Hepatic Hemangiomas – Causes, Symptoms, Treatment

Hepatic hemangiomas are benign, hypervascular, venous malformations that occur in the liver. They are the most common benign mesenchymal tumors of the liver. Hemangiomas are lined by endothelial cells with a thin fibrous stroma. They are also known as cavernous or capillary hepatic hemangiomas. They are generally asymptomatic and incidentally found on imaging. Often found as solitary lesions, but multiple lesions may also be present. They are categorized by size. Small hemangiomas are 1 cm to 2 cm, typical hemangiomas are 2 cm to 10 cm, and giant hemangiomas are greater than 10 cm.[rx][rx][rx]

Hemangiomas may occur in various other regions of the body, such as the spinal cord, orbits, or vertebral bodies, but this article will focus on hepatic hemangiomas.

Types

• Typical hepatic hemangioma
• Atypical hepatic hemangioma
  • Giant hepatic hemangioma
  • Flash filling hepatic hemangioma – can account for up to 16% of all hepatic hemangiomas
  • Calcified hepatic hemangioma
  • Hyalinized hepatic hemangioma
  • Other unusual imaging patterns
    • Hepatic hemangioma with capsular retraction
    • Hepatic hemangioma with surrounding regional nodular hyperplasia
    • Hepatic hemangioma with fatty infiltration
    • Pedunculated hepatic hemangioma
    • Cystic hepatic hemangioma – rare
    • Fluid-fluid level containing hepatic hemangioma – rare

Causes of Hepatic Hemangiomas

The etiology is not completely understood for hepatic hemangiomas. They sporadically occur without any known predisposing factors. When hemangiomas are greater than 10 cm, they are considered giant hemangiomas. Since they are considered vascular malformations, they enlarge by ectasia rather than hyperplasia or hypertrophy. In pregnancy, the hemangioma may grow secondary to the increase in hormones (estrogen and progesterone); however, estrogen receptors have not been proven in all tumors, and some tumors may even grow in the absence of estrogen therapy.[rx]

IH and CH are both vascular tumors of infancy but differ in their underlying cause and clinical course. The underlying pathogenesis in both cases is only partially understood. In the case of IH, it is theorized lesions form as a product of dysregulation of vasculogenesis and angiogenesis. Hypoxic stress appears to be a triggering signal, prompting over-expression of VEG-F and other angiogenic factors, leading to an abnormal proliferation of fetal endothelial cells. [rx]

In the case of CH, somatic activating mutations are implicated in their pathogenesis. Recent studies have demonstrated mutations in the alleles GNAQ and GNA11 in CH. Interestingly, both RICH and NICH demonstrate similar mutations, suggesting their different clinical behavior may be the result of post-natal factors or epigenetics.[rx]

Several associated abnormalities include focal nodular hyperplasia of the liver and Kasabach-Merritt syndrome, which consists of multiple hemangiomas throughout the body, elevated fibrin degradation products, and thrombocytopenia.

Symptoms of Hepatic Hemangiomas

HH is usually asymptomatic, however, symptoms may present when a HH is larger than > 5 cm[rx].

• Symptoms are nonspecific, patients usually describe abdominal pain, discomfort, and fullness in the right upper quadrant, secondary to stretching and inflammation of the Glisson’s capsule.
• Tumors > 10 cm present with abdominal distention[rx,rx]. The location of the liver mass may cause pressure and compression of adjacent structures causing other symptoms such as nausea, early satiety, and postprandial bloating.
• Less commonly associated symptoms include fever, jaundice, dyspnea, high-output cardiac failure, and haemobilia[rx–rx].
• Giant HH may cause a life-threatening coagulation disorder known as Kasabach-Merrit syndrome (thrombocytopenia, disseminated intravascular coagulation, and systemic bleeding) presenting with coagulopathy secondary to thrombocytopenia, anemia, hypofibrinogenemia, a decrease in prothrombin time, and increase in D-dimer. This syndrome has been reported with an incidence ranging from 0.3% of all HH to 26% in tumors > 15 cm[rx,rx].
• Another serious complication is bleeding from spontaneous or traumatic rupture (in peripherally located and exophytic giant lesions), however, the risk is extremely low (0.47%)[rx].

If a hemangioma is larger than 4 cm in diameter, it may cause the following symptoms:

• Abdominal discomfort and bloating
• Nausea
• Loss of appetite
• Pain
• A sense of fullness after eating a small meal
• Poor appetite
• Feeling full quickly when eating a meal
• Nausea
• Vomiting
• Feeling bloated after eating

Diagnosis of Hepatic Hemangiomas

Histopathology

• Microscopically, these appear as cavernous vascular spaces, hence the alternative name of cavernous hemangiomas. They are lined by endothelium and contain a fibrous stroma and blood products. In larger hemangiomas, a fibrous nodule or collagen scar may be seen.
• Grossly, the lesions are a sponge-like consistency with a red to brown coloration. They are encased in a thin capsule and well circumscribed. They range from millimeters in size to some greater than 10 cm.

History and Physical

• Generally, hepatic hemangiomas are asymptomatic and found in imaging studies for other reasons, for example, laparotomy or autopsy. Hemangiomas greater than 4 cm, however, tend to cause abdominal pain and discomfort.
• The most common symptoms are right upper quadrant pain, generalized abdominal pain, or abdominal fullness. If there is bleeding within the lesion, this can lead to expansion and inflammation of Glisson’s capsule and lead to acute abdominal pain. When the hemangioma becomes large, symptomatology is related to compression of adjacent structures (i.e., early satiety from gastric compression).
• Physical exam and laboratory testing are usually non-contributory. Rarely, there will be a palpable mass or changes in the liver function tests.

Evaluation

Hepatic hemangiomas can be characterized, and diagnosis can be made by computed tomography (CT), magnetic resonance imaging (MRI), or ultrasound (US). It is important to note though, that multiple modalities are required for definitive diagnosis. Percutaneous biopsy is generally not recommended due to the risk of fatal hemorrhage. Diagnosis can be complicated further in the setting of cirrhosis or extra-hepatic malignancy. Thus additional testing/imaging may be required.[rx][rx][rx]

• Ultrasound demonstrates – a homogenous, well-defined, hyperechoic mass. If the patient has hepatic steatosis, the hemangioma may appear as hypoechoic. Color Doppler does not add additional diagnostic value. When lesions are larger than 5 cm, some heterogeneity may be demonstrated. Giant hemangiomas are lobulated, heterogeneous masses with a hyperechoic border. The imaging characteristics of hemangiomas on ultrasound are not diagnostic. Therefore, additional imaging is usually required.
• On a non-contracted CT – a hemangioma may appear as a well-circumscribed mass that is generally the same density or hypodense to blood vessels and liver. When large enough, there may be some heterogeneity and a low-density central scar. Calcifications are rarely seen.
• Contrasted CT – demonstrates 88% sensitivity and 84% to 98% specificity for the diagnosis of a hemangioma. On contrasted CT, the typical hemangioma demonstrates peripheral, discontinuous, nodular enhancement on arterial phase images with progressive centripetal filling on venous phase images. On delayed phase images, there is persistent complete filling. Giant hemangiomas follow a similar pattern. However, there may be a central scar, which does not fill/enhance.
• Computerized tomography (CT) scanning – which combines a series of X-ray images taken from different angles around your body and uses computer processing to create cross-sectional images (slices) of the liver
• Magnetic resonance imaging (MRI) – a technique that uses a magnetic field and radio waves to create detailed images of the liver
• Scintigraphy – a type of nuclear imaging that uses a radioactive tracer material to produce images of the liver
• Angiography – is the best option for atypical HH that is difficult to diagnose with another imaging test. HH appears as a snowy-tree or cotton wool with a large feeding vessel and diffuse pooling of contrast that continues during the delayed phase. Technetium-99m pertechnetate-labeled red blood cell pool scintigraphy, single-photon emission computed tomography, and positron emission tomography/CT are other imaging modalities available to diagnose HH in patients with atypical tumors, a history of chronic liver disease, or malignancy[rx,rx].
• Needle aspiration biopsy – is not recommended because of the high risk of hemorrhage and a low diagnostic yield[rx–rx].

Other variations include

Atypical hemangiomas may appear to enhance in a centrifugal pattern from the inside.

• In the background of hepatic cirrhosis, the hemangioma may lose the characteristic enhancement pattern, and the flash-filling of small hemangioma can often mimic a hepatocellular carcinoma (HCC).
• MRI is 90% sensitive and 91% to 99% specific for diagnosing hepatic hemangiomas. The typical hemangioma appears hypointense on T1-weighted images and hyperintense on T2-weight images. They are well-circumscribed and homogenous. On postcontrast imaging, the lesions demonstrate the typical peripheral, discontinuous, nodular enhancement with a delayed centripetal filling of the lesion, similar to that of CT. Smaller hemangiomas demonstrate flash-filling and again, may mimic HCC in the setting of hepatic cirrhosis.
• Another modality that may be employed is the Technetium-99m pertechnetate-labeled red blood cell scan with single-photon emission CT (SPECT). There is similar sensitivity to that of MRI for lesions greater than 1 cm but has not been proven to have the same diagnostic value. Hemangiomas show hypoperfusion or a focal defect during the early dynamic scan with increased tracer uptake peaking approximately 30 to 50 minutes post-injection. The tracer remains within the lesion on delayed phase images. False negatives may occur secondary to fibrosis or thrombosis.

Treatment of Hepatic Hemangiomas

In asymptomatic patients, treatment is not necessary. Observation and long-term follow up may be a consideration; however, most patients do not require imaging follow up in lesions less than 5cm unless there is rapid growth or diagnosis is uncertain. As mentioned before, a percutaneous biopsy is not indicated given the risk of hemorrhage.[rx][rx][rx]

In symptomatic patients or those with hemangiomas large enough causing mass effect, surgical resection should be considered after other causes of pain have been excluded. Surgical resection options are liver resection, hepatic artery ligation, enucleation, and in severe cases liver transplantation. Surgery is not entirely curative for symptoms, as it has been reported that 25% of those undergoing resection had persistence of symptoms.

Surgery continues to be the most common treatment for HH. Surgical management includes liver resection, enucleation, hepatic artery ligation, and liver transplantation. The most common procedures worldwide are liver resection and enucleation (open surgery, laparoscopy, or robot)[rx–rx].

The choice of procedure depends on the size, number of lesions, location, surgeon experience, and institutional resources. Both techniques carry minimal postoperative morbidity.

In the last years, several studies have evaluated enucleation vs hepatectomy and most have concluded that enucleation is associated with lower morbidity, shorter operation time, less blood loss, and fewer complications[rx,rx,rx]. However, when HH is larger than 10 cm, Zhang et al[rx] found no difference in operation time, blood loss, complications, or hospital stay between enucleation and resection.

Enucleation is technically easier in peripherally located HH, when done in centrally located HH the procedure causes a longer vascular inflow occlusion time, longer operating time and more blood loss[rx]. Centrally located HH (Segments I, IV, V and VIII) are treated with extended right and left hepatectomy. This therapy may remove 60% to 80% of liver parenchyma, which conveys a higher risk of postsurgical liver failure. Some lesions are suitable for a wedge resection[rx].

Improvement in laparoscopic surgery has increased the cases treated with minimally invasive surgery for either resection or enucleation. Laparoscopic liver surgery is preferred in small, left lateral lesions with minor resections[rx,rx].

A recent retrospective study compared open versus laparoscopic liver surgery for HH; results favored laparoscopic therapy with less blood loss, lower complication rates, and a shorter postoperative hospital stay. However, baseline patient characteristics between the two groups were not equal as surgeons decided open or laparoscopic surgery based on tumor characteristics[rx].

Liver transplantation for benign solid tumors is not considered a first-line treatment due to morbidity and organ shortage. A study published in 2015 analyzed data from the United Network of Organ Sharing from 1988 to 2013 and found 147 (0.17%) liver transplants in US patients were performed for benign tumors of the liver, including 25 for HH[rx].

Liver transplantation is reserved for unresectable giants HH causing severe symptoms (respiratory distress, abdominal pain), failure of previous interventions, or life-threatening complications such as Kasabach Merrit syndrome[rx,rx].

Complications

Complications depend on the size and location of the hemangioma and include:

• Mechanical complications:
  • Rupture (spontaneous or from physical trauma)
  • Compression (pushing) against surrounding organs such as the stomach (leading to feelings of fullness soon after beginning a meal); bile ducts (leading to jaundice); or the liver capsule (which causes pain)
• Bleeding complications, either inside the tumor or outside the tumor into the abdominal cavity
• Degenerative complications, such as blood clotting inside the hemangioma, or the development of calcifications (calcium deposits in the tumor) or scar tissue

References