AJR 2000; 175:165-170
© American Roentgen Ray Society
Hepatic Angiosarcoma
Findings on Multiphasic Contrast-Enhanced Helical CT Do Not Mimic Hepatic Hemangioma
Mark S. Peterson1,
Richard L. Baron1 and
Sheila C. Rankin2
1
Department of Radiology, University of Pittsburgh School of Medicine, 200
Lothrop St., Pittsburgh, PA 15213-2582.
2
Department of Radiology, Guy's Hospital, St. Thomas St., London SE1 9RT,
United Kingdom.
Received September 27, 1999;
accepted after revision November 24, 1999.
Presented at the annual meeting of the American Roentgen Ray Society, San
Francisco, April 1998.
Address correspondence to M. S. Peterson.
Abstract
OBJECTIVE. The objective of our study was to identify multiphasic
contrast-enhanced helical CT findings of angiosarcoma of the liver to
determine whether this tumor could be confused with hemangioma of the
liver.
CONCLUSION. Angiosarcoma of the liver is a multifocal tumor with a
variety of findings on multiphasic contrast-enhanced helical CT. None of the
findings would usually be confused with the typical findings of hepatic
hemangioma.
Introduction
Angiosarcoma of the liver is the most common primary mesenchymal tumor or
sarcoma of the liver, more common than fibrosarcoma, malignant fibrous
histiocytoma, or leimyosarcoma
[1]. Despite its rarity, there
is considerable interest in angiosarcoma because of its association with
malignant transformation caused by environmental or occupational exposure to
carcinogens [1]. Angiosarcoma
is known to be associated with exposure to thorotrast (colloidal solution of
thorium dioxide), vinyl chloride, arsenic, and radiation
[1,
2]. Angiosarcoma has also been
associated with hemochromatosis and von Recklinghausen's disease
[1]. An aggressive, often
symptomatic malignancy, angiosarcoma is virtually incurable, with the median
survival time reported to be just 6 months
[1].
Probably because of its rarity, relatively little has been written of
angiosarcoma in the radiology literature. Older isolated case reports have
described cases of angiosarcoma that can mimic hemangioma on
99mTc-labeled RBC scans
[3,
4] or enhanced axial CT scans
[5,
6]. With the advent of helical
CT and the opportunity to image tumors during sequential time frames, we
undertook this study to document the helical CT findings of angiosarcoma and
to determine whether these lesions can mimic hemangioma on multiphasic
contrast-enhanced helical CT.
Materials and Methods
A review of the medical and radiology records of our two institutions from
the past 5 years identified six patients with angiosarcoma of the liver
examined with multiphasic contrast-enhanced helical CT. We did not identify
any cases of angiosarcoma of the liver that were not evaluated with
multiphasic contrast-enhanced helical CT in that time. The patients were five
males and one female (age range, 4-80 years; mean, 66 years). The diagnosis of
angiosarcoma was established by histopathology in all cases: one each by
percutaneous biopsy, transjugular biopsy, needle biopsy at surgical
exploration, open surgical biopsy, surgical pathology of an explanted liver
from a liver transplant recipient, and autopsy.
Unenhanced and biphasic contrast-enhanced helical CT imaging were performed
for all six patients. One-hundred fifty milliliters of iodinated contrast
material ([iothalamate meglumine injection USP 60%] Conray or [ioversol
injection 68%] Optiray 320; Mallinckrodt, St. Louis, MO) was injected at a
rate of 2.5-5 ml/sec. Imaging was performed at approximately 28 and 70 sec
after initiation of the injection for biphasic imaging during arterial and
portal venous phases of parenchymal enhancement. Helical CT images (HiSpeed
Advantage, General Electric Medical Systems, Milwaukee, WI; or Tomoscan AV,
Philips Medical Systems, Einthoven, The Netherlands) were obtained with 7- or
10-mm collimation and a pitch of 1.0-1.5. In one patient, additional delayed
images were obtained 4 min after contrast injection.
All CT images were then reviewed by consensus of two radiologists with
expertise in abdominal imaging to determine the numbers and locations of
tumors and the size of the largest tumor in each patient. The patterns of
tumor attenuation and enhancement in each individual patient were then
recorded as homogeneous or heterogeneous and as hypoattenuating,
isoattenuating, or hyperattenuating relative to adjacent normal liver
parenchyma and the aorta and hepatic artery on unenhanced, arterial phase, and
portal venous phase contrast-enhanced images. For practical purposes and to
avoid biasing the data, when there were more than nine lesions of a particular
type, a total of 10 lesions of that type were recorded. All studies were also
reviewed to assess the presence or absence of thorotrast, splenic metastases,
and intratumoral hemorrhage, excluding intratumoral hemorrhage that may have
been caused by a preceding biopsy.
Results
Angiosarcoma was multifocal in all six patients (Figs.
1A,1B,1C,2A,2B,3A,3B,3C,3D,3E,4A,4B,5,6A,6B).
One patient had three tumors, and the other five patients had more than 10
tumors each. In addition to multiple tumor nodules, one patient also had a
dominant diffusely infiltrative lobar mass (Fig.
2A,2B).
The diameter of the largest tumor in each patient ranged from 2.8 to 24
cm.
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Fig. 1B. —63-year-old man with multifocal angiosarcoma. Arterial phase
contrast-enhanced helical CT scan shows heterogeneous enhancement of tumors
(long arrows), most of which are hyperattenuated to normal liver but
hypoattenuated to aorta. One lesion (short arrow) is hypoattenuated
to both liver and aorta.
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Fig. 1C. —63-year-old man with multifocal angiosarcoma. Portal venous phase
contrast-enhanced helical CT scan shows that most lesions that were
hyperattenuated in B (long arrows) are now nearly
isoattenuated to liver, but are hypoattenuated to vessels. Large lesion
(short arrow) remains hypoattenuated to both liver and vessels.
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Fig. 2A. —54-year-old man with multifocal angiosarcoma. Arterial phase
(A) and portal venous phase (B) contrast-enhanced helical CT
scans show large infiltrative mass (large straight arrows) involving
entire left hepatic lobe, small mass (small straight arrow) in right
hepatic lobe, and splenic metastasis (curved arrow). Tumors are
hypoattenuated to surrounding liver and aorta. Note masses remain
hypoattenuated to surrounding liver and aorta during portal venous phase
(B).
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Fig. 2B. —54-year-old man with multifocal angiosarcoma. Arterial phase
(A) and portal venous phase (B) contrast-enhanced helical CT
scans show large infiltrative mass (large straight arrows) involving
entire left hepatic lobe, small mass (small straight arrow) in right
hepatic lobe, and splenic metastasis (curved arrow). Tumors are
hypoattenuated to surrounding liver and aorta. Note masses remain
hypoattenuated to surrounding liver and aorta during portal venous phase
(B).
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Fig. 3A. —65-year-old man with multifocal angiosarcoma and intratumoral
hemorrhage. Unenhanced helical CT scan shows multiple low-attenuation liver
masses (arrows), hypoattenuated to liver and isoattenuated to aorta.
High-attenuation intratumoral hemorrhage in right hepatic lobe mass
(straight arrow) was attributed to recent needle biopsy.
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Fig. 3B. —65-year-old man with multifocal angiosarcoma and intratumoral
hemorrhage. Arterial phase contrast-enhanced helical CT scan shows multiple
liver masses (arrows), both hypo- and hyperattenuated to liver. Note
single posterior left lobe nodule (open curved arrow) with peripheral
nodular enhancement isoattenuated to aorta.
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Fig. 3C. —65-year-old man with multifocal angiosarcoma and intratumoral
hemorrhage. Portal venous phase contrast-enhanced helical CT scan shows that
although most tumor nodules (straight arrow) remain hypoattenuated to
liver, one (solid curved arrow) is homogeneously hyperattenuated to
liver. Posterior left lobe nodule shows increased peripheral enhancement
(open curved arrow) isoattenuated to aorta, mimicking hepatic
hemangioma.
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Fig. 3D. —65-year-old man with multifocal angiosarcoma and intratumoral
hemorrhage. Four-minute delayed contrast-enhanced helical CT scan shows that
many liver nodules (solid curved arrow) have become isoattenuated to
liver, although some (straight arrow) are hypoattenuated to liver.
Posterior left lobe nodule shows increased enhancement (open curved
arrow) isoattenuated to aorta, simulating hepatic hemangioma.
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Fig. 3E. —65-year-old man with multifocal angiosarcoma and intratumoral
hemorrhage. Four-minute delayed contrast-enhanced helical CT scan at more
caudal level than D. Note unusual layering effects of
contrast-opacified blood and nonopacified blood in tumor nodules
(arrows).
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Fig. 4A. —64-year-old woman with thorotrast-induced angiosarcoma. Arterial
phase contrast-enhanced helical CT scan shows tumor nodules (solid curved
arrows) hypoattenuated to both liver and aorta. Accumulation of
high-attenuation thorotrast is seen in liver (straight arrows),
spleen (arrowhead), and gastrohepatic ligament lymph nodes (open
curved arrow).
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Fig. 5. —80-year-old man with multifocal angiosarcoma with intratumoral
hemorrhage and hemoperitoneum. Portal venous phase helical CT scan shows
fluid-fluid level (curved arrow) from hemorrhage in right hepatic
lobe tumor. Note also hemoperitoneum (arrowhead) anterior to left
hepatic lobe tumor (straight arrows).
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Fig. 6A. —69-year-old man with hemochromatosis and multifocal angiosarcoma
diagnosed after liver transplantation. Arterial phase contrast-enhanced
helical CT scan shows small tumor nodule (arrow), hyperattenuated to
liver but hypoattenuated to aorta.
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Fig. 6B. —69-year-old man with hemochromatosis and multifocal angiosarcoma
diagnosed after liver transplantation. Portal venous phase contrast-enhanced
helical CT scan shows small tumor nodule (arrow) that remains
hyperattenuated to liver and isoattenuated to aorta. Note diffusely
heterogeneous enhancement of liver parenchyma. Diffuse and multifocal tumor
was found at pathologic evaluation of explanted native liver.
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The patterns of tumor attenuation and enhancement relative to both liver
parenchyma and vessels are summarized in
Table 1. Many angiosarcoma
lesions were hypoattenuating to the liver on both arterial and portal venous
phase images (Figs.
1A,1B,1C,2A,2B,3A,3B,3C,3D,3E,4A,4B,5).
A few were hyperattenuating on arterial phase images (Figs.
1A,1B,1C,
3A,3B,3C,3D,3E,
and
6A,6B),
some becoming isoattenuating on portal venous phase images (Fig.
1A,1B,1C),
clearly different from blood pool attenuation. Most patients had no
intrapatient variability in tumor appearances (Figs.
2A,2B,
4A,4B,
5, and
6A,6B),
although minor intrapatient variability was seen in two patients (Figs.
1A,1B,1C
and
3A,3B,3C,3D,3E).
Several tumors showed a fluid-fluid level, likely from prior intratumoral
hemorrhage (Fig. 5). An
unusual pattern of layered linear high-attenuation central enhancement was
seen in multiple lesions in one patient (Fig.
3A,3B,3C,3D,3E).
Despite the varied enhancement patterns seen in angiosarcoma, only one lesion
of many in only one patient was isoattenuating to vessels on unenhanced images
and showed features of peripheral nodular enhancement isoattenuating to
vessels on both arterial and portal venous phases of enhancement, which could
simulate hepatic hemangioma (Fig.
3A,3B,3C,3D,3E).
Thorotrast was identified in the liver, spleen, and upper abdominal lymph
nodes of one patient (Fig.
4A,4B).
Two patients had splenic metastases that appeared hypodense to surrounding
splenic tissue (Fig.
2A,2B),
similar in enhancement to the angiosarcoma liver tumors. Two patients had
intratumoral hemorrhage, one of whom also had rupture of liver tumor with
hemoperitoneum (Fig. 5).
Discussion
The clinical course of angiosarcoma of the liver is usually not confused
with that of the indolent, much more common, hepatic hemangioma. Nonetheless,
because earlier anecdotal case reports have suggested that imaging features of
angiosarcoma of the liver could be confused with those of hepatic hemangioma,
it is important to recognize the spectrum of imaging features of angiosarcoma,
particularly those shown with the multiphasic contrast-enhanced helical CT
technique.
Angiosarcoma is a tumor of malignant spindle cells of endothelial cell
derivation that can form poorly organized vessels, grow along preformed
vascular channels, be arranged in sinusoidal or large cavernous spaces, or
form solid nodules or masses
[1,
2]. The histology is known to
vary in different locations within an individual liver
[7]. We believe that the
pleomorphic histopathology of angiosarcoma correlates with the various
patterns of tumor enhancement we observed. Although most tumors in our series
were hypoattenuating to normally enhanced liver (Figs.
2A,2B,
4A,4B,
and 5), some were
hyperattenuating (Figs.
1A,1B,1C,
3A,3B,3C,3D,3E,
and
6A,6B),
reflecting increased tumor vascularity. The one patient who underwent 4-min
contrast-enhanced delayed imaging had focal lesions with layering of
contrast-opacified blood and non-opacified blood
(Fig. 3E), probably in
sinusoidal or cavitary spaces of the tumor.
The CT appearance of hepatic hemangioma has been extensively studied, with
many reports in the radiology literature
[8,
9]. Although, in the past,
reports described contrast enhancement features of hemangiomas relative to
liver parenchyma enhancement, at least one recent study performed with faster
scanning techniques [10] has
described typical CT findings of centripetal nodular enhancement that
approximate the density of the contrast-opacified blood in the aorta or
hepatic artery during all phases of imaging, including unenhanced imaging. The
earlier CT case reports of angiosarcoma mimicking hemangioma can likely be
attributed to imaging in a single temporal phase, often during the delayed
phase of contrast enhancement, and to assessment of lesion enhancement
relative to liver parenchyma, not to the aorta or hepatic artery.
The temporal assessment of the various patterns of angiosarcoma lesion
enhancement in comparison with patterns of normal vascular enhancement now
possible with multiphasic helical CT allows confident exclusion of the
diagnosis of hemangioma. In our experience, the pattern of progressive
centripetal nodular enhancement seen with hemangioma is not typical of the
patterns of enhancement seen with angiosarcoma. In only one lesion of many in
only one of our patients was a similar pattern of lesion enhancement seen
(Fig.
3A,3B,3C,3D,3E).
In none of our patients, however, was hemangioma a prospectively considered
diagnosis. The imaging appearance of this solitary lesion is uncommon for
angiosarcoma and, in the presence of multiple other lesions not typical of
hemangioma, would not be confused with a hemangioma.
At gross pathology, two patterns of growth have been reported for
angiosarcoma: a large solitary mass or, more commonly, multifocal or
multinodular lesions [1]. Our
experience is consistent with prior reports that multifocal tumor is typical
of angiosarcoma: each of our six patients had multiple tumor masses. This
typical finding of multiplicity of lesions is atypical of hemangiomas, which
are more often solitary than multiple, and, when multiple, are rarely as
numerous as the large number of lesions seen in our patients with
angiosarcoma.
Angiosarcoma associated with vinyl chloride exposure is also of interest in
that a previously reported response to vinyl chloride exposure is the
development of intralobular and capsular fibrosis and splenomegaly
[11]. This histopathology has
been reported in patients exposed to vinyl chloride both with and without
complicating angiosarcoma and is similar to the histopathology of chronic
arsenic poisoning, which is also associated with angiosarcoma. The patterns of
fibrosis associated with exposure to either vinyl chloride or arsenic could
also simulate cirrhosis of other more common causes.
Aside from the difficulty with the overlap in appearance of fibrosis from
toxin exposure with fibrosis of hepatic cirrhosis of a more common cause, the
histopathologic diagnosis of angiosarcoma may be difficult to make with needle
biopsy alone. The one patient in our series who underwent liver
transplantation (Fig.
6A,6B)
had been biopsied both percutaneously under CT guidance and with multiple
needle passes at laparoscopy before transplantation. Despite the multiple
biopsies, no angiosarcoma was proven until the explanted native liver was
examined after transplantation. This experience illustrates the occasional
difficulty, despite repeated biopsies, in establishing the diagnosis of
angiosarcoma.
Angiosarcoma has reportedly been associated with spontaneous tumor rupture
and intraperitoneal hemorrhage
[12]. Two of our patients had
intratumoral hemorrhage, one of whom had intratumoral layering of fluids of
different attenuations as well as a hemoperitoneum
(Fig. 5). The propensity to
hemorrhage probably reflects the vascular nature of the tumor, with tumor
rupture and hemoperitoneum likely caused by tumors arising in subcapsular
locations.
Splenic metastases from angiosarcoma have reportedly occurred in 16% of
patients [1]. Two of our
patients had splenic metastases (Fig.
2A,2B),
which, like the primary liver tumors, were hypoattenuating or hypovascular to
liver.
Thorium dioxide colloidal solution, or thorotrast, was introduced as a
radiographic contrast agent in 1928
[2] and used until the early
1950s. Thorotrast accumulates in the cells of the reticuloendothelial system
and is retained throughout life. Because thorium is an alpha particle emitter
with a biologic half-life of 200-400 years, the cumulative effect of the
radiation exposure places patients at increased risk for tumors, notably
cholangiocarcinoma, hepatocellular carcinoma, and angiosarcoma
[2]. Although thorotrast has
long been associated with angiosarcoma, only one patient in our series had
thorotrast accumulation in the liver, spleen, and lymph nodes (Fig.
4A,4B).
Because thorotrast has not been used for several decades and the latency
period of thorotrast-induced angiosarcoma has been reported to average 37
years [2], it is likely that
most of the cohort of patients exposed to thorotrast have by now either
developed hepatic tumors or died of other causes. For this reason, we believe
that detection of thorotrast accumulation on CT will become increasingly rare,
with few additional thorotrast-induced tumors detected.
A limitation of our study is the potential selection bias of patients who
were referred to medical centers that specialize in the diagnosis and
treatment of liver disease. Although the rarity of angiosarcoma makes it
difficult, if not impossible, to draw conclusions about the absolute or
relative incidence of specific imaging features, we believe that our findings
are representative of this tumor. Another limitation of this study is the
limited direct correlation of CT imaging findings with gross pathology
specimens and correlative histopathology specimens because only one patient
underwent transplantation and an autopsy was performed on only one patient
In summary, angiosarcoma is a multifocal tumor with varied enhancement
patterns on multiphasic contrast-enhanced helical CT, likely related to
pleomorphic tumor histology, that virtually encompasses the entire spectrum of
appearances of liver masses. Fortunately, however, when strict application of
current hemangioma diagnostic imaging criteria are applied, it is extremely
rare for angiosarcoma to mimic hemangioma.
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Abstract
Introduction
