AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Hemangioma is the most common benign tumor affecting the liver. Hepatic hemangiomas are mesenchymal in origin and usually are solitary. Some authorities consider them to be benign congenital hamartomas. Hemangiomas are composed of masses of blood vessels that are atypical or irregular in arrangement and size. Etiology remains unknown.

Pathophysiology

Although no definite familial or genetic mode of inheritance has been described, Moser et al reported a large family of Italian origin in which 3 female patients in 3 successive generations had large symptomatic hepatic hemangiomas. The authors postulated that restriction of the disease to the female sex could be explained by sex-dependent differences in penetrance, the expression of a presumed liver-hemangioma gene, or the production of proliferative factors, such as female sex hormones.

Several pharmacologic agents have been postulated to promote tumor growth. Steroid therapy, estrogen therapy, and pregnancy can increase the size of an already existing hemangioma. One recent study prospectively evaluated 94 women with hepatic hemangiomas, with a mean follow-up period of 7.3 years (range, 1-17 y). An increase in the size of the hemangiomas was seen in 23% of women who received hormonal therapy as opposed to 10% of control subjects (P=0.05). Hemangiomas have also been reported in pregnant women following ovarian stimulation therapy with clomiphene citrate and human chorionic gonadotropin.

Frequency

United States

The reported incidence rate of hepatic hemangiomas is approximately 2%. The prevalence rate at necropsy is as high as 7.4%. The widespread use of noninvasive abdominal imaging modalities has led to increased detection of asymptomatic lesions in vivo.

Sex

Women, especially with a history of multiparity, are affected more often than men. The female-to-male ratio is 4-6:1. Female patients often present at a younger age and with larger tumors.

Age

Hepatic hemangiomas can occur at all ages. Most hepatic hemangiomas are diagnosed in individuals aged 30-50 years.

• Female patients often present at a younger age and with larger tumors.
• Hepatic hemangiomas are rare in infancy.
• They recently have been detected prenatally in a growing fetus.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

• Hemangiomas present a diagnostic challenge because they can be mistaken for hypervascular malignancies of the liver and can coexist with (and occasionally mimic) other benign and malignant hepatic lesions, including focal nodular hyperplasia, hepatic adenoma, hepatic cysts, hemangioendothelioma, hepatic metastasis, and primary hepatocellular carcinoma.
• The disorder is asymptomatic and often is detected incidentally when the liver is imaged for other reasons.
• Very rarely, patients may present with symptoms of an enlarging liver lesion or with shock from rupture of the lesion.

Physical

• Hepatic hemangiomas can occur as part of well-defined clinical syndromes.
• • In Klippel-Trenaunay-Weber syndrome, hepatic hemangiomas occur in association with congenital hemiatrophy and nevus flammeus, with or without hemimeganencephaly.
  • In Kasabach-Merritt syndrome, giant hepatic hemangiomas are associated with thrombocytopenia and intravascular coagulation.
  • Osler-Rendu-Weber disease is characterized by numerous small hemangiomas of the face, nares, lips, tongue, oral mucosa, gastrointestinal tract, and liver.
  • Von Hippel-Lindau disease is marked by cerebellar and retinal angiomas, with lesions also in the liver and pancreas.
  • Multiple hepatic hemangiomas have been reported in patients with systemic lupus erythematosus.
• Cutaneous hemangiomas are a common finding. Whether or not they are associated with hepatic hemangiomas is unclear.
• Pathology
  • Hemangiomas usually are solitary. Multiple and diffuse hepatic lesions are seen infrequently. Sizes range from 2 mm to more than 20 cm. Grossly, these lesions often appear as having a flat surface or as bulging subcapsular lesions.
  • Lesions are reddish-blue and well demarcated from surrounding tissue. Large tumors may become pedunculated.
  • Histologically, the tumor is thin walled. Its vascular spaces are lined by a single layer of endothelial cells that are separated by fibrous septa.
• Clinical features
• • Cavernous hemangiomas of the liver usually are small and asymptomatic. They most often are discovered when the liver is imaged for another reason or when the liver is examined at laparotomy or autopsy. Larger and multiple lesions may produce symptoms.
  • Right upper quadrant pain or fullness is the most common complaint. In some cases, pain is explained by thrombosis and infarction of the lesion, hemorrhage into the lesion, or compression of adjacent tissues or organs. In other cases, pain is unexplained.
  • The only findings upon physical examination are, infrequently, an enlarged liver or the presence of an arterial bruit over the right upper quadrant.
  • Rarely, hemangiomas may present as a large abdominal mass. Other atypical presentations include (1) cardiac failure from massive arteriovenous shunting, (2) jaundice from compression of the bile ducts, (3) gastrointestinal bleeding from hemobilia, and (4) fever of unknown origin.
  • An illness that resembles a systematic inflammatory process has been described with findings of fever, weight loss, anemia, thrombocytosis, increased fibrinogen level, and elevated erythrocyte sedimentation rate.
• Differential diagnosis: Hepatic hemangiomas should be differentiated from other benign and malignant space-occupying liver lesions.
• • Benign lesions include cysts, adenomas, focal nodular hyperplasia, and regenerating nodules.
  • Malignant lesions include hepatocellular carcinoma and metastasis.
• Complications
• • Complications depend on the size and location of the tumor. Large tumors can rupture spontaneously or after blunt trauma.
  • Patients may present with signs of circulatory shock and hemoperitoneum.
  • Early satiety, nausea, and vomiting may occur when large lesions compress the stomach, producing gastric outlet obstruction.
  • One case has been reported of lower extremity edema caused by compression of the inferior vena cava by a cavernous hemangioma of the caudate lobe of the liver.

Causes

Oral contraceptives and steroids may accelerate the growth of a hemangioma. Whether or not these drugs actually induce the formation of the hemangioma is unclear.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Benign liver tumors (eg, cysts, adenomas, regenerating nodules, focal nodular hyperplasia, abscesses)
Malignant liver tumors (eg, hepatocellular carcinoma, hepatic metastases)

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Routine laboratory tests
• • Results usually are normal.
  • Thrombocytopenia can result from sequestration and destruction of platelets in large lesions.
  • Hypofibrinogenemia has been attributed to intratumoral fibrinolysis.
  • Normal alpha-fetoprotein, CA 19-9, and carcinogenic embryonic antigen (CEA) levels bolster clinical suspicion of a benign hepatic mass lesion.

Imaging Studies

• The modalities used to aid in the diagnosis of hepatic hemangiomas include ultrasonography (US), dynamic contrast-enhanced computed tomography (CT), nuclear medicine studies using technetium (Tc) 99m-labeled RBCs, magnetic resonance imaging (MRI), hepatic arteriography, and digital subtraction angiography (DSA).
• Ultrasound
• • This is the most commonly employed initial diagnostic tool. It is widely available and inexpensive. Hepatic hemangiomas usually are echogenic, but their sonographic appearance is variable and nonspecific.
  • Addition of color Doppler to routine US provides qualitative and quantitative data and increases the sensitivity and specificity of the test. Serial US examinations can be used to monitor any increase in size of the hemangioma over time.
  • Recent work has studied the use of microbubble-enhanced US. Lesions show peripheral puddles and pools of enhancement that expand in a centripetal pattern during the portal venous phase of enhancement. With delayed imaging, the lesion may completely "fill in." However, complete enhancement might not occur in large lesions where central thrombosis or scarring may be present. In one recent study, the addition of a contrast agent to routine US improved sensitivity from 78% to 100% and specificity from 23% to 92%.
  • In general, the US finding of a suspected hemangioma should be diagnostically integrated with CT scan or MRI to assure a correct diagnosis.
• Computed tomography
• • Dynamic contrast-enhanced CT scanning is preferred to routine CT scanning. When requesting a CT scan to investigate a liver mass, the physician should inform the radiologist about the need for nonenhanced, arterial, portal venous and delayed imaging (the so-called triple phase CT with delayed imaging).
  • First, the liver is imaged by CT before the administration of intravenous contrast. The next series of images is obtained about 30 seconds after the injection of contrast, at the time that contrast is entering the liver via the hepatic artery. Portal venous imaging occurs 60 seconds later, as contrast is returning to the liver from the mesenteric veins via the portal vein. Finally, delayed images are obtained several minutes later.
  • Hepatic hemangiomas are typically hypodense on precontrast imaging. In arterial phase, there may be enhancement of the peripheral portions of the lesion. There may be ring enhancement or globular enhancement. The center of the lesion typically remains hypodense.
  • In portal venous phase and in delayed images, contrast enhancement progresses centripetally. The center of the lesion may only become hyperdense in delayed images.
• Magnetic resonance imaging
• • MRI is highly sensitive and specific in the diagnosis of hepatic hemangioma. Typically, hemangiomas have low signal intensity on T1-weighted images and high signal intensity on T2-weighted images. When gadolinium is employed as an intravenous contrast agent, hemangiomas enhance in a fashion similar to that seen on dynamic CT.
  • Diagnostic accuracy diminishes for all imaging modalities when assessing a liver lesion that is less than 2 cm in diameter. MRI and 99mTc-RBC single-photon emission computerized tomography (SPECT) (see Nuclear medicine studies below) are the most accurate radiologic studies to establish a diagnosis of small hepatic hemangiomas.
  • Giant cavernous hemangiomas (ie, > 5 cm in diameter) may exhibit internal fluid levels on MRI and CT scan images. This finding is attributed to the separation of blood cells and serous fluid due to extremely slow blood flow through the tumor.
• Nuclear medicine studies
• • Tc-99m pertechnetate-labeled RBC pool studies have been used for many years to help diagnose hepatic hemangiomas. For lesions that are greater than 2 cm in diameter, the sensitivity of the test has been reported at 82%. The specificity is up to 100%. SPECT with 99mTc-labeled RBCs improves the sensitivity of the test for detecting small hemangiomas.
  • Some investigators consider SPECT with 99mTc-labeled RBCs to be the criterion standard to establish a diagnosis of hepatic hemangiomas. However, the test may still miss some lesions. Also, pedunculated giant liver hemangiomas have been reported to mimic hypervascular gastric tumors on SPECT.
  • SPECT technology is not available universally. The authors continue to regard MRI as the diagnostic test of choice at most centers. Nuclear medicine studies may be used to confirm the diagnosis when a probable hemangioma is detected on US. Nuclear medicine studies may also help to clarify the nature of a lesion when the diagnosis is equivocal on CT or MRI.
• Accuracy of imaging studies: The diagnostic capabilities of US, Doppler color US, dynamic CT scan, and MRI were compared in a retrospective study of 27 patients with 35 hemangiomas. Sensitivities were reported as follows:

  Accuracy of Imaging Studies

  Imaging Tools	Sensitivity (%)
  US	46
  Combined B-mode and color Doppler US	69
  Contrast-enhanced CT scan	66
  T2-weighted MRI	96
  Gadolinium-enhanced MRI combined with dynamic CT scan	100

• Arteriography: The diagnostic accuracy of noninvasive tests has obviated the need for hepatic arteriography in most cases. However, this invasive modality still may be useful in helping diagnose some hepatic hemangiomas.
• • Branches of the hepatic artery may be displaced and crowded together or stretched around the lesion, with normal vascular tapering.
  • Hemangiomas are characterized by the early opacification of irregular areas or lakes, with persistence of contrast in these areas long after arterial emptying. The hemangioma may appear as a ring or C-shaped lesion with an avascular center.

Procedures

• Liver biopsy
• • Percutaneous biopsy of a hepatic hemangioma carries an increased risk of hemorrhage. Liver biopsy is contraindicated in most circumstances where a hemangioma is high in the differential diagnosis of a hepatic mass.
  • Liver biopsy can help provide an unequivocal histologic diagnosis and may shorten the diagnostic workup. One study reported the safe performance of US-guided 18-gauge core needle biopsy in 51 hemangiomas ranging in size from 7-114 mm.
  • Some authorities contend that either percutaneous liver biopsy or laparoscopic liver biopsy may be reasonable to perform in cases where a small liver lesion must be differentiated from hepatocellular carcinoma. However, since 2001, hepatologists and surgeons have been increasingly resistant to include liver biopsy in the diagnostic workup of suspected hepatocellular carcinoma. The diagnosis of most hepatocellular carcinomas can be made by using a combination of CT and MRI. Liver biopsy is only used when radiologic study results and alpha fetoprotein testing are equivocal.

Histologic Findings

Microscopically, hemangiomas are composed of cavernous vascular channels. The channels are lined by single layers of flattened endothelium and are separated by fibrous septa. These vascular spaces may contain thrombin, calcifications, or prominent scarring with hyalinization (sclerosed hemangioma). Phleboliths are rare. Malignant transformation has not been reported.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

Most hepatic hemangiomas are small and asymptomatic at the time of diagnosis, and they are likely to remain that way. Studies have shown that most small and large hemangiomas did not change in size or become symptomatic when monitored for up to 92 months. In addition, malignant transformation has not been reported in hepatic hemangiomas. For these reasons, most hepatic hemangiomas may be left safely alone.

• Radiologic study follow-up
• • Once the diagnosis of hepatic hemangioma is confirmed by radiologic studies, it remains uncertain whether follow-up radiologic studies are warranted to reassess the size of the tumor. In the authors' practices, patients typically undergo US at 6 months and at 12 months after the initial diagnosis. Providing that no change in hemangioma size has occurred, long-term follow-up radiologic studies are probably not necessary.
  • However, there are a number of important exceptions to this practice. Certainly, patients with a new onset of abdominal pain deserve a follow-up imaging study. The same is true for patients who are undergoing treatment with estrogens or have become pregnant. Finally, patients with large hemangiomas (ie, >10 cm) may deserve long-term follow-up radiologic studies, perhaps annually, because of their probable increased risk of complications.
• No medical therapy is known to reduce the size of hepatic hemangiomas or to eliminate hepatic hemangiomas.

Surgical Care

Hepatic hemangiomas warrant therapy if they are causing significant symptoms. Unfortunately, in some individuals, determining if the symptoms are caused by a hemangioma or by another process (eg, irritable bowel syndrome) is difficult. Surgical treatment may be appropriate for cases of rapidly growing tumors. Surgery may also be warranted in cases where a hepatic hemangioma cannot be differentiated from hepatic malignancy on imaging studies.

• Management of large hemangiomas
• • The management of a large (ie, >10 cm) hepatic hemangioma is controversial. Certainly, large symptomatic hemangiomas should undergo treatment; however, the management of the large asymptomatic lesion is not clear-cut. Some surgeons have advocated resection for such lesions because of the potential risk of spontaneous rupture, intratumoral hemorrhage, or high-output congestive heart failure. However, a recent literature search identified only 32 published cases of spontaneous rupture in adults without a history of trauma. Congestive heart failure is even less frequently identified as a complication. In the authors' opinions, patients with large asymptomatic hemangiomas should be monitored carefully. Treatment should only be offered if symptoms or complications develop.
  • Therapeutic modalities include surgical resection, surgical enucleation, arterial embolization, radiofrequency ablation, hepatic irradiation, and orthotopic liver transplantation. Surgical resection and enucleation are the treatments of choice.
• Surgical resection
• • The size and location of a lesion will influence the surgeon's decision to perform either a formal segmental resection of the hemangioma or an enucleation of the hemangioma. Typically, these procedures are performed using an open approach, but laparoscopic surgery can be performed in some cases. Hepatic lobectomy may be necessary in the case of large lesions.
  • In general, both surgical resection and enucleation are safe and are well tolerated by patients. Mortality rates of 0% have been reported in large series. Typically, postoperative morbidity is minimal, and the average length of hospital stay is 6 days.
  • In the absence of tumor-promoting factors, such as estrogen therapy, hemangiomas rarely recur after successful resection.
• Arterial embolization
• • Surgical resection may not be possible in certain cases because of the massive or diffuse nature of the lesion, its proximity to vascular structures, or the patient's comorbidities. Arterial embolization is an option in such circumstances. Branches of the hepatic artery can be embolized with polyvinyl alcohol and other substances.
  • Arterial embolization may be an appropriate initial line of therapy in the patient experiencing acute rupture or intratumoral hemorrhage. Once the patient is stabilized, formal surgical resection of the hepatic hemangioma can be performed.
  • Embolization results in shrinking of the tumor, thereby minimizing the risk of complications. Pain, fever, and nongranulomatous arteritis with eosinophilic infiltration are recognized complications of this procedure.
  • The long-term success rate of embolization (without subsequent surgical resection) is not well studied.
• Surgical ligation of feeding vessels: Transhepatic compression sutures using polytetrafluoroethylene (PTFE) pledgets and selective ligation of large feeding vessels have been described. In one case, this technique successfully reduced intratumoral shunting that otherwise would have led to intractable cardiac failure.
• Radiofrequency ablation: Both percutaneous radiofrequency ablation and laparoscopic radiofrequency ablation have been used successfully to improve abdominal pain in small numbers of patients with symptomatic hepatic hemangiomas.
• Hepatic irradiation: Hepatic irradiation with a dose of 30 Gy in 15 fractions over 3 weeks has been reported to produce complete regression of hepatic hemangiomas, with minimal morbidity.
• Orthotopic liver transplantation: This option is occasionally offered to symptomatic patients with large or diffuse lesions. Several cases have now been reported in the medical literature.

Consultations

• Consultation with a surgeon is warranted if resection is the choice of therapy.

Diet

• No special dietary management is required.

Activity

• No restriction of physical activity is indicated for most patients with hepatic hemangiomas.
• Patients with large hemangiomas may need to be instructed to avoid trauma to the right upper abdominal quadrant.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

No medications are useful to shrink or eradicate hepatic hemangiomas.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• No inpatient care is required for routine follow-up. Hospitalization is limited to the time when surgery is planned as a treatment option.

Further Outpatient Care

• See Medical Care.

In/Out Patient Meds

• No medical therapy is indicated.

Complications

• Rupture with resultant hemoperitoneum
• Intratumoral bleeding
• Compression of bile ducts and nearby arteries and veins
• Gastric compression
• Hemobilia
• High-output congestive heart failure

Prognosis

• Overall, a patient with a hepatic hemangioma has an excellent prognosis. Malignant transformation has not been described.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Missing the liver lesion
• Mislabeling as another benign or malignant liver tumor
• Failure to follow up

Special Concerns

• A hepatic hemangioma is known to enlarge during pregnancy, increasing the risk of rupture.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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Article Last Updated: Feb 1, 2007