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Original Research |
1 Department of Medical Imaging, Tornoto General Hospital, University of
Tornoto, 585 University Ave., Toronto, ON M5G 2N2, Canada.
2 Imaging Research, Sunnybrook Health Sciences Centre and Departments of Medical
Biophysics and Medical Imaging, University of Toronto, Toronto, ON,
Canada.
3 Present address: Department of Diagnostic Imaging, Foothills Medical Center,
University of Calgary, Calgary, AB, Canada.
Received December 12, 2006;
accepted after revision July 16, 2007.
Address correspondence to T. K. Kim
(taekyoung.kim{at}uhn.on.ca).
Abstract
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MATERIALS AND METHODS. Sixty-two patients who underwent contrast-enhanced sonography and were confirmed to have FNH (n = 43) or hepatic adenoma (n = 19) were assessed retrospectively for arterial phase enhancement, filling direction, stellate arteries, and portal phase enhancement. An algorithm was applied to these interpreted features to determine the contrast-enhanced sonography diagnosis.
RESULTS. All lesions were hypervascular in the arterial phase.
Centrifugal filling was more common in FNH (39 and 32 of 43, 91% and 74%
[reader 1 and reader 2]) than in adenoma (3 and 3 of 19, 16%). Centripetal or
mixed filling was more common in adenoma (16 and 16 of 19, 84%) than in FNH (4
and 11 of 43, 9% and 26%) (p < 0.001, 
= 0.61). Stellate
arteries characterized FNH (29 and 26 of 43, 67% and 60%) but not adenoma (3
and 2 of 19, 16% and 11%) (p < 0.001, = 0.36). Sustained
portal phase enhancement was more common in FNH (37 and 39 of 43, 86% and 91%)
than in adenoma (9 and 12 of 19, 47% and 63%) (p < 0.02, =
0.79). The sensitivity, specificity, positive predictive value, and negative
predictive value of sonography for diagnosing FNH were 95% and 86%, 74% and
79%, 89% and 90%, and 88% and 71%, (reader 1 and reader 2, respectively).
CONCLUSION. FNH is predicted on the basis of arterial phase centrifugal filling and stellate vascularity on contrast-enhanced sonography. Adenoma is less reliably predicted on the basis of centripetal or mixed filling without stellate vascularity. Sustained portal phase enhancement is more common in FNH than in adenoma but contributes less to the differentiation of these lesions.
Keywords: contrast-enhanced sonography • focal nodular hyperplasia • hepatic adenoma • liver neoplasms
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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FNH is a proliferation of normal non-neoplastic hepatocytes that are abnormally arranged; it is frequently associated with a central stellate area of fibrosis and anomalous arteries [10]. FNH is virtually always discovered by incidental observation. By comparison, hepatic adenoma is a true neoplasm that is considered to occur under proliferative stimulation of hepatocytes, most commonly by the use of oral contraceptives [11]. Although adenoma may be discovered incidentally in identical circumstances to FNH, affected patients may also present with acute abdominal pain from rupture, and there is a recognized risk of complicating malignant transformation.
Therefore, with knowledge of a hypervascular liver mass in the appropriate clinical setting, differentiation of FNH and adenoma is important because therapeutic approaches differ drastically [4, 12]. Confirmed FNH is treated conservatively, whereas adenoma is treated by cessation of any exogenous hormone therapy and surgical removal of large or symptomatic lesions [13].
State-of-the-art MRI allows reliable diagnosis of classic FNH [14], and a recent publication on gadobenate dimeglumine-enhanced MRI claims a further advantage for this technique [3]. However, there are many atypical cases of FNH that are difficult to differentiate from adenoma on imaging alone. Furthermore, although both CT and MRI can be used to diagnose an adenoma complicated by either hemorrhage or rupture, most adenomas present as nonspecific asymptomatic solid masses [15].
FNH has a distinctive appearance on arteriography, showing an artery entering the lesion, branching, and supplying the mass centrifugally [16]. Kudo et al. [17] used sonography with an intraarterial injection of carbon dioxide microbubbles in four cases of FNH to show this characteristic vascular pattern. In contrast to FNH, adenoma has subcapsular feeding arteries that account for the centripetal blood flow of the lesion [5]. The vascularization of an adenoma is not as fine and orderly as the pattern seen in FNH [15]. However, such techniques for the visualization of vascularity require arterial access and are invasive as a routine test.
Color Doppler sonography has been suggested for characterization of focal liver masses [18]. However, initial optimism that color Doppler sonography alone could provide sufficient information for a diagnosis has not been substantiated. In a series of color Doppler sonography studies in six FNHs [19], central stellate vasculature was seen in only two and nonspecific peripheral intratumoral flow, in the remaining four lesions. Wang et al. [20] evaluated seven FNHs with color Doppler sonography and found the characteristic vascular pattern in four. Quaia et al. [21], in their study of 452 focal hepatic lesions including 26 FNHs, reported that color Doppler sonography is specific, but not sensitive, for the diagnosis of FNH. Although color Doppler sonography may provide supportive evidence of a suspicion of a certain disorder, further imaging tests or biopsy are usually performed to confirm FNH in many institutions.
Recent advances in contrast-enhanced sonography using a low mechanical index (< 0.2) and perfluorocarbon contrast agents enable real-time imaging of perfusion and vascularity in liver tumors [22, 23] with greater sensitivity and specificity than color Doppler imaging [21, 24]. The purpose of this study was to determine whether contrast-enhanced sonography provides features for differentiating FNH from adenoma.
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Subjects
The study population, seen between January 2000 and September 2005,
comprised 62 consecutive patients, 10 men and 52 women, who underwent
contrast-enhanced sonography of a focal liver mass suggestive of either FNH or
adenoma in whom the diagnosis was confirmed either by histopathology or by MRI
showing classic features of FNH and interval stability on imaging for at least
1 year. Exclusion criteria included patients seen during the time interval of
our study who had a contrast-enhanced sonography diagnosis of FNH or adenoma
that lacked MRI confirmation, follow-up, or biopsy; patients with confirmation
by CT only; and patients with acute symptomatology suggestive of ruptured
adenoma.
The 43 patients with confirmed FNH comprised eight males and 35 females having an age range of 14-81 years (mean age, 39 years). The 19 patients with adenoma comprised two men and 17 women with an age range of 19-74 years (mean age, 38 years). None of the 62 patients was scanned at the time of acute rupture, and 34 were totally asymptomatic. One patient had a history of prior resection for ruptured adenoma. None of the patients had a previous history of malignancy or known risk for HCC.
Twenty-six of 62 patients had multiple masses (n = 2-20 masses; mean, 4.5). In 20 of 26 patients, all masses had the same diagnosis; and in the remaining six of 26 patients, there were hepatic hemangiomas in addition to FNH (n = 5) or adenoma (n = 1). There were multiple adenomas in 10 of 19 patients and multiple FNHs in 13 of 43, including three patients with hemangiomas in addition to multiple FNHs (n = 2) or adenomas (n = 1). In three patients, there was one FNH and hemangioma(s). The number of hemangiomas ranged from one to 15 (mean, 6.3). Only one mass per patient, which was first scanned at the time of contrast-enhanced sonography and was not a hemangioma, was included in the study group. The maximum linear dimension of the 43 FNHs ranged from 1.3 to 6.8 cm (mean ± SD, 3.7 ± 1.5 cm). The size of 19 adenomas ranged from 3.1 to 12.3 cm (mean, 6.5 ± 2.6 cm). The mean size of the adenomas was significantly larger than that of the FNHs (Student's t test, p < 0.001).
The echogenicity of FNH on gray-scale sonography was hypoechoic in 25 of 43, isoechoic in 10 of 43, and hyperechoic in eight of 43. Echogenicity of adenomas on gray-scale sonography was hypoechoic in 12 of 19, isoechoic in three of 19, and hyperechoic in four of 19. Color Doppler sonography of the lesion was obtained in 33 of 43 FNHs and 18 of 19 adenomas. Internal flow was detected in 26 of 33 FNHs and 14 of 18 adenomas (Fisher's exact test, p = 0.274). Central linear or branching vasculature was identified in 16 of 33 FNHs and five of 18 adenomas (Fisher's exact test, p = 0.127).
In this retrospective study, percutaneous biopsy was ordered by clinicians after all imaging if adenoma was suspected or if imaging features were atypical for FNH. Thus, five of 43 patients with FNH had confirmation of their diagnosis by percutaneous needle biopsy, and the remaining 38 patients with FNH were diagnosed by MRI findings and follow-up imaging for at least 1 year that showed no change in lesion size. Initial MRI and contrast-enhanced sonography were performed within 1-12 months (mean interval, 4 months) for FNH. All 19 adenomas were confirmed at histopathology by either surgical resection (n = 9) or percutaneous needle biopsy (n = 10).
Sonography
Because of the extended period of patient accrual, contrast-enhanced
sonography was performed on multiple scanners: Aplio (Toshiba) (n =
20), Acuson Sequoia (Siemens Medical Solutions) (n = 18), HDI-5000
(Philips Medical Systems) (n = 18), and iU-22 (Philips) (n =
6). The imaging parameters and contrast-specific imaging techniques for each
scanner are summarized in Table
1. Three radiologists, also authors, who had 10, 6, and 3 years of
experience in contrast-enhanced sonography, performed the scanning. The
radiologists who performed contrast-enhanced sonography were not blinded to
the preexisting imaging and clinical findings because the contrast-enhanced
sonographic examinations were performed as a routine imaging test for the
evaluation of focal liver masses. The microbubble contrast agent used in this
study was Definity (perflutren lipid microspheres, Bristol-Myers Squibb),
injected via a peripheral venous route.
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Baseline gray-scale sonography was performed to identify each hepatic lesion, after which low-mechanical-index (0.07-0.2) contrast-enhanced sonography was performed after a contrast agent bolus injection of 0.1-0.3 mL. Injections were repeated three to six times (median, five times) separated by an interval of 6-7 minutes to allow elimination of the bubbles. Multiple digital cine clips and still frames were acquired to show arterial phase wash-in of contrast material to the peak of arterial enhancement, and then subsequent changes through the extended portal venous phase to 5 minutes. The arterial phase was defined as the time from 0 to 35 seconds after completion of the saline flush. The first injection comprised a continuous observation for 5 minutes to show the salient features of lesion enhancement.
Because a low-mechanical-index technique may show rapid sensitive detection of the microbubbles, a hypervascular mass may show instant enhancement of the entire lesion without vessel clarity. Therefore, subsequent injections included slightly higher-mechanical-index or high-mechanical-index flash-replenishment techniques to facilitate the assessment of the filling pattern and vessel morphology. A slightly higher mechanical index, still in the range of a conventional low mechanical index (< 0.2), shows flow in the larger vessels with a more rapid flow rate without detecting slowly flowing bubbles in the capillary beds. By comparison, in flash-replenishment techniques, a short burst of higher mechanical index (> 0.4), applied at the peak of arterial phase enhancement, disrupts the microbubbles in the field of view. With the use of high imaging frame rates (> 12 Hz), subsequent replenishment of the microbubbles, which enter the feeding vessels first, improves the visualization of vessel morphology.
Image Analysis
One author radiologist who did not participate in the image analysis
selected the digital cine clips (AVI files) and still frames from the
contrast-enhanced sonography image files in the study group, which were then
organized for review on a workstation. This radiologist had 8 years of
experience with cross-sectional abdominal imaging and 5 years of experience
with contrast-enhanced sonography. Gray-scale or color Doppler images were not
included in the image analysis. Image files were randomized for presentation
so that the FNHs and adenomas were not grouped by diagnosis. Review was
performed by two independent readers blinded to the identification, clinical
history, biopsy results, and other imaging findings. The reviewers were both
authors and included a staff radiologist who had 3 years of experience in
contrast-enhanced sonography and a radiology fellow who had 12 months of
training. They obtained nine of the 62 scans reviewed, although none within a
3-month time frame before the blinded reading.
For each lesion, the two readers were asked to document arterial phase enhancement (hyper-, iso-, or hypovascular) and filling direction (centrifugal, centripetal, or mixed), presence of a transient peripheral unenhanced zone, stellate arteries or a central scar or necrosis, and portal phase enhancement (hyper-, iso-, or hypoechoic, relative to the adjacent normal liver parenchyma). Centrifugal filling was defined as initial central enhancement that progressed to the periphery of the lesion over time. Centripetal filling was defined as initial peripheral enhancement that progressed to the center of the lesion over time. The arterial phase filling pattern was considered mixed if the enhancement occurred throughout the lesion and did not show either a centrifugal or a centripetal filling direction. A transient peripheral unenhanced zone was defined as a nonenhancing rimlike area in the periphery of the lesion in the arterial phase that gradually disappeared during the time of the arterial phase as the enhancement filled the entire lesion from the center out. Central stellate arteries were defined by the presence of enhancing central arteries with a spoked-wheel or starlike morphology. A central scar was defined as a central stellate hypoechoic linear or plicated area without contrast enhancement in the portal venous phase (Fig. 1A, 1B, 1C, 1D). Central necrosis was defined as an irregular area without contrast enhancement that often had an eccentric location in the lesion in all phases.
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Statistical Analysis
Fisher's exact test was used to evaluate the difference between FNH and
adenoma in the frequency of each imaging finding, including arterial phase
filling pattern, enhancement relative to the liver in the portal venous phase,
central stellate arteries, a transient peripheral unenhanced zone, and a
central scar. A p value less than 0.05 was considered statistically
significant. Kappa statistics were calculated to assess interobserver
agreement in each assessed finding. Agreement was graded as < 0.20,
poor; 0.20-0.39, fair; 0.40-0.59, moderate; 0.60-0.79, substantial; or
0.80-1.00, almost perfect
[25].
Receiver operating characteristic (ROC) curves were calculated to determine the diagnostic performance of contrast-enhanced sonography in differentiating FNH from adenoma. True-positive cases were defined as FNH that was correctly diagnosed. False-positive cases were defined as FNH that was incorrectly diagnosed as adenoma. The diagnostic capability was determined by calculating the area under the ROC curve (Az) for each reader. Confidence level ratings of the images were also used to calculate the sensitivity, specificity, and accuracy for each reader in the diagnosis of FNH. Ratings of 1-3 indicated a reading of FNH, and ratings of 4 or 5 indicated a reading of adenoma. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in differentiating FNH from adenoma were then calculated.
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Arterial Phase Features on Contrast-Enhanced Sonography
The imaging findings on contrast-enhanced sonography are summarized in
Table 2. All 62 lesions showed
hypervascularity in the arterial phase. Centrifugal filling (Figs.
1A,
1B,
1C,
1D and
2A,
2B,
2C) was more commonly observed
in FNH (39/43 [91%] and 32/43 [74%], for readers 1 and 2, respectively) than
in adenoma (3/19 [16%] for both readers). On the other hand, centripetal
filling (Fig. 3A,
3B,
3C,
3D) was more common in adenoma
(10/19 [53%] and 9/19 [47%]) than in FNH (1/43 [2%] and 3/43 [7%]). Mixed
filling (Fig. 4A,
4B,
4C,
4D) was also more common in
adenoma (6/19 [32%] and 7/19 [37%]) than in FNH (3/43 [7%] and 8/43 [19%]). A
statistically significant difference of arterial phase filling direction was
seen between FNH and adenoma (p < 0.001 for both reviewers).
Substantial interobserver agreement ( = 0.61) was achieved.
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A transient peripheral nonenhancing zone (Fig.
2A,
2B,
2C) was frequently, but not
always, visualized in cases having a centrifugal arterial phase pattern. As
the lesion enhanced from its center to the periphery of the mass, an apparent
peripheral nonenhancing zone became thinner over time and rapidly disappeared
as the entire lesion enhanced. This finding was never seen in cases with
either a centripetal or a mixed pattern of arterial enhancement. The
interobserver agreement was moderate ( = 0.50).
Stellate arteries were more commonly visualized in FNH (29/43 [67%] and
26/43 [60%]) than in adenoma (3/19 [16%] and 2/19 [11%]) (p <
0.001 for both reviewers; = 0.36). They were shown in the early
arterial filling phase for a short time (typically < 2 seconds) until
further progression of the enhancement obscured the vascular morphology in the
lesion (Figs. 1A,
1B,
1C,
1D and
2A,
2B,
2C). The interobserver
agreement was fair ( = 0.36).
Portal Venous Phase Features on Contrast-Enhanced Sonography
Most FNHs (37/43 [86%] and 39/43 [91%]) showed sustained portal venous
phase enhancement (isoechogenicity or hyperechogenicity of the lesion relative
to the liver for the duration of observation to 5 minutes) (Fig.
1A,
1B,
1C,
1D). Adenoma showed less
consistency of portal venous phase enhancement and negative portal venous
phase enhancement or washout (Fig.
4A,
4B,
4C,
4D) in 10 of 19 (53%) and
seven of 19 (37%) adenomas as often as sustained enhancement. Infrequent
washout was seen also in FNH (6/43 [14%] and 4/43 [9%]). A statistically
significant difference was seen in the portal venous phase enhancement between
FNH and adenoma (p = 0.011 and 0.014). Substantial interobserver
agreement as to portal venous enhancement ( = 0.79) was seen.
A central scar was seen as a central stellate hypoechoic linear or plicated area without contrast-enhancement during the extended observation of the portal venous phase to 5 minutes. A central scar (Fig. 1A, 1B, 1C, 1D) was shown uncommonly in FNH (23/43 [53%] and 13/43 [30%]). However, a small area of central necrosis in adenomas was misdiagnosed as a central scar in four of 19 (21%) and three of 19 (16%) adenomas. Although infrequent, central necrosis was seen only in adenomas (3/19 [16%] and 4/19 [21%]).
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Previous publications about contrast-enhanced sonography with both first- and second-generation contrast agents have documented many of the features for the diagnosis of FNH shown in the present study [23, 26, 27]. These include homogeneous arterial phase enhancement, sustained enhancement in the portal venous phase, a central scar, and stellate arteries. Leen et al. [24] describe the improved ability of contrast-enhanced sonography to diagnose a liver mass when compared with conventional unenhanced sonography. Those authors include similar features to ours for the diagnosis of FNH, although it is not clear how many FNHs there were in a total 127 unknown liver lesions, nor whether any had a final diagnosis of adenoma. Nicolau et al. [28] attempted to refine criteria for differentiation of benign from malignant lesions by showing the value of all phases of contrast enhancement on contrast-enhanced sonography in a study that included 13 FNHs, but no adenomas, in a population of 152 liver lesions. Features of adenoma on contrast-enhanced sonography are described in a recent study by Dietrich et al. [2] using a different second-generation contrast agent and somewhat different scanning parameters. In their study, however, all eight of eight (100%) adenomas showed washout within 30 seconds after injection of the contrast agent, compared with our result of washout seen in 10 of 19 (53%) and seven of 19 (37%) adenomas and never within 30 seconds. These differences might be attributed to the relatively high mechanical index (0.2-0.3) used in their study, or possibly to the use of a different contrast agent. However, we do not explain the difference in the portal venous phase washout at this time.
In this study, the early arterial filling direction and the vascular morphology were successfully visualized on contrast-enhanced sonography in most FNHs and adenomas. As expected, centrifugal filling and central stellate arteries were more common in FNH than in adenoma. Arterial filling of both FNH and adenoma occurs during an extremely short time, requiring a high frame rate and real-time imaging to assess the arterial filling direction. At present, contrast-enhanced sonography is the only non-invasive imaging technique to show the pattern of arterial filling in these rapidly enhancing liver lesions without an unacceptable radiation dose. A transient peripheral unenhanced zone is another finding highly suggestive of FNH. We believe that this finding reflects a peripheral part of the lesion that is initially not enhanced because the enhancement begins from the center. A transient peripheral unenhanced zone is less commonly seen than centrifugal enhancement in FNH, but, once seen, reliably predicts that the lesion has centrifugal filling. The identification of this zone requires enhancement of the liver surrounding the lesion in order to be perceived. Therefore, in lesions that are in a liver that fills later than the lesion, the zone will not be appreciated.
A central scar in FNH represents fibrous connective tissue radiating from its center. The visualization of a central scar is one of the most important findings to make a confident diagnosis of FNH at pathology and on MRI [29]. In this study, however, identification of a central scar was not as reliable as the arterial phase filling direction for differentiation of FNH and adenoma on contrast-enhanced sonography. A central scar was seen as a stellate, linear, or plicated nonenhancing area, best visualized in the extended observation of the portal venous phase. It was frequently difficult to identify a central scar, especially in small FNHs. Further, unlike MRI, on which a central scar shows enhancement in the delayed phase of contrast-enhanced T1-weighted imaging, no delayed enhancement was seen in the central scar on contrast-enhanced sonography. This can be explained by the strictly intravascular contrast agent used for contrast-enhanced sonography, which is different from the MRI contrast agents that show interstitial leaks and accumulation in fibrotic tissue. Unlike a central scar, which is typically stellate, linear, or plicated in shape and is located in the center, central necrosis in adenoma is irregular in shape and often has an eccentric location. However, a small area of central necrosis in adenomas can be erroneously diagnosed as a central scar, as was seen in four of 19 (21%) and three of 19 (16%) adenomas as assessed by the two readers in this study.
Initial publications on contrast-enhanced sonography suggest negative enhancement in the portal venous phase (washout) is diagnostic of malignant liver tumors, whereas sustained enhancement of the lesion equal or greater than that of the normal liver during the extended observation of the portal venous phase to 5 minutes has been considered a hallmark of a benign diagnosis [30, 31]. In our study, the portal venous phase enhancement of FNH was in agreement with previous publications because most lesions were interpreted by both readers as showing sustained enhancement. However, a considerable number of hepatic adenomas (10/19 [53%] and 7/19 [37%]) showed negative enhancement of the lesion in the portal venous phase.
The role of percutaneous needle biopsy for the differentiation of FNH and adenoma is often debated. A confident diagnosis of FNH can be made with a core biopsy if the sample is obtained under imaging control and if the lesion contains benign-appearing hepatocytes and prominent arteries, lacks portal veins, and shows ductules at the interface between the hepatocytes and the fibrous regions [32, 33].
The ROC analysis in our study shows that contrast-enhanced sonography has high diagnostic performance in differentiating FNH from adenoma, although somewhat lower than that of MRI with the liver-specific contrast agent gadobenate dimeglumine [3]. This difference might be related to the strict diagnostic criteria we applied for FNH, which resulted in the exclusion of many typical and easily diagnosed cases of FNH from our study group, leading to underestimation of the overall diagnostic performance of contrast-enhanced sonography. Furthermore, because of the long time of patient accrual, we included patients who underwent scanning with prototype contrast-enhanced sonography scanners. Today, newer software developed specifically for contrast-enhanced sonography, in particular maximum-intensity-projection techniques, can better show these features.
Having acquired experience with the patient population described in this study, we now make positive diagnoses of FNH on the basis of the results of contrast-enhanced sonography without biopsy in many cases. If clinically appropriate, an asymptomatic patient with classic FNH might have no further imaging. However, any lesion with washout in the portal venous phase is always referred for biopsy, recognizing that malignant lesions and adenomas may both show this feature. If adenoma is suspected on clinical or imaging features, biopsy is also recommended.
Our study has some limitations. First, the blinded reading was performed in cases with a confirmed diagnosis of FNH or adenoma only. Therefore, tumors with frequent hypervascularity, such as hemangiomas, HCCs, or metastases, were not included. This selection bias improved accuracy because no other diagnoses were possible. In our experience, however, lesions such as hemangioma and HCC have distinct clinical or enhancement characteristics differentiating them from both FNH and adenoma. During contrast-enhanced sonography, hemangioma lacks linear vascularity and shows peripheral nodular enhancement and centripetal progression, regardless of how rapidly the lesion enhances. Therefore, contrast-enhanced sonography does not face the diagnostic problem that may be encountered on CT and MRI when only a single image in the arterial phase may show enhancement [34]. Further, the clinical presentations and laboratory findings of HCC are quite different from those of FNH and adenoma, and the requirement for differentiation of HCC from either FNH or adenoma is rare. Metastases should be considered a differential diagnosis when a lesion with washout in the portal venous phase is seen on contrast-enhanced sonography. However, most metastases show rapid and complete washout within 1 minute after injection of the contrast material, which is quite different from adenomas in our experience [35].
A second limitation is the lack of histologic confirmation of a large proportion of the FNH lesions. We applied strict diagnostic criteria in these cases, including typical findings of FNH on MRI [29] as well as interval stability for at least 1 year. These strict criteria, however, excluded many typical FNHs that were diagnosed only on contrast-enhanced sonography as well as patients without follow-up imaging. Our review of the literature on imaging features of FNH using all techniques suggests that other authors have encountered a substantial number of lesions confirmed only by imaging [3, 21, 24, 28] because there appears to be a similar reluctance to biopsy these asymptomatic and insignificant lesions if they can be diagnosed by noninvasive techniques.
Third, the blinded reviewers performed the contrast-enhanced sonography examination in nine of 62 subjects. However, because all demographic information was removed from the imaging files, and questions dealt exclusively with observations of the imaging features, it is difficult to believe that recollection of a certain case shown in a blinded reading format would occur. Finally, it is a limitation that the person performing the contrast-enhanced sonography had access to all clinical and imaging results. Because the data were acquired completely by a blinded review of the sonograms, this limitation is minor.
In conclusion, the evaluation of early arterial phase imaging on contrast-enhanced sonography contributes most to the differentiation of FNH and adenoma by showing the arterial phase filling direction and arterial morphology. In the appropriate clinical milieu, FNH is reliably predicted by arterial phase centrifugal filling and stellate vascularity with sustained enhancement in the portal venous phase, whereas adenoma is less reliably predicted by centripetal or mixed filling without stellate vascularity. Portal venous phase enhancement contributes less to the differentiation of FNH and adenoma. Washout, seen most often with adenoma, always raises the possibility of malignancy, and therefore necessitates biopsy.
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