Cavernous Hepatic Hemangioma

Etiology

The etiology of hepatic hemangiomas is not completely understood. 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. Some tumors may even grow in the absence of estrogen therapy.[4] Several associated abnormalities include focal nodular hyperplasia of the liver and Kasabach-Merritt syndrome, consisting of multiple hemangiomas throughout the body, elevated fibrin degradation products, and thrombocytopenia.

Epidemiology

Hepatic hemangiomas are 5 times more common in females than males. They can be seen in any age group, but the majority are diagnosed in those between the ages of 30 and 50 (60 % to 80%). The prevalence may be higher, but since they are generally asymptomatic, they are not often diagnosed unless the patient is undergoing abdominal imaging for unrelated causes.

Histopathology

Microscopically, cavernous hepatic hemangiomas appear as cavernous vascular spaces. They are lined by endothelium and contain a fibrous stroma. In larger hemangiomas, a fibrous nodule or collagen scar may be seen. Grossly, the lesions are sponge-like in consistency and red to brown. They are encased in a thin capsule and well-circumscribed. They range from millimeters in size to more than 10 cm.

History and Physical

Generally, hepatic hemangiomas are asymptomatic and found in imaging studies for other reasons, such as 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 bleeding occurs within the lesion, this can lead to expansion and inflammation of the capsule of Glisson and acute abdominal pain. When the hemangioma becomes large, symptomatology is related to the compression of adjacent structures (ie, early satiety from gastric compression). Physical exams and laboratory testing are usually non-contributory. Rarely are a palpable mass or changes in liver function tests observed.

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 that multiple modalities are required for a 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.[5][6][7] 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-contrast CT, a hemangioma may appear as a well-circumscribed mass with the same density or hypodense to blood vessels and liver. There may be some heterogeneity and a low-density central scar when large enough. Calcifications are rarely seen. Contrasted CT demonstrates 88% sensitivity and 84% to 98% specificity for diagnosing 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.

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 hepatocellular carcinoma. 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 CT. Smaller hemangiomas demonstrate flash-filling and may mimic hepatocellular carcinoma in the setting of hepatic cirrhosis. Another modality employed is the Technetium-99m pertechnetate-labeled red blood cell scan with single-photon emission CT. There is similar sensitivity to MRI for lesions greater than 1 c,m, but it 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 / Management

In asymptomatic patients, treatment is not necessary. Observation and long-term follow-up may be considered; however, most patients do not require imaging follow-up in lesions less than 5 cm unless rapid growth or diagnosis is uncertain. As mentioned before, a percutaneous biopsy is not indicated, given the risk of hemorrhage.[8][9][10] In symptomatic patients or those with hemangiomas large enough to cause mass effects, 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.(B2)

Non-surgical Treatment Options

• Hepatic artery embolization: manage acute bleeding symptoms and decrease size before surgical resection
• Radiotherapy: rarely utilized and reserved for those lesions associated with Kasabach-Merritt Syndrome. It may aid in decreasing the tumor size but has increased secondary risks of malignancy.
• Interferon alfa-2a: may work as an anti-angiogenic agent, but success has not been proven.

Differential Diagnosis

Cholangiocarcinomas demonstrate delayed persistent enhancement on CT and MRI; however, they tend to be heterogeneous on CT/MRI and less hyperintense on T2-weighted images. Additionally, they often invade or obstruct vasculature and bile ducts. Hypervascular metastases should be considered in the setting of extra-hepatic malignancy. These tend to be multiple at the time of presentation and show contrast washout on delayed phase images. Hepatic angiosarcomas also tend to be multiple at the time of presentation, demonstrate vascular invasion, and are more aggressive. These also tend to show contrast washout on delayed phase imaging. Lesions may also be present within the spleen.

Prognosis

Most patients with hepatic hemangiomas show no symptoms, but symptoms are more likely to be present in patients with large lesions. The prognosis tends to be favorable.

Complications

Complications may include spontaneous rupture or abscess formation, but these are rare. Symptomatic patients with these tumors, especially those with abdominal pain, can be attributed to concomitant GI diseases, particularly IBS, as the lesion itself does not result in symptoms.[11] Women with hepatic hemangiomas may encounter complications if they become pregnant, as the increased estrogen accompanying pregnancy may cause the hemangioma to grow. Other complications can include compression of other structures, bleeding, clot accumulation, and calcification.