The lollipop sign: A new cross-sectional sign of hepatic epithelioid hemangioendothelioma

Abstract

In four cases of hepatic epithelioid hemangioendothelioma (HEHE), multiple liver lesions were depicted on enhanced computed tomography (CT) and/or magnetic resonance imaging (MRI) scans. A peculiar sign, a hepatic or portal vein terminating at or just within the periphery of some of the liver lesions, was noted in all four; the images look like a lollipop. Imaging findings of HEHE can suggest other diseases, but this sign buttressed by other radiological findings, seems to be specific for this entity.

Full text

European Journal of Radiology 59 (2006) 460–464
The lollipop sign: A new cross-sectional sign of hepatic
epithelioid hemangioendothelioma
Ahmad I. Alomari ∗
Division of Vascular and Interventional Radiology, Department of Radiology, Children’s Hospital Boston and Harvard Medical School,
300 Longwood Ave, Boston, MA 02115, United States
Received 31 December 2005; received in revised form 19 March 2006; accepted 20 March 2006
Abstract
In four cases of hepatic epithelioid hemangioendothelioma (HEHE), multiple liver lesions were depicted on enhanced computed tomography
(CT) and/or magnetic resonance imaging (MRI) scans. A peculiar sign, a hepatic or portal vein terminating at or just within the periphery of some
of the liver lesions, was noted in all four; the images look like a lollipop. Imaging findings of HEHE can suggest other diseases, but this sign
buttressed by other radiological findings, seems to be specific for this entity.
© 2006 Elsevier Ireland Ltd. All rights reserved.
Keywords: Epithelioid hemangioendothelioma; Liver neoplasms; Diagnostic imaging
1. Introduction
Hepatic epithelioid hemangioendothelioma (HEHE) is a rare
vascular mesenchymal neoplasm with borderline malignant
potential. Establishing the diagnosis even with histopatholog-
ical findings can be challenging.
In four patients with histologically proven HEHE, a hepatic or
portal vein tapering and terminating at or just within the edge of a
well defined peripherally enhancing (or non-enhancing) lesion
with an avascular core was seen on CT and/or MRI images,
which can be called the lollipop sign. This specific radiological
finding seems not to have been described previously.
2. Patients and methods
Eight patients with histologically proven HEHE were
referred to the Vascular Anomalies Center at Children’s Hos-
pital Boston for clinical consultation and further management.
Patients without a biopsy proven diagnosis of HEHE were
excluded from the study. Kaposiform and infantile hemangioen-
dothelioma, histologically and biologically separate entities,
were also excluded from this study.
∗Tel.: +1 617 355 7043; fax: +1 617 730 0541.
E-mail address: ahmad.alomari@childrens.harvard.edu.
Medical records and imaging studies on the eight patients
were reviewed retrospectively. The study was reviewed and
accepted by the hospital’s Institutional Review Board.
Five of the eight patients had at least one CT or MRI study
of the liver.
The images from these five patients were reviewed to evalu-
ate the enhancement and involvement of the hepatic and portal
veins. One histologically proven HEHE patient with completely
calcified multiple lesions of the liver was then excluded because
the presence of calcification did not allow proper evaluation of
the lesion’s core vascularity and enhancement pattern.
None of the study patients had evidence of any other malig-
nancy.
3. Results
The clinical and cross-sectional findings from the four study
patients are described below. Each had histologically proven
HEHE and demonstrated the lollipop sign.
3.1. Case 1
A 20-year-old woman presented with severe abdominal pain.
Imaging of the chest, abdomen and pelvis with enhanced CT
scans demonstrated multicentric disease involving the liver,
lungs, spine and bony pelvis. Liver function tests and tumor
0720-048X/$ – see front matter © 2006 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.ejrad.2006.03.022

A.I. Alomari / European Journal of Radiology 59 (2006) 460–464 461
Fig. 1. (a) An enhanced CT image showing multiple hypodense large parenchy-
mal nodules in both liver lobes. The nodule in Couinaud’s segment 7 demon-
strates a well-defined hypodense area with the right hepatic vein (RHV) entering
and terminating in the periphery of the lesion (arrow). This configuration resem-
bles a lollipop. The subcapsular lesion shows subtle peripheral enhancement and
extensive central hypodense area, suggestive of necrosis. Note capsular retrac-
tion as well. (b) The peripheral lesion demonstrate abrupt “cut-off” of a tributary
of the RHV at the edge of a well-defined hypodense area; another example of
the lollipop sign (arrow).
markers for common liver malignancies were unremarkable.
Percutaneous biopsy of the liver lesions showed histological
changes of HEHE. Enhanced CT scan of the liver (Fig. 1) illus-
trates the lollipop sign.
3.2. Case 2
A 20-year-old female presented at the age of 18 with a 2-
year history of a lump in the head. Skull X-rays revealed a large
osteolytic lesion in the left temporal region. Enhanced CT of
the chest, abdomen and pelvis (Fig. 2) demonstrates the lollipop
sign seen in the hepatic lesions.
3.3. Case 3
This 24-year-old woman underwent an ultrasound scan for
abdominal pain and distension. The scan showed a solitary liver
lesion. Percutaneous biopsy of the liver lesion showed histologi-
Fig. 2. An enhanced CT image showing numerous variable size hypodense large
hepatic nodules. The lesion in segment 6 (arrow) demonstrates well-defined
hypodense area with the peripheral enhancement and “cut-off” of the RHV at
its edge; a lollipop sign. Note the central hypodensity.
cal changes of HEHE. MRI of the abdomen was obtained. Fig. 3
summarizes the radiological findings.
3.4. Case 4
A 40-year-old woman presented with intermittent abdominal
pain and distension. At first, the patient was treated for a liver
abscess. The diagnosis of HEHE in this patient was consider-
ably delayed. At age 44, with the persistence of the symptoms,
imaging showed many liver and lung nodules (Fig. 4). Liver
function tests and an infectious disease workup were negative.
CT scan of the brain was normal. CT guided biopsy confirmed
the diagnosis of HEHE.
4. Discussion
In 1982, Weiss and Enzinger described 41 cases of a
unique tumor characterized by an “epithelioid” or “histiocy-
toid” endothelial cell. The majority of these tumors arise from a
medium or large sized vein. The name “epithelioid hemangioen-
dothelioma” was coined to designate this biologically borderline
neoplasm [1]. The tumor generally affects adults, with a strong
female predominance [1–4], as was seen in the study patients.
The lollipop sign presented may improve the recognition of
HEHE on cross-sectional imaging. This sign is a combination
of two structures: the hypodense well defined tumor mass on
enhanced images (the candy in the lollipop) and the histolog-
ically occluded vein (the stick). Ill-defined nodules, cavitating
lesions and complex and exophytic tumors do not exhibit this
exact finding or meet the criteria listed above. The presence of
a central enhancing scar and irregular or strong enhancement of
the lesions do not meet the criteria of the lollipop sign. The vein
should terminate smoothly at the edge or just within the rim of
the lesion. Vessels that traverse the entire lesion or are displaced
and collateral veins cannot be included in the sign.
A characteristic histological feature of HEHE is the infil-
tration of sinusoids, intrahepatic venules and veins; the tumor
surrounds the hepatic and portal veins and venules narrowing or

462 A.I. Alomari / European Journal of Radiology 59 (2006) 460–464
Fig. 3. (a) An out-of-phase MRI image shows multiple peripheral liver lesions.
The smaller lesion in the left liver lobe is uniformly hypointense with a tributary
of the left portal vein ending at is edge (arrow). The large subcapsular lesion
in the right liver lobe is more complex and heterogeneous. Central necrosis and
marked capsular retraction are evident. (b) A T2-weighted image of the liver
shows another lollipop sign composed of a hyperintense subcapsular lesion and
a hepatic vein tributary (arrow).
occluding their lumens (Fig. 5)[5–7]. Radiologically, this patho-
logical feature was documented on the all cross-sectional scans
obtained on all the four study patients. Two forms of venous
involvement are noted. The first form is smooth tapering of the
affected hepatic or portal vein in the periphery of the lesion
(Fig. 4a). The second form demonstrates complete occlusion or
“cut-off” sign of the vein at the edge of the lesion (Fig. 1b).
Recommended CT imaging protocol includes a pre-contrast
and post-contrast venous phase. The former is essential to rule
out calcification and the later to demonstrate the enhancement
pattern and the effect of the tumor on adjacent veins.
MR imaging may include T1- and T2-weighted images.
Ferumoxides-enhanced T1-weighted images more clearly define
the extent of tumor than Gadolinium-enhanced study [12].
Fig. 4. (a) A venous phase CT image of the liver showsa sharply defined lesion in
the dome of the liver. The RHV is smoothly tapering in the medial peripheral side
of the lesion (arrow). Note another smaller lesion anteromedially.Corresponding
MRI findings are seen on inversion recovery sequence (b).
Fig. 5. Gross image of native liver. A dominant lesion (large arrow) is seen
in close proximity to portal vein (PV) and inferior vena cava (IVC). Note the
occlusive effect on the adjacent PV by perivenous tumor extension. (From Ref.
[15] with permission.)

A.I. Alomari / European Journal of Radiology 59 (2006) 460–464 463
Three-dimensional reformat of the CT and multiplanar MRI
images can clearly demonstrated hepatic or portal veins orthog-
onal to the axial plane.
Common CT findings of HEHE include multifocal vari-
able size low attenuation parenchymal nodules. Two radiolog-
ical forms may be identified. A multifocal nodular pattern is
observed in the early stage. These nodules grow and coalesce,
forming large confluent masses preferentially involving the liver
periphery [8,9]. Post-contrast images may show only some
peripheral enhancement [10–12]. Calcification, central hypo-
density and capsular retraction are frequently seen. Metastatic
disease was noted in about 25–45.1% of the patients in three
large series [2,4,5]. The lungs, lymph nodes, spleen, bone and
other solid organs are among the frequent targets of HEHE
metastases.
HEHE lesions demonstrate a hypointense signal on MRI T1-
weighted sequences. The majority of the lesions showed imme-
diate peripheral post-contrast enhancement on T1-weighted
images [3,13]. Normal liver parenchymal enhancement is higher
than tumor enhancement. Central areas of hypointense signal,
similar to the CT finding, can also be noted [9]. The T2-weighted
sequence usually demonstrates heterogeneous high signal inten-
sity lesions. The degree of heterogeneity depicted with MRI is
more complex than that seen on CT images. Central areas of
reduced signal may correspond to areas of hemorrhage, coagu-
lation necrosis, and calcification [12].
The differential diagnosis of multiple liver lesions is exten-
sive. It includes congenital and infantile hemangiomas, cysts,
abscesses, hepatic peliosis, focal nodular hyperplasia, adeno-
mas, focal nodular hyperplasia, regenerating nodules, hepato-
cellular carcinoma and metastases. The latter may mimic HEHE
causing a diagnostic dilemma. However, lack of a primary malig-
nancy is a useful clinical factor in arriving at the correct diag-
nosis. This unique lollipop sign improves the specificity of the
diagnosis of HEHE since none of the lesions included in the dif-
ferential diagnosis exhibits the venous involvement and pattern
of enhancement that resemble a lollipop.
Epithelioid hemangioendothelioma is the prototype of a
group of vascular tumors characterized by an epithelioid or his-
tiocytoid endothelial cells [14]. The tumor can be difficult to
diagnose on the basis of biopsy specimens [10,13,15]. Macro-
scopically, lesions are generally white and firm, rubbery or hard
[5]. The outer margins of the tumor masses are red mottled areas
with signs of congestion [2]. Histologically, lesions are com-
posed of dendritic, intermediate and epithelioid cells [2,8].
HEHE has a variable clinical and biological course between
that of benign endothelial tumors (hemangiomas) and malig-
nant angiosarcomas [16,4] with a slowly progressive phenotype
[17]. In this study, the period between the clinical presenta-
tion and last imaging study ranged from 2 to 13 years. This
is consistent with the known indolent nature of this tumor. Clin-
ical presentation is often non-specific. Patients with HEHE can
be asymptomatic and the tumor detected incidentally. However,
symptomatic patients frequently present with right upper quad-
rant pain or weight loss, but some patients may present with
liver failure, the Budd–Chiari syndrome, or portal hypertension
[2].
Surgical resection of focal nodules the standard treatment for
focal disease and can achieve a cure. However, due to the exten-
sive liver involvement with numerous nodules or diffuse form at
the time of clinical presentation, complete surgical resection is
often impossible [18].
This study is not without limitations. Patients in this retro-
spective review were referred to our institution already having
had the imaging studies and percutaneous biopsies performed
at outside hospitals. While there were different protocols for
imaging the liver in these patients, all of them demonstrated the
lollipop sign at least in one hepatic lesion. It is important to note
that the number of patients involved in this study was limited due
to the rarity of this tumor. Further studies are needed to assess
the exact incidence of this sign in cross-sectional imaging of
HEHE.
In conclusion, HEHE may have radiological cross-sectional
findings seen with other liver lesions. While these findings may
suggest the diagnosis, the lollipop sign seem to be able to dif-
ferentiate this entity from more common liver diseases.
Acknowledgment
The author thanks Dr. N. Thorne Griscom for carefully
reviewing the manuscript.
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