solitary necrotic nodule of the liver: contrast-enhanced sonography

Solitary Necrotic Nodule of the Liver:Contrast-Enhanced Sonography

Yang Wang, MD, Xiaoling Yu, MD, Jie Tang, MD, Hua Li, MD, Liping Liu, MD, Yongyan Gao, MD

From the Department of Ultrasound, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853 China

Received 5 September 2006; accepted 22 January 2007

ABSTRACT: Purpose. To report contrast-enhanced

sonography (CEUS) for solitary necrotic nodule

(SNN) of the liver and to assess its clinical value.

Methods. CEUS was performed in 17 patients with

pathologically proven SNN. Contrast pulse sequencing

and the contrast agent SonoVue were used to depict

lesion vascularity at a low mechanical index. The

enhancement patternswere evaluated in real time.

Results. Lesions were depicted as perfusion defects

throughout all phases on CEUS.

Conclusions: CEUS can be a convenient imaging

modality for the differential diagnosis of SNN and may

obviate the need for further imaging studies. VVC 2007

Wiley Periodicals, Inc. J Clin Ultrasound 35:177–181,

2007; Published online in Wiley InterScience (www.

interscience.wiley.com). DOI: 10.1002/jcu.20342

Keywords: contrast-enhanced ultrasound; liver;

solitary necrotic nodule

Solitary necrotic nodule of the liver (SNN) is arare benign lesion of uncertain etiology.1–8

Most SNNs are asymptomatic. They are often in-cidental findings on abdominal imaging and fre-quently misinterpreted as metastases.1,2 Due totheir benign nature, a correct diagnosis is neededto avoid unnecessary surgical resection. Manydiagnostic modalities have been used for the dif-ferential diagnosis of SNN, including sonography,CT, and MRI. SNN is usually first detected viasonography, after which contrast-enhanced CTand/or contrast-enhanced MRI examinations arerequired to assess lesion vascularity, because ab-sence of enhancement in all phases on CT or MRIstrongly suggests SNN.3

Contrast-enhanced sonography (CEUS) can gr-eatly improve depiction of intralesional vascularity

compared with conventional color Doppler sonog-raphy.9,10 Recently, the advent of second-genera-tion contrast agents and dedicated softwareallows real-time evaluation of enhancement pat-tern and accurate characterization of focal liverlesions.11–13 However, to our knowledge there hasbeen no report of CEUS of SNN in the English lit-erature. Thus, the purpose of this article is toreport the initial experience with CEUS of SNNand to assess its clinical value.

MATERIALS AND METHODS

Patients

From April 2005 to September 2006, CEUS wasperformed in 17 consecutive patients with SNNwho were first examined with conventional so-nography in our hospital. The patients werereferred to sonographic examination for routinecheck-up (n ¼ 11), screening for possible meta-stasis after surgical treatment of breast cancer(n ¼ 1) or incidentally detected hepatic lesion atother hospitals (n ¼ 5). There were 8 men and 9women with a mean (6SD) age of 49 6 11 years(range, 32–71 years). All patients had a well-defined predominantly hyperechoic nodule lo-cated in the right lobe. The mean (6SD) diameterof the nodule was 2.4 6 0.6 cm (range, 1.3–3.5cm). No blood flow signal was detected within thenodules on color Doppler examination. Nine nod-ules had a lobulated shape, whereas 8 noduleshad a regular oval shape. The clinical and sono-graphic findings are presented in Table 1.

Contrast Agent

The contrast agent used in this study was Sono-Vue (Bracco, Milan, Italy), which was supplied as

Correspondence to: Y. Wang

' 2007 Wiley Periodicals, Inc.

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a lyophilized powder and reconstituted with 5 mlof saline to form a homogeneous microbubble sus-pension that contains 8 �l/ml of sulfur hexafluor-ide stabilized by a phospholipid shell.

Contrast-Enhanced Sonography

CEUS was performed with a Sequoia 512 scanner(Siemens Ultrasound, Mountain View, CA) equippedwith contrast pulse sequencing software whichpermits real-time depiction of lesion blood perfu-sion under low mechanical index. The softwarealso has a function of live dual image display thatallows for simultaneous visualization of both tis-sue image and contrast agent image. A 1–4-MHz4V1 vector transducer was used. After unen-hanced sonographic examination using gray-scale color/power Doppler techniques, contrastpulse sequencing was activated and patientswere asked to suspend respiration. A bolus injec-tion of 2.4 ml SonoVue was administered via theantecubital vein, followed by a 5-ml saline flush.Continuous imaging at a low mechanical index(range, 0.15–0.18) was initiated at the sametime. Dual image display was used to help locatetarget lesion during examination. The targetlesion was observed continuously for at least 5minutes after the beginning of SonoVue injection,and the entire process was recorded on the harddisk of the scanner. Digital cine clips were ana-lyzed off-line under the consensus of 2 investiga-tors (Y.W., X.L.Y.) who combined had performedmore than 200 CEUS examinations for focal he-patic lesions.

Pathology

After CEUS examination, all patients underwentsonographically guided 18-gauge core needle bi-opsy using an automated gun (Magnum Bard,Covington, GA). Each lesion was biopsied 3times. The specimens were fixed in 10% formalinand then stained with hematoxylin-eosin forpathologic study under light microscopy. Twopathologists, each with more than 15 years expe-rience examining focal hepatic lesions, studiedthe specimens independently. In case of disagree-ment, final diagnosis was made by consensus.

RESULTS

All lesions were depicted as well-demarcated per-fusion defects throughout all phases on CEUS(Figures 1 and 2). This nonenhancement patternwas different from that of other solid hepaticlesions. No adverse effect was observed.

Microscopically, tissues obtained from thelesion were completely necrotic and separated bya fibrous capsule from normal liver parenchyma(Figure 1). The pathologic features were consist-ent with SNN in all cases.

DISCUSSION

In 1983, Shepherd1 first described the solitary ne-crotic nodule of the liver, an uncommon nonmalig-nant lesion with a characteristic histologic appear-ance. As yet, the pathogenesis of this entity is stilldebated. Hypotheses such as parasitic granulomaand sclerosing hemangiomahave been proposed.4–8

TABLE 1

Clinical and Sonographic Features of Solitary Necrotic Nodules

Case No. Sex/Age Location Shape/Size

Blood Signal on

Color/Power Doppler

1 M/55 Deep in right lobe Lobulated/1.8 cm No

2 F/53 Deep in right lobe Lobulated/3.0 cm No

3 M/39 Deep in right lobe Oval/2.6 cm No

4 M/38 Deep in right lobe Oval/2.8 cm No

5 F/32 Deep in right lobe Oval/2.1 cm No



8 F/32 Deep in right lobe Oval/1.8 cm No

9 M/46 Subcapsular anterior surface of right lobe Lobulated/3.2 cm No

10 F/62 Subcapsular anterior surface of right lobe Lobulated/2.9 cm No

11 M/48 Subcapsular posterior surface of right lobe Oval/3.5 cm No

12 F/65 Subcapsular posterior surface of right lobe Oval/1.9 cm No




16 F/58 Subcapsular anterior surface of right lobe Oval/2.3 cm No

17 F/48 Subcapsular anterior surface of right lobe Oval/1.4 cm No

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SNNs are usually first detected via sono-graphic examination. Some sonographic featuressuch as lobulated shape, well-delineated margin,and close proximity to hepatic inflow structures

are suggestive of SNN but are nondiagnostic.8

Because conventional color/power Doppler imag-ing is insensitive to slow flow and deeply locatedblood vessels, lack of blood flow signal cannot

FIGURE 1. A 55-year-old woman with a lobulated hepatic lesion 5 years after curative breast cancer resection. (A) Gray-scale sonogram shows a

lobulated hypoechoic lesion comprised of 3 nodules (arrows) in segment 6 of the liver. (B) CEUS scan obtained at 18 seconds (arterial phase) after

contrast injection shows no vascularity in the lesion. (C) CEUS scan obtained at 40 seconds (portal phase) after contrast injection shows no vascu-

larity in the lesion. (D) CEUS scan at 120 seconds (late phase) still shows no vascularity in the lesion. (E) Core biopsy specimen is completely ne-

crotic and separated by a fibrous capsule (arrow) from normal liver parenchyma (hematoxylin-eosin stain; original magnification, 40�).

FIGURE 2. A 39-year-old man with a 3-cm oval hepatic lesion detected incidentally via CT in another hospital. (A) Gray-scale sonogram shows a

well-defined lesion comprised of alternating hypoechoic and hyperechoic layers. (B) CEUS scan obtained at 18 seconds (arterial phase) after con-

trast injection shows no enhancement of the lesion. (C) CEUS scan obtained at 40 seconds (portal phase) after contrast injection shows no

enhancement of the lesion. (D) CEUS scan obtained at 120 seconds (late phase) still shows no enhancement of the lesion. (E) Contrast-enhanced

CT scan performed in another hospital shows no enhancement of the lesion.

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ensure total absence of blood perfusion withinthe lesion. Second-level examination (contrast-enhanced CT or contrast-enhanced MRI) is oftenrequired to assess lesion vascularity. SNN is usu-ally depicted as a well-defined lesion with noenhancement on contrast CT or MRI,7 whilesome SNNs may have subtle peripheral enhance-ment on contrast MRI.9

CEUS can overcome the limitations of conven-tional color/power Doppler sonography and hasbeen shown to improve the assessment of vascu-larity in focal hepatic lesions.10–15 First-genera-tion contrast agents such as Levovist require ahigh mechanical index to obtain a harmonicresponse from destructed bubbles, thereby limit-ing the accuracy of real-time imaging.10,11 In con-trast, second-generation microbubble contrastagents can survive multiple capillary passages ata low mechanical index, enabling continuousreal-time assessment of intralesional vascular-ity.12–14 SonoVue, a second-generation contrastagent consisting of microbubbles filled with sul-fur hexafluoride has been widely used in Chinafor characterization of focal hepatic lesions inrecent years.

As one of the largest hospitals in China, weperform more than 300 CEUS examinations forfocal hepatic lesions annually. Seventeenpatients with no previous history of hepaticmalignancy were suspected to have SNNs, asthe incidentally found lesions did not showenhancement throughout all phases on CEUS.Because absence of vascularity could be identi-fied with confidence, no further imaging studywas performed. Patients underwent percutane-ous, sonographically guided core biopsy insteadof hepatic resection, and the specimens were typ-ical for SNN. To our knowledge, the largest se-ries of SNNs reported so far comprised only 7cases.6 However, we encountered 17 cases in lessthan 2 years. Thus, we believe the incidence ofSNN may be higher than expected. BecauseCEUS is safe, inexpensive, and easily accessibleafter conventional songography, more SNNpatients may be screened out by this imagingtechnique, instead of more expensive imagingtechniques such as CT or MRI.

Though CEUS achieved a very high diagnosticaccuracy in this study, 2 important points mustbe mentioned. First, though absence of enhance-ment is characteristic of SNN, it is not unique tothis entity. Lesions such as liver cancer afterthermal ablation may also be depicted as perfu-sion defects on CEUS.15 Diagnosis of SNN shouldtake into account medical history and conven-tional sonographic features as well. Second,

CEUS requires considerable operator experienceand may be influenced by respiration. Patientcooperation is required for accurate interpreta-tion of lesion vascularity.

This study also has limitations. The pathologicdiagnosis of SNN was made on biopsy specimensinstead of gross specimens obtained at surgicalexcision. Specimen obtained by biopsy may misssome valuable information such as parasitic eggsor larvae in the necrotic tissue, preventing expla-nation of the exact etiology. Most patients did notundergo contrast-enhanced CT or MRI, so that acomparison between CEUS with those well-established imaging modalities could not be done.

In conclusion, SNNs of the liver appear aswell-defined perfusion defects on CEUS. CEUScan be a convenient imaging modality for the dif-ferential diagnosis of SNN and may limit theneed for further imaging studies.

REFERENCES

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solitary necrotic nodule of the liver: contrast-enhanced sonography

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