eMedicine Specialties > Gastroenterology > Liver

Hemangiomas, Hepatic

David C Wolf, MD, FACP, FACG, AGAF, Medical Director of Liver Transplantation, Westchester Medical Center, Professor of Clinical Medicine, Division of Gastroenterology and Hepatobiliary Diseases, Department of Medicine, New York Medical College
Unnithan V Raghuraman, MD, FRCP, FACG, FACP, Consulting Staff, Department of Gastroenterology, St John Medical Center

Updated: Dec 22, 2008

Introduction

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.¹ 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 therapy² , estrogen therapy, and pregnancy³ can increase the size of an already existing hemangioma. One study prospectively evaluated 94 women with hepatic hemangiomas, with a mean follow-up period of 7.3 years (range, 1-17 y).⁴ 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.⁵

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.

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 may be seen in infancy. They have also been detected prenatally in a growing fetus.⁶

Clinical

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.
• 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.7
• Clinical features
  • Hepatic hemangiomas are more common in the right lobe of the liver than in the left lobe. 
  • Hemangiomas of the liver are usually small and asymptomatic. They are most often 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. Goodman noted that symptoms are experienced by 40% of patients with 4-cm hemangiomas and by 90% of patients with 10-cm hemangiomas.⁸
  • 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 the following: (1) cardiac failure from massive arteriovenous shunting, (2) jaundice from compression of the bile ducts, (3) gastrointestinal bleeding from hemobilia,⁹ and (4) fever of unknown origin.10
  • 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.11
• Complications
  • Complications depend on the size and location of the tumor.
  • Rarely, large tumors 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.
• Infantile hemangiomas
  • Hepatic hemangiomas may be seen in 5-10% of children aged 1 year. They typically regress during childhood.
  • Reports have described infants with massive hepatic hemangiomas and hypothyroidism. In these cases, the tumor was found to express type 3 iodothyronine deiodinase, which resulted in an increased rate of inactivation of thyroid hormone.¹²

Physical

Infrequently, patients may present with an enlarged liver, an abdominal mass, or an arterial bruit over the right upper quadrant.   
 
Cutaneous hemangiomas are a common finding. It is unclear whether or not they are associated with hepatic hemangiomas.¹³

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.

Differential Diagnoses

Other Problems to Be Considered

Hepatic hemangiomas should be differentiated from other benign and malignant space-occupying liver lesions. Benign liver tumors include cysts, adenomas, regenerating nodules, focal nodular hyperplasia, and abscesses. Malignant liver tumors include hepatocellular carcinoma and hepatic metastases.

Workup

Laboratory Studies

• Routine laboratory tests
  • Results are usually 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 used 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 ultrasound provides qualitative and quantitative data and increases the sensitivity and specificity of the test. Serial ultrasound examinations can be used to monitor any increase in size of the hemangioma over time.
  • The use of microbubble-enhanced ultrasonography has been studied. Lesions show peripheral puddles and pools of enhancement that expand in a centripetal pattern during the portal venous phase of enhancement.14 With delayed imaging, the lesion may completely "fill in."15 However, complete enhancement might not occur in large lesions where central thrombosis or scarring may be present.
  • In one study, the addition of a contrast agent to routine ultrasonography improved sensitivity from 78% to 100% and specificity from 23% to 92%.¹⁶ Unfortunately, contrast-enhanced ultrasonography is available at relatively few medical centers.
  • In general, the finding on ultrasonography of a suspected hemangioma should be diagnostically integrated with CT scan or MRI to ensure 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 the 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 the 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 used as an intravenous contrast agent, hemangiomas enhance in a fashion similar to that seen on dynamic CT. The sensitivity for detection of hepatic hemangioma is upwards of 90%.¹⁷
  • Giant cavernous hemangiomas (ie, >5 cm in diameter) may exhibit internal fluid levels on MRI and CT scan images.¹⁸ This finding is attributed to the separation of blood cells and serous fluid because of extremely slow blood flow through the tumor.
• Nuclear medicine studies
  • Planar scintigraphic studies using Tc-99m pertechnetate-labeled red blood cells have been used for many years to help in diagnosing hepatic hemangiomas. Sensitivity for hemangiomas greater than 2 cm in diameter was said to be as high as 82%, with a specificity of up to 100%.19
  • Single-photon emission computerized tomography (SPECT) using Tc-99m pertechnetate-labeled RBCs is more accurate than planar imaging in helping to diagnose hepatic hemangioma.²⁰ However, it is not available at all medical centers.
  • SPECT is more specific than MRI, but it is less sensitive. This is particularly true for lesions near the heart or major blood vessels.²⁰
  • 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.²¹
• 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 to 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.
• Accuracy of imaging studies
  • The diagnostic capabilities of ultrasonography, Doppler color ultrasound, dynamic CT scan, and MRI were compared in a retrospective study of 27 patients with 35 hemangiomas.22
  • Sensitivities reported in the study were as follows:
    • Ultrasonography – 46% sensitivity
    • Combined B-mode and color Doppler ultrasound – 69% sensitivity
    • Contrast-enhanced CT scan - 66% sensitivity
    • T2-weighted MRI - 96% sensitivity
    • Gadolinium-enhanced MRI combined with dynamic CT scan - 100% sensitivity
• Imaging of hemangiomas less than 2 cm
  • Diagnostic accuracy diminishes for all imaging modalities when assessing a liver lesion that is less than 2 cm in diameter.
  • MRI and 99mTc-RBC SPECT are the most accurate radiologic studies to establish the diagnosis of a small hepatic hemangioma.
• The authors continue to regard MRI as the diagnostic test of choice for hepatic hemangioma at most centers. Nuclear medicine studies may be used to confirm the diagnosis when a probable hemangioma is detected on ultrasonography. Nuclear medicine studies may also help to clarify the nature of a lesion when the diagnosis is equivocal on CT or MRI.

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 ultrasound-guided 18-gauge core needle biopsy in 51 hemangiomas ranging in size from 7-114 mm.²³ However, the authors do not recommend its performance.
  • 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.²⁴ 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

Medical Care

• 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 ultrasonography 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. One article described how 14 patients underwent surgical or angiographic therapy for "incapacitating symptoms" that were related to a hepatic hemangioma. One half of these patients remained symptomatic after therapy, implying that the hemangioma was not responsible for their complaints.¹⁷

Surgical treatment may be appropriate in 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 literature search identified only 32 published cases of spontaneous rupture in adults without a history of trauma.²⁸ 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.²⁹
  • 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.^30,31
  • 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.³²
• Radiofrequency ablation: Both percutaneous and laparoscopic radiofrequency ablation have been used successfully to improve abdominal pain in small numbers of patients with symptomatic hepatic hemangiomas.^33,34
• 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.³⁵
• 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.³⁶

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

No medications are useful to shrink or eradicate hepatic hemangiomas.

Follow-up

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.

Inpatient & Outpatient Medications

• 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

Medicolegal 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

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Keywords

hepatic hemangiomas, hepatic hemangioma, hemangioma, cavernous hemangioma, liver tumor, liver lesions, liver hemangioma

Contributor Information and Disclosures

Author

David C Wolf, MD, FACP, FACG, AGAF, Medical Director of Liver Transplantation, Westchester Medical Center, Professor of Clinical Medicine, Division of Gastroenterology and Hepatobiliary Diseases, Department of Medicine, New York Medical College
David C Wolf, MD, FACP, FACG, AGAF is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American College of Physicians, and American Gastroenterological Association
Disclosure: Nothing to disclose.

Coauthor(s)

Unnithan V Raghuraman, MD, FRCP, FACG, FACP, Consulting Staff, Department of Gastroenterology, St John Medical Center
Unnithan V Raghuraman, MD, FRCP, FACG, FACP is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, and American Society of Gastrointestinal Endoscopy
Disclosure: Nothing to disclose.

Medical Editor

Vivek V Gumaste, MD, Associate Professor of Medicine, Mt Sinai School of Medicine, Adjunct Clinical Assistant, Mt Sinai Hospital; Director, Division of Gastroenterology, City Hospital Center, Elmhurst, NY
Vivek V Gumaste, MD is a member of the following medical societies: American College of Gastroenterology and American Gastroenterological Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Oscar S Brann, MD, FACP, Associate Clinical Professor, Department of Medicine, University of California at San Diego; Consulting Staff, Mecklenburg Medical Group
Oscar S Brann, MD, FACP is a member of the following medical societies: American Gastroenterological Association
Disclosure: Nothing to disclose.

CME Editor

Alex J Mechaber, MD, FACP, Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine
Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine
Disclosure: Nothing to disclose.

Chief Editor

Julian Katz, MD, Clinical Professor of Medicine, Drexel University College of Medicine; Consulting Staff, Department of Medicine, Section of Gastroenterology and Hepatology, Hospital of the Medical College of Pennsylvania
Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Law Medicine and Ethics, American Trauma Society, Association of American Medical Colleges, and Physicians for Social Responsibility
Disclosure: Nothing to disclose.

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