*Rajendran V R. **Baby Manoj 
* Associate Professor, ** DNB trainee 
Dept. of Radiodiagnosis , 
Medical College, Calicut-673008

Address for Correspondence:
Dr V R Rajendran
Assoc Professor,Dept of Radiodiagnosis
Calicut Medical college,Calicut-8
Kerala,India
E-MaiL:vrajendran@satyam.net.in

Introduction : 
Infantile Hepatic Hemangio Endothelioma is a rare benign vascular tumour of liver , usually presenting in infancy with cardiac failure. A case is reported, where the condition was found in one of the identical twins , the other child being normal.

Case report: 
A 2 month old female child was referred for ultrasound study of the abdomen. The general condition of the child was poor with history of recurrent respiratory infections. Present admission was for respiratory distress and cardiac failure. . The clinical impression was hepatoblastoma as the both lobes of liver were enlarged with nodular surface.
On Ultrasonography, the liver showed gross hepatomegaly involving both the lobes with multiple mixed echoic lesions of varying sizes, ranging from 5 to 7 cm. On colour Doppler imaging the liver showed imperceptible signals but power Doppler showed lace like pattern of subtle flow within in these lesions. There was enlargement of the hepatic artery with reduction in size of aorta below the origin of coeliac trunk. 
The NECT showed hepatomegaly with multiple hypodense lobulated lesions showing well circumscribed margins. No calcifications were noted. On contrast administration peripheral enhancement occurred, with a variable degree of centripetal enhancement which was prolonged and persistent.

	Figure1 NCCT – Hepatomegaly with  multiple hypodense     lesions
	Figure2 CECT –Two minutes:  Delayed section shows peripheral    prolonged and persistent enhancement -
	Figure3 CECT- Six minutes delayed section shows centripetal          enhancement almost filling the entire lesion
	Figure4 CECT – 45 minutes delayed section shows total filling of lesion      indistinguishable from adjacent parenchyma
	Figure5 USG- Hepatomegaly with multiple mixed echoic lesions in parenchyma
	Figure6 CDI – No appreciable flow demonstrated
	Figure7 PDI -shows lace like pattern of subtle flow with      in these lesions

Discussion.
Benign hepatic tumors account for about one third of all hepatic tumors in children. The majority of these tumors are of vascular origin, usually hemangioendotheliomas or cavernous hemangiomas.( 1 ) Infantile Hepatic Hemangio Endothelioma ( IHHE) is a type of capillary hemangioma, which is seen almost exclusively in children. It is the most common symptomatic vascular tumor, with 85% of cases presenting in the first 6 months of life. 45% of cases are associated with cutaneous hemangioma. IHHE is found more commonly in girls than in boys in the ratio of 2: 1. It may be single or multiple, focal or diffuse, noncapsulated, ranging from 1-15cm in size, mainly involving the portal area. Solitary lesions are more common than multiple lesions. The tumor may appear as an asymptomatic abdominal mass or more commonly present with congestive heart failure, thrombocytopenia, jaundice or hemorrhage( 2,3). The lesions of the liver consist of gray or pink nodules, some of them with a hemorrhagic center varying in diameter from 1 to 3cm. . Microscopically, they are capillarized vascular channels, lined by one or more layer of plump endothelial cells secondary to extensive proliferation of endothelial cells forming multiple spongy nodules of varying sizes. Proliferation of the endothelial cells may obliterate and sequestrate the bile ducts within the tumor. The lesions show arteriovenous malformations, hemorrhage, thrombosis, fibrosis and calcification and is termed giant if size is more than 7 cm. (13,14,15).Though IHHE are generally accepted as being benign liver tumors of vascular origin, they have a high frequency of malignant degeneration progressing on to malignant hemangio endothelial sarcomas.
Histopathologically, these tumors are classified into two types - 
Benign: Proliferation of the vessel by a single layer of endothelial cells and the center of the lesion including cavernous areas, causing puddling on angiography. 
Malignant: Hyperchromatic endothelial cells with a more pleomorphic & multilayered lining with budding and branching patterns

NATURAL HISTORY

The tumor has a proliferating and an involuting phase. In the first proliferating phase the tumor grows rapidly reaching peak growth rate by approximately fourth month. By about one year it enters an involuting stage where it stops growing. Over the next 3-5 years they involute and disappear spontaneously


PRESENTATION

Over 85% of the affected children present in the first six months of life. Patients can present with a lump in upper abdomen, pain in right hypochondrium, tachypnea, cutaneous hemangiomas, petechial hemorrhages and jaundice. 
A baby presenting with pronounced hepatomegaly and congestive cardiac failure in the absence of physical finding of primary cardiac disease is strongly indicative of hemangiomatous tumor of liver. Hepatomegaly and congestive cardiac failure occur in 25% of cases. Thrombocytopenia due to trapping of thrombocytes (Kassabach-Merrit syndrome) produce an increase in bleeding time and clotting time , which along with CCF is often fatal, with a mortality rate of 30% within 6 months. Occasional rupture with hemoperitonium may also be seen and patients may go into shock. In an infantile hemangioendothelioma arising from the liver, the alpha feto-protein is usually normal - though rarely it may be elevated. The aggressive form of hemengioendothelioma is kaposihemangioendothelioma which is associated with platelet trapping and is resistant to treatment with INF-alpha.

Imaging findings of infantile hemangioendotheliomas:

Chest films - may show cardiomegaly with or without features of CCF and fine speckled calcifications in relation to liver. 
Plain abdominal films - may show hepatomegaly or an upper abdominal mass which may have punctate calcifications with marked displacement of the stomach and of bowel loops ( 3,5)
Ultrasonography Shows solitary or multiple lesions , discrete or diffuse , with variable echotexture ranging from hypoechogenic to iso echogenic or strongly echogenic patterns( 1,6,7) depending on cellular content and presence of large sinusoids with areas of hemorrhage, fibrosis and calcification. Occasionally, the lesions may show streaky or even anechoic channels with calcification (8)
Doppler studies; A variable Doppler pattern of blood flow is noted from liver with increased velocity. There is a frequency shift of 3 KHz which is higher than hemangioma but lower than hepatocellular carcinoma. Usually, there is an increase in the diameter of aorta above celiac axis with slight dilatation of the hepatic artery without significant hyper perfusion. Occasionally color Doppler shows imperceptible signals but power Doppler shows lace like pattern of subtle flow with in these lesions.( 11,12)
Computed Tomographic Imaging : The CT scan gives the exact size and spread of lesion. In non contrast scans, the lesions are solitary or multiple , homogenous or inhomogeneous, with or without calcifications. Following contrast administration, there is early massive enhancement, which is either diffuse or peripheral. The common pattern is early peripheral enhancement known as iris effect followed by progressive opacification of central part in delayed scan at about 20 minutes. On delayed scans, multiple lesions usually become isodense with the surrounding liver, though solitary ones can show varying degrees of centripetal enhancement. (8)
Magnetic Resonance Imaging : Dilated vessels with flow void are seen in the lesions on MR imaging, T1 weighted images show inhomogeneous hypo intense lesions, while T2 weighted images show inhomogeneous very high signal intensity lesions in the liver(3,5,6)

In ultrasonography, CT , and MR imaging, the abdominal aorta superior to the level of celiac artery may appear abnormally enlarged compared with the infra hepatic aorta, which is related to increased blood flow. Dilatation of the hepatic veins and the celiac artery may also be seen ( 1,3,6,8)

Angiography : The appearance of these tumors is somewhat different from the cavernous hemangiomas on angiography. . There is a hyper vascular mass in the liver which shows feeding vessels which are stretched and distorted with focal narrowing and occlusions , but fail to taper. There are irregular spaces which retain contrast medium in the capillary phase with or without arteriovenous shunting. Early venous drainage to the hepatic veins is also a feature. Selective coeliac angiography shows slight dilatation of the common hepatic artery. Capillary phase shows an inhomogeneous sinusoidal pooling of the contrast medium, without filling of the hepatic veins in the right liver lobe. There is opacification of small draining veins in the left liver lobe(9,10)


Management : 

The management of these patients depends upon symptoms. If a patient is asymptomatic, then no treatment is required. But when patient presents with cardiac failure or hemoperitoneum and shock secondary to rupture of IHHE, they require urgent and quick management. When the patient does not respond to medical line of treatment for congestive cardiac failure, he can be treated with therapeutic embolisation using polyvinyl alcohol or detachable silicon balloon or by surgical hepatic artery ligation. Usually infantile hemangioendothelioma resolves on its own within 2 years. Regression may be accelerated with steroid therapy. Surgery is reserved for cases, where congestive heart failure or coagulopathy cannot be managed medically [3,5].
Glucocorticoids are used as the first line therapy against the lesion. A dramatic slowing and subsequent regression occur in approximately 30 % of the patients. However, some slowing of the disease is achieved in rest of the cases. The mechanism by which glucocorticoids act as anti-angiogenic agents is not clear. But they are known to inhibit synthesis of metalloproteinases, overexpressed by the endothelial cells. When glucocorticoids fail low dose INF - µ is used subcutaneously, another anti-angiogenic agent.. A higher percentage of patients respond to INF - µ compared to gluococorticoids. Most of the treatment failure cases are Kaposi hemangioendotheliomas which are very aggressive, accompanied by platelet trapping and thrombocytopenia

Differential Diagnosis :

Cavernous hemangioma : Rarely present in infancy. It is the most common primary liver tumor in older age group and usually associated with other hemangiomas in the body. Cavernous hemangioma rarely presents with congestive cardiac failure. Ultrasonography shows solitary echogenic mass or multiple poorly reflective defects with scattered internal echoes. CT scan shows hypodense lesion with peripheral enhancement with subsequent variable opacification of the central part of hemangioma. . On angiography a well circumscribed mass is seen, with pooling of contrast saccules for more than 20 seconds with normally tapering vessels.( 4)

Hepatoblastoma : This is the most common symptomatic malignant tumour presenting before the age of 5 years. It may be single or multiple and commonly involves the right lobe of the liver. Commonly , the child presents with abdominal mass and is severely ill with weight loss, anorexia, pallor and weakness. The alpha feto-protein and HCG levels are usually elevated. Plain films show hepatomegaly or soft tissue mass with a different pattern of calcification. USG shows hyperechoic nonhomogeneous mass with hypoechoic areas within it secondary to necrosis and hemorrhage.. Duplex doppler sonography shows high velocity flow with frequency shift of 5 KHz in the hepatic artery - much higher than infantile hemangioendothelioma. A CT scan is a good preoperative modality to evaluate the lobar extension of tumor in the liver and metastases. CT scans show non enhancing, hypodense mass with variable calcification. Angiography shows hypervascular mass, stretching of intrahepatic vessels and puddling of contrast - but there is no early draining vein suggestive of AV shunting. 

Mesenchymal Harmartoma : This is thought to be a developmental anomaly rather than a true neoplasm. Usually, the patient presents with abdominal distension, fever, vomiting and constipation. The alpha feto-protein levels are within normal limits. Plain films show a soft tissue mass. USG shows a predominantly cystic mass with multiple echogenic septae. CT and MR imaging show a predominantly cystic mass of water attenuation with internal septae. Angiography shows an avascular to hypovascular mass with variable displacement of adjacent vascular and non vascular structures.

References : 

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