adrenal Rest TumorAdrenal rest tumor is an ectopic collection of ad-renocortical cells in an extra-adrenal site (23).This tumor may be nonfunctional or hormonallyactive and manifesting as an endocrine syndrome(24). Histologically, hepatic adrenal rest tumors(HARTs) are composed of low columnar orcuboidal clear cells, similar to adrenocortical tu-mors. Among the histologic constituents ofHART, the presence of fat within the tumor is the

Figure 11. Hepatic invasion by a primarily ret-roperitoneal teratoma. (a) Contrast-enhancedCT scan shows a predominantly fatty mass witha peripheral rim and central chunky calcification(arrow). (b) Photograph of the gross specimenshows that the mass is cystic with solid areas andpapillary fronds. (c) Photomicrograph (originalmagnification, �400; hematoxylin-eosin stain) ofa portion of the mass shows mature adipose tis-sue (arrow) and blood vessels.

Figure 12. Nonenhanced CT scan shows a heter-ogeneous lesion in the right lobe that contains mac-roscopic fat (arrow). Histopathologic analysis dem-onstrated a hepatic adrenal rest tumor.


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most characteristic feature. At imaging, HART istypically subcapsular, demonstrating macroscopicfat and hypervascularity (23) (Fig 12). Differen-tiation of HART from angiomyolipoma or HCCwith steatosis may be difficult at both imagingand histologic analysis.

Pseudolipoma of the Glisson CapsuleAlso known as hepatic pseudolipoma, pseudo-lipoma of the Glisson capsule was described byRolleston in 1891. Pseudolipoma refers to an en-capsulated lesion containing degenerated fat thatis enveloped by a liver capsule. It is thought torepresent a detached colonic epiploic appendixthat develops a fibrous capsule and lodges in theperitoneal cavity (25). When this lesion is in closeproximity to the liver, it may become attached tothe liver capsule. Differential diagnoses of thisuncommon entity include serosal metastasis andfibrosing subcapsular necrotic nodule (25). Atimaging, it appears as a well-circumscribed nod-ule on the liver surface with a center of either fator soft-tissue attenuation.

Xanthomatous Lesions inLangerhans Cell HistiocytosisLangerhans cell histiocytosis (LCH) is a multisys-tem disorder of variable clinical severity. It ischaracterized by inappropriate proliferation ofLangerhans cells, the antigen presenting cells(26,27). Hepatic involvement is uncommon andusually seen in patients with extensive LCH. Theliver lesions are characteristically located in the

periportal region and have been staged into fourdifferent histologic phases: proliferative, granulo-matous, xanthomatous, and fibrous (27). Xan-thomatous lesions appear uniformly hyperechoicat sonography, have low attenuation at CT, anddisplay characteristics of fat at MR imaging (26).

Malignant Fat-containing Liver Lesions

Hepatocellular CarcinomaHepatocellular carcinoma (HCC) is the com-monest primary hepatic malignant neoplasm thatcommonly develops in a cirrhotic liver. Small(�1.5 cm) well-differentiated HCCs are oftenassociated with a diffuse-type fatty change (Fig13a). Larger tumors have patchy fatty metamor-phosis (Fig 13b). Fatty change can be seen in upto 35% of small HCCs and is associated with adecrease in the number of intratumoral arterieswithout any difference in intratumoral portaltracts (28). In contradistinction to the uniform fatdeposition in adenomas, fat deposition in HCCsis usually patchy (Fig 13a). Macroscopic fatwithin HCC is well demonstrated on CT scans(Fig 13a). HCC with fatty change appears hyper-intense on T1-weighted images and demonstratessignal intensity drop on chemical shift images.The hyperintensity of HCC on T1-weightedimages is attributed to a number of factors,

Figure 13. Hepatocellular carcinoma. (a) CT scan shows patchy macroscopic fat deposition (�) in a large,heterogeneously enhancing hepatoma. (b) Photomicrograph (original magnification, �200; hematoxylin-eosinstain) shows fat vacuoles within tumor cells (arrow).


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including hemorrhage, intratumoral deposition offat, and/or the copper and zinc content of sur-rounding liver parenchyma (29).

LiposarcomaLiposarcoma is an uncommon malignant mesen-chymal tumor that accounts for 15% of all sarco-mas. Metastatic spread of retroperitoneal andextremity liposarcomas is relatively common, butthe liver is involved in only 10% of cases (Fig 14).Most hepatic liposarcomas are metastatic; iso-lated cases of primary hepatic liposarcomas havebeen reported (30,31).

Hepatic MetastasesIn general, liver metastases do not contain fat.Exceptional examples of hepatic metastases withfoci of fat exist (Fig 15).

ConclusionsFat-containing liver tumors constitute a heteroge-neous group of tumors with characteristic histo-logic and variable imaging findings. Identificationof fat within a liver lesion can be critical in charac-terizing it. The imaging characteristics of the fat

components of a lesion combined with other im-aging features of the lesion are helpful in narrow-ing the differential diagnosis. Although the pres-ence of fat can be documented with CT or US,MR imaging is the most specific imaging tech-nique for demonstrating both microscopic andmacroscopic fat.

Figure 14. Hepatic liposarcoma. (a) Serial surveillance contrast-enhanced CT scan obtained after resectionof an extremity liposarcoma shows a fatty hepatic metastasis (arrow). (b) Photomicrograph (original magnifica-tion, �200; hematoxylin-eosin stain) shows lipoblasts with hyperchromatic nuclei (arrow) in a vascular stroma,an appearance consistent with a liposarcoma.

Figure 15. Contrast-enhanced CT scan shows he-patic metastases containing foci of fat (arrow). The me-tastases were from an intestinal tumor synthesizing va-soactive intestinal peptide.


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This article meets the criteria for 1.0 category 1 credit toward the AMA Physician’s Recognition Award. To obtaincredit, see www.rsna.org/education/rg_cme.html.


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Documents

Fat-containing Lesions of the Liver: Radiologic-Pathologic Correlation1