Orthopedic Surgery for Hemangioma Treatment & Management


Background

Hemangiomas are abnormal proliferations of blood vessels that may develop in any vascularized tissue. They may be asymptomatic or may cause symptoms such as pain and swelling. Considerable debate exists as to whether these lesions are neoplasms, hamartomas, or vascular malformations. Mulliken strongly supported classification of hemangiomas as neoplasms, whereas Godanich and Capanacci appeared to favor a hamartomatous classification. [12]

There seems to be a consensus that the term hemangioma should refer to hemangiomas of infancy, which have a predictable natural history that includes absence at birth followed by a period of growth over 6-18 months and then a period of involution that may take several years. Hemangiomas affecting the musculoskeletal system are more accurately termed vascular malformations. These are present from birth and do not involute spontaneously. [34]

Hemangiomas occur most often in skin or subcutaneous tissue, and dermatologists, pediatricians, and primary care medical physicians typically treat these readily identifiable processes. One common example is the senile or cherry hemangioma, which is a benign, self-limited, small, red-purple skin papule seen in elderly patients. Another is the strawberry nevus, which is seen in approximately 0.5% of infants and spontaneously involutes in the vast majority of cases. Visceral hemangiomas are far less common but may have greater consequences when they result in organ dysfunction.

Orthopedists most commonly are called upon to treat hemangiomas of the deep soft tissues and bone. Skeletal muscle is the most common site for hemangioma of the deep soft tissue. Intramuscular hemangiomas may cause symptoms such as pain and swelling for which patients seek treatment. Hemangioma of bone may be symptomatic or may be purely an incidental finding. Most commonly, hemangiomas are localized to a single area, but multiple hemangiomas may occur in a single individual in a process known as hemangiomatosis. [56789]

Some authors have defined hemangiomatosis as multiple hemangiomas occurring in noncontiguous bones. Devaney et al defined skeletal-extraskeletal angiomatosis as a benign vascular proliferation involving the medullary cavity of bone and at least one other type of tissue. [10]

Rarely, hemangiomas may be associated with other pathologic processes, such as the consumptive coagulopathy of Kasabach-Merritt syndrome and tumor-induced osteomalacia. Gorham disease is a process of massive osteolysis, which is believed to be within the spectrum of hemangiomatous disease. Hemangiomas occurring in the setting of multiple enchondromatosis are part of the spectrum of Maffucci syndrome.

For patient education resources, see the Skin Conditions and Beauty Center, as well as Bruises.

Pathophysiology

Hemangiomas are benign lesions with increased numbers of blood vessels. They can affect numerous tissue types (individually or in combination), including skin, subcutaneous tissue, viscera, muscle, synovium, and bone, but they do not spread to avascular tissue such as cartilage.

Gorham disease is a process in which variably progressive dissolution of bone occurs. This process may affect a single bone or may cross joint spaces. Its etiology is thought to be related to excess vascularity of the involved bone. The exact pathogenesis of Gorham disease is unknown at this time. Various theories involve hormone and cytokine stimulation of osteoclast function, with heightened sensitivity of osteoclast precursors to interleukin (IL)-6 leading to increased bone resorption locally. [11]

Some have argued that epithelioid hemangiomas are not a distinct clinicopathologic entity but rather a misdiagnosed hemangioendothelioma, which is a tumor with malignant potential, unlike hemangioma. [12Identification of WWTR1-CAMTA1 fusion as the genetic hallmark of epithelioid hemangioendothelioma, regardless of anatomic location, provides an objective and powerful diagnostic tool that can be used to distinguish the two entities. [13The WWTR1-CAMTA1 fusion was used in a retrospective study with good results to reinforce prior data that epithelioid hemangiomas are benign lesions and not low-grade malignant soft-tissue tumors. [14]

Etiology

Hemangiomas

The etiology of hemangiomas is unclear. Angiogenesis likely plays a role in the vascular excess present. Cytokines, such as basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) are known to stimulate angiogenesis. Excesses of these angiogenic factors or decreases of angiogenesis inhibitors (eg, interferon gamma, tumor necrosis factor [TNF]-β, and transforming growth factor [TGF]-β) have been implicated in the development of hemangiomas. [15]

Gorham disease

The etiology of Gorham disease is unknown but is thought to be related to increased vascularity of the affected bones. The resultant hyperemia has been hypothesized to uncouple the balance between osteoblasts and osteoclasts, leading to bone resorption at a far greater rate than bone formation. [16]

Kasabach-Merritt syndrome

Although the etiology is not entirely clear, development of Kasabach-Merritt syndrome seems to be related to stagnation of blood flow within a large hemangioma, which leads to platelet trapping and a subsequent consumptive coagulopathy.

Tumor-induced osteomalacia

The mechanisms behind osteomalacia have not been fully elucidated.

Epidemiology

Intramuscular hemangiomas

Most deep soft tissue hemangiomas probably are asymptomatic and small and go completely unnoticed; therefore, the exact incidence and prevalence are impossible to determine with any degree of certainty. That said, intramuscular hemangiomas are uncommon compared with other types of hemangiomas.

Muscle hemangiomas accounted for 10 of 570 hemangiomas reported by Geschickter and Keasbey. [17Watson and McCarthy estimated that intramuscular hemangiomas accounted for 0.8% of all benign vascular tumors. [18Intramuscular hemangiomas occur most often in young people (range, 2 months to 66 years), with 80-90% presenting in persons younger than 30 years. Males and females are affected with nearly equal frequency.

Synovial hemangiomas

Synovial hemangiomas are extremely rare. They can arise from any surface that is lined by synovium, particularly tendon or joint space. They typically occur in childhood and adolescence, with few reports of the disease in infants. [19]

Osseous hemangiomas

Hemangiomas of bone accounted for approximately 1% of primary bone tumors from which biopsies were taken in Dahlin and Mirra's series. [20Hemangiomas of bone may occur in patients of any age. Approximately 25% present in persons in the fifth decade of life; however, hemangiomas have been reported in patients as young as 2 years and as old as 77 years.

Approximately two thirds of osseous hemangiomas occur in the cranium or vertebrae, and hemangioma is the most common benign tumor of vertebrae. Vertebral hemangiomas are found in approximately 10-12% of autopsy specimens and have a slight predominance in females (2:1 ratio). [21]

Hemangiomatosis

Hemangiomatosis and skeletal-extraskeletal angiomatosis are rare conditions.

Gorham disease

Gorham disease (ie, massive osteolysis, disappearing bone disease) is very rare (see the image below). The disease typically occurs in the second or third decade of life with most patients younger than 40 years.

Radiograph of a patient with Gorham disease showinRadiograph of a patient with Gorham disease showing dissolution of bone.

Kasabach-Merritt syndrome

Kasabach-Merritt syndrome is a rare complication of large hemangiomas in which platelets are trapped and a consumptive coagulopathy ensues.

Prognosis

Intramuscular hemangiomas

A significant number of intramuscular hemangiomas are associated with relatively mild symptoms, such as intermittent aching or discomfort with exercise. These may require no treatment and may have no significant sequelae. Unfortunately, those symptomatic enough to indicate treatment are those most likely to be incompletely excised, and thus to recur. Recurrence rates following surgery range from 18-50%. [22]

Synovial hemangiomas

Outcomes for diffuse synovial hemangiomas are similar to those for intramuscular hemangiomas. Patients with localized synovial hemangiomas tend to have excellent results following surgical excision.

Hemangiomas of bone

Many osseous hemangiomas remain asymptomatic, require no treatment, and have no significant sequelae.

In a small series, patients with symptomatic or locally aggressive vertebral hemangiomas treated with interventional or surgical modalities had good results, with either complete resolution of symptoms or only mild symptoms reported by the patients. [23 All patients returned to their prior levels of activity and reported minimal or no residual pain in daily activities.Hemangiomatosis

Hemangiomatosis often becomes symptomatic during childhood, yet is nearly impossible to excise. Therefore, treatment with chemotherapy has been tried with variable success.

Gorham disease

The rarity of Gorham disease precludes a clear assessment of its prognosis. Results of treatments have varied.


History and Physical Examination

Intramuscular hemangiomas

Intramuscular hemangiomas occur most often in young adults, with 80-90% presenting in individuals younger than 30 years. They occur most often in the lower extremities, especially the thigh, and typically present with a palpable mass, but the overlying skin typically is not discolored.

Intramuscular hemangiomas can be asymptomatic or can present with symptoms including increased girth of the extremity, increased temperature in the area, discoloration of the overlying skin, and pain. They typically are compressible and decrease in size with elevation of the extremity. Exercise often exacerbates the symptoms of pain and swelling due to vascular dilation from increased blood flow through the hemangioma. Larger hemangiomas may be associated with a bruit or thrill.

Often, intramuscular hemangiomas cannot be distinguished definitively from soft-tissue sarcomas on the basis of clinical examination alone.

Large intramuscular hemangiomas occasionally may be associated with significant shunting of blood flow. This is uncommon, but in rare cases, it may lead to heart murmurs, congestive heart failure, or both. If significant shunting exists within the hemangioma, the presentation may be similar to that of an arteriovenous fistula (AVF). In this case, it may be possible to elicit the Branham sign, a reflex bradycardia following compression of the AVF, due to reduction in the shunt.

Synovial hemangiomas

Synovial hemangiomas are rare. In tendinous synovium, they typically present as a painless mass. In the synovium of a joint, they may present with recurrent effusions, progressive onset of pain, limited range of motion, limping, and even mechanical symptoms suggesting intra-articular derangement. [2419 A palpable, spongy, compressible mass may be present, and it may decrease in size with elevation of the extremity. The synovium is particularly hypertrophic and causes recurrent hemarthrosis.

The knee is by far the most commonly involved joint, where the presentation may be confused with meniscal or ligamentous pathology. [25 Both localized and diffuse forms exist.

Osseous hemangiomas

Hemangiomas of bone are often incidental findings and the vast majority are asymptomatic but may cause pain and swelling. Those in the skull may be associated with swelling, erythema, tenderness, or facial deformity.

A locally aggressive subtype of vertebral hemangiomas, though rare (only ~1-2% of lesions), is now well reported. This subtype may cause problems ranging from back pain to nerve root or cord compression and fractures. These locally aggressive vertebral hemangiomas can mimic other pathologies (eg, primary bony malignancy or metastatic disease) and therefore must be accurately diagnosed. [2627]

Osseous hemangiomas may be solitary (affecting a single bone) or focal (affecting one bone or, according to some authors, contiguous bones in a focal site). Various authors define hemangiomatosis differently. Some authors define it as multiple hemangiomas located in noncontiguous bones. The condition of multiple bony hemangiomas also has been referred to as cystic angiomatosis of bone when no soft-tissue component is present. Skeletal-extraskeletal angiomatosis has been defined as hemangiomas affecting the medullary canal of a bone, as well as one nonosseous site. The nonosseous site most often is adjacent soft tissue, but alternatively, it may be noncontiguous viscera.

Other authors define hemangiomatosis as lesions involving skin, muscle, and bone, which usually become symptomatic during childhood, with diffuse, persistent swelling and discoloration, with or without pain. Hemangiomatosis can also present with pathologic fracture.

Rarely, hemangioma may be associated with induction of osteomalacia. It is one of many tumor types that may cause osteomalacia.

Gorham disease

Gorham disease can present with dull localized aching pain, swelling, progressive deformity, weakness, and/or muscle atrophy. Patients are often asymptomatic during the osteolytic process until a pathologic fracture occurs or a mass develops. Hemangiomas and vascular malformations can also be present in as many as 60% of patients. [11 The disease is rarely suspected prior to radiographic evaluation. Patients are usually younger than 40 years.

Kasabach-Merritt syndrome

Kasabach-Merritt syndrome can present with diffuse petechiae and ecchymosis in association with a large soft-tissue mass. If platelet counts drop low enough, spontaneous hemorrhage may result.



Laboratory Studies

If a patient presents with history, physical examination findings, and imaging study findings consistent with hemangioma, no laboratory studies are necessary.

For patients with intramuscular hemangiomas who manifest petechiae, easy bruising, or ecchymoses, Kasabach-Merritt syndrome should be considered. In this syndrome, a complete blood count (for hemoglobin, hematocrit, and platelets) and coagulation studies (eg, prothrombin time [PT], activated partial thromboplastin time [aPTT], thrombin time [TT], fibrinogen, fibrinogen degradation products [FDPs]) are recommended for evaluation. Hemoglobin and hematocrit can be decreased if hemorrhage is significant. Platelet counts can fall to 20,000/μL or less. PT may be mildly elevated. Serum fibrinogen may be decreased, and FDPs may be elevated.

If tumor-induced osteomalacia is suspected on the basis of radiographic findings, serum calcium, phosphorus, parathyroid hormone (PTH), and alkaline phosphatase (ALP) should be checked. Serum calcium will be in the low-to-normal range, marked hypophosphatemia will be present, PTH will be within the reference range, and ALP will be elevated.

Imaging Studies

Intramuscular hemangiomas

Radiography

Soft-tissue hemangiomas may be seen on radiographs as soft-tissue shadows, though they are typically isodense with muscle. [2829 They may cause benign-appearing periosteal reaction or chronic cortical thickening and remodeling in adjacent bone (see the image below).

Cortical thickening of the tibia adjacent to an inCortical thickening of the tibia adjacent to an intramuscular hemangioma of the leg.

Phleboliths within the soft-tissue mass are diagnostic but are not common. These small, round, calcified densities occur within organizing thrombi within the vascular structures of hemangiomas (see the image below).

Radiograph showing phleboliths in an intramuscularRadiograph showing phleboliths in an intramuscular hemangioma of the thigh.

Magnetic resonance imaging

After plain radiography, magnetic resonance imaging (MRI) is the imaging modality of choice for soft-tissue hemangiomas, including those of muscle and synovium (see the image below). [282930]

T1 and T2 MRI images of intramuscular hemangioma oT1 and T2 MRI images of intramuscular hemangioma of the leg. Note the serpentine quality of the vessels and that the hemangioma is high signal on both T1 and T2. This indicates that the hemangioma is predominantly of water density.

Hemangiomas show increased signal on both T1- and T2-weighted images, frequently with areas of signal void. These void areas may be indicative of dense fibrous tissue, thrombi, phleboliths, or regions of high flow.

The diagnosis of hemangioma may be made with MRI when these signal characteristics are present and when the serpentine pattern of the vascular structures is depicted, usually with interposed fat as well. The margins of hemangiomas range from very infiltrative and irregular to well marginated.

Increased signal with gadolinium enhancement also may be helpful in distinguishing hemangiomas from other soft-tissue masses.

Angiography

Angiography reveals a highly vascular lesion with vessels oriented parallel to one another. [2829 The lesions may be high-flow or low-flow. This distinction between high-flow and low-flow lesions can be important in treatment decisions, in that the former are more likely to benefit from embolization than the latter.

Ultrasonography

A study by Tang et al found color Doppler ultrasonography (US) to have a high rate of diagnosis for imtramuscular hemangioma. [31 

Synovial hemangiomas

Radiography

Synovial hemangiomas result in nonspecific changes on plain radiographs, occasionally including a vague soft-tissue density. [32 Erosion of bone is rarely present.

Magnetic resonance imaging

MRI is useful in the diagnosis of synovial hemangiomas. The signal characteristics are similar to those of intramuscular hemangiomas (increased signal on T1 and T2, and depiction of vascular structures). In addition, MRI can provide information as to whether a synovial hemangioma is localized and pedunculated or diffuse (see the image below). This information helps in planning treatment. Finally, MRI can be used to diagnose other pathologic processes in the differential diagnosis of a synovial hemangioma (eg, meniscal tear).

MRI of a pedunculated synovial hemangioma of the kMRI of a pedunculated synovial hemangioma of the knee. (T2 image with time to repetition [TR]=25.4, time to echo [TE]=9.0/1.)

Angiography

This study reveals pooling over the mass, consistent with a vascular process.

Osseous hemangiomas

Radiography

Hemangiomas of bone have different radiographic characteristics in different anatomic locations. In the skull, they produce lytic lesions that are well circumscribed and may have a honeycomb appearance. Frequently, fine, radiating striations are present, creating a sunburst or sunray appearance. The cortex often is expanded in the skull.

In the vertebral bodies, the parallel vertical trabeculae have a pathognomonic appearance, often referred to as "corduroy cloth," "honeycomb," or "jailhouse" appearance (see the image below). The cortex is not expanded in the vertebrae. [33]

Radiograph of a vertebral hemangioma illustrating Radiograph of a vertebral hemangioma illustrating the corduroy or jailhouse appearance of striations.

In the long bones, radiographic findings typically are less specific, with a coarse or bubbly appearance. Occasionally, the appearance may be primarily or completely lytic with a sclerotic rim.

Computed tomography

Computed tomography (CT) occasionally is used in identification of osseous hemangiomas but generally is not used to evaluate soft-tissue hemangiomas. Vertebral body hemangiomas have a distinctive polka-dot appearance on axial CT (see the image below).

Axial cut on CT scan illustrating the polka dot apAxial cut on CT scan illustrating the polka dot appearance of an intraosseous vertebral hemangioma.

Magnetic resonance imaging

The characteristic MRI appearance is a hyperintense, mottles, or "starburst" signal on T1-weighted and T2-weighted images. Vertebral hemangiomas can be identified by the jailhouse appearance on sagittal sections (see the first image below), similar to that seen on radiographs, and by the polka-dot appearance seen on axial sections (see the second image below).

MRI (sagittal cut) illustrating the jailhouse appeMRI (sagittal cut) illustrating the jailhouse appearance of a vertebral hemangioma.
Axial cut on CT scan illustrating the polka dot apAxial cut on CT scan illustrating the polka dot appearance of an intraosseous vertebral hemangioma.

A study by Cross et al found that characteristic findings associated with vertebral hemangiomas were absent in 35% of plain films, 20% of CT scans, and 48% of MRI scans of aggressive lesions, resulting in an inability to make an accurate diagnosis. [34]

Gorham disease

Radiography

Massive osteolysis is evidenced by what appears to be dissolution of a bone or of adjacent bones in which the ends become tapered, as in the image below. The disease is characterized by intramedullary and subcortical radiolucent foci that appear as patchy osteoporosis. The disease slowly progresses in an irregular fashion and may evolve into an extraosseous process. It may present as an intraosseous process demonstrating a scooped-out appearance of the bony tissue.

Radiograph of a patient with Gorham disease showinRadiograph of a patient with Gorham disease showing dissolution of bone.

Procedures

Intramuscular hemangiomas

The differential diagnosis for the clinical and radiographic findings associated with intramuscular hemangiomas includes soft-tissue sarcoma. Therefore, when the clinical and radiographic findings are equivocal, biopsy is indicated (see the images below). Biopsy can be performed by means of needle or open techniques. Excessive bleeding should be anticipated in most cases.

Low-power view of the histology of an intramusculaLow-power view of the histology of an intramuscular hemangioma. Note the vascular channels.
High-power view of the histology of an intramusculHigh-power view of the histology of an intramuscular hemangioma. Red blood cells are visible within the vascular channels.

Osseous hemangiomas

The most significant entities in the differential diagnosis of hemangioma of bone are osseous angiosarcoma and metastatic disease. [35 As with soft-tissue hemangiomas, when the clinical and radiographic findings are equivocal, biopsy is indicated. Biopsy can be performed by means of needle or open techniques. [36]

Histologic Findings

Hemangiomas may have a spectrum of histologic findings. [37In a simplistic classification schema, hemangiomas can be divided into the following three types:

  • Capillary (small-vessel)
  • Cavernous (large-vessel)
  • Mixed

Capillary hemangiomas have abundant vessels approximately 10-100 μm in diameter with walls one to three cells thick. The vessels tend to run in parallel. There is a single layer of endothelial cells with no shedding and no anaplasia. Cavernous hemangiomas have a similar appearance, but the lumina are bigger.

A cellular type also has been described in which a much higher number of cells are present, distinct lumina are still identifiable, and no shedding or anaplasia is seen. There may be smaller areas within a cellular type that resemble capillary hemangiomas.

Using a more refined classification schema, Enzinger and Weiss divided localized hemangiomas into seven categories, as follows [38:

  • Capillary hemangioma, including juvenile
  • Cavernous hemangioma
  • Venous hemangioma
  • Arteriovenous hemangioma (racemose hemangioma)
  • Epithelioid hemangioma
  • Hemangioma of granulation tissue
  • Miscellaneous hemangiomas of deep soft tissue (including many of the hemangiomas important to orthopedists, specifically synovial and intramuscular hemangiomas)

Cells within a hemangioma can be stained for factor VIII; positivity indicates that the cells are endothelial. A group in New Zealand defined three suggested phases of hemangioma development (proliferative, involuting, and involuted) by histochemical and immunohistochemical means. Findings included the following:

  • Both CD31 and von Willebrand factor (vWF) stained vascular endothelial cells in tumors of each phase
  • Proliferating cell nuclear antigen was predominant in the proliferative and involuting hemangiomas, but negligible in the involuting phase
  • Mast cells were identified predominately in the involuting phase hemangiomas
  • Vascular endothelial growth factor (VEGF) was identified primarily during the proliferative phase
  • Basic fibroblast growth factor (bFGF) was identified during the proliferative and early involuting phases

Whereas these studies generally are not necessary for diagnosis, they provide insight into the biology and development of hemangioma.

Electron microscopy can be used to identify Weibel-Palade bodies. These bodies are rod-shaped, ranging from 0.1 to 0.3 μm in length, and contain parallel tubules that localize factor VIII–associated antigen. They are relatively specific to endothelial cells.

Intramuscular hemangiomas

Intramuscular hemangiomas may be capillary, cavernous, or mixed in type. They can be distinguished from skeletal-muscle angiosarcomas because they do not develop the freely anastomosing sinusoidal pattern seen in certain angiosarcomas. In addition, hemangiomas do not have the nuclear pleomorphism and hyperchromatism seen in angiosarcomas. It may be more difficult to distinguish hemangiomas from hemangioendotheliomas, but hemangioendotheliomas may have shedding and cellular atypia. Hemangiomas can be differentiated from angiolipomas by the absence of lipoblasts in hemangiomas.

Synovial hemangiomas

Synovial hemangiomas are of the cavernous type. The matrix between the vessels may be edematous, myxoid, or focally hyalinized. The cells may contain significant amounts of hemosiderin.

Osseous hemangiomas

Most hemangiomas of bone are cavernous, though they may also be a mixture of capillary and cavernous. There may be reactive new-bone formation, which can appear similar to an osteoblastoma. Hemangioendothelioma of bone may be distinguished by a plumper endothelial lining and varying degrees of cellular atypia.

Gorham disease

Histologic findings in Gorham disease can include benign hemangiomatosis, lymphangiomatosis, or sinusoidal channels of vascular or lymphatic origin. [11The vascular component appears as densely packed fibrovascular tissue at sites of bony destruction and as capillarylike lumens at sites of bone preservation.



Approach Considerations

Intramuscular hemangiomas

The natural history of many intramuscular hemangiomas is that of gradual fatty replacement, atrophy, and involution over time, as suggested by their greater frequency in individuals younger than 30 years and their relative rarity in older adults. Many intramuscular hemangiomas are asymptomatic or produce only mild symptoms with activity, even during the active adolescent years.

Treatment may be considered if pain is substantial, but because of the poor success rate of treatment and the apparent self-limited nature of most intramuscular hemangiomas, indications for treatment are few. The more localized the extent of the disease, the more likely it is to be controlled successfully by surgical excision.

Synovial hemangiomas

The natural history of synovial hemangiomas may be similar to that of their intramuscular counterparts, but their rarity makes this difficult to document. The focal type more frequently is amenable to surgical excision than is the diffuse type.

Osseous hemangiomas

Symptomatic or locally aggressive vertebral hemangiomas are usually treated conservatively when symptoms are limited to mild-to-moderate pain, whereas neurologic deficit and intractable pain are widely accepted in the literature as common indications for surgical intervention. [34]

Hemangiomatosis

Both osseous hemangiomatosis and skeletal-extraskeletal angiomatosis often become symptomatic during childhood, with pain and diffuse swelling. Perhaps even more significantly, extraskeletal manifestations of hemangiomatosis can lead to hepatic dysfunction and cardiac complications. Because of the extensive nature of the disease, chemotherapy has been used with some success.

Gorham disease

The natural history of Gorham disease is poorly defined. Extent and pace of bone loss are variable. No standard treatment is currently available for Gorham disease. Regression of lesions or stabilization of disease has been reported with steroids, radiation, surgery, bisphosphonates, zoledronic acid, and interferon alfa. [11 Because of the unpredictable natural history and the potentially devastating effects of progressive disease, treatment generally should be instituted upon diagnosis.

Kasabach-Merritt syndrome

Kasabach-Merritt syndrome is a potentially life-threatening coagulopathy that is related to platelet trapping in a large cavernous hemangioma. Approximately 30% of patients who develop this complication die from hemorrhage or infection. Surgical resection of the hemangioma often is difficult. Consequently, steroids, radiation therapy, interferon alfa-2a, and pentoxifylline have been used in attempts at treatment.

Tumor-induced osteomalacia

Tumor-induced osteomalacia results in diffuse osteopenia with marked hypophosphatemia, low serum calcium, and increased serum alkaline phosphatase. Because osteomalacia generally resolves with excision of the tumor, surgical treatment usually is indicated.

Future developments

The true nature of hemangiomas remains controversial, with no clear consensus on an inciting cause, nor agreement as to whether hemangiomas are neoplasms, hamartomas, or malformations. Future investigations likely will attempt to answer these questions, and may lead to innovations in therapy. Work is underway on the therapeutic use of angiogenic cytokines and angiogenesis inhibitors, including systemic administration of the antiangiogenic proteins AGM-1470 and angiostatin or of the matrix metalloproteinase inhibitor batimastat, and gene gun therapy with interleukin (IL)-12.

Nonoperative Therapy

Intramuscular hemangiomas

Observation is appropriate for asymptomatic or mildly symptomatic hemangiomas of skeletal muscle and bone. If symptoms cannot be managed adequately by activity modification and nonnarcotic analgesics, further treatment may be considered. Embolization may be used to provide symptomatic relief of intramuscular hemangiomas. When surgical excision is planned, embolization also may be used preoperatively to decrease intraoperative blood loss and postoperative recurrence. [39]

Synovial hemangiomas

Although local pedunculated synovial hemangiomas are removed surgically, more diffuse lesions may be treated with intra-articular low-dose radiation therapy, open excision, or both when sufficiently symptomatic.

Osseous hemangiomas

Hemangiomas of bone rarely require treatment. If symptoms are significant enough to warrant consideration of treatment, it is important to confirm the diagnosis; more aggressive neoplasms (eg, metastatic renal cell carcinoma) may masquerade as hemangioma.

Radiation may be considered for symptomatic hemangiomas in surgically inaccessible sites, such as vertebral hemangiomas. [4041However, some authors have found that selective arterial embolization is safer and more effective in the treatment of symptomatic vertebral lesions.

Bleacher et al proposed a management algorithm for symptomatic and locally aggressive vertebral hemangiomas, [23 in which symptomatic patients were divided into those with pain only and those with neurologic deficits. Patients with pain were treated with transarterial embolization or vertebroplasty after failing conservative management, whereas patients who presented with neurologic deficits were treated with transarterial embolization, decompressive laminectomy, and vertebroplasty.

Symptomatic and locally aggressive vertebral hemangiomas have been reported in the pediatric population; however, because of the paucity of clinical data in this group of patients, no clinical guidelines have been established in the literature. Accordingly, treatment should be individualized. [21]

Hemangiomatosis

Chemotherapy has been used in the treatment of extensive hemangiomatosis, particularly when the vascular proliferation is life- or limb-threatening.

Gorham disease

No standard treatment is currently recognized for Gorham disease. Regression of lesions or stabilization of disease has been reported with steroids, radiation, surgery, bisphosphonates, zoledronic acid, and interferon alfa. [11Local resection with arthroplasty has been reported, with no evidence of recurrence in periarticular disease.

Kasabach-Merritt syndrome

Kasabach-Merritt syndrome is treated with supportive measures, particularly transfusion of platelets. [42Steroids also have been used in the treatment of Kasabach-Merritt syndrome, with some success. Sirolimus has shown some success when steroids are ineffective. [43]

Good results of treatment with pentoxifylline were reported by de Prost et al. [44Pentoxifylline acts to restore blood flow and seems to possess antithrombotic activity as well. Pharmacologic management with interferon alfa-2a has also been attempted.

Radiation therapy has had variable success. Surgical resection of the hemangioma often is difficult.

In a study evaluating the clinical characteristics, treatments, and outcomes of neonates with Kasabach-Merritt syndrome, Wang et al concluded that steroid therapy had a low degree of efficacy and was associated with a high rate of relapse, whereas arterial embolization was effective. [45Accordingly, they recommended that a combination of steroid therapy and embolization therapy be considered as first-line treatment of neonatal Kasabach-Merritt syndrome and that vincristine be considered if that approach is ineffective.

Surgical Therapy

Intramuscular hemangiomas

Angiography is an important aspect of preoperative planning when the vascular supply of the lesion is in question and when preoperative embolization is considered. Embolization of high-flow lesions may be performed by interventional radiology to decrease intraoperative blood loss and to decrease the risk of postoperative recurrence. Low-flow lesions are not treatable by embolization. Instead, sclerosing agents may be used to decrease blood flow through low-flow hemangiomas.

Surgical excision attempts to achieve a marginal border unless the hemangioma is contained within a single muscle belly that can be excised completely to achieve a wide margin. The rate of local recurrence following wide excision has been reported as less than 10%, whereas local recurrence rates after marginal excision range from 25% to much higher. Meticulous hemostasis is essential in the prevention of postoperative hematoma.

Excision of symptomatic intramuscular hemangiomas can provide permanent relief. However, because complete excision is required for long-lasting satisfactory results, this treatment option generally is restricted to hemangiomas contained within a single muscle belly. Even so, complete resection is not always possible; when incompletely resected, hemangiomas nearly always recur. In addition, surgery can be associated with large-volume blood loss, even when preoperative embolization is employed.

Laser knife excision of hemangiomas is a technique developed to allow better control of intraoperative bleeding. Preoperative ultrasound-guided hook-wire localization may aid in defining the extent of a hemangioma during excision. Wang et al found it to be safe and effective for nonpalpable intramuscular hemangiomas and concluded that it may provide a better cosmetic result and improved functional recovery. [46 Radiation has been used to treat soft-tissue hemangiomas in surgically inaccessible or potentially dangerous sites.

Postoperatively, the surgical site is wrapped in a compressive dressing. The patient is required to maintain a minimal level of activity. Both of these measures are instituted to prevent the occurrence of postoperative hematoma.

Osseous hemangiomas

Transarterial embolization can be a definitive treatment option or a preoperative intervention [47followed by surgical decompression for the treatment of symptomatic vertebral hemangiomas. Significant blood loss has been described as a complication of surgical treatment of locally aggressive vertebral hemangioma in patients with neurologic deficits. [1123]

A multicenter study using data compiled by the AOSpine Knowledge Forum Tumor Investigators found that formal en-bloc resection was not required for symptomatic primary spinal hemangiomas and that aggressive intralesional resection during index surgery was capable of yielding excellent rates of local control and long-term survival. [48]

Synovial hemangiomas

Local pedunculated synovial hemangiomas are removed surgically, often through an arthroscope.

Complications

In both intramuscular and osseous hemangiomas, hemorrhage can occur spontaneously during biopsy or during surgical resection; such hemorrhages can be massive. [2623Furthermore, hemangiomas typically recur following incomplete surgical excision. Some large hemangiomas may result in shunting of the blood to a degree significant enough to cause congestive heart failure.

Rarely, cord compression and neurologic deficits can result from vertebral hemangiomas. Approximately 30% of patients with Kasabach-Merritt syndrome die of hemorrhage or infection. Osteomalacia is an uncommon complication that has been associated with hemangioma.

Follow-up is required to assess symptomatic relief and to monitor for possible recurrence.



Approach Considerations

Intramuscular hemangiomas

The natural history of many intramuscular hemangiomas is that of gradual fatty replacement, atrophy, and involution over time, as suggested by their greater frequency in individuals younger than 30 years and their relative rarity in older adults. Many intramuscular hemangiomas are asymptomatic or produce only mild symptoms with activity, even during the active adolescent years.

Treatment may be considered if pain is substantial, but because of the poor success rate of treatment and the apparent self-limited nature of most intramuscular hemangiomas, indications for treatment are few. The more localized the extent of the disease, the more likely it is to be controlled successfully by surgical excision.

Synovial hemangiomas

The natural history of synovial hemangiomas may be similar to that of their intramuscular counterparts, but their rarity makes this difficult to document. The focal type more frequently is amenable to surgical excision than is the diffuse type.

Osseous hemangiomas

Symptomatic or locally aggressive vertebral hemangiomas are usually treated conservatively when symptoms are limited to mild-to-moderate pain, whereas neurologic deficit and intractable pain are widely accepted in the literature as common indications for surgical intervention. [34]

Hemangiomatosis

Both osseous hemangiomatosis and skeletal-extraskeletal angiomatosis often become symptomatic during childhood, with pain and diffuse swelling. Perhaps even more significantly, extraskeletal manifestations of hemangiomatosis can lead to hepatic dysfunction and cardiac complications. Because of the extensive nature of the disease, chemotherapy has been used with some success.

Gorham disease

The natural history of Gorham disease is poorly defined. Extent and pace of bone loss are variable. No standard treatment is currently available for Gorham disease. Regression of lesions or stabilization of disease has been reported with steroids, radiation, surgery, bisphosphonates, zoledronic acid, and interferon alfa. [11 Because of the unpredictable natural history and the potentially devastating effects of progressive disease, treatment generally should be instituted upon diagnosis.

Kasabach-Merritt syndrome

Kasabach-Merritt syndrome is a potentially life-threatening coagulopathy that is related to platelet trapping in a large cavernous hemangioma. Approximately 30% of patients who develop this complication die from hemorrhage or infection. Surgical resection of the hemangioma often is difficult. Consequently, steroids, radiation therapy, interferon alfa-2a, and pentoxifylline have been used in attempts at treatment.

Tumor-induced osteomalacia

Tumor-induced osteomalacia results in diffuse osteopenia with marked hypophosphatemia, low serum calcium, and increased serum alkaline phosphatase. Because osteomalacia generally resolves with excision of the tumor, surgical treatment usually is indicated.

Future developments

The true nature of hemangiomas remains controversial, with no clear consensus on an inciting cause, nor agreement as to whether hemangiomas are neoplasms, hamartomas, or malformations. Future investigations likely will attempt to answer these questions, and may lead to innovations in therapy. Work is underway on the therapeutic use of angiogenic cytokines and angiogenesis inhibitors, including systemic administration of the antiangiogenic proteins AGM-1470 and angiostatin or of the matrix metalloproteinase inhibitor batimastat, and gene gun therapy with interleukin (IL)-12.

Nonoperative Therapy

Intramuscular hemangiomas

Observation is appropriate for asymptomatic or mildly symptomatic hemangiomas of skeletal muscle and bone. If symptoms cannot be managed adequately by activity modification and nonnarcotic analgesics, further treatment may be considered. Embolization may be used to provide symptomatic relief of intramuscular hemangiomas. When surgical excision is planned, embolization also may be used preoperatively to decrease intraoperative blood loss and postoperative recurrence. [39]

Synovial hemangiomas

Although local pedunculated synovial hemangiomas are removed surgically, more diffuse lesions may be treated with intra-articular low-dose radiation therapy, open excision, or both when sufficiently symptomatic.

Osseous hemangiomas

Hemangiomas of bone rarely require treatment. If symptoms are significant enough to warrant consideration of treatment, it is important to confirm the diagnosis; more aggressive neoplasms (eg, metastatic renal cell carcinoma) may masquerade as hemangioma.

Radiation may be considered for symptomatic hemangiomas in surgically inaccessible sites, such as vertebral hemangiomas. [4041However, some authors have found that selective arterial embolization is safer and more effective in the treatment of symptomatic vertebral lesions.

Bleacher et al proposed a management algorithm for symptomatic and locally aggressive vertebral hemangiomas, [23 in which symptomatic patients were divided into those with pain only and those with neurologic deficits. Patients with pain were treated with transarterial embolization or vertebroplasty after failing conservative management, whereas patients who presented with neurologic deficits were treated with transarterial embolization, decompressive laminectomy, and vertebroplasty.

Symptomatic and locally aggressive vertebral hemangiomas have been reported in the pediatric population; however, because of the paucity of clinical data in this group of patients, no clinical guidelines have been established in the literature. Accordingly, treatment should be individualized. [21]

Hemangiomatosis

Chemotherapy has been used in the treatment of extensive hemangiomatosis, particularly when the vascular proliferation is life- or limb-threatening.

Gorham disease

No standard treatment is currently recognized for Gorham disease. Regression of lesions or stabilization of disease has been reported with steroids, radiation, surgery, bisphosphonates, zoledronic acid, and interferon alfa. [11Local resection with arthroplasty has been reported, with no evidence of recurrence in periarticular disease.

Kasabach-Merritt syndrome

Kasabach-Merritt syndrome is treated with supportive measures, particularly transfusion of platelets. [42Steroids also have been used in the treatment of Kasabach-Merritt syndrome, with some success. Sirolimus has shown some success when steroids are ineffective. [43]

Good results of treatment with pentoxifylline were reported by de Prost et al. [44Pentoxifylline acts to restore blood flow and seems to possess antithrombotic activity as well. Pharmacologic management with interferon alfa-2a has also been attempted.

Radiation therapy has had variable success. Surgical resection of the hemangioma often is difficult.

In a study evaluating the clinical characteristics, treatments, and outcomes of neonates with Kasabach-Merritt syndrome, Wang et al concluded that steroid therapy had a low degree of efficacy and was associated with a high rate of relapse, whereas arterial embolization was effective. [45Accordingly, they recommended that a combination of steroid therapy and embolization therapy be considered as first-line treatment of neonatal Kasabach-Merritt syndrome and that vincristine be considered if that approach is ineffective.

Surgical Therapy

Intramuscular hemangiomas

Angiography is an important aspect of preoperative planning when the vascular supply of the lesion is in question and when preoperative embolization is considered. Embolization of high-flow lesions may be performed by interventional radiology to decrease intraoperative blood loss and to decrease the risk of postoperative recurrence. Low-flow lesions are not treatable by embolization. Instead, sclerosing agents may be used to decrease blood flow through low-flow hemangiomas.

Surgical excision attempts to achieve a marginal border unless the hemangioma is contained within a single muscle belly that can be excised completely to achieve a wide margin. The rate of local recurrence following wide excision has been reported as less than 10%, whereas local recurrence rates after marginal excision range from 25% to much higher. Meticulous hemostasis is essential in the prevention of postoperative hematoma.

Excision of symptomatic intramuscular hemangiomas can provide permanent relief. However, because complete excision is required for long-lasting satisfactory results, this treatment option generally is restricted to hemangiomas contained within a single muscle belly. Even so, complete resection is not always possible; when incompletely resected, hemangiomas nearly always recur. In addition, surgery can be associated with large-volume blood loss, even when preoperative embolization is employed.

Laser knife excision of hemangiomas is a technique developed to allow better control of intraoperative bleeding. Preoperative ultrasound-guided hook-wire localization may aid in defining the extent of a hemangioma during excision. Wang et al found it to be safe and effective for nonpalpable intramuscular hemangiomas and concluded that it may provide a better cosmetic result and improved functional recovery. [46 Radiation has been used to treat soft-tissue hemangiomas in surgically inaccessible or potentially dangerous sites.

Postoperatively, the surgical site is wrapped in a compressive dressing. The patient is required to maintain a minimal level of activity. Both of these measures are instituted to prevent the occurrence of postoperative hematoma.

Osseous hemangiomas

Transarterial embolization can be a definitive treatment option or a preoperative intervention [47followed by surgical decompression for the treatment of symptomatic vertebral hemangiomas. Significant blood loss has been described as a complication of surgical treatment of locally aggressive vertebral hemangioma in patients with neurologic deficits. [1123]

A multicenter study using data compiled by the AOSpine Knowledge Forum Tumor Investigators found that formal en-bloc resection was not required for symptomatic primary spinal hemangiomas and that aggressive intralesional resection during index surgery was capable of yielding excellent rates of local control and long-term survival. [48]

Synovial hemangiomas

Local pedunculated synovial hemangiomas are removed surgically, often through an arthroscope.

Complications

In both intramuscular and osseous hemangiomas, hemorrhage can occur spontaneously during biopsy or during surgical resection; such hemorrhages can be massive. [2623Furthermore, hemangiomas typically recur following incomplete surgical excision. Some large hemangiomas may result in shunting of the blood to a degree significant enough to cause congestive heart failure.

Rarely, cord compression and neurologic deficits can result from vertebral hemangiomas. Approximately 30% of patients with Kasabach-Merritt syndrome die of hemorrhage or infection. Osteomalacia is an uncommon complication that has been associated with hemangioma.

Follow-up is required to assess symptomatic relief and to monitor for possible recurrence.

0 comments:

Post a Comment