Confluent focal nodular hyperplasia mimicking liver cancer: Value
of liver-specific contrast-enhanced MRI for diagnosis
Yu-Chi Chenga, Chih-Ming Chianga, Cheng-Chung Wub, Jyh-Wen Chaia,c,*
aDepartment of Radiology, Taichung Veterans General Hospital, Taichung, Taiwan, ROC
bSection of General Surgery, Taichung Veterans General Hospital, Taichung, Taiwan, ROC
cDivision of Radiology, College of Medicine, China Medical University, Taichung, Taiwan, ROC
Received November 8, 2010; accepted July 22, 2011
Focal nodular hyperplasia is the second most common benign hepatic tumor. Unlike adenoma as well as the malignant neoplasms, focal
nodular hyperplasia can often be managed successfully without surgery. Use of liver-specific contrast-enhanced magnetic resonance imaging
allows clinicians to confirm the diagnosis noninvasively in some patients, allowing select patients to avoid surgery. We report a case of a patient
who presented with the rare profile of multiple, confluent lesions that were diagnosed, using magnetic resonance imaging with gadolinium-
dimeglumine, as focal nodular hyperplasia. This complicated case was managed successfully and noninvasively based on algorithm found in
the recent literature that allows patients to avoid unnecessary surgery.
Copyright ? 2012 Elsevier Taiwan LLC and the Chinese Medical Association. All rights reserved.
Keywords: focal nodular hyperplasia; gadobenate dimeglumine; Gd-BOPTA; MRI
Focal nodular hyperplasia (FNH), typically found in young
to middle-aged asymptomatic women, is the second most
common benign liver tumor after hemangioma, with a cited
prevalence in adults of between 1%1and 8%.2Reported
prevalence rates may rise because an increasing number of
FNH lesions are being found incidentally due to improvements
in imaging technology.3
FNH presents with a single lesion in roughly 70% of
patients, and with two to four lesions in the vast majority of
the remaining patients.4We identified only five case reports
involving a patient with more than four FNH, and the reports
noted the rarity of such a presentation.4e8FNH is not asso-
ciated with significant malignancy potential and is uncom-
monly associated with rupture and hemorrhage. Therefore, it
usually can be managed conservatively.3,9This high likelihood
for conservative management emphasizes the need to non-
invasively diagnose FNH.
In this report, we describe our use of a published algorithm
for the identification of benign liver lesions10in a young
patient who presented with multiple, confluent liver lesions
first suspected to represent hepatocellular carcinoma. We
discuss the current literature on the use of liver-specific
contrast agents for magnetic resonance imaging (MRI) and
demonstrate the efficacy of recently described techniques for
the diagnosis of patients with complicated FNH in real-world
2. Case report
An 18-year-old woman was referred to our institution for
evaluation of liver lesions detected on an ultrasound exami-
nation. The ultrasound study was performed to evaluate the
patient’s symptoms of mild, intermittent epigastric pain of 6
months’ duration. The patient’s personal history was negative
for alcohol ingestion, oral contraceptive use, or infection with
* Corresponding author. Dr. Jyh-Wen Chai, Department of Radiology,
Taichung Veterans General Hospital, 160, Section 3, Taichung-Kang Road,
Taichung 407, Taiwan, ROC.
E-mail address: email@example.com (J.-W. Chai).
Available online at www.sciencedirect.com
Journal of the Chinese Medical Association 75 (2012) 355e358
1726-4901/$ - see front matter Copyright ? 2012 Elsevier Taiwan LLC and the Chinese Medical Association. All rights reserved.
hepatitis B or C. Laboratory evaluation revealed normal serum
levels of aminotransferases, gamma glutamyltranspeptidase,
alkaline phosphatase, bilirubin, and a-fetoprotein.
Unenhanced computed tomography (CT) showed iso-
attenuation of a mildly enlarged left lobe (Fig. 1A). Hepatic
arterial-phase (HAP) CT imaging demonstrated a large lesion
with a mosaic pattern of enhancement involving both lobes of
the liver (Fig. 1B). The tumor measured approximately
16 ? 12 ? 11 cm3; however, neither splenomegaly nor dila-
tation of the biliary tract was noted. On portal venous-phase
(PVP) imaging, there was less heterogeneous enhancement,
but some washout effect from the large tumor and mild
enhancement of a portion of the external capsule and internal
septa of the lesion (Fig. 1C). Hepatocellular carcinoma (HCC),
one of the most common hepatic malignancies in this high-
prevalence area, was suspected, and the patient initially was
prepared for surgery. Preoperative abdominal angiography
revealed a large, hypervascular hepatic tumor (Fig. 1D). After
further review of the patient’s history, clinical presentation,
and imaging studies, which collectively did not provide
a high-probability diagnosis, MRI was recommended.
Precontrast MRI showed a large hepatic tumor with an iso-
intense mosaic pattern on gradient-echo (GRE) T1-weighted
images (T1WI) and an iso-intense pattern on fast spin-echo
T2-weighted images (T2WI). These results are shown in
Fig. 2A and B. Portions of the lesion had slightly lower signal
intensity on the out-of-phase imaging compared with the in-
phase images, and a small nodular shadow within the tumor
appeared to have low signal on out-of-phase imaging and high
signal on in-phase GRE chemical shift images, suggestive of
focal fatty infiltration within the tumor. On dynamic MRI after
intravenous injection of the liver-specific agent gadobenate
dimeglumine [(Gd-BOPTA) Multihance; Bracco Imaging
SpA, Milan, Italy], the tumor demonstrated a hyperintense
mosaic pattern on HAP images (Fig. 2C), but became iso-
intense to surrounding liver parenchyma in the PVP (Fig. 2D)
and in the 6-minute early-delayed-phase images (Fig. 2E). The
internal reticular septa and external capsule appeared to have
a mildly low signal on T1WI images, a low- to isointense
signal on T2WI images, a hypointense signal in the arterial
phase, and delayed enhancement on later phases of dynamic
Subsequently, in the 1-hour and 3-hour delayed images, the
mosaic pattern of the large tumor appeared homogeneously
isointense or of slightly higher intensity compared to the
surrounding normal hepatic parenchyma (Fig. 2F). These
findings indicated the presence of normal functioning hepa-
tocytes and excessive hepatocellularaccumulationof
Fig. 1. Non-enhanced CT scan of the abdomen in an 18-year-old woman with mild, intermittent epigastric pain. (A) Isoattenuated or slightly hypoattenuated
hepatic parenchyma is noted throughout most of the left lobe and a portion of the right lobe of the liver; (B) the hepatic arterial-phase CT image reveals a large
mass with a mosaic pattern of enhancement and less-enhanced septa (arrows); (C) the large mass demonstrates homogeneous enhancement on the portal venous
phase images, with a slight washout effect (*) and capsular enhancement (arrowheads); and (D) abdominal angiography reveals a huge mass with dense tumor
blush (white arrows). CT ¼ computed tomography.
356 Y.-C. Cheng et al. / Journal of the Chinese Medical Association 75 (2012) 355e358
gadobenate within the mosaic lesions. The low-intensity
external capsule and internal septa were visualized in the
delayed images, suggesting fibrotic components.
Based on the characteristic morphological, hemokinetic
and functional information, a tentative diagnosis of focal
nodular hyperplasia with confluent multiple lesions was made.
Needle biopsy confirmed the diagnosis. No further surgical
intervention was performed. After four years of follow-up, the
patient is well, without symptoms, and a repeat MRI showed
no change in the hepatic lesion.
Unlike adenoma or hemangioma, FNH is not associated
with potential for malignancy or rupture.3,9As noted in
a recent paper on the identification of liver lesions (that
provided our algorithm for diagnostic imaging)10“.accurate
diagnosis of a liver lesion often precedes proper man-
agement.” FNH is an apt example of the clinical value of
noninvasive diagnosis because accurate diagnosis allows
patients to avoid unnecessary surgery.
The classic lesion of FNH is a small mass with septa
radiating from an obvious central scar. The lesion has clear
boundaries from surrounding normal parenchyma, but no true
capsule. The lesion does not have normal cord architecture11;
blood vessels are malformed, the mass as a whole is hyper-
vascular, and there is clear bile duct proliferation.1,12The lack
of connection between the malformed bile canalicular systems
leads to slowed biliary excretion.9
Nonclassic FNH also exists. The lesion may not show
abnormal nodular architecture or malformation of vessels, but
bile duct proliferation is always present.1Large lesions may
occur with either classic or nonclassic FNH, and both may
manifest with more than one lesion.1
Both CT and MRI have been used to diagnose FNH. A
study comparing imaging of benign and malignant focal
hepatic lesions with multidetector row helical CT and
gadobenate dimeglumine-enhanced MRI found that MRI had
better diagnostic accuracy and sensitivity for lesion identifi-
cation and characterization than CT.13
comparable with results from earlier studies, which showed
that MRI could consistently characterize over 90% of identi-
fied lesions.14,15Gd-BOPTA, the contrast agent used in most
of the studies identified and which was also used in our
patient, is particularly helpful for liver imaging because the
gadobenate ion is selectively taken up by hepatocytes and then
excreted into the bile. This distinguishes it from conventional
contrast agents, which are almost exclusively excreted through
Our findings with Gd-BOPTAeenhanced
dynamic MRI fit the descriptions found in the literature,1e3,9
and enabled us to determine how lesion anatomy and physi-
ology can result in the characteristic imaging findings.
In conclusion, we applied algorithm from the recent liter-
ature to noninvasively diagnose FNH that presented with
multiple confluent lesions in a young woman. The MRI find-
ings allowed avoidance of unnecessary surgery. In addition,
since MRI involves no radiation exposure, the patient can
continue to be repeatedly monitored without concern for
This finding is
Fig. 2. MRI of the liver tumor using Gd-BOPTA. (A) The large tumor exhibits an isointense mosaic pattern (white arrows) with irregular hypointense septa on the
precontrast gradient echo T1-weighted image; (B) fast-spin echo T2-weighted imaging with fat saturation shows a large lobulated tumor that is isointense to normal
hepatic parenchyma. Some parts of the tumor (*) are mildly low in intensity on out-of-phase imaging compared to the in-phase images, indicating mild fatty
infiltration; (C) on hepatic arterial-phase images the tumor shows intense mosaic enhancement pattern, and the irregular septa and capsules appear hypointense; (D)
on portal venous-phase imaging, the tumor is isointense to surrounding liver parenchyma, and most septa are hyperintense; however, some have low signal
intensity; (E) on the 6-minute early delayed-phase images, the irregular septa, capsule and eccentric scar appear hyperintense (black arrowhead), and the tumor is
homogeneously isointense; and (F) on the 3-hour delayed images, most of the tumor is hyperintense, and the fibrous septa, pseudocapsule and scar are hypointense
(black arrow). Gd-BOPTA ¼ gadobenate dimeglumine; MRI ¼ magnetic resonance imaging.
357Y.-C. Cheng et al. / Journal of the Chinese Medical Association 75 (2012) 355e358
complications associated with ionizing radiation. Given two
recent review articles on the use of MRI for liver lesions,17,18
it is clear that clinicians now have the capacity to make
accurate, noninvasive diagnoses with confidence for many
patients with FNH and other primary hepatic lesions.
1. Terkivatan T, van den Bos IC, Hussain SM, Wielopolski, de Man RA,
Ijzermans JNM. Focal nodular hyperplasia: lesion characteristics on state-
of-the-art MRI including dynamic gadolinium-enhanced and super-
paramagnetic iron-oxide-uptake sequences in a prospective study. J Magn
Reson Imaging 2006;24:864e72.
2. Marin D, Brancatelli G, Federle MP, Lagalla R, Catalano C, Passariello R,
et al. Focal nodular hyperplasia: typical and atypical MRI findings with
emphasis on the use of contrast media. Clin Radiol 2008;63:577e85.
3. Marin D, Iannaccone R, Laghi A, Catalano C, Murakami T, Hori M, et al.
Focal nodular hyperplasia: intraindividual comparison of dynamic
gadobenate dimeglumine and ferucarbotran-enhanced magnetic resonance
imaging. J Magn Reson Imaging 2007;25:775e82.
4. Colle I, Op de Beeck B, Hoorens A. Hautekeete. Multiple focal nodular
hyperplasia. J Gastroenterol 1998;33:904e8.
5. Kim J, Nikiforov YE, Moulton JS, Lowy AM. Multiple focal nodular
hyperplasia of the liver in a 21-year-old woman. J Gastrointest Surg
6. Mihai C, Mihai B, Crumpei F, Barr C, Ferariu D, Gergescu S, et al.
Multiple focal liver lesions e diagnosis challenges. Case report. Med
7. Fujino T, Nishizaka M, Yufu T, Sunagawa K. A case of multiple focal
nodular hyperplasia in the liver which developed after heart trans-
plantation. Intern Med 2011;50:43e6.
8. Kayhan A, Venu N, Lakadamyali H, Jensen D, Oto A. Multiple
progressive focal nodular hyperplasia lesions of liver in a patient with
hemosiderosis. World J Radiol 2010;2:405e9.
9. Grazioli L, Morana G, Kirchin MA, Schneider G. Accurate differentiation
of focal modular hyperplasia from hepatic adenoma at gadobenate
dimeglumine-enhanced MR imaging: prospective study. Radiology
10. Kim J, Ahmad SA, Lowy AM, Buell JF, Pennington LJ, Moulton JS, et al.
An algorithm for the accurate identification of benign liver lesions. Am J
11. Kew MC. Hepatic tumors and cysts. In: Feldman M, Friedman LS,
Brandt LJ, editors. Sleisenger and Fordtrans gastrointestinal and liver
disease. 8th ed. Philadelphia: Saunders; 2006. p. 2024.
12. Chen WH, Peng CM, Chou CM, Chen HC, Jan YJ. Focal nodular
hyperplasia of the liver in a 5-year-old girl. J Chin Med Assoc
13. Lee HY, Lee JM, Kim SH, Shin KS, Lee JY, Han JK, et al. Detection and
characterization of focal hepatic lesions: comparative study of MDCTand
14. Semelka RC, Marin DR, Balci NC. Focal liver lesions: comparison of
dual-phase CT and multisequence multiplanar MR imaging including
15. Grazioli L, Morana G, Federle MP, Brancatelli G, Testoni M, Kirchin MA,
et al. Focal nodular hyperplasia: morphologic and functional information
from MR imagingwith gadobenate
16. Kirchin MA, Pirovano GP, Spinazzi A. Gadobenate dimeglumine (Gd-
BOPTA): an overview. Invest Radiol 1998;33:798e809.
17. vandenBos I, HussainSM,
Ijzermans JN, Preda A, et al. Magnetic resonance imaging of liver
lesions: exceptions and atypical lesions. Curr Prob Diagn Radiol
18. van den Bos I, Hussain SM, de Man RA, Zondervan PE, Uzermans JNM,
Krestin GP. Primary hepatocellular lesions: imaging findings on state-of-
the-art magnetic resonance imaging, with pathologic correlation. Curr
Prob Diagn Radiol 2008;37:104e14.
J MagnReson Imaging
358Y.-C. Cheng et al. / Journal of the Chinese Medical Association 75 (2012) 355e358