DOI:10.2214/AJR.04.1096
AJR 2005; 185:1024-1032
© American Roentgen Ray Society
Hepatocellular Carcinoma in the Cirrhotic Liver with Helical CT and MRI: Imaging Spectrum and Pitfalls of Cirrhosis-Related Nodules
Yong Yeon Jeong1,
Nam Yeol Yim1 and
Heoung Keun Kang1
1 Department of Diagnostic Radiology, Chonnam National University Medical
School, 8 Hack-Dong, Dong-Ku, Gwang-Ju 501-757, South Korea.
Received July 11, 2004;
accepted after revision November 23, 2004.
Address correspondence to Y. Y. Jeong.
Abstract
OBJECTIVE. This article reviews the imaging spectrum of
cirrhosis-related nodules on CT and MRI and differentiates between
hepatocellular carcinoma (HCC) and common focal lesions that can simulate HCC
in the cirrhotic liver.
CONCLUSION. Knowledge of cirrhotic nodules and focal lesions and how
they mimic HCC will improve the diagnosis and characterization of focal
lesions in cirrhotic liver on CT and MRI.
Introduction
Hepatocellular carcinoma (HCC) is one of the most common internal
malignancies worldwide. HCC usually develops in a cirrhotic liver and is the
result of a multistep process. A regenerative nodule (RN) in liver cirrhosis
might be the first step in hepatocarcinogenesis, subsequently developing into
HCC though a low-grade dysplastic nodule (DN), a high-grade DN, and then early
HCC in a multistep fashion [1].
Contrast-enhanced helical CT and MRI have been identified as accurate,
noninvasive imaging techniques in the detection of HCC in a cirrhotic liver.
This study will review the imaging spectrum of cirrhosis-related nodules on CT
and MRI and differentiate between HCC and common focal lesions that can
simulate HCC in the cirrhotic liver.
Hepatocarcinogenesis in Liver Cirrhosis and Pathology
Hepatocarcinogenesis in liver cirrhosis is a multistep anaplastic process
that progresses from RN via DN to HCC (Fig.
1). A stepwise carcinogenesis for HCC has been proposed based on
gradually increasing size and cellular density. At some point during the
process of hepatocarcinogenesis, the formation of new tumor vessels
(neoangiogenesis and capillarization) leads to a gradual change in blood
supply. Although complex, the blood supply to the various nodules in the
cirrhotic liver has shown a sequential decrease in the portal venous blood
supply and an increase in the hepatic arterial blood supply as the condition
progresses from DN to overt HCC
[2]
(Fig. 2). Although
neovascularity within HCC can be used for early detection and characterization
of these lesions on imaging, the overlap in the blood supply patterns of the
various types of cirrhotic nodules makes definitive diagnosis challenging.
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Fig. 1 —Drawing shows stepwise development of hepatocellular
carcinoma from regenerative nodule in cirrhotic liver using new terminology
for nodular lesions. Brown cells indicate malignant transformation. There is
gradually increasing size from regenerative nodule to hepatocellular
carcinoma. (Adapted with permission from
[1])
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Fig. 2 —Drawing shows intranodular hemodynamic change during
hepatocarcinogenesis in cirrhotic liver. Light red and blue areas indicate
variation of blood supply in cirrhotic nodules. As grade of malignancy
increases, hepatic arterial flow to nodular lesions tends to increase, and
portal venous supply tends to decrease. (Adapted with permission from
[2])
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Imaging Findings of Cirrhotic Nodules
Regenerative Nodules
RNs invariably have a portal venous blood supply with minimal contribution
from the hepatic artery [2]. At
dynamic contrast-enhanced CT, RNs are difficult to visualize because they are
isoattenuating on the arterial phase and portal venous phase (Figs.
3A,
3B,
3C,
3D, and
3E). RNs are usually isointense
on both T1- and T2-weighted images and have no enhancement on hepatic arterial
phase (HAP) images. RNs with thick septa are visualized as round nodules
surrounded by enhancing fibrous septa on delayed-phase MRI (Figs.
3A,
3B,
3C,
3D, and
3E). Siderotic RNs appear on
unenhanced CT as predominantly high-attenuation nodules throughout the liver.
Siderotic RNs have characteristic imaging features including hypointensity on
both T1- and T2-weighted gradient-echo images
[3] (Figs.
4A and
4B).
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Fig. 3A —Regenerative nodules in cirrhotic liver in 47-year-old woman.
Arterial phase CT shows nodular hepatic surface and paraumbilical varix
(arrow). There are no enhancing lesions within liver.
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Fig. 3E —Regenerative nodules in cirrhotic liver in 47-year-old woman.
Delayed-phase T1-weighted gradient-echo MR image shows enhancement of fibrous
septa of multiple, small regenerative nodules within hepatic parenchyma.
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Dysplastic Nodules
The blood supply to DNs is usually from the portal venous system, but a
minority may also be fed by hepatic arteries. At dynamic contrast-enhanced CT,
DNs are difficult to visualize because they are similar to the surrounding
parenchyma in the arterial and portal phase images. DNs are generally
hyperintense on T1-weighted images and isointense or hypointense on
T2-weighted images (Figs. 5A,
5B, and
5C). Although the signal
intensities of DNs are protean and overlap considerably with small HCCs, DNs
are almost never hyperintense on T2-weighted images
[3]. Therefore, the
contrast-enhancement pattern in DNs on dynamic MRI would be similar to those
on dynamic CT.
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Fig. 5A —Dysplastic nodule in 60-year-old man with cirrhosis.
T1-weighted gradient-echo MR image shows small hyperintense nodule
(arrow) in inferior segment of right hepatic lobe in comparison with
adjacent liver parenchyma.
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Fig. 5B —Dysplastic nodule in 60-year-old man with cirrhosis.
T2-weighted fat-saturated fast spin-echo MR image shows lesion
(arrow) has lower signal intensity than surrounding liver
parenchyma.
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DNs with Foci of HCC
The common pattern of DNs with foci of HCC is an isoattenuating nodule on
dynamic contrast-enhanced CT. The unique MRI appearance of DNs with foci of
HCC is a nodule within a nodule, consisting of a hyperintense focus within a
hypointense nodule on T2-weighted images
(Fig. 6). The central nodule
of high signal intensity may also show enhancement during the HAP and
represents the focus of HCC
[4].
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Fig. 6 —Dysplastic nodule with subfocus of hepatocellular carcinoma
in 58-year-old man. T1-weighted in-phase gradient-echo MR image shows
hyperintense areas (thin arrow) in background hypointense nodules
(thick arrows) suggestive of nodule-within-nodule appearance.
Microscopic examination of surgical specimen revealed dysplastic nodule with
subfocus of hepatocellular carcinoma.
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Hepatocellular Carcinoma
Most HCCs develop increased arterial flow through the tumor vessel; they
show intense enhancement during the arterial phase of dynamic CT and MRI
(Figs. 7A,
7B,
8A, and
8B). However, a small minority
appear hypovascular. The imaging characteristics of HCC vary greatly with the
size of the lesion.
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Fig. 8A —Hypervascular hepatocellular carcinoma on dynamic
contrast-enhanced MRI in 62-year-old man. Arterial phase T1-weighted
gradient-echo MR image shows heterogeneous enhancing mass (arrows) in
medial segment of left hepatic liver.
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Fig. 8B —Hypervascular hepatocellular carcinoma on dynamic
contrast-enhanced MRI in 62-year-old man. Delayed-phase T1-weighted
gradient-echo MR image reveals hypointensity of mass with capsular
enhancement. Hepatocellular carcinoma was found in surgical specimen.
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Small HCCs of 2 cm or less usually show enhancement in the HAP images, with
rapid washout in the portal venous phase (Figs.
9A and
9B). Small HCCs can exhibit
variable signal intensity on T1-weighted images, but almost all are
hyperintense on T2-weighted images
[3]. Some HCCs have
hyperintensity on the T1-weighted images, probably because of the presence of
fat (Figs. 10A,
10B, and
10C), glycoproteins, or copper
[5].
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Fig. 9B —Small hepatocellular carcinoma on dynamic contrast-enhanced
CT in 49-year-old man. Portal venous phase CT scan shows lesion has capsular
enhancement (arrow). Patient underwent surgical resection.
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Fig. 10A —Well-differentiated hepatocellular carcinoma with fat in
61-year-old man. T1-weighted in-phase gradient-echo MR image (TR/TE = 120/4.2
msec) shows hyperintense mass (arrows) with hypointense capsule in
lateral segment of liver.
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Fig. 10B —Well-differentiated hepatocellular carcinoma with fat in
61-year-old man. T1-weighted opposed-phase gradient-echo MR image (TR/TE =
120/2.1 msec) shows reduced signal intensity of mass (arrow).
Chemical shift imaging is useful to detect fat-containing hepatocellular
carcinoma.
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Fig. 10C —Well-differentiated hepatocellular carcinoma with fat in
61-year-old man. T2-weighted fat-saturated fast spin-echo MR image shows
intermediate hyperintense lesion. Surgical specimen showed hepatocellular
carcinoma with fatty metamorphosis.
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Large HCCs may have a number of characteristic features, such as a mosaic
pattern, a tumor capsule, an extracapsular extension with formation of
satellite nodules, and vascular invasion (Figs.
11,
12A, and
12B). Large HCCs have a
heterogeneous pattern of enhancement in the arterial phase on CT (Figs.
7A and
7B). Portal venous phase CT
shows a capsule or enhancing septation. On T1- and T2-weighted images, the
mosaic pattern appears as areas of variable signal intensities, whereas on
gadolinium-enhanced images, the lesions enhance in a heterogeneous fashion
during the arterial and later phases. The tumor capsule is hypointense on both
T1- and T2-weighted images in most cases
[1].
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Fig. 11 —Hepatocellular carcinoma with mosaic appearance in
64-year-old man. Portal venous phase contrast-enhanced T1-weighted
gradient-echo MR image reveals large hepatocellular carcinoma
(arrows) and enhancement of fibrous capsule. Patient underwent
segmental resection.
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Fig. 12A —Hepatocellular carcinoma with portal vein thrombosis in
69-year-old man. Arterial phase CT scan shows low-attenuating mass (white
arrows) in lateral segment of left hepatic lobe. There is heterogeneous
enhancing lesion (black arrows) within left portal vein. Cirrhosis
and ascites are seen.
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Fig. 12B —Hepatocellular carcinoma with portal vein thrombosis in
69-year-old man. Delayed-phase CT scan reveals hypoattenuating thrombi in left
portal vein. Hypoattenuating hepatocellular carcinoma (arrows) with
capsular enhancement is noted.
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Lesions Mimicking HCC in Patients with Cirrhosis
The enhancing nodule on an HAP image usually represents an HCC; however,
some enhancing nodules on HAP images may be simulating the HCC.
Dysplastic Nodules
A minority of DNs show early enhancement after administration of contrast
material, and these may be a significant source of false-positive reports
(Figs. 13A,
13B, and
13C) because DNs and HCCs may
be hyperintense on T1-weighted images. One very helpful distinction between
HCCs and DNs is that HCCs have a moderate hyperintensity on T2-weighted images
[3].
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Fig. 13A —Dysplastic nodule with enhancement in 52-year-old man. An
8-mm dysplastic nodule is seen as slightly hyperintense on T1-weighted
gradient-echo MR image (A) and hypointense (arrow) on
T2-weighted fast spin-echo MR image (B) compared with hepatic
parenchyma.
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Fig. 13B —Dysplastic nodule with enhancement in 52-year-old man. An
8-mm dysplastic nodule is seen as slightly hyperintense on T1-weighted
gradient-echo MR image (A) and hypointense (arrow) on
T2-weighted fast spin-echo MR image (B) compared with hepatic
parenchyma.
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Fig. 13C —Dysplastic nodule with enhancement in 52-year-old man.
Arterial phase T1-weighted gradient-echo MR image shows enhancing nodule.
Hypointensity on T2-weighted image is helpful finding for differentiating
dysplastic nodule from hepatocellular carcinoma. Patient underwent segmental
resection.
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Hemangioma
Small hemangiomas can appear with flash filling during the arterial phase
and thus simulate HCC. These lesions always show enhancement on delayed-phase
images (Figs. 14A,
14B, and
14C), whereas HCC exhibits a
washout of the contrast material, becoming either isoattenuating or
hypoattenuating relative to liver tissue. Heavily T2-weighted images can
distinguish between atypically enhancing hemangiomas and hypervascular HCCs
[6].
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Fig. 14A —Early enhancing hemangioma in 46-year-old man. Arterial
(A), portal venous (B), and delayed-phase (C) CT scans
show enhancing hemangioma (arrow, A) similar to that of
appropriate vessels. Persistent enhancement on these images is important for
differentiating early enhancing hemangioma from hepatocellular carcinoma.
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Fig. 14B —Early enhancing hemangioma in 46-year-old man. Arterial
(A), portal venous (B), and delayed-phase (C) CT scans
show enhancing hemangioma (arrow, A) similar to that of
appropriate vessels. Persistent enhancement on these images is important for
differentiating early enhancing hemangioma from hepatocellular carcinoma.
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Fig. 14C —Early enhancing hemangioma in 46-year-old man. Arterial
(A), portal venous (B), and delayed-phase (C) CT scans
show enhancing hemangioma (arrow, A) similar to that of
appropriate vessels. Persistent enhancement on these images is important for
differentiating early enhancing hemangioma from hepatocellular carcinoma.
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Nontumorous Arterioportal Shunt
These lesions appear as an area of wedge-shaped high attenuation with or
without internal branching structures on the HAP image and as slightly high
attenuation or isoattenuation with the liver on portal and delayed-phase
images (Figs. 15A,
15B, and
15C). These lesions are
usually subcapsular, without mass effect, and do not bulge the liver capsule
[7]. The signal intensity on
T1- and T2-weighted images of arterioportal shunt appears isointense compared
with the hyperintensity of HCC on T2-weighted images.
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Fig. 15B —Nontumorous arterioportal shunt in 45-year-old man. Arterial
phase T1-weighted gradient-echo MR image shows wedge-shaped intensely
enhancing lesion (short arrows) in subcapsular portion of right
hepatic liver with markedly enhancing vein (long arrow).
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Fig. 15C —Nontumorous arterioportal shunt in 45-year-old man. On
portal-venous phase T1-weighted gradient-echo MR image, enhancing lesion on
arterial phase MR image changes to iso-signal intensity compared with adjacent
hepatic parenchyma.
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Aberrant Vessels
When third hepatic inflow tracts (accessory cystic veins, aberrant right
gastric veins, or capsular veins) are present, systemic venous blood directly
enters the hepatic sinusoids. A focal enhancing lesion is seen on HAP imaging.
Common locations of the aberrant portal venous supply include the
pericholecystic area, anterior to the porta hepatis, adjacent to the falciform
ligament, and the subcapsular area
[7] (Figs.
16A and
16B).
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Fig. 16B —Aberrant vessel in 61-year-old man. Delayed-phase CT scan
shows no abnormalities. Perfusion disorder probably corresponds to third
hepatic inflow tracts (aberrant right gastric veins or parabiliary venous
system).
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Confluent Fibrosis
When the fibrosis is concentrated focally, a finding often referred to as
focal confluent fibrosis, it can create mass lesions that simulate tumors on
imaging. These lesions often radiate from the porta hepatis and are
wedge-shaped and widest at the capsular surface. Confluent fibrosis shows
hyperintensity on T2-weighted images that is similar to the appearance of
malignancy. The most common sites for confluent fibrosis are the anterior and
medial segments of the liver, but it can be present anywhere in the liver. The
reliable finding in helping to differentiate confluent fibrosis from HCC is
associated parenchymal atrophy with capsular retraction
[8] (Figs.
17A,
17B,
17C, and
17D).
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Fig. 17A —Focal confluent fibrosis in 50-year-old man. Drawing shows
wedge-shaped zone of fibrosis in right hepatic lobe. Lesion abnormality will
appear round rather than wedge-shaped, simulating tumor.
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Fig. 17B —Focal confluent fibrosis in 50-year-old man. Axial
T2-weighted single-shot fast spin-echo MR image shows irregular, round-shaped
area of fibrosis (arrows) in right hepatic liver, simulating tumor.
Confluent fibrosis associated with cirrhosis is always of hyperintensity on
T2-weighted images.
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Conclusion
Cirrhotic livers are mainly composed of fibrosis together with a broad
spectrum of focal nodular lesions ranging from RN to premalignant DN to overt
HCC. HCC often can be distinguished from DN at dynamic CT and MRI on the basis
of identification of enhancement on the HAP image. The knowledge of how
cirrhotic nodules and focal lesions mimic HCC will improve the diagnosis and
characterization of focal lesions in cirrhotic liver on CT and MRI.
Acknowledgments
We thank Bonnie Hami, department of radiology, University Hospitals of
Cleveland, for editorial assistance in the preparation of the manuscript.
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Abstract
Introduction
