Imaging of hepatic epithelioid hemangioendothelioma: a

pictorial review

Poster No.: C-1764

Congress: ECR 2013
Type: Educational Exhibit
Authors: 1 1 2 1 2
S. Bivol , C. E. B#la#a , N. Leo , C. Guettier , P. Bucur , A.
2 3 4 2 1
Elmaleh , Z. Dhina-Louison , H. Lemaissi , M. Lewin ; Paris/FR,
2 3 4
Villejuif/FR, Vincennes/FR, Bretigny/Orge/FR
Keywords: Pathology, Neoplasia, Surgery, Biopsy, MR, CT, Oncology, Liver,
Abdomen
DOI: 10.1594/ecr2013/C-1764

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Page 1 of 25
Learning objectives

To define the hepatic epithelioid hemangioendothelioma (HEH) among the other primary
vascular liver tumours.

To recognise the radiological appearance of the tumour and to identify some

imaging features that will narrow down the differential diagnosis.

Background

Primary vascular tumors of the liver in adult patients include hemangioma, epithelioid
hemangioendothelioma, angiosarcoma and hemangiopericytoma.

Some of these are benign and common, like angioma, others are rare and low-
grade malignant tumors, like epithelioid hemangioendothelioma. Angiosarcoma and
hemangipericytoma are very uncommon and agressive lesions.

The hepatic epithelioid hemangioendothelioma (HEH) is developing from the

vascular elements of mesenchymal tissue. Liver involvement occurs most often as a
primary tumour and has a behaviour between benign hemangioma and aggressive
hemangiosarcoma with extra hepatic spread.

ETIOLOGY:

The exact causes have not been clearly identified.

PATHOLOGY:

Macroscopically, two types was described: the nodular type, with multiple

lesions located in periphery of the liver ("peripheral pattern") and the later

confluent type with extensive lesions ("diffuse pattern").

Page 2 of 25
Fig. 1: Epithelioid hemangioendothelioma.The macroscopic view of a large tumor
show a white mass with irregular margins and central fibrosis, findings that correspond
to the imaging appearance of the intraparenchymal lesion.Hepatocytes are obliterated
and replaced with a myxoid and hyalinized stroma with a progressive sclerosis and
eventual calcification.
References: RADIOLOGY, PARIS SUD UNIVERSITY, PAUL BROUSSE - Paris/FR

Microscopically, HEH originates from endothelial cells with positive

immunohistochemistry for factor VIII-related antigen and for the endothelial

markers CD31 and CD34.Weibel-Palade bodies are seen at electron microscopy inside
tumorous cells.

Page 3 of 25
Fig. 2: Epithelioid hemangioendothelioma. Hematoxylin-eosin strain shows malignant
cells in the hepatic sinusoids. Intravascular growth of these cells is responsible for the
tumor infarction and central fibrosis.
References: RADIOLOGY, PARIS SUD UNIVERSITY, PAUL BROUSSE - Paris/FR

Page 4 of 25
Fig. 3: Epithelioid hemangioendothelioma. Hemangioendothelioma cells are typically
positive for CD31.
References: RADIOLOGY, PARIS SUD UNIVERSITY, PAUL BROUSSE - Paris/FR

Page 5 of 25
Fig. 4: Epithelioid hemangioendothelioma. Hemangioendothelioma cells are positive
for CD34.
References: RADIOLOGY, PARIS SUD UNIVERSITY, PAUL BROUSSE - Paris/FR

CLINICAL RELEVANCE:

Symptoms are nonspecific abdominal pain, weight loss, fatigue. Other symptoms include
jaundice, fever, hepatomegaly, ascites or hemoperitoneum. Budd Chiari syndrome can
occur if the tumor invades the hepatic veins.

TREATMENT:

Treatment options vary from simple surveillance to surgical resection

and orthotopic liver transplant.

Imaging findings OR Procedure details

Page 6 of 25
Imaging findings

Modalities: US, CT (nonenhanced and enhanced), MRI (T1, T2, Diffusion, ADC, T1C+
sequences) PET-FDG, arteriography.

Ultrasound:

On ultrasound HEH presents as multiples peripheral hypoechoic masses or mixed hypo-

hyperechoic masses, with a hypoechoic rim. (Fig. 5 on page 9, Fig. 6 on page 10)

In diffuse lesions, US shows areas of overall decreased echogenicity that contain, in

some cases, calcified foci.

There is no correlation between sonographic pattern and the size of the lesion.

CT:

Unenhanced CT images reveal nodular foci of decrease attenuation because of their

myxoid stroma. In diffuse lesions, precontrast CT scans show large and confluent areas
of overall low attenuation.

After contrast administration, the tumor takes a small amount of contrast medium in the
central zone and sometimes areas of hyper vascularization can be detected. The tumor
enhancement pattern is similar to a target or halo, produced by a nonenhanced outer rim
of avascular tissue juxtaposed with an enhanced inner peripheral rim. Depending on the
predominance of myxoid and hyalinized elements and the degree of central fibrosis, the
center of the tumor may appear enhanced or non enhanced, on delayed phase.

The vascularity of diffuse lesions is moderate but delayed enhancement is consistent

with fibrosis. (Fig. 7 on page 10 , Fig. 8 on page 11)

Central calcifications, areas of necrosis or hemorrhage can be also seen on CT.

MRI

MRI reveals the target aspect of the lesion: hypointense centrally with a peripheral thin
hypointense rim in T1-weighted images, hyper intense centrally surrounded by lower
signal intensity and peripheral thin hypointense rim in T2-weighted images. After contrast
administration, the target pattern is more evident, with three concentric layers: a thick
enhancing inner rim, a thin nonenhancing outer rim and a hypointense central zone.

A delayed central enhancement can usually be seen in larger lesions. (Fig. 9 on page
12,

Page 7 of 25
Fig. 10 on page 13)

Imaging of CT and MR are similar. Changes in hepatic contours are more evident in
diffuse lesions, including capsular retraction which is centered over a peripheral mass and
suggestive for HEH, but not specific. In addition, a compensatory enlargement, usually
in the left and caudate lobe in patient with predominant lesions located in the right lobe,
may be seen. Portal vein tumor thrombus, obliteration of hepatic veins or sign of portal
hypertension may be also encountered.

Two radiological signs are particularly interesting:

1. The capsular retraction adjacent to hepatic tumors is not common, although

this finding has been described in a variety of tumors: hepatic carcinoma,
cholangiocarcinoma, colorectal metastases, hemangioma or confluent fibrosis. Many
radiologists consider this sign to be associated with central cholangiocarcinoma but it
was first described in epitheloid hemangioendotelioma. (Fig. 11 on page 14)

2. The "lollipop sign" is a characteristic radiological aspect which show the abrupt "cut-
off" of the hepatic or portal vein. (Fig. 12 on page 15, Fig. 13 on page 16)

PET-FDG:

In some case reports on positron-emission tomography (PET) scan, an increased

fluorodeoxyglucose (FDG) uptake by HEH has been described.

PET demonstrates moderate to intense uptake in the tumors, also seen in adjacent lymph
nodes and extrahepatic sites of disease, and has a potential interest for staging desease
or to detect recurrences. (Fig. 14 on page 17)

Arteriography: hyper vascular, hypo vascular or avascular lesions, based on the degree
of sclerosis and hyalinization.

Major differential diagnosis

Hemangioma (especially in cirrhotic liver)

Hemangiomas are likely to decrease in size due to progressive cirrhosis. Capsular

retraction is a rare finding and was described in a very few cases in non-cirrhotic liver.
(Fig. 16 on page 19)

Page 8 of 25
Focal confluent fibrosis

Capsular retraction is associated with segmental or lobar shrinkage and it is common in

advanced cirrhosis. ( Fig. 19 on page 22)

Treated hepatocellular carcinoma or metastases

There is a history of chemotherapy or resection for liver tumor. Capsular retraction is

common whereas some treated metastases may show cystic or necrotic transformation.

Cholangiocarcinoma

Hepatic cholangiocarcinoma presents like a heterogeneous mass with capsular

retraction, sometimes with satellite lesions and intrahepatic duct dilatation. (Fig. 18 on
page 21)

Images for this section:

Page 9 of 25
Fig. 5: Sagittal gray-scale US image of the liver shows a large, subcapsular,
predominantly hypoechoic mass with irregular margins, in the left hepatic lobe.

Fig. 6: Transverse gray-scale US image of the liver shows multiples nodules with a
variable appearance, hypo, iso and hyper echoic. The central lesion is slightly hyper
echoic, with a peripheral hypo echoic rim and a central hypoechoic area.

Page 10 of 25
Fig. 7: Axial unenhanced CT image shows hypoattenuating intraparenchymal lesions in
the right liver (a). Axial contrast enhanced CT in arterial phase (b), venous phase (c)
and at 5 minutes after injection, show slight central enhancement and more pronounced
peripheral enhancement of these lesions.

Page 11 of 25
Fig. 8: Axial unenhanced CT images shows multiples areas of overall attenuation(a).
After contrast administration, CT images shows minimal enhancement in the arterial and
portal phase(b,c) with complete filling in the delayed phase(d).

Page 12 of 25
Fig. 9: Dynamic contrast-enhanced MRI of the liver show a large intraparenchymal lesion
in the right hepatic lobe.On T1-weighted images (a), the lesion is overall hypointense with
a central area of lower signal intensity than the remainder of the lesion. After intravenous
administration of gadolinium, the tumor demonstrate a moderate peripheral enhancement
(b,c) and delayed central enhancement due to fibrosis (d).

Page 13 of 25
Fig. 10: In-out-of-phase MRI images shows a large peripheral lesion in the right liver
with an overall hypointense, heterogeneous signal and a more hypointense signal in
the center due to central necrosis (a,b). The lesion exhibit high signal intensity on both
diffusion-weighted(DWI) and T2 weighted imaging.

Page 14 of 25
Fig. 11: Axial contrast-enhanced T1-weighted MR image, arterial phase: capsular
retraction is evident and centered over a large peripheral mass, suggestive for HEH
(arrow).

Page 15 of 25
Fig. 12: "Lollipop sign". Enhanced CT, portal phase: a hepatic vein terminating just within
the periphery of one lesion (arrow).

Page 16 of 25
Fig. 13: "Lollipop sign": the mass in the right lobe of the liver demonstrates abrupt cut-
off of the posterior segmental branch of portal vein (arrow). This configuration resembles
a lollipop.

Page 17 of 25
Page 18 of 25
Fig. 14: FDG-PET study depicts focal intense FDG uptake at the site of the primary tumor
(SUVmax =4)

Fig. 15: Pulmonary enhanced CT. MIP image reconstruction shows diffuse micronodular
lung metastases.

Page 19 of 25
Fig. 16: Dynamic contrast-enhanced MRI of the liver with axial T2 and Diffusion weighted
images. Small rapidly enhancing subcapsular hemangioma in a cirrhotic liver with similar
enhancement to the aorta.

Page 20 of 25
Fig. 17: Targetlike MR imaging appearance of HEH. Axial T2-weighted MR image shows
a large intraparenchymal lesion (arrow) with a central region of hyperintense signal
surrounded by lower signal intensity. The central signal hyperintensity correspond to
hemorrhage, necrosis, or both, and peripheral hyperintensity is consistent with tumor
cellularity and adjacent edema.

Page 21 of 25
Fig. 18: MRI of intrahepatic cholangiocarcinoma a) T2-weighted sequence showing
a heterogeneous hyperintense lesion. b) T1-weighted images showing a hypointense
lesion. c-d) T1-weighted images after gadolinium injection, in portal (c) and delayed (d)
phase, showing progressive enhancement

Page 22 of 25
Fig. 19: Dynamic enhanced MRI, delayed phase. Focal confluent fibrosis in a cirrhotic
liver.Confluent hepatic fibrosis usually appears as wedge-shaped with capsular retraction
(arrow), with gradual, delayed enhancement.

Page 23 of 25
Conclusion

Final diagnosis of HEH requires a tumor biopsy, followed by histopathologic findings.The

prognosis depends on whether extrahepatic metastases are present at the time of
diagnosis. Extrahepatic involvement includes the peritoneal lymph nodes, omentum and
mesentery and may be associated with calcification. Thoracic disease (intrapulmonary or
pleural), cutaneous or intramuscular metastases may be observed in some cases. (Fig.
15 on page )

In the absence of extrahepatic disease, radical resection is an option, liver transplantation

being considered the best option if metastatic desease.

Some imaging findings are highly characteristic for HEH and need to be remembered:
predominant distribution at the periphery of the liver, intratumoral calcifications, changes
of the liver contour (capsular retraction and compensatory hypertrophy of the normal
liver), invasion of portal and hepatic veins ("lollipop sign"), tumors composed of concentric
zones ("target sign"), changes of nodular lesions to large coalescent masses.

References

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Pathologic Correlation. Hepatic Epithelioid Hemangioendothelioma.

Radiographics 2012; 32:789-794.

2. Earnest F 4th, Johnson CD. Case 96: hepatic epithelioid hemangioendothelioma.

Radiology 2006; 240(1):295-298.

3. Alomari AI. The lollipop sign: a new cross-sectional sign of hepatic epithelioid
hemangioendothelioma. Eur J Radiol 2006;59(3):460-464.

4. Lyburn ID, Torreggiani WC, Harris AC, et al. Hepatic epithelioid

hemangioendothelioma: sonographic, CT, and MR imaging appearances. AJR Am J
Roentgenol 2003;180(5):1359-1364.

5. Silvana C. Faria, Karthik Ganesan, Irene Mwangi,Masoud Shiehmorteza, Barbara

Viamonte, SameerMazhar, Michael Peterson, Yuko Kono, Cynthia

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Santillan, Giovanna Casola, Claude B. Sirlin. MR Imaging of Liver Fibrosis: Current State
of the Art. RadioGraphics 2009; 29:1615-1635.

6. Nicholas C. Gourtsoyiannis, Pablo R. Ros.Radiologic-Pathologic Correlationsfrom

Head to Toe. Understanding the Manifestations of Disease;Springer-Verlag Berlin
Heidelberg 2005; 4: 784-785.

7.Michael P. Federle. Diagnostic imaging abdomen. Amirsys, 2004; II.1:132-135.

Personal Information

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