Liver haemangioma

INTRODUCTION
Haemangioma is the most common benign tumour of the liver (prevalence has ranged from 0.4 to 20 percent).

• At necropsy, the prevalence of liver haemangioma is 2–5%.
• Hepatic hemangiomas are also referred as cavernous hemangiomas because of the cavernous vascular space seen histologically.
• Hemangiomas are vary in size from a few millimeters to more than 20 cm.
• most of them are of less than 5 cm.
• Larger ones ( >5 cm) are referred to as giant hemangiomas.
• The size of liver haemangioma is greater in women than in men as well as the occurrence.
  
• In most of the cases they are solitary and many on the surface of roght lobe, but in 40 % of patients, hemangiomas may occur in multiples in bilateral lobes.
• Diagnosis is mostly made in the age range between 30 to 50 years.
• A symptomatic patient is mostly a young woman.

ETIOLOGY

1. In incompletely understood etiology, they are considered to be vascular malformation or hamartomas of congenital origin that enlarge by ectasia rather than by hyperplasia or hypertrophy.
2. Hormonal influence over tumor growth is suggested by enlargement during pregnancy and estrogen and progesterone therapy and regression after withdrawal of therapy.

PATHOLOGY

• On macroscopic examination, haemangioma may be located at the surface of the liver or inside the liver, can be found in both lobes of the liver but more oftenly in the right lobe.
• Lesions are well circumscribed and often surrounded by a thin capsule.
• The larger lesion may be pedunculated and on gross examination appear as cystic lesions with a dark color.
• On section it appears round or wedge shaped, dark red in colour and has a honeycomb pattern with spongy consistency and a fibrous capsule which may be calcified.
• Large hemangiomas may develop a collagenous scar or fibrous nodule as thrombosis occurs.
• On microscopic examination, liver haemangioma are composed of large vascular channels lined by mature, flattened endothelial cells, enclosed in a loose fibroblastic stroma with various amounts of connective tissue.
• Occasionally, there is a marked fibrous component.

In a few cases, they are associated with

• focal nodular hyperplasia of the liver,
• extrahepatic haemangioma or
• Rendu–Osler– Weber disease and
• bile duct hamartomas.

PRESENTATION

In most cases, liver haemangioma is asymptomatic and is recognized fortuitously by ultrasonography performed for symptoms that are either non specific or unrelated to haemangioma. Hemangiomas are typically discovered incidentally at laparotomy, autopsy, or during an imaging test performed for unrelated conditions.

• In a few patients, liver haemangioma is recognized because of abdominal pain which is often due to associated irritable colon.
• In one report, for example, abdominal pain was due to other causes in 54 percent of patients .
• The most common symptoms are abdominal pain and right upper quadrant discomfort or fullness.
• Lesions >4 cm are more likely to cause symptoms .
• Acute abdominal pain can result from thrombosis or bleeding within the tumor and associated stretching and inflammation of Glisson's capsule.
• Discomfort from an acute thrombosis can last up to three weeks and be associated with fever and abnormal liver function tests.
• Giant hemangiomas in children have been associated with high output cardiac failure and hypothyroidism. Hypothyroidism is due to the presence of high levels of 3 iodothyronine deiodinase activity in the hemangioma tissue, which catalyzes the conversion of thyroxine and triiodothyronine to biologically inactive hormones, reverse triiodothyronine, and 3,3'-diiodothyronine.
• High output cardiac failure is reported in numerous case reports.
• Cutaneous hemangiomas in children may be a marker for hepatic hemangiomas.
• The presence of a single large cutaneous hemagioma was generally associated with a single hepatic hemangioma while multiple or milliary cutaneous hemangiomas were associated with the presence of multiple hepatic hemangiomas.
  
• Large haemangiomas can be complicated by thrombocytopenia, consumptive coagulopathy, and microangiopathic anaemia (Kasabach–Merritt syndrome).

Clinical examination is normal in most cases, except in the few patients in whom a large haemangioma results in a palpable tumour. A bruit is seldom heard over the hemangioma.

Liver tests are normal, except in patients in whom haemangioma is associated with an unrelated diffuse liver disease.

DIAGNOSIS

Radiology. A plain X-ray may show a calcified capsule.

Ultrasonography

• liver haemangioma appears as a well-defined hyperechoic area.
• If the liver is fatty, haemangioma may be as echoic as, or even less echoic, than the rest of the liver parenchyma.
• The hemangioma may be hypoechoic in patients with fatty infiltration of the liver due to the bright signal from the surrounding parenchyma.
• Blood flow within the hemangioma can be demonstrated by color Doppler in only 10 to 50 percent of hemangiomas, and thus color Doppler does not improve the accuracy of ultrasound.
• Sonographic findings also depend upon the size of the hemangioma.

One study characterized 158 hemangiomas as follows:

• Lesions <2>
• Lesions between 2 and 5 cm were mainly echogenic.
• Lesions >5 cm had mixed echogenicity probably because of intratumoral thrombosis and fibrosis.

CT

• On a computed tomography (CT) scan without contrast, liver haemangioma appears as a hypodense area.
• Calcifications are seen in approximately 10 percent of cases.
• On a CT scan after intravenous injection of a contrast bolus, there is an irregular, globular enhancement in the periphery of the lesion; this anomaly is very characteristic; after several minutes, the area of enhancement increases towards the center of the lesion.
• Peripheral nodular or globular enhancement representing venous lakes is seen in up to 94 percent of hemangiomas >4 cm in size.
• A pattern of globular enhancement isodense to the aorta is seen in 67 percent of hemangiomas, a feature that helps distinguish them from hepatic metastases.
• The lesions classically opacify after a delay of three or more minutes and remain isodense or hyperdense on delayed scans.
• Possible exceptions are hemangiomas >4 cm, in which the center of the lesion may not opacify completely.
• Variations in vascular enhancement among hemangiomas may be due to differences in the size of the vascular spaces, the presence of cystic spaces, and the amount of scar tissue within hemangiomas.
• Absence of enhancement is seen in hemangiomas with large cystic areas or scar tissue.

MRI

The most sensitive and specific procedure for diagnosing hepatic haemangioma is magnetic resonance imaging (MRI):

• The typical MRI appearance is a smooth, well-demarcated homogeneous mass that has low signal intensity on T1-weighted images and is hyperintense on T2-weighted.
• The presence of intratumoral fibrosis results in areas of low intensity on T2-weighted images.
• In a few patients, haemangioma appears as an hypervascular area and/or is associated with an arterioportal shunt.
• Administration of gadolinium results in early peripheral discontinuous nodular or globular enhancement on arterial phase imaging with progressive centripetal enhancement or "filling-in" on delayed scans similar to that seen on CT scanning.
• This enhancement pattern is typical of most hemangiomas >2 cm;
• tumors <2>
• Small hemangiomas that demonstrate rapid uniform enhancement are sometimes indistinguishable from hypervascular metastases of hepatocellular carcinoma.

Arteriography is no longer used for the diagnosis of haemangioma.

• Large arterial branches are displaced.
• The hepatic arteries divide to form small vessels before filling the vascular space. Prolonged, up to 18 s, opacification of the lesion may be shown.

SPECT
Scanning with 99Tcm-labelled human red cells is no longer used for the diagnosis of haemangioma (labelled red cells accumulate within the haemangioma).

• The diagnosis of haemangioma is reinforced by the absence of changes of the lesion on a second series of imaging procedures (ultrasound or CT scan) six months later.
• Single-photon emission CT (SPECT) using 99mTc-RBC increases the spatial resolution of planar scintigraphy, providing sensitivity and accuracy close to that of MRI for lesions >1 cm.
• SPECT with 99mTc-labelled red blood cells shows persistent blood pool activity within the lesion.
• The best use of 99mTc-RBC SPECT is for lesions >2 cm to confirm a suspected hemangioma seen as a hyperechoic lesion in ultrasound and to clarify the diagnosis when CT findings are unclear.

Imaging in patients with cirrhosis — The diagnosis of a hepatic hemangioma can frequently be made confidently with ultrasound in patients without a prior history of malignancy or chronic liver disease.

In contrast, the hyperechoic metastases and hepatocellular carcinoma (HCC) may have similar sonographic characteristics and are more likely in such patients. As a result, multiple imaging modalities and serum AFP determination may be required to differentiate a benign hemangioma from a malignant lesion in these settings.

• This was illustrated in a study that included 1982 patients with cirrhosis of whom 166 (8 percent) had a focal lesion. Of these 166 patients:
• Ultrasound showed the presence of a hemangioma-like lesion in 44 patients with a normal AFP.
• Contrast-enhanced CT confirmed hemangioma in 12 of the 44 patients.
• 99mTc-RBC confirmed hemangioma in 10 of the remaining 32 patients.
• Fine needle aspiration biopsy (FNAB) confirmed the presence of HCC in the remaining 22 patients.
• During follow-up a further 26 hemangioma-like lesions were identified on US, 22 of which were confirmed as HCC and four as dysplastic nodules.

BIOPSY -

• It is generally admitted that liver biopsy may be dangerous because of the risk of haemoperitoneum.
• However, liver biopsy has been performed in some patients without being complicated by intraperitoneal bleeding.
• Because liver haemangioma is soft, the tumour is pushed by the liver biopsy needle and therefore, often no fragment of the tumour is collected.

NATURAL HISTORY

1. Unchanged - Usually, liver haemangioma does not increase in size with time.
2. Growth- However, it has been reported that, during pregnancy or during estrogen therapy, the tumour may grow. In a small number of patients, in the absence of pregnancy and oestrogen therapy, the tumour may increase in size.
3. Spontaneous rupture of liver haemangioma is very rare. It usually occurs in large hemangiomas that are peripherally located, however, follow-up of giant hemangiomas (tumors >5 cm in size) has shown that even these rarely enlarge or rupture.
4. Traumatic rupture of cavernous hemangioma following blunt trauma to the abdomen is also rare but highlights that traumatic rupture of the liver may be associated with underlying liver pathology.
5. Iatrogenic rupture or intratumoral bleeding has been described following liver biopsy or fine needle aspiration, which has resulted in a reluctance of most physicians to perform such tests in patients with known or suspected hemangiomas.
6. Other complication –

• Thrombosis, which results in a triad of symptoms consisting of fever, right upper quadrant abdominal pain, and normal white cell count.
• thrombocytopenia,
• consumptive coagulopathy, and
• microangiopathic anaemia (Kasabach–Merritt syndrome).
• In the few cases with arterioportal shunt, heart failure can develop. Large haemangiomas can result in abdominal discomfort.

TREATMENT

• In most patients, liver haemangioma needs no treatment.
• Asymptomatic patients, particularly those with lesions <1.5>
• A close radiologic follow-up is required in patients with lesions >5 cm, particularly those in a sub capsular location.
• Complicated liver haemangioma must be treated surgically by liver resection, enucleation, hepatic artery ligation, and liver transplantation.
• Patients who have pain or symptoms suggestive of extrinsic compression of adjacent structures should be considered for surgical resection.
• Orthotopic liver transplantation has also been used successfully to treat symptomatic patients with unresectable giant hemangiomas and hemangiomas associated with Kasabach-Merritt syndrome.
• Spontaneous rupture of liver haemangioma can be treated by transcatheter hepatic arterial embolization, which can be followed by surgical resection.

Non-surgical techniques include

• hepatic artery embolization,
• radiotherapy, and
• interferon alpha-2a.

Interferon alpha-2a has been used in infants with life-threatening hemangiomas in extrahepatic sites, although success has not been uniform. Its efficacy for hepatic hemangiomas has not been well studied. Interferon probably works as an antiproliferative/antiangiogenic agent.

• Neither oral contraceptives nor pregnancy are contraindicated in women with uncomplicated liver haemangioma.

Hepatic haemangiomatosis
Hepatic haemangiomatosis, i.e. haemangioma involving the liver entirely and diffusely, is very rare. It can be isolated or associated with extrahepatic haemangioma or with Rendu– Osler–Weber disease. A case has been reported in a patient receiving metoclopramide. Heart failure , intraperitoneal bleeding and Kasabach–Merritt syndrome are common.