DOI:10.2214/AJR.05.1455
AJR 2007; 189:W247-W250
© American Roentgen Ray Society
Atypical Focal Nodular Hyperplasia with Cluster-Like Internal Cysts Due to Fibrinoid Necrosis
Raimund Kottke1,
Marius Horger1,
Heiko Schimmel2 and
Manfred Wehrmann2
1 Department of Diagnostic Radiology, Eberhard-Karls-University,
Hoppe-Seyler-Strasse 3, 72076 Tübingen, Germany.
2 Institute of Pathology, Eberhard-Karls-University, Tübingen,
Germany.
Received August 19, 2005;
accepted after revision October 10, 2005.
Address correspondence to R. Kottke
(raimundkottke{at}hotmail.com).
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Keywords: abdominal imaging • CT • focal nodular hyperplasia • liver • MRI
Introduction
Focal nodular hyperplasia (FNH) is a benign condition of the liver
occurring predominantly in young and middle-aged women. It is the second most
common benign hepatic tumor, after hemangioma, with a prevalence of
approximately 0.9% [1]. Because
most cases are asymptomatic, FNH is often an incidental finding on imaging.
The pathogenesis is unclear, although a preexisting arterial malformation or
vascular injury with subsequent hyperplastic response and proliferation of
vessels and bile ducts has been suggested
[2]. Differentiation from
hepatic adenoma, hepatocellular carcinoma, and hypervascularized metastasis is
essential because asymptomatic FNH does not necessitate biopsy or surgical
intervention [3].
Case Report
A 47-year-old man with newly diagnosed Hodgkin's lymphoma underwent CT for
routine staging. The scans showed a solid-cystic tumor 13 cm in diameter and
involving almost the entire right lobe of the liver. The rest of the liver
parenchyma had decreased attenuation owing to hepatic steatosis and was
otherwise unremarkable. No other focal lesions were detected.
The tumor consisted of solid parts with multiple hypodense cyst-like
formations. On unenhanced CT, the solid tissue was slightly hyperattenuating
compared with fatty liver parenchyma (50 vs 30 H)
(Fig. 1A). The tumor had broad
contact with the liver capsule. After IV administration of contrast material,
the solid parts exhibited homogeneous intense contrast enhancement in the
arterial and portal venous phases (100 H)
(Fig. 1B). In the equilibrium
phase, tumor hyperdensity (80 H) persisted. The cystic parts showed neither
septation nor contrast enhancement. There was no tumor capsule. Solitary small
spots of calcification were found in both the solid and the cystic parts of
the tumor (Figs. 1A and
1B).
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Fig. 1A —47-year-old man with large focal nodular hyperplasia in right
lobe of liver. Unenhanced transverse CT scan shows large mass with
heterogeneous density. Ill-defined hyperdense outer ring (50 H) and
inhomogeneous center with areas of lower attenuation (25 H) are evident, as is
small solitary calcification within mass. Liver parenchyma had decreased
attenuation (30 H) owing to steatosis.
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Fig. 1B —47-year-old man with large focal nodular hyperplasia in right
lobe of liver. Contrast-enhanced transverse CT scan in portal venous phase
shows large tumor with solid and cystic elements. Solid parts exhibit strong
and homogeneous contrast enhancement (100 H), whereas central cystic parts are
not enhanced. Cystic parts are better defined than in A.
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For further evaluation, MRI of the liver was performed on a 1.5-T unit
(Gyroscan Intera, Philips Medical Systems) with a body coil. MR images
revealed a lobulated tumor located mainly in liver segments VI and VII with a
mass effect rather than invasive growth. The mass presented slightly low
signal intensity compared with liver parenchyma on T1-weighted images (not
shown) and moderately high signal intensity on T2-weighted images. The cystic
parts of the tumor exhibited, correspondingly, different signal intensity from
the solid parts with particularly high signal intensity on T2-weighted images
(Fig. 1C). After IV
administration of contrast material (gadopentetate dimeglumine, Magnevist,
Schering [now Bayer Schering Pharma AG]), the tumor exhibited homogeneous
early enhancement throughout the solid parts with good demarcation from normal
liver parenchyma (Fig. 1D). The
cystlike components did not become enhanced. Pathologic vessels with a
corkscrew configuration originating from the right hepatic artery were
visualized. Venous draining vessels were seen along the liver capsule next to
the mass.
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Fig. 1C —47-year-old man with large focal nodular hyperplasia in right
lobe of liver. Transverse fat-saturated T2-weighted fast spin-echo MR image
(TR/TE, 1,600/70) shows large heterogeneous hepatic mass with markedly high
signal intensity corresponding to cystic parts and slightly high signal
intensity of surrounding solid focal nodular hyperplasia tissue.
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Fig. 1D —47-year-old man with large focal nodular hyperplasia in right
lobe of liver. Arterial phase transverse gadopentetate
dimeglumine–enhanced fat-saturated T1-weighted gradient-recalled echo MR
image shows homogeneously hypervascularized solid tumor parts with arterial
feeding vessel originating from hepatic artery (9.28/4.66; body coil).
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The diagnosis was unclear after MRI. Because of the tumor size and
heterogeneity, malignant hepatic tumor could not be excluded. The differential
diagnosis included hydatid cyst and biliary tumors, including biliary
cystadenoma and cystadenocarcinoma. The laboratory values were unremarkable.
Therapy for Hodgkin's lymphoma was planned. Open biopsy was performed, and
because the intraoperative findings were inconclusive, complete surgical
resection was performed.
Histopathologic examination showed that the tumor consisted of moderately
thickened (two or three cells thick) hepatic plates with features
characteristic of FNH: malformed-appearing vessels, cholangiolar
proliferation, and abnormal nodular architecture lacking normal portal tracks
(Figs. 1E and
1F). Multiple large areas of
fibrinoid necrosis corresponding to the cystic lesions seen on imaging were
the most striking atypical finding (Figs.
1G and
1H). In contrast to the
findings of classic FNH, there was neither a central scar nor prominent
radiating fibrous septa. Histopathologic examination yielded the diagnosis of
FNH of the mixed hyperplastic and adenomatous type with unusual pseudocystic
degenerative changes. No signs of malignancy were found.
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Fig. 1E —47-year-old man with large focal nodular hyperplasia in right
lobe of liver. Pathologic image shows parenchyma of focal nodular hyperplasia
separated from normal liver tissue by subtle fibrous septa (arrow).
Irregular sinusoidal endothelial lines have positive immunoreaction for CD34,
indicating strong endothelialization of sinus. T = tumor, L = normal liver. (H
and E, x200)
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Fig. 1F —47-year-old man with large focal nodular hyperplasia in right
lobe of liver. Pathologic image shows parenchyma of focal nodular hyperplasia
separated from normal liver tissue by subtle fibrous septa (long
arrow) and hepatocellular proliferation consisting of thickened
hepatic plates (short arrow) two or three cells thick. T =
tumor, L = normal liver. (H and E, x200)
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Fig. 1G —47-year-old man with large focal nodular hyperplasia in right
lobe of liver. Photomicrograph shows subtle neoductular cholangiolar
proliferation. Thick-walled artery (A) of medium caliber is associated with
small fibrous septa. (Cytokeratin 7 immunostain, x200)
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Discussion
FNH has been classified according to pathologic findings into classic FNH,
which accounts for approximately 80% of cases, and nonclassic FNH
[1]. Nonclassic FNH can be
subdivided into telangiectatic FNH, FNH with cytologic atypia, and mixed
hyperplastic and adenomatous FNH, the last being the least common subtype,
accounting for only approximately 2% of cases of FNH.
Classic FNH is characterized by abnormal nodular architecture, malformed
vessels, and cholangiolar proliferation. In most cases, it presents as a
circumscribed solitary lesion with a diameter less than 5 cm. Multiple lesions
occur in 20–25% of patients with FNH. On imaging, a typical feature of
FNH is a central stellate scar with radiating fibrous septa containing
thick-walled vessels delivering an excellent blood supply. On sonography, FNH
is often not well visualized, being isoechoic in approximately 50% of cases.
With power Doppler technique or use of sonographic contrast material,
additional information can be gained.
On unenhanced CT, FNH is either hypoattenuating or isoattenuating in
relation to liver parenchyma. On unenhanced MR images, the most common
appearance of FNH is isointensity or hypointensity on T1-weighted images and
isointensity or slight hyperintensity on T2-weighted images. The lesion often
has a lobulated appearance with good demarcation from the surrounding liver
parenchyma but does not have a capsule. FNH typically becomes enhanced with an
intense uniform blush on images acquired immediately after contrast
administration and fades rapidly to near isodensity or isointensity
approximately 1 minute after contrast administration. When found, the central
scar is of low signal intensity on images obtained immediately after contrast
administration and gradually becomes enhanced to hyperintensity, reflecting
diffusion of contrast material from the vascular to the interstitial
compartment and allowing discrimination from tumor necrosis
[4]. In typical FNH, hepatic
adenoma is the first differential diagnosis because of the presence of similar
CT and MRI findings except for the central scar. There have been only few
reports about the imaging appearance of nonclassic FNH
[5].
Lack of a central scar is the most common atypical imaging feature of FNH
[3,
6]. Other known atypical
features are lesion heterogeneity, atypical contrast enhancement patterns
(persistent enhancement in the portal venous phase, lack of enhancement of the
central scar, pseudocapsular enhancement on delayed imaging), and high signal
intensity on T1-weighted MR images
[3,
5,
7,
8]. Internal necrosis and
hemorrhagic foci are rare because growth is proportional to blood supply from
the central scar [4,
9]. Calcification has been
described as an uncommon (1% of cases) feature of FNH and can lead to
confusion with fibrolamellar hepatocellular carcinoma
[6,
10].
We present the case of a man with a large inhomogeneous and
hypervascularized liver tumor. The lesion contained multiple cystic elements
up to 2.5 cm in diameter with a cluster-like arrangement. CT revealed solitary
spots of calcification. Arterial hypervascularization, calcification, and
inhomogeneity due to hemorrhage or necrosis are found in hepatocellular
adenoma; however, male sex, early contrast enhancement, the presence of
feeding vessels, and lack of a capsule made that diagnosis unlikely.
Conventional hepatocellular carcinoma usually occurs in a setting of
chronic liver disease with elevated levels of tumor markers and has a contrast
enhancement type different from that of FNH. Tumor size, intense early
contrast enhancement, and the presence of calcifications are compatible with
fibrolamellar hepatocellular carcinoma, a rare subtype of hepatocellular
carcinoma that has slow growth and a better prognosis than hepatocellular
carcinoma. Fibrolamellar hepatocellular carcinoma, however, typically occurs
in young adults, has a capsule, and exhibits heterogeneous enhancement. It has
broad areas of fibrosis that can mimic a stellate scar, which presents
hypointensity on T2-weighted MR images. In our case, there were no clinical
symptoms to raise suspicion of underlying malignant disease.
Liver lesion configuration and lack of evidence of an extrahepatic primary
tumor made the presence of a secondary malignant neoplasm unlikely in this
case. Hydatid disease caused by infection with Echinococcus
multilocularis can present as multiple small (1–10 mm) ill-defined
cysts, necrosis, and small calcifications in the right liver lobe. In our
case, distribution of solid and cystic parts, intense contrast enhancement of
solid parts, and the size of the cysts did not support this diagnosis.
Cholangitis with abscess formation was excluded because of lack of clinical
and laboratory signs of infection. Biliary cystadenoma and cystadenocarcinoma
can appear as large multilocular cystic hepatic tumors, but biliary
cystadenoma has a thick fibrous capsule and internal septa and, like FNH,
predominantly occurs in middle-aged women.
In this case, the contrast dynamics of the solid tumor parts were
compatible with FNH; however, male sex and the presence of calcifications and,
in particular, large cystic elements made FNH seem extremely unlikely. The
histopathologic diagnosis after surgical resection was surprising. The
multifocal areas of necrosis on CT and MRI in this case of hepatic FNH were
unique and, to our knowledge, have not been previously described. In this
case, large FNH of the hyperplastic and adenomatous subtype with multiple
pseudocysts and solitary calcifications made diagnosis difficult. Because
asymptomatic FNH does not necessitate treatment, it may be useful to be aware
that large lesions of FNH, in addition to having known typical and less common
imaging features, can also present as multiple pseudocystic areas
corresponding to necrosis.
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Introduction
Case Report
