AJR 2002; 179:759-762
© American Roentgen Ray Society
Focal Nodular Hyperplasia Inducing Hepatic Vein Obstruction
Anne-Sophie Rangheard1,
Valérie Vilgrain1,
Pascale Audet1,
Dermot O'Toole2,
Marie-Pierre Vullierme1,
Dominique Valla3,
Jacques Belghiti4 and
Yves Menu1
1 Department of Radiology, Hospital Beaujon, 100 ave. du Général
Leclerc, 92110 Clichy, France.
2 Department of Gastro-Enterology, Hospital Beaujon, 92110 Clichy, France.
3 Department of Hepatology, Hospital Beaujon, 92110 Clichy, France.
4 Department of Visceral Surgery, Hospital Beaujon, 92110 Clichy, France.
Received June 11, 2001;
accepted after revision February 26, 2002.
Address correspondence to A.-S. Rangheard.
Abstract
OBJECTIVE. The records of 10 patients with focal nodular hyperplasia
inducing intrahepatic vein obstruction were reviewed. The purpose of this
study was to describe and emphasize the imaging features of these
findings.
CONCLUSION. Focal nodular hyperplasia may be responsible for hepatic
vein obstruction with hepatic vein collaterals. The relatively large size and
central location of the lesions seem to play important roles in the
obstruction of the hepatic veins.
Introduction
Focal nodular hyperplasia is the second most common benign liver lesion
after hemangioma and accounts for 8% of all primary hepatic tumors
[1,
2]. It typically affects women
of childbearing age. The exact pathogenesis of focal nodular hyperplasia is
not known, but it seems to be the result of a hyperplastic, rather than a
neoplastic, process. Vascular malformation or injury has been suggested as the
triggering mechanism of hepatocellular hyperplasia
[1,
3,
4]. Focal nodular hyperplasia
is classically described as a nodular, hypervascular homogenous lesion with a
central stellate scar containing malformed vascular structures with radiating
fibrous septa [1]. The only
radiologic finding may be a subtle mass effect with compression of adjacent
structures, which has been previously described in large focal nodular
hyperplasia [2]. However,
vascular compression, especially hepatic vein obstruction, remains rare; to
our knowledge, only one case has been reported in the literature
[5]. We describe the clinical
findings of 10 patients with focal nodular hyperplasia resulting in hepatic
vein obstruction and compare all findings with those of a series of 64
patients with focal nodular hyperplasia seen during the same period.
Materials and Methods
Patients
We retrospectively reviewed the records of 74 patients with focal nodular
hyperplasia from 1995 to 2000. All patients were women between 18 and 70 years
old (mean age, 38 years). We classified the records into a control group
(n = 64) and a group having focal nodular hyperplasia with hepatic
vein obstruction (compressive group) (n = 10). All patients had
undergone sonography, CT, or contrast-enhanced MR imaging of the liver, or all
three examinations. Helical CT was performed in all patients with a triphasic
dynamic exploration during the arterial, portal, and delayed phases after
injection of iodine contrast medium. All MR imaging included fast T2-weighted
sequences and T1-weighted dynamic gradient-echo sequences after IV injection
of gadopentetate dimeglumine.
Image Interpretation
Two radiologists reviewed all images from the two groups in consensus.
Diagnosis of focal nodular hyperplasia was made in the presence of a typical
appearance on CT or MR imaging and by histologic sampling in atypical
cases.
A lesion was considered to have typical appearance if it was homogeneous,
was unencapsulated, and showed regular or lobulated margins on sonography, CT,
or MR imaging. On CT, a typical lesion was slightly hypoattenuating or
isoattenuating and enhanced on the arterial phase after injection of contrast
medium, except for a central hypoattenuating scar that later enhanced
[6,
7]. On MR imaging, a typical
lesion was isointense or nearly isointense on T1- and T2-weighted imaging and
showed a central scar that enhanced on delayed gadolinium-enhanced T1-weighted
sequences [2].
The number, size, and location of the lesions were assessed. Focal nodular
hyperplasia was classified as central (near the hepatic veins' confluence or
the inferior vena cava), peripheral (far from these venous structures), or
central and peripheral.
Vascular structures, including hepatic and portal veins, were analyzed at
imaging. Venous compression was diagnosed if a stenosis without complete flow
interruption was found at the level of the focal nodular hyperplasia. Venous
occlusion was diagnosed if no venous flow could be seen at the level of the
lesion. Venous compression and venous occlusion were classified as distal if
involving the distal third of the hepatic veins and proximal if involving the
two thirds proximal portion of the hepatic veins. Venous collateral pathways
were defined by abnormal vessels between hepatic veins. These collaterals were
classified as intrahepatic if they were surrounded by liver parenchyma or
subcapsular when they were beneath the liver capsule. We searched for
abnormalities of the liver showing transient hepatic attenuation
differences.
Results
In the control group (n = 64), 42 patients had solitary lesions
and 22 had multiple lesions. Forty-three patients in the control group
underwent histologic analysis of the lesions.
In the other patients, diagnosis was made on the basis of a typical
appearance at imaging. For patients with multiple focal nodular hyperplasia,
only the largest lesions (diameter, 20-80 mm; mean, 44 mm) were analyzed.
Forty-four lesions (69%) measured 20-50 mm, and 20 lesions (31%) were 55-80
mm. Seven lesions (11%) were central, 55 (86%) were peripheral, and two (3%)
were peripheral and central.
In the compressive group (patients having focal nodular hyperplasia
[n = 10]), all focal nodular hyperplasias were typical at imaging
except in two patients with calcifications. Those patients did not undergo
biopsy despite the relative rarity of this finding (occurrence, 1.4%
[8]); all other imaging
criteria were present. Follow-up of the lesions in this group was 12-36 months
(mean, 23 months). No change in lesion size was noted.
Two patients had multiple lesions. Lesion size ranged from 35 to 120 mm
with a mean diameter of 76 mm. Five lesions were classified as having central
location in the liver, one was peripheral, and four were central and
peripheral. All patients had compression of one or more hepatic veins, and all
were revealed to have collateral pathways on sonography, CT, or MR imaging.
Main trunk obstruction of the right hepatic vein was found in six patients
with secondary collateral pathways between right and patent middle hepatic
veins; the pathways were intrahepatic in five patients and both intrahepatic
and subcapsular in one patient (Fig.
1A,1B).
Proximal compression of two branches of the right hepatic vein was encountered
in one patient with a resulting subcapsular pathway between the right and
middle hepatic veins. One patient had occlusion of the middle hepatic vein
with a collateral pathway between the right and middle hepatic veins. Two
patients had occlusion of the left and middle hepatic veins with subcapsular
and intrahepatic collateral pathways between the left, middle, and right
hepatic veins (Figs.
2A,2B,2C,2D
and
3A,3B,3C,3D,3E,3F).
Partial inferior venous cava compression was encountered in six patients and
portal vein compression in three patients (one case involving the left portal
branch and two cases involving the right). In these three patients with portal
vein compression, a transient hepatic attenuation difference was present on
enhanced CT and MR imaging.
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Fig. 1B. —39-year-old woman with 12-cm focal nodular hyperplasia in
right liver (segments VI and VII). Coronal time-of-flight MR angiogram shows
subcapsular collateral pathway (arrows) between middle and right
hepatic veins.
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Fig. 2A. —40-year-old woman with 10-cm focal nodular hyperplasia in
liver segment I. Arterial phase contrast-enhanced CT scan shows strongly
enhancing mass in segment I with central scar (arrowhead).
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Fig. 2B. —40-year-old woman with 10-cm focal nodular hyperplasia in
liver segment I. Portal phase contrast-enhanced CT scan at same level as
A shows obstruction of middle hepatic vein, associated with
intrahepatic (arrow) and subcapsular (arrowhead) venous
pathway between middle and right hepatic veins.
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Fig. 2C. —40-year-old woman with 10-cm focal nodular hyperplasia in
liver segment I. T2-weighted MR image shows isointense mass with central
hyperintensity corresponding to central scar (arrowhead). Inferior
vena cava is compressed by mass (arrow).
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Fig. 2D. —40-year-old woman with 10-cm focal nodular hyperplasia in
liver segment I. Portal phase gadolinium-enhanced T1-weighted MR image shows
enhancement of venous collateral pathway (arrowheads).
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Fig. 3A. —42-year-old woman with 4-cm focal nodular hyperplasia located
centrally in liver. Sonogram reveals isoechoic mass (arrowhead) in
segments II, IV, and VIII that obstructs middle hepatic vein
(arrow).
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Fig. 3B. —42-year-old woman with 4-cm focal nodular hyperplasia located
centrally in liver. Sonogram obtained at level below A shows
intrahepatic venous collateral pathway (single solid arrow) between
middle (double solid arrows) and right (open arrow) hepatic
veins.
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Fig. 3C. —42-year-old woman with 4-cm focal nodular hyperplasia located
centrally in liver. Sonogram obtained in more cranial section than B
clearly shows distal segment of intrahepatic venous collateral pathway
(solid arrow). Pathway drains into right hepatic vein (open
arrow).
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Fig. 3E. —42-year-old woman with 4-cm focal nodular hyperplasia located
centrally in liver. T2-weighted MR image shows slightly hyperintense lesion in
central liver that obstructs middle hepatic vein (curved arrow). Note
calcified central scar (straight arrow).
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Fig. 3F. —42-year-old woman with 4-cm focal nodular hyperplasia located
centrally in liver. T2-weighted MR image caudal to D shows intrahepatic
collateral pathway between middle and right hepatic veins
(arrow).
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Of the 10 compressive group patients in our series, seven were examined
with Doppler sonography. In all seven patients, Doppler sonography confirmed
the reverse of flow in obstructed hepatic veins to other hepatic veins through
venous anastomoses. No patients were found to have hepatic vein
thrombosis.
Biologically, in the compressive group, 
-glutamyltransferase levels
varied from 70 to 240 U/L, with a mean level of 145 U/L. Alkaline phosphatase
levels were normal except in two patients, one with a level of 235 U/L and one
with a level of 293 U/L. In the control group, alkaline phosphatase levels and
-glutamyltransferase levels were normal.
Discussion
Among the atypical findings that may be observed in focal nodular
hyperplasia lesions, association with hepatic vein obstruction seems rare and,
to our knowledge, has been reported in only one case report
[5]. In our study, comparison
of the compressive and control groups revealed several interesting
differences. First, the mean size of the focal nodular hyperplasia leading to
obstruction of the hepatic veins was larger in the compressive group than in
the control group. Sixty percent of lesions in the compressive group were
larger than 50 mm, but only 31% of lesions in the control group were that
large. Second, 90% of the lesions were located centrally or centrally and
peripherally in the compressive group compared with only 14% in the control
group. Third, liver blood tests were not identical in the two groups, and we
saw a tendency toward a more abnormal biochemical profile in patients in the
compressive group.
Although the mechanism of hepatic vein obstruction is not completely
understood, we may hypothesize that large central lesions may compress venous
structures [3,
9]. In all our patients, direct
compression of at least one hepatic vein was associated with collateral
pathways that drain the blood from one hepatic vein to the other. The slow
growth of focal nodular hyperplasia may have led to progressive hepatic vein
compression that favored development of collaterals.
Two patients in the compressive group had calcifications in the focal
nodular hyperplasia. Although this finding has been reported previously, it is
rare, estimated to occur in approximately 1.4% of patients with focal nodular
hyperplasia [8]. Calcifications
in focal nodular hyperplasia lesions may be associated with a predominant
myxomatous stroma, which could lead to a more pronounced compression.
Benign conditions, such as large aortic aneurysm and large infected liver
cyst in autosomal dominant disease, may also compress hepatic veins in a
manner similar to focal nodular hyperplasia
[10]. Furthermore, compression
of hepatic veins to hydatid cysts with hepatic vein collaterals has been
described [10]. Our
observations are in distinction from the observation of Kojima
[11], who described
vein-to-vein anastomoses in the periphery of a giant cavernous hemangioma of
the liver without vein obstruction. In our series, hepatic vein obstruction
was present in all patients, and Doppler sonography, when performed, confirmed
the blood derivation through venous collaterals.
Finally, none of our patients had imaging findings suggestive of
endoluminal invasion. Involvement of hepatic veins may be seen in other liver
tumors. The most common is hepatocellular carcinoma. Although vascular tropism
of hepatocellular carcinoma is well known, invasion of hepatic veins is less
frequent than invasion of portal veins
[10] and appears on imaging as
a venous enlargement containing a tumor. To our knowledge, hepatocellular
carcinoma causing compression of main hepatic veins and development of hepatic
vein collaterals has never been reported. Similarly, other malignant tumors of
the liver, such as metastatic lesions, lead to hepatic vein invasion
[10]. Hepatic vein thrombosis
has also been described in inflammatory or infectious liver processes.
In conclusion, large and centrally located focal nodular hyperplasia may be
responsible for a hepatic vein obstruction with hepatic vein collaterals. Such
vascular consequences are mainly observed in benign and chronic conditions.
The association of these vascular abnormalities with a hypervascular tumor
should raise the possibility of a focal nodular hyperplasia.
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Abstract
Introduction
