Hepatic Hemangiomas

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Background

Hemangioma is the most common benign tumor affecting the liver.[1] 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.

The etiology of these lesions remains unknown, although 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.

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.[2] 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,[3] estrogen therapy, and pregnancy[4] 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).[5] 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.[6]

Epidemiology

United States data

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- and age-related demographics

Women, especially with a history of multiparity, are affected more often than men. The female-to-male ratio is 4-6:1.

Hepatic hemangiomas can occur at all ages, but most 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.[7, 8]

Prognosis

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

Complications

Complications depend on the size and location of the tumor. It needs to be emphasized that the following complications are rarely described:

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 angiosarcoma, hepatic metastasis, and primary hepatocellular carcinoma.[9]

Hepatic hemangiomas can occur as part of well-defined clinical syndromes. In Klippel-Trenaunay-Weber syndrome, hepatic hemangiomas occur in association with congenital hemi-atrophy and nevus flammeus, with or without hemi-megalencephaly. In Kasabach-Merritt syndrome, giant hepatic hemangiomas are associated with thrombocytopenia and intravascular coagulation. In this condition, patients are typically male and younger than 1 year.[10] The goal of treatment is eradication of the hemangioma, with subsequent control over the patient's coagulopathy.[11]

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.[12]

Infantile hemangioma is a common tumor in infancy. It may be seen in 5-10% of children aged 1 year. The hemangiomas typically regress during childhood.[8] Typically, the tumors affect the skin and subcutaneous tissue. Occasionally, they affect the liver. Case reports have described the regression of infantile hemangiomas after treatment with propranolol.[13, 14]

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.[15]

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.[9] Larger and multiple lesions may produce symptoms that necessitate surgery. Goodman noted that symptoms are experienced by 40% of patients with 4-cm hemangiomas and by 90% of patients with 10-cm hemangiomas.[16]

Right upper quadrant pain or fullness is the most common complaint.[9] 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, seen infrequently, are an enlarged liver or the presence of an arterial bruit over the right upper quadrant.

Up to 40% of hepatic hemangiomas grow over time, at about a modest rate of 2 mm per year in linear dimension and 17.4% per year in volume, based on data from a 10-year retrospective study.[17] In a separate retrospective study, hemangiomas increased in size in 61.0% of patients, with the highest growth period in those younger than 30 years (0.46 ± 0.41 cm per year) and slowest growth period in those older than 50 years (0.16 ± 0.42 cm per year).[18] Hemangiomas sized 8-10 cm grew at 0.80 ± 0.62 cm per year, whereas those larger than 10 cm grew at a rate of 0.47 ± 0.91 cm per year.[18]

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,[19] and (4) fever of unknown origin.[20]

An illness that resembles a systematic inflammatory process has been described with the findings of fever, weight loss, anemia, thrombocytosis, increased fibrinogen level, and elevated erythrocyte sedimentation rate.[21]

Physical Examination

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 in adults. It is unclear whether or not they are associated with hepatic hemangiomas.[22]

Laboratory Studies

Routine laboratory tests

Results of routine laboratory studies are usually normal, although 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 the clinical suspicion of a benign hepatic mass lesion.

Imaging Studies

The modalities used to aid in the diagnosis of hepatic hemangiomas include ultrasonography, dynamic contrast-enhanced computed tomography (CT) scanning, nuclear medicine studies using technetium-99m (99m Tc)–labeled red blood cells (RBCs), magnetic resonance imaging (MRI), hepatic arteriography, and digital subtraction angiography (DSA).

Ultrasonography

Ultrasonography 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.

The addition of color Doppler to routine ultrasonography provides qualitative and quantitative data and increases the sensitivity and specificity of the test. Serial ultrasonographic 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 (progressing inward toward the center) during the portal venous phase of enhancement.[23] With delayed imaging, the lesion may completely "fill in."[24] 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 the sensitivity from 78% to 100% and specificity from 23% to 92%.[25] Unfortunately, contrast-enhanced ultrasonography is available at relatively few medical centers.[26]

In general, the finding on ultrasonography of a suspected hemangioma should be diagnostically integrated with computed tomography (CT) scanning or magnetic resonance imaging (MRI) to ensure a correct diagnosis.

Computed tomography scanning

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 scanning with delayed imaging).

First, the liver is imaged by CT scanning 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 for the diagnosis of hepatic hemangioma.[27, 28] 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 scanning. Typically, hemangiomas follow the signal intensity of blood. However, hemangiomas smaller than 2 cm may exhibit homogeneous enhancement in late arterial-phase imaging and can be mistaken for hepatocellular carcinoma or a hypervascular metastasis.[29] The sensitivity for detection of hepatic hemangioma is upwards of 90%.[30]

Giant cavernous hemangiomas (ie, >5 cm in diameter) may exhibit internal fluid levels on MRI and CT scan images.[31] This finding is attributed to the separation of blood cells and serous fluid because of extremely slow blood flow through the tumor.

In the setting of hepatic fibrosis and cirrhosis, MRI features of hepatic hemangioma appear similar to those of normal livers.[32]

In the authors' opinions, MRI with arterial and delayed contrast is the test of choice for investigating a liver mass of unclear origin. This is particularly the case when hepatic hemangioma is suspected.

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 is reported to be as high as 82%, with a specificity of up to 100%.[33]

Single-photon emission computerized tomography (SPECT) scanning using Tc-99m pertechnetate-labeled RBCs is more accurate than planar imaging in helping to diagnose hepatic hemangioma.[34] 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.[34]

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.[35]

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 ultrasonography, dynamic CT scanning, and MRI were compared in a retrospective study of 27 patients with 35 hemangiomas.[36]

Sensitivities reported in the study were as follows[36] :

Hepatic angiosarcoma is a rare tumor that tends to grow rapidly. Although hepatic angiosarcoma is classically associated with risk factors, including exposure to Thorotrast, vinyl chloride, or arsenic, many cases have occurred in which no discrete risk factor has been identified. Unfortunately, hepatic angiosarcoma may occasionally be mistaken for hepatic hemangioma on MRI, and vice versa. In the case of a suspected hemangioma with an atypical enhancement pattern, it is reasonable to perform a follow-up radiologic study in a few months to rule out rapid interval growth of the lesion.[37, 38]

Features of angiosarcoma on multiphasic CT scanning and MRI include the following[39] :

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 scanning 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 ultrasonographically guided 18-gauge core needle biopsy in 51 hemangiomas ranging in size from 7-114 mm.[40] However, the authors do not recommend its performance.

Some authorities contend that either a 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 scanning and MRI.[41] 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.

Pathology

Hemangiomas are usually solitary. Multiple and diffuse hepatic lesions are seen infrequently. Sizes range from 2 mm to more than 20 cm. On gross examination, 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.[42, 43]

Medical Care

Most hepatic hemangiomas are small and asymptomatic at the time of diagnosis, and they are likely to remain that way. In one prospective study, an increase in hemangioma size was noted in only one of 47 patients who were rescanned 1-6 years after the initial diagnosis.[44] In addition, malignant transformation has not been reported in hepatic hemangiomas. For these reasons, most hepatic hemangiomas may be left safely alone.

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

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

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.

Possible utility of growth factor and kinase inhibitors

Until relatively recently, no medical therapy capable of reducing the size of hepatic hemangiomas had been described. A case report in 2008 demonstrated reduction in the size of hepatic hemangiomas in a patient treated for colon cancer. The patient had received bevacizumab, a monoclonal antibody capable of inhibiting the activity of vascular endothelial growth factor (VEGF).[45]

Sorafenib, a multikinase inhibitor, was used in the management of a 76-year-old man with a giant cavernous hemangioma measuring more than 20 cm in diameter. Tumor volume decreased from 1492 mL at baseline to 665 mL after 78 days of treatment with sorafenib 600 mg/day.[46]

Surgical Care

Hepatic hemangiomas warrant therapy if they are causing significant symptoms.[47] 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.[30]

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

Hepatic hemangiomas have been treated with a wide array of therapies. Traditionally, surgical resection and surgical enucleation are the treatments of choice.[48] Minimally invasive therapies for hepatic hemangioma include arterial embolization, radiofrequency ablation, and hepatic irradiation. Orthotopic liver transplantation has been performed as treatment in rare circumstances.

The classic indications for either surgery or minimally invasive therapy are the relief of symptoms due to the hemangioma or the treatment of a spontaneously ruptured hemangioma. The latter event is potentially life-threatening. However, emergent surgical resection of the ruptured hemangioma is associated with a high mortality rate. In one study, the risk of rupture was 3.2% for giant hemangiomas, particularly with exophytic lesions and those located peripherally.[49]

The top priority in a patient with a ruptured hepatic hemangioma is hemodynamic stabilization. Some authors have recommended surgical ligation of the hepatic artery as a next step. Others have recommended arterial embolization instead. Once the patient is stabilized, formal surgical resection of the hepatic hemangioma can be performed.[50]

The management of a large (ie, >10 cm) hepatic hemangioma is controversial. Certainly, large symptomatic hemangiomas should undergo treatment. However, the management of a large asymptomatic lesion is not clear-cut. Some surgeons have advocated resection of such lesions because of the potential risk of spontaneous rupture, intratumoral hemorrhage, or high-output congestive heart failure. However, more recent literature searches identified only 33 published cases of spontaneous rupture in adults without a history of trauma.[51, 52] A 2011 review described only 46 published cases of spontaneous rupture over the last century.[53] The risk for traumatic rupture is also low,[54] with only 51 cases described over the last century.[53] Congestive heart failure is even less frequently identified as a complication.

A retrospective cohort study used a patient survey to assess the outcomes of 289 patients with hemangiomas greater than 4 cm in size.[55] Twenty percent of the 233 patients in the nonoperative group reported hemangioma-related symptoms, including life-threatening complications in 2%. Fourteen percent of the 56 patients undergoing surgery for hepatic hemangioma experienced perioperative complications, including life-threatening complications in 7%. The authors concluded that operative treatment should be reserved for patients with severe symptoms or complications of their disease.[55]

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.[56]

In a study of 172 patients with hepatic hemangiomas, Fu et al examined the safety of enucleation surgery for centrally located lesions versus that for peripheral lesions (76 and 96 patients, respectively).[57] In both groups, the frequency of major complications was low, although vascular inflow occlusion time, operating time, and hospital stay were longer in the central lesion group, and the volume of blood loss was greater. No hospital mortality occurred in either group. The authors concluded that enucleation is safe for both centrally and peripherally located hemangiomas, but that the surgery is technically more demanding for the former.

In the absence of tumor-promoting factors, such as estrogen therapy, hemangiomas rarely recur after successful resection.[58]

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.[59, 60, 61] One report described 26 patients with symptomatic giant hemangiomas who underwent successful embolization with bleomycin mixed with lipiodol.[62]

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.[63]

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.[64, 65, 66, 67, 68]

Hepatic irradiation

Hepatic irradiation with a dose of 15-30 Gy in 15-22 fractions over several weeks has been used to treat symptomatic hemangiomas. Tumor regression and symptom relief were noted in most patients, with minimal morbidity.[69, 70]

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.[71, 72]

Diet and Activity

No special dietary management is required, and 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 Summary

Medications are not commonly used to shrink or eradicate hepatic hemangiomas. Relatively recent studies have reported the regression of hemangiomas after treatment with bevacizumab and sorafenib.

Author

David C Wolf, MD, FACP, FACG, AGAF, FAASLD, 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

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Salix; Gilead; Abbvie<br/>Received research grant from: Vital Therapies.

Coauthor(s)

Unnithan V Raghuraman, MD, FACG, FACP, FRCP, Consulting Staff, Department of Gastroenterology, St John Medical Center

Disclosure: Nothing to disclose.

Specialty Editors

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

BS Anand, MD, Professor, Department of Internal Medicine, Division of Gastroenterology, Baylor College of Medicine

Disclosure: Nothing to disclose.

Additional Contributors

Vivek V Gumaste, MD, Associate Professor of Medicine, Mount Sinai School of Medicine of New York University; Adjunct Clinical Assistant, Mount Sinai Hospital; Director, Division of Gastroenterology, City Hospital Center at Elmhurst; Program Director of GI Fellowship (Independent Program); Regional Director of Gastroenterology, Queens Health Network

Disclosure: Nothing to disclose.

References

  1. Dickie B, Dasgupta R, Nair R, et al. Spectrum of hepatic hemangiomas: management and outcome. J Pediatr Surg. 2009 Jan. 44(1):125-33. [View Abstract]
  2. Moser C, Hany A, Spiegel R. [Familial giant hemangiomas of the liver. Study of a family and review of the literature]. Praxis (Bern 1994). 1998 Apr 1. 87(14):461-8. [View Abstract]
  3. Takahashi T, Kuwao S, Katagiri H, et al. Multiple liver hemangiomas enlargement during long-term steroid therapy for myasthenia gravis. Dig Dis Sci. 1998 Jul. 43(7):1553-61. [View Abstract]
  4. Giannitrapani L, Soresi M, La Spada E, et al. Sex hormones and risk of liver tumor. Ann N Y Acad Sci. 2006 Nov. 1089:228-36. [View Abstract]
  5. Glinkova V, Shevah O, Boaz M, et al. Hepatic haemangiomas: possible association with female sex hormones. Gut. 2004 Sep. 53(9):1352-5. [View Abstract]
  6. Spitzer D, Krainz R, Graf AH, et al. Pregnancy after ovarian stimulation and intrauterine insemination in a woman with cavernous macrohemangioma of the liver. A case report. J Reprod Med. 1997 Dec. 42(12):809-12. [View Abstract]
  7. Dreyfus M, Baldauf JJ, Dadoun K, et al. Prenatal diagnosis of hepatic hemangioma. Fetal Diagn Ther. 1996 Jan-Feb. 11(1):57-60. [View Abstract]
  8. Dong KR, Zheng S, Xiao X. Conservative management of neonatal hepatic hemangioma: a report from one institute. Pediatr Surg Int. 2009 Jun. 25(6):493-8. [View Abstract]
  9. Bajenaru N, Balaban V, Săvulescu F, Campeanu I, Patrascu T. Hepatic hemangioma -review-. J Med Life. 2015. 8 Spec Issue:4-11. [View Abstract]
  10. Reischle S, Schuller-Petrovic S. Treatment of capillary hemangiomas of early childhood with a new method of cryosurgery. J Am Acad Dermatol. 2000 May. 42(5 Pt 1):809-13. [View Abstract]
  11. Aslan A, Meyer Zu Vilsendorf A, Kleine M, Bredt M, Bektas H. Adult Kasabach-Merritt Syndrome due to Hepatic Giant Hemangioma. Case Rep Gastroenterol. 2009 Nov 20. 3(3):306-312. [View Abstract]
  12. Suzuki T, Tsuchiya N, Ito K. Multiple cavernous hemangiomas of the liver in patients with systemic lupus erythematosus. J Rheumatol. 1997 Apr. 24(4):810-1. [View Abstract]
  13. Tan ST, Itinteang T, Leadbitter P. Low-dose propranolol for multiple hepatic and cutaneous hemangiomas with deranged liver function. Pediatrics. 2011 Mar. 127(3):e772-6. [View Abstract]
  14. Starkey E, Shahidullah H. Propranolol for infantile haemangiomas: a review. Arch Dis Child. 2011 Sep. 96(9):890-3. [View Abstract]
  15. Huang SA, Tu HM, Harney JW, et al. Severe hypothyroidism caused by type 3 iodothyronine deiodinase in infantile hemangiomas. N Engl J Med. 2000 Jul 20. 343(3):185-9. [View Abstract]
  16. Goodman Z. Benign tumors of the liver. Okuda K, Ishak KG. Neoplasms of the liver. Tokyo: Springer-Verlag; 1987. 105-25.
  17. Hasan HY, Hinshaw JL, Borman EJ, Gegios A, Leverson G, Winslow ER. Assessing normal growth of hepatic hemangiomas during long-term follow-up. JAMA Surg. 2014 Dec. 149(12):1266-71. [View Abstract]
  18. Li J, Huang L, Liu C, et al. New recognization of the natural history and growth pattern of hepatic hemangioma in adults. Hepatol Res. 2015 Oct 22. [View Abstract]
  19. Mikami T, Hirata K, Oikawa I, et al. Hemobilia caused by a giant benign hemangioma of the liver: report of a case. Surg Today. 1998. 28(9):948-52. [View Abstract]
  20. Lee CW, Chung YH, Lee GC, et al. A case of giant hemangioma of the liver presenting with fever of unknown origin. J Korean Med Sci. 1994 Apr. 9(2):200-4. [View Abstract]
  21. Pol B, Disdier P, Le Treut YP, et al. Inflammatory process complicating giant hemangioma of the liver: report of three cases. Liver Transpl Surg. 1998 May. 4(3):204-7. [View Abstract]
  22. Lorette G, Georgesco G, Sirinelli D, et al. [Cutaneous immature hemangioma and hepatic angioma: there is no frequent association]. Ann Dermatol Venereol. 1996. 123(12):789-90. [View Abstract]
  23. Brannigan M, Burns PN, Wilson SR. Blood flow patterns in focal liver lesions at microbubble-enhanced US. Radiographics. 2004 Jul-Aug. 24(4):921-35. [View Abstract]
  24. Dietrich CF, Mertens JC, Braden B, et al. Contrast-enhanced ultrasound of histologically proven liver hemangiomas. Hepatology. 2007 May. 45(5):1139-45. [View Abstract]
  25. von Herbay A, Vogt C, Willers R, et al. Real-time imaging with the sonographic contrast agent SonoVue: differentiation between benign and malignant hepatic lesions. J Ultrasound Med. 2004 Dec. 23(12):1557-68. [View Abstract]
  26. Strobel D, Seitz K, Blank W, et al. Tumor-specific vascularization pattern of liver metastasis, hepatocellular carcinoma, hemangioma and focal nodular hyperplasia in the differential diagnosis of 1,349 liver lesions in contrast-enhanced ultrasound (CEUS). Ultraschall Med. 2009 Aug. 30(4):376-82. [View Abstract]
  27. Higashihara H, Murakami T, Kim T, et al. Differential diagnosis between metastatic tumors and nonsolid benign lesions of the liver using ferucarbotran-enhanced MR imaging. Eur J Radiol. 2010 Jan. 73(1):125-30. [View Abstract]
  28. Vossen JA, Buijs M, Liapi E, Eng J, Bluemke DA, Kamel IR. Receiver operating characteristic analysis of diffusion-weighted magnetic resonance imaging in differentiating hepatic hemangioma from other hypervascular liver lesions. J Comput Assist Tomogr. 2008 Sep-Oct. 32(5):750-6. [View Abstract]
  29. Albiin N. MRI of focal liver lesions. Curr Med Imaging Rev. 2012 May. 8(2):107-16. [View Abstract]
  30. Farges O, Daradkeh S, Bismuth H. Cavernous hemangiomas of the liver: are there any indications for resection?. World J Surg. 1995 Jan-Feb. 19(1):19-24. [View Abstract]
  31. Obata S, Matsunaga N, Hayashi K, et al. Fluid-fluid levels in giant cavernous hemangioma of the liver: CT and MRI demonstration. Abdom Imaging. 1998 Nov-Dec. 23(6):600-2. [View Abstract]
  32. Duran R, Ronot M, Di Renzo S, Gregoli B, Van Beers BE, Vilgrain V. Is magnetic resonance imaging of hepatic hemangioma any different in liver fibrosis and cirrhosis compared to normal liver?. Eur J Radiol. 2015 May. 84(5):816-22. [View Abstract]
  33. Kinnard MF, Alavi A, Rubin RA, et al. Nuclear imaging of solid hepatic masses. Semin Roentgenol. 1995 Oct. 30(4):375-95. [View Abstract]
  34. Krause T, Hauenstein K, Studier-Fischer B, et al. Improved evaluation of technetium-99m-red blood cell SPECT in hemangioma of the liver. J Nucl Med. 1993 Mar. 34(3):375-80. [View Abstract]
  35. Tsai CC, Yen TC, Tzen KY. Pedunculated giant liver hemangioma mimicking a hypervascular gastric tumor on Tc-99m RBC SPECT. Clin Nucl Med. 1999 Feb. 24(2):132-3. [View Abstract]
  36. De Franco A, Monteforte MG, Maresca G, et al. [Integrated diagnosis of liver angioma: comparison of Doppler color ultrasonography, computerized tomography, and magnetic resonance]. Radiol Med. 1997 Jan-Feb. 93(1-2):87-94. [View Abstract]
  37. Okano A, Sonoyama H, Masano Y, et al. The natural history of a hepatic angiosarcoma that was difficult to differentiate from cavernous hemangioma. Intern Med. 2012. 51(20):2899-904. [View Abstract]
  38. Heo SH, Jeong YY, Shin SS, Chung TW, Kang HK. Solitary small hepatic angiosarcoma: initial and follow-up imaging findings. Korean J Radiol. 2007 Mar-Apr. 8(2):180-3. [View Abstract]
  39. Pickhardt PJ, Kitchin D, Lubner MG, Ganeshan DM, Bhalla S, Covey AM. Primary hepatic angiosarcoma: multi-institutional comprehensive cancer centre review of multiphasic CT and MR imaging in 35 patients. Eur Radiol. 2015 Feb. 25(2):315-22. [View Abstract]
  40. Heilo A, Stenwig AE. Liver hemangioma: US-guided 18-gauge core-needle biopsy. Radiology. 1997 Sep. 204(3):719-22. [View Abstract]
  41. Bruix J, Sherman M, Llovet JM, et al. Clinical management of hepatocellular carcinoma. Conclusions of the Barcelona-2000 EASL conference. European Association for the Study of the Liver. J Hepatol. 2001 Sep. 35(3):421-30. [View Abstract]
  42. Craig JR, Peters RL, Edmondson HA. Tumors of the liver and intrahepatic bile ducts. Atlas of tumor pathology. Washington, D.C.: Armed Forces Institute of Pathology; 1989. Second series, fasc. 26: 56-62.
  43. Ishak KG, Markin RS. Liver. Damjanov I, Linder J, eds. Anderson's Pathology. 10th ed. Mosby: St. Louis, Mo; 1996. 1834.
  44. Gibney RG, Hendin AP, Cooperberg PL. Sonographically detected hepatic hemangiomas: absence of change over time. AJR Am J Roentgenol. 1987 Nov. 149(5):953-7. [View Abstract]
  45. Mahajan D, Miller C, Hirose K, McCullough A, Yerian L. Incidental reduction in the size of liver hemangioma following use of VEGF inhibitor bevacizumab. J Hepatol. 2008 Nov. 49(5):867-70. [View Abstract]
  46. Yamashita S, Okita K, Harada K, et al. Giant cavernous hepatic hemangioma shrunk by use of sorafenib. Clin J Gastroenterol. 2013 Feb. 6(1):55-62. [View Abstract]
  47. Miura JT, Amini A, Schmocker R, et al. Surgical management of hepatic hemangiomas: a multi-institutional experience. HPB (Oxford). 2014 Oct. 16(10):924-8. [View Abstract]
  48. Belli G, D'Agostino A, Fantini C, et al. Surgical treatment of giant liver hemangiomas by enucleation using an ultrasonically activated device (USAD). Hepatogastroenterology. 2009 Jan-Feb. 56(89):236-9. [View Abstract]
  49. Mocchegiani F, Vincenzi P, Coletta M, et al. Prevalence and clinical outcome of hepatic haemangioma with specific reference to the risk of rupture: A large retrospective cross-sectional study. Dig Liver Dis. 2016 Mar. 48(3):309-14. [View Abstract]
  50. Jain V, Ramachandran V, Garg R, Pal S, Gamanagatti SR, Srivastava DN. Spontaneous rupture of a giant hepatic hemangioma - sequential management with transcatheter arterial embolization and resection. Saudi J Gastroenterol. 2010 Apr-Jun. 16(2):116-9. [View Abstract]
  51. Corigliano N, Mercantini P, Amodio PM, et al. Hemoperitoneum from a spontaneous rupture of a giant hemangioma of the liver: report of a case. Surg Today. 2003. 33(6):459-63. [View Abstract]
  52. Ribeiro MAF, Papaiordanou F, Goncalves JM, Chaib E. Spontaneous rupture of hepatic hemangiomas: A review of the literature. World J Hepatol. 2010 Dec 27. 2(12):428-33. [View Abstract]
  53. Donati M, Stavrou GA, Donati A, Oldhafer KJ. The risk of spontaneous rupture of liver hemangiomas: a critical review of the literature. J Hepatobiliary Pancreat Sci. 2011 Nov. 18(6):797-805. [View Abstract]
  54. Plackett TP, Lin-Hurtubise KM. Hepatic hemangiomas and parachuting. Aviat Space Environ Med. 2008 Oct. 79(10):986-8. [View Abstract]
  55. Schnelldorfer T, Ware AL, Smoot R, Schleck CD, Harmsen WS, Nagorney DM. Management of giant hemangioma of the liver: resection versus observation. J Am Coll Surg. 2010 Dec. 211(6):724-30. [View Abstract]
  56. Arnoletti JP, Brodsky J. Surgical treatment of benign hepatic mass lesions. Am Surg. 1999 May. 65(5):431-3. [View Abstract]
  57. Fu XH, Lai EC, Yao XP, et al. Enucleation of liver hemangiomas: is there a difference in surgical outcomes for centrally or peripherally located lesions?. Am J Surg. 2009 Aug. 198(2):184-7. [View Abstract]
  58. Zhu H, Obeidat K, Ouyang J, Roayaie S, Schwartz ME, Thung SN. Recurrent giant hemangiomas of liver: Report of two rare cases with literature review. World J Gastrointest Surg. 2012 Nov 27. 4(11):262-6. [View Abstract]
  59. Deutsch GS, Yeh KA, Bates WB 3rd, Tannehill WB. Embolization for management of hepatic hemangiomas. Am Surg. 2001 Feb. 67(2):159-64. [View Abstract]
  60. Srivastava DN, Gandhi D, Seith A, et al. Transcatheter arterial embolization in the treatment of symptomatic cavernous hemangiomas of the liver: a prospective study. Abdom Imaging. 2001 Sep-Oct. 26(5):510-4. [View Abstract]
  61. Zeng Q, Li Y, Chen Y, et al. Gigantic cavernous hemangioma of the liver treated by intra-arterial embolization with pingyangmycin-lipiodol emulsion: a multi-center study. Cardiovasc Intervent Radiol. 2004 Sep-Oct. 27(5):481-5. [View Abstract]
  62. Bozkaya H, Cinar C, Besir FH, Parıldar M, Oran I. Minimally invasive treatment of giant haemangiomas of the liver: embolisation with bleomycin. Cardiovasc Intervent Radiol. 2014 Feb. 37(1):101-7. [View Abstract]
  63. Rokitansky AM, Jakl RJ, Gopfrich H, et al. Special compression sutures: a new surgical technique to achieve a quick decrease in shunt volume caused by diffuse hemangiomatosis of the liver. Pediatr Surg Int. 1998 Nov. 14(1-2):119-21. [View Abstract]
  64. Hinshaw JL, Laeseke PJ, Weber SM, Lee FT Jr. Multiple-electrode radiofrequency ablation of symptomatic hepatic cavernous hemangioma. AJR Am J Roentgenol. 2007 Sep. 189(3):W146-9. [View Abstract]
  65. Park SY, Tak WY, Jung MK, et al. Symptomatic-enlarging hepatic hemangiomas are effectively treated by percutaneous ultrasonography-guided radiofrequency ablation. J Hepatol. 2011 Mar. 54(3):559-65. [View Abstract]
  66. Fan RF, Chai FL, He GX, et al. Laparoscopic radiofrequency ablation of hepatic cavernous hemangioma. A preliminary experience with 27 patients. Surg Endosc. 2006 Feb. 20(2):281-5. [View Abstract]
  67. van Tilborg AA, Nielsen K, Scheffer HJ, et al. Bipolar radiofrequency ablation for symptomatic giant (>10 cm) hepatic cavernous haemangiomas: initial clinical experience. Clin Radiol. 2013 Jan. 68(1):e9-e14. [View Abstract]
  68. Sharpe EE 3rd, Dodd GD 3rd. Percutaneous radiofrequency ablation of symptomatic giant hepatic cavernous hemangiomas: report of two cases and review of literature. J Vasc Interv Radiol. 2012 Jul. 23(7):971-5. [View Abstract]
  69. Gaspar L, Mascarenhas F, da Costa MS, Dias JS, Afonso JG, Silvestre ME. Radiation therapy in the unresectable cavernous hemangioma of the liver. Radiother Oncol. 1993 Oct. 29(1):45-50. [View Abstract]
  70. Biswal BM, Sandhu M, Lal P, et al. Role of radiotherapy in cavernous hemangioma liver. Indian J Gastroenterol. 1995 Jul. 14(3):95-8. [View Abstract]
  71. Tepetes K, Selby R, Webb M, et al. Orthotopic liver transplantation for benign hepatic neoplasms. Arch Surg. 1995 Feb. 130(2):153-6. [View Abstract]
  72. Vagefi PA, Klein I, Gelb B, et al. Emergent orthotopic liver transplantation for hemorrhage from a giant cavernous hepatic hemangioma: case report and review. J Gastrointest Surg. 2011 Jan. 15(1):209-14. [View Abstract]
  73. Okano A, Sonoyama H, Masano Y, et al. The natural history of a hepatic angiosarcoma that was difficult to differentiate from cavernous hemangioma. Intern Med. 2012. 51(20):2899-904. [View Abstract]
  74. Ozmen E, Adaletli I, Kayadibi Y, et al. The impact of share wave elastography in differentiation of hepatic hemangioma from malignant liver tumors in pediatric population. Eur J Radiol. 2014 Sep. 83(9):1691-7. [View Abstract]
  75. Hsi Dickie B, Fishman SJ, Azizkhan RG. Hepatic vascular tumors. Semin Pediatr Surg. 2014 Aug. 23(4):168-72. [View Abstract]
  76. Hardie AD, Egbert RE, Rissing MS. Improved differentiation between hepatic hemangioma and metastases on diffusion-weighted MRI by measurement of standard deviation of apparent diffusion coefficient. Clin Imaging. 2015 Jul-Aug. 39(4):654-8. [View Abstract]
  77. Kumar N, Adam SZ, Goodhartz LA, Hoff FL, Lo AA, Miller FH. Beyond hepatic hemangiomas: the diverse appearances of gastrointestinal and genitourinary hemangiomas. Abdom Imaging. 2015 Oct. 40 (8):3313-29. [View Abstract]
  78. Bai DS, Chen P, Qian JJ, et al. Modified laparoscopic hepatectomy for hepatic hemangioma. Surg Endosc. 2015 Nov. 29(11):3414-21. [View Abstract]