CLINICAL REVIEW

David W. Eisele, MD, Section Editor

TREATMENT GUIDELINE FOR HEMANGIOMAS AND VASCULAR MALFORMATIONS OF THE HEAD AND NECK
Jia Wei Zheng, DDS, MD,1 Qin Zhou, MS,1 Xiu Juan Yang, MS,1 Yan An Wang, DDS, MD,1 Xin Dong Fan, DDS, MD,1 Guo Yu Zhou, DDS, MD,1 Zhi Yuan Zhang, DDS, MD,1 James Y. Suen, MD2
1

Department of Oral and Maxillofacial Surgery, College of Stomatology, Ninth Peoples Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China. E-mail: zhzhy@omschina.org.cn 2 Department of Otolaryngology - Head & Neck Surgery, University of Arkansas for Medical Sciences, 4301 West Markham, #543, Little Rock, AR 72205-1799 Accepted 27 August 2009 Published online 18 November 2009 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/hed.21274

Abstract: Vascular anomalies are among the most common congenital and neonatal dysmorphogenesis, which are separated into hemangiomas and vascular malformations. They can occur in various areas throughout the body, with 60% being located in the head and neck. The true mechanism of pathogenesis of vascular anomalies is still unclear. Various treatment methods have been reported, and there are still controversies over the selection of different treatment modalities. Based on the clinical and basic research and current literature, the Chinese Division of Oral and Maxillofacial Vascular Anomalies formulated a treatment guideline for hemangiomas and vascular malformations of the head and neck, which will be modied and updated periodically based on new medical eviC 2009 Wiley Periodicals, Inc. Head dence and research. V Neck 32: 10881098, 2010 Keywords: hemangioma; vascular malformation; treatment guideline; head and neck

Based on the endothelial cell characteristics and clinical behaviors of vascular anomalies,
Correspondence to: Z. Y. Zhang
C 2009 Wiley Periodicals, Inc. V

Mulliken and Glowacki1 in 1982 categorized these lesions into 2 main categories: hemangiomas and vascular malformations. This classication is, in general, correct and up-to-date and has been widely accepted worldwide, but limitations exist in which specic entities such as tufted angiomas, hemangioendotheliomas, and hemangiomas with segmental distribution patterns are not included. In 1996, the International Society for the Study of Vascular Anomalies (ISSVA) added the rapidly involuting congenital hemangioma, noninvoluting congenital hemangioma, Kaposiform hemangioendothelioma, tufted angioma, and pyogenic granuloma to the list of vascular tumors. The subsequent modied classication by Waner and Suen2 in 1999 is more practical and easily used clinically, in which hemangiomas are subdivided into supercial, deep-seated, and mixed type, and vascular malformations are subdivided according to the predominant channel anomaly into either venular (capillary), arterial, venous, lymphatic,

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or combinations. Arterial and arteriovenous malformations (AVMs) are high-ow, whereas venular, venous, and lymphatic malformations are slow-ow. Hemangiomas and vascular malformations are 2 different disease entities with different histopathologic features, clinical characteristics, and natural course. There are various treatment modalities for hemangiomas and vascular malformations depending on the stage and type of the lesion3; each has its pros and cons and is under incessant renewal. Based on the results of clinical and basic scientic research, and with reference to the latest international literature, a Treatment Guideline for Hemangiomas and Vascular Malformations of Head and Neck Region was formulated. We hope this publication will serve as a guide for the treatment of hemangiomas and vascular malformations of the head and neck region. The development of modern medicine is ever changing, with new theories, views, diagnostic techniques, and treatment procedures appearing continuously. Therefore, this guideline will be modied and updated periodically based on new medical evidence and research.

TREATMENT OF HEMANGIOMAS Characteristics and Treatment Principle. Hemangiomas are common vascular tumors that occur in as many as 2.5% of neonates4 and can be separated into congenital or infantile. Congenital hemangiomas comprise the rapid involuting congenital hemangiomas (RICH) and the noninvoluting congenital hemangiomas (NICH), and are much less common than those which happen shortly after birth but occurs within the rst month of life. The RICH hemangiomas are present at birth, involute over the rst few months of life, and require no treatment, whereas the NICH hemangiomas are present at birth and do not involute with time. Those can be surgically removed later in childhood. The infantile hemangioma is a true benign neoplasm that is able to resolve by itself. The natural course of the infantile hemangioma has 3 distinct phases: proliferative, involution, and involuted phase. Infantile hemangioma usually does not appear at birth, but it has 2 rapid proliferation phases (12 months after birth and 45 months after birth). The growth of the hemangioma at the early phase can be rapid and unpredictable; early intervention may impede the progress into

the rapid proliferation phase, preventing voluminous hemangiomas from developing. The inuence of hemangiomas on children is various, and can be life-threatening when involving the larynx and trachea. Hemangiomas involving the eyelids can result in visual impairment such as amblyopia and refractive errors or even blindness. Massive hemangiomas can also lead to ulceration, necrosis, and infection of important structures. Disgurement can also lead to psychological issues such as inferiority complex, unsociable, stubbornness, and low self condence. With regard to the extent of nal resolution of the hemangioma, there is presently no objective assessment and predictability. Principles of treatment selection.5 The treatment of hemangiomas is dependent on the primary site and various stages of growth Early treatment of even small hemangiomas of the face is subject to controversy and must be critically re-evaluated, especially with regard to long-term aesthetic results and therapeutic sequelae. An active observation is usually the most adequate regimen also for hemangiomas involving the face. Except on rare occasions, surgical treatment should not be used as the rst choice of treatment. When the larynx or trachea is involved, early intervention is usually indicated to prevent airway obstruction. If eyelid involvement is threatening vision or if cartilage destruction is obvious, treatment should be initiated.

Choice of Treatment Methods. Small isolated or multiple skin lesions on the face in infants can be considered for early treatment using lasers or surgery to try to prevent progression into the proliferative phase. Imiquimod is a novel immunomodier, which can be used for small and intermediate-sized hemangiomas6 located in inconspicuous sites, with alternate day topical application, for a cycle of 3 to 5 months. The advantages are the ease of use, controllability, safety, and lack of local irritation or systemic effects. The disadvantage is that it may cause hyperpigmentation; thus care has to be taken for application on the face for aesthetic reasons. Laser therapy is indicated for treatment of supercial proliferating hemangiomas. This mode of therapy may accelerate the regression and reduce the size of the lesion, creating

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favorable situations for subsequent treatments.7 If the lesion continues to enlarge during laser therapy, supplementary pharmacotherapy should be considered. The advantage of laser therapy is the simplicity of use, which can be repeated at an interval of 2 to 4 weeks. The choice of laser should be based on the location, size, and depth of the lesion. Flash lamppumped pulsed dye laser has a wavelength of 585 nm or 595 nm, allowing selective destruction of the blood vessels, and is the only laser that delivers photocoagulation of the targeted vessels while keeping the overlying skin intact. It is therefore useful for treatment of supercial hemangiomas and those at the involution stage. However, this laser has little effect on subcutaneous and deep-seated hemangiomas because of the limited penetration depth. Neodymium: yttrium-aluminum-garnet (Nd:YAG) laser has a wavelength of 1064 nm and penetration depth of up to 5.0 mm. It is therefore suitable for larger and up to 2 cm deep hemangiomas. Percutaneous laser therapy can be utilized for deep hemangiomas. During the treatment process, cooling devices should be used to lower the temperature to protect the epidermis from thermal damage. The effectiveness of laser therapy is 77% to 100%; the smaller the lesion, the better the result. It must be addressed that although different laser systems are effective for supercial or deep hemangiomas, a systemic therapy with steroids or b-blockers (still in clinical trials) should be preferred as rst-line therapy. Severe side effects such as tissue necrosis and scarring are very often observed by the uncritical use of laser systems. Therefore, laser therapy of proliferating hemangiomas is applied only in selected cases,8 especially regarding modern treatment concepts. Drug therapy is indicated for mixed hemangiomas, proliferative hemangiomas, and hemangiomas that affect vital organs or are lifethreatening. Oral corticosteroid has been used for more than 30 years, and has been the rstline treatment for severe problematic hemangiomas during the past years. The effective rate is 84%,9 with a signicant relationship between dosage and effectiveness. The best results are observed for patients aged 6 months and younger; the older the age, the poorer the treatment outcome. Oral prednisolone is more effective than intravenous injection of methylprednisolone. The regimen for oral corticosteroid10 is oral prednisolone (3.05.0 mg/kg)

every other morning for 6 to 8 weeks. The dosage is tapered after that for 2 or 3 weeks. The treatment can be repeated for 2 or 3 cycles when necessary at an interval of 4 to 6 weeks. For more localized hemangiomas, such as orbital or parotid lesions, intralesional steroids can be very effective. The dose of triamcinolone was 1 to 2 mg/kg of body weight (maximum of 60 mg) at monthly intervals, depending on the age of the patient and size of the lesion.11 Pingyangmycin (bleomycin A5) has been administered intralesionally for hemangiomas based specically on a high sclerosing effect on vascular endothelium, with greater than 90% success rate12 and 49% complete resolution. It has been proven to be an easy, safe, and effective therapeutic modality in complicated cutaneous hemangiomas13 and suitable for proliferative hemangiomas which respond poorly to steroids and/or laser therapy. Clinically, Pingyangmycin hydrochloride (8 mg/syringe) is dissolved with 2% lidocaine and then mixed with normal saline and dexamethasone (5 mg/1 mL). The injection begins from 1 point of the lesion toward the center, inltrates evenly within the lesion via change of the injection direction until the surface of the lesion appears pale. Compression is applied for 15 to 30 minutes after injection to prevent effusion of the solution. The injection can be repeated every 2 to 3 weeks; each dosage is not more than 8 mg, and reduced accordingly for infants (1/42/3). For cutaneous supercial or mucosal hemangiomas, the concentration of Pingyangmycin is 1.0 mg/mL; for subcutaneous or deep hemangiomas, the concentration of Pingyangmycin is 1.5 to 2.0 mg/mL. For hemangiomas that are unresponsive to steroids or rebound after steroids, vincristine14 can be very effective. The dose is 0.5 to 1.0 mg/ kg given intravenously once a week over 6 weeks and then discontinued. This cycle can be repeated if necessary. Infants with KasabachMerritt syndrome, which is caused by Kaposiform hemangioendothelioma, have lifethreatening conditions and are best treated with steroids and/or vincristine. In cases with fulminate life-threatening platelet consumptive coagulapathy (platelet counts below 50 109/L), which is more common in the trunk and extremities than the head and neck, diluted ethanol embolotherapy was reported to be very effective. Alpha-interferon has been shown to be effective15 but can have a serious side effect of spastic diplegia, which is permanent and disabling. This

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drug is not recommended except in cases in which other drugs have been ineffective. Recently, 2 groups16,17 reported the use of bblockers such as propranolol for problematic hemangiomas with dramatic shrinkage and control of the hemangiomas. There was no rebound noted, and toxicity was minimal. More experience is necessary to determine the role of b-blocker drugs, but the initial results are very promising. The role of conventional surgery in cases of nonresponse to a steroid or b-blocker therapy is superior to laser therapy especially if the nasal tip is affected. However, the central role of conventional surgery is crucial in corrective measurements and therapy of residual or remnant disease. When resecting hemangiomas, the surgeon must decide whether the result from surgical intervention would be more cosmetically acceptable than that from medical treatment or watchful waiting. The surgical indications for proliferating hemangioma are: (1) hemangiomas located in the nose and lip that do not respond well to other treatments, (2) hemangiomas in the eyelids that impair sight and aesthetics, (3) hemangiomas occurring on the forehead and scalp, and (4) repeated bleeding from the hemangiomas. Residual deformities after conservative or laser therapy can be corrected surgically. The aim of surgery is to remove or re-contour the residual deformity, scar, hypertrophied abnormality, hyperpigmentation, or brofatty tissues to improve cosmetics and function. Local wound care is helpful to alleviate pain and infection in ulcerated lesions.18 Wet compresses can be used to debride the ulcer in conjunction with topical mupirocin, bacitracin, or metronidazole.

dermal pigmentation is scarcely achieved by laser therapy.

Choice of Treatment Methods. Telangiectasia is most commonly found around the head or extremities. Depending on the diameter of the vessel, the following lasers can be chosen: (1) 532 nm potasium-titanyl-phosphate (KTP) laser, mainly for ne vascular pathology; (2) pulsed dye laser (PDL) with wavelengths of 580 nm, 585 nm, 590 nm, and 595 nm. A wavelength of 595 nm is suitable for most telangiectasia. Long pulsed dye 595 nm and long pulsed turnable 1064 nm gentle YAG laser has better effects on deeper lesions. In cases of spider nevus, CO2 laser can be used for excision or exfoliative treatment but may leave scars. Also used are 585 nm, 595 nm long PDL, and long pulsed turnable 1064 nm gentle YAG laser for thermocoagulation. In cases of nevus ammeus or port wine stain, there are 2 main types of treatment. The rst is selective thermocoagulation using 580 nm, 585 nm, 590 nm, and 595 nm long PDL, but the success rate is less than 25%. This method is suitable for most whites, but for only a few Chinese patients with mild symptoms, easily causing changes in the skin texture and scarring. Another method is photodynamic therapy (PDT). There are currently 2 types of laser: copper vapor laser (578 nm) and krypton ion laser (413 nm). The latter is based on the nonthermal PDT principle, utilizing the combination of the wavelength and photosensitizer (hematoporphyrin monomethyl ether) for treatment, thus avoiding damage to the supercial epidermis and achieving the effect of selectively targeting malformed venules and keeping the surrounding epidermal tissue intact. This is presently the rst choice of treatment19 for venular malformations. The disadvantage is that with the use of a photosensitizer, the patient should avoid exposure of sunlight and direct strong light for 48 hours, causing a certain amount of inconvenience. Syndromes accompanying venular malformations should be treated with 2 or more of the above-mentioned laser treatments interchangeably, for example, using the exfoliative lasers (CO2 laser, Er:YAG laser) and PDL (585 nm, 595 nm) interchangeably, or using the exfoliative laser and 1064 nm gentle YAG laser interchangeably, or the exfoliative lasers with photodynamic laser interchangeably. For serious

TREATMENT OF VENULAR AND CAPILLARY MALFORMATIONS Characteristics and Treatment Principle. Venular malformations include nevus ammeus or port wine stain, telangiectasia, spider nevus (spider angioma), or relevant syndromes such as Sturge-Weber syndrome. The main treatment option is laser therapy. Depending on the type of lesion, various laser devices and methods are available and can be selected. A variety of laser systems are effective for various manifestations of naevi, and this should be performed in specialized centers. Complete restitution and normal

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facial venular malformations, laser therapy and cosmetic surgery should be employed in 1 or multiple stages.

TREATMENT OF VENOUS MALFORMATIONS Characteristics and Treatment Principle. Venous malformations are common developmental vascular deformities of the head and neck region. They are present from birth and, unlike hemangiomas, they do not have a cycle of growth and subsequent spontaneous regression. They grow proportionately during infancy and childhood. The clinical features are bluish, compressible, and nonpulsating masses, usually involving various supercial or deep anatomic areas. The patients normally do not have many clinical symptoms, although swelling and pain are not uncommon. Extensive venous malformations can cause a localized intravascular coagulopathy. The treatment for venous malformations can be complicated. In the past years, many attempts for treating venous malformations have been made. Besides sclerotherapy and surgery, a broad variety of techniques have been described in the literature: irradiation, electrocoagulation, cryotherapy, intravascular magnesium or copper needles, laser and compression.20 A surgical approach is indicated in well-circumscribed malformations of moderate size, in which the possibilities of anatomic and functional restoration are maximal. However, surgical treatment of more extensive lesions can often lead to loss of motor function, nerve damage, and massive bleeding. Sclerotherapy is an alternative method of treatment for venous malformations, and is used to reduce the size of the lesion, or preoperatively as a support to surgery or as a postoperative complement.21 There are many types of sclerosing agents used to destroy the vascular endothelium through different mechanisms: chemical agents (iodine or alcohol), osmotic agents (salicylates or hypertonic saline), detergents (morrhuate sodium, sodium tetradecyl sulfate, polidocanol, and diatrizoate sodium), and anti-cancer drugs which change the surface tension of the cell, producing tissue maceration. Extensive venous malformation should be investigated with venograms before treatment through injection of contrast agent to understand the venous ow. Contrast agent remaining in the veins after 5 minutes indicates a low-drainage venous malfor-

mation, whereas contrast agent disappearing quickly in less than 5 minutes indicates a highdrainage venous malformation. The status of drainage in venous malformation provides important information for selection of different sclerosing agents: for low-drainage venous malformations, intralesional injection of Pinyangmycin (bleomycin A5) at a concentration of 1.5 to 2.0 mg/mL is sufcient to achieve the best results.22 The maximum dose per injection of Pingyangmycin is 8 mg. The mechanism involves direct destruction of the endothelial cell, inammatory reaction, formation of a thrombus and brosis leading to obstruction of the vessels, and shrinkage of the lesions. Being a mild sclerosing agent, Pingyangmycin is not suitable for high-drainage venous malformation alone, as it hardly remains within the lesions and ows away immediately after injection, resulting in poor sclerosing effect. High-drainage venous malformations require an injection of ethanol or 5% sodium morrhuate, as these stronger sclerosing agents have intense destructive effects on the endothelial cells once within the vessels and thus able to achieve the treatment objective. Sclerotherapy using sodium morrhuate has denite effectiveness in the treatment of venous malformation.21 However, because it is toxic to the liver and kidneys, each injection should not be more than 5 mL; care should be taken not to inject into the arteries to prevent severe complications. For high-drainage venous malformation, surgical compartmentalization can be performed followed by injection to increase the duration of the sclerosing agents within the lesion, reduce the dosage, and thus improve the treatment effectiveness. Different sclerosing agents can be combined or utilized alternatively to achieve the best results, and brin glue23 can also be combined with different sclerosing agents to aggregate the drugs and increase the time of pharmaceutical effect. Ethanol is recognized as the most effective sclerosing agent in the treatment of venous malformation; it has an effective rate of 100%,24 has a low recurrence rate, and is nontoxic to the liver and kidneys within the safety amount. Digital subtraction angiography (DSA)-guided percutaneous ethanol injection is a recent advance in the treatment of venous malformation, which is suitable for grade 2 and 3 (diameter greater than 5 cm) facial and cervical venous

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malformations, according to the MRI classication of Goyal et al25; grade 2A, well dened, with a diameter greater than 5 cm; grade 2B, ill dened, less than or equal to 5 cm in diameter; grade 3, ill dened, greater than 5 cm in diameter. Because ethanol injection can result in severe pain, the treatment is usually performed under general anesthesia. Ethanol injection can also cause severe soft tissue edema; thus for lesions involving the base of the tongue, pharynx, and larynx, it is suggested that a prophylactic tracheotomy be performed. The treatment should always be performed under the guidance of DSA. If there is no DSA facility, it can be performed under normal X-ray equipment to determine the extent of the lesion and the volume of ethanol injection, and more important, to ensure the injection is within the lesion. After disinfection of the surgical elds, a sterilized 21-gauge buttery needle is placed into the lesions, adjusting the depth and direction until blood ows through the connecting catheter. The contrast agent is injected, the venous drainage is observed, and the volume of contrast is recorded. The volume of ethanol is 2/3 to 3/4 of the contrast agent, and the maximum volume is 1 mL/kg body weight.24 Ethanol is then administrated quickly into the lesions; the blood pressure and heart rate of the patients are monitored simultaneously. If the venous drainage is fast, the main reux veins should be compressed during injection. Dexamethasone (0.1 mg/kg) is applied before the procedure, and 3 times a day after the procedure to minimize edema. The blood pressure and kidney function of the patients are monitored routinely after the procedure, with intravenous infusion of Ringers solution and sodium bicarbonate to prevent kidney damage due to hemoglobinuria. Antibiotics are prescribed to prevent infection post-treatment when necessary. Ethanol is a strong sclerosing agent. The mechanism of treatment of venous malformation lies in degeneration of the hemoglobin and destruction of the endothelial cells, leading to acute inammatory reaction and formation of blood clots, thrombosis, and brosis, eventually leading to occlusion of the malformed veins and resolution of the lesions. Clinical studies have conrmed that ethanol injection is 1 of the effective modalities in the treatment of massive venous malformations. However, ethanol is an irritating sclerosing agent, and severe complications will occur if owing into the normal circu-

lation in large amounts. Therefore, this procedure should be done carefully by experienced specialists. During injection, the ethanol must be ensured to be injected into the lesions rather than the surrounding tissues and vital anatomic structures under radiologic imaging guidance.26 Care should be taken not to damage the facial nerves during treatment of parotid venous malformations. Hemoglobinuria may occur if the dosage exceeds 30 mL in a single injection, but no cases of renal impairment have been reported when this has occurred. The hemoglobinuria is a squeal of the ethanol admixing with venous blood, crenating or destroying red blood cells, releasing its hemoglobin, and this being cleared by the kidneys. Prophylactic Ringers or other intravenous combinations administered during this self-limited period of hemoglobinuria is judicious and can be easily performed. The injection should not be too supercial to prevent cutaneous or mucosal ulceration and/or necrosis. The vital signs, especially the breathing and blood pressure of the patients, should be monitored regularly after treatment.2528 Nd:YAG laser therapy has been proven to be effective in the management of supercial venous malformations, but for deeper lesions, especially those located in the parotid, masseteric, and deep facial areas, most of the laser energy will be absorbed by the skin, resulting in insufcient penetration of the laser beam; if the power is increased, severe damage of the overlying skin will result in unwanted scarring. Nd:YAG laser therapy after surgical exposure of the deep lesions is a preferred option under this circumstance. Nd:YAG laser irradiation at 30 to 70 W/cm2, combined with simultaneous cooling photocoagulates the malformations while avoiding damage to the facial nerves.29 For larger and thicker lesions, mucosal lesions of the pharynx and larynx, application of low-power laser at several times allows shrinkage of the malformations in layers from supercial to deep and avoids damage to the adjacent normal tissues. Glomovenous malformation (GVM) is an autosomal condition that is characterized by multiple venous malformations in the skin. They differ from standard venous malformations by being multiple, slightly raised, or blue or bluish-purple in appearance. Histopathologically, these lesions differ from the typical venous malformation by the presence of numerous glomus cells (abnormally formed smooth muscle cells).

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From studying families with these lesions, the gene is located on chromosome 1p, which is called glomulin. The treatment of choice for isolated cutaneous GVMs is surgical excision. However, this may be impractical in cases with multiple or large segmental lesions. Sclerotherapy with sodium tetradecyl sulfate, polidocanol, and hypertonic saline has been reported to be effective in patients with multiple GVMs that are located on the extremities, whereas the use of sclerosants including polidocanol, pure ethanol, and Ethibloc was unsuccessful in a series of 7 patients with large facial GVMs.30,31 Ablative therapy with argon and CO2 lasers is of potential benet for small, supercial lesions. Treatment with the PDL may also help to atten GVMs and provide pain relief.32 In summary, a number of treatment methods are available for venous malformation of the head and neck region. Best results can usually be achieved for localized lesions when the appropriate modality is employed. But difculties and challenges still exist for lesions affecting the glottis, pharynx, tongue, and oor of the mouth. It is suggested to use a multidisciplinary approach for multiple and voluminous lesions, and patency of the airway should be assured during treatment.
Choice of Treatment Methods. For supercial venous malformation of the mucosal surface, such as the oral tongue, oropharynx, or larynx, Nd:YAG laser, intralesional injection of sclerosants such as Pinyangmycin and cosmetic surgery can be used. Patients with deep, localized, low-drain age venous malformations are candidates for sclerotherapy, especially Pingyangmycin injection. Deep, high-drainage venous malformations are preferably treated with ethanol embolization, laser irradiation after surgical exposure of the lesions, or sclerotherapy combined with surgery. There is still lack of effective treatment methods for massive venous malformations. Planned staged therapy and combined therapy is recommended (eg, sclerotherapy surgery, intralesional suture sclerotherapy, laser surgery). In cases of extensive venous malformations, a calculation of therapeutic effect of sclerosing with Pingyangmycin or ethanol versus the potential and severe side effects should always be performed. The therapy for extensive venous malformations has to be oriented to the

underlying symptoms. Even in severe cases, a conventional surgical therapy with inclusion of perioperative safety measurements (like continuous auto-transfusion systems, neuromonitoring, etc) is a more preferable approach as sclerosing therapy with uncalculated local and systemic side effects. Also minor surgical exposures may cause symptom alleviation in many cases like removal of pain causing phleboliths.

TREATMENT OF ARTERIOVENOUS MALFORMATIONS Characteristics and Treatment Principle. AVMs of the head and neck region include soft tissue and intraosseous AVMs. Soft tissue AVMs used to be called plexiform hemangioma and arteriovenous stula, whereas intraosseous AVMs used to be called central hemangioma of the jaw. With profound understanding of the pathogenesis of AVMs, endovascular embolotherapy has become the treatment of choice. Embolization and surgery is often combined for extended cases to improve their facial contour and oral function. Ligation of the external carotid artery and/or branches or embolization of the feeding arteries with any embolizing agents causes more harm than benet and should not be used.33 Choice of Treatment Methods. Once the diagnosis of AVM is conrmed, an angiography and embolization should be considered. The purpose of embolization is to control the growth of AVMs and frequent bleeding. The key to embolization is to use sufcient liquid embolizing agents to eradicate the nidus. The currently used liquid agents are ethanol and N-butyl-2-cyanoacrylate (NBCA). Successful embolization is completed when active bleeding has stopped, localized pulsation has disappeared, the lesion becomes lighter in color, the expanded veins in the neck return to normal, and new bone is formed in the cystic zones. For females with AVMs who are planning to become pregnant, it is best to do the embolization before pregnancy, because the hormonal changes during pregnancy may accelerate the progress of AVMs. Ethanol is probably the most effective sclerosing agent that can denature blood proteins and denude the vascular wall of endothelial cells. The following points need to be kept in mind when using ethanol for embolization of AVMs: (1) inject ethanol through a catheter or

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directly penetrate to the nidus of the malformation; (2) avoid injection of ethanol into normal tissues; (3) perform the procedure under general anesthesia and monitor the vital signs closely; (4) limit the dosage to 1 mL/kg for every procedure; (5) ensure good postoperative monitoring, intravenous infusion, and minimize complications after treatment; (6) assure regular revisits, and repeat embolization when necessary. The use of tissue glue or coil to perform embolization does not directly destroy the endothelial cells, and therefore this is only a palliative modality for AVMs, whereas ethanol embolization may cure the AVMs. However, the risks with use of ethanol are higher, and the procedure requires skill and experience. If the procedure is not adequately performed, tissue necrosis and more serious complications such as cardiopulmonary disruptions due to pulmonary arterial hypertension may occur. Utilizing a SwanGanze catheter to monitor the changes of the pulmonary arterial pressure can help prevent cardiopulmonary sequelae. Soft tissue AVMs can be divided into 3 types: inltrative, nidus, and stula.24 For inltrative AVMs, it is suggested to use a mixture of ethanol and contrast at a ratio of 1:1 for embolization, whereas nidus and arteriovenous stula require absolute alcohol for embolization.34 If AVMs of the soft tissues affect important anatomic structures with severe disgurements, the most effective treatment is preoperative embolization and radical resection. Intraosseous high-ow vascular malformations include arterial malformation and arteriovenous malformation. Varix is usually noted in AVMs of the jaw. Successful intervention therapy is to place the embolizing materials into the center of the nidus,35,36 to produce blood clots and eliminate the cause of bleeding. Because AVMs of the alveolar bone have a unique collateral arterial blood supply, and because of the large size of the nidus, it is hard to completely destroy the varix simply through embolization via the superior or inferior dentoalveolar arteries. Direct puncture of the nidus and transarterial embolization (which is called double interventional therapy) is required in this circumstance to achieve cure. The embolizing materials used for AVMs of the alveolar bone include mainly bered platinum coils and ethanol. The procedure is to deliver the coils into the nidus rst to decrease the blood ow within the lesions, and then perform ethanol embolization

either through the arteries or direct puncture. Intraosseous arterial malformation of the jaw has no varix, but inltrative deformities in nature; therefore, superselective transarterial embolization of the feeding arteries rather than coil embolization through direct puncture is the adequate treatment option. Surgery is indicated when embolization fails or endovascular access of the nidus is not possible. Surgery is very difcult because of the vascularity, the lack of distinct margins, or involvement of major structures such as facial nerves, muscles, eyes, and tongue.37 Surgery should be performed only by a surgeon experienced with AVMs and the ability to reconstruct immediately. It is common for AVMs to recur after surgery, and the surgeon must be willing to reoperate. The goal of surgery must be to resect the entire nidus or the AVM will recur. The nidus is very difcult to dene because of the diffuse feeder vessels and the draining vein which do not necessarily have to be resected. As mentioned previously, ligation only of the carotid vessels or the major branches is not helpful and should never be performed except in cases with life-threatening hemorrhage. Lasers are less effective with AVMs and should rarely be used. It should be addressed that the only cure of soft tissue AVMs is the radical resection which is, in extended cases, possible only after a preoperative angioembolization. In unresectable cases, the value of angiogenesis-inhibiting agents has to be discussed. Embolization only can be performed on arteriovenous stulas or on selected otherwise not resectable cases, but one has to point out the potential of collateral vascular feeding and recurrences.

TREATMENT OF LYMPHATIC MALFORMATIONS Characteristics and Treatment Principle. Lymphatic malformations can be divided into 2 types: macrocystic and microcystic. The treatment options include surgery, sclerotherapy, and laser therapy. Surgery used to be the mainstay or even the only treatment choice and still remains the rst choice in the hands of many surgeons. However, with technical advancements and accumulation of clinical experience in laser therapy and sclerotherapy, it is suggested to decide the treatment plan on the basis of location and type of lesion individually, rather than doing surgery irrespective of the type of

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lymphatic malformations. The close quarters of the head and neck provide for a tedious dissection that often results in sacricing vital structures and signicant impairment after surgery. In these cases, surgery may have to be avoided, and an alternate therapy should be pursued.
Choice of Treatment Methods. Supercial oral mucosal microcystic lymphatic malformations can be treated with intralesional injection of Pinyangmycin (1.0 mg/mL)38 and laser therapy. After treatment, the cystic lesions will gradually disappear with resurfacing of the oral linings. If the lesion is extensive and multiple, surgery can be utilized to debulk, with residual lesions treated with sclerotherapy or laser therapy to enhance the treatment results. Treatment for deep-seated microcystic lymphatic malformations still presents great difculties; the results of surgical resection alone are disappointing, and this approach may lead to secondary oromaxillofacial deformities. In selected cases, preoperative intralesional injection of Pinyangmycin can make subsequent operation easier and improve outcomes because of the shrinkage of the lesions after sclerotherapy. Sclerotherapy is the mainstay of treatment for macrocystic lymphatic malformations, with excellent effect;39 surgery can be used as a complementary means. Ethanol was the most common sclerosing agent used in the past, followed by doxycycline, sodium tetradecyl sulfate (STS),40 and OK-432.41 Response varied with the type of lymphatic malformation, with 100%, 86%, and 43% of the patients reporting good to complete response for macrocystic, microcystic, and combined-type lymphatic malformations, respectively. Intralesional injection of Pinyangmycin (1.5 2.0 mg/mL)39 or OK-43241 is used more often these days for macrocystic lymphatic malformations and is the rst choice of treatment in many institutions. Percutaneous sclerotherapy with doxycycline is also a safe and effective method for lymphatic malformations,42,43 especially for patients with macrocystic lesions with an average radiographic resolution of 93% and minimal adverse effects. After injection, the sclerosant will diffuse within the cystic cavities, inducing inammatory reactions, activating the white blood cells which produce some kinds of cytokines to increase the permeability of the lymphatic endo-

thelium, leading to brosis of the cystic linings, and thus shrinkage of the cystic spaces. Before injection, the uid contents should be aspirated as much as possible to ensure the sclerosant inltrating into the cystic walls. Percutaneous sclerotherapy with Ethibloc (alcoholic solution of zein) was another safe and effective procedure in the treatment of macrocystic and mixed lymphatic malformations.44 Whether microcystic or macrocystic, ethanol is universally successful in ablating these lesions, thus largely obviating any need for surgical interventions. Ethanol (98%) can be injected into the lymphatic vessels where it acts on the proteins destroying their structure and triggering their clotting. These clots can obstruct vessels and then reduce the volume of the malformation, acting as an embolizing agent. In addition, ethanol has a direct effect on the internal surface on the vessels, damaging the cells that form the internal layer of the vessels. This effect destroys the vessel wall and results in its occlusion. Both actions combined could have as a consequence the destruction of the abnormal vessels that constitute the lesions. Macrocyst access is most frequently performed with ultrasound guidance and placement of a coaxial 5F pigtail catheter system. Massive lesions may accept larger catheters such as 8 to 10F size. In multilocular lesions, each macrocyst is treated with separate catheter placement. Following complete drainage of the macrocysts, contrast cystogram with uoroscopy is performed to document the native cyst volume, containment of contrast without extravasation, and complete evacuation of contrast with aspiration. Following contrast aspiration, the macrocysts are treated with dual-drug chemoablation, 50% original volume sequential intracystic injections of STS 3% (2 minute dwell time) followed by aspiration and injection of ethanol 98% solution (dwell time 15 minutes). The synergistic drug combination has resulted in outcomes of macrocyst ablation of greater than 95% with the majority of patients (85%) responding in a single treatment. Following aspiration of the ethanol, catheters are connected to suction drainage for 3 days prior to catheter removal. Large macrocystic lymphatic malformations in the neck or oor of the mouth can result in breathing and deglutition problems in which emergency surgery is often mandatory. Surgical resection should be as radical as possible in the given anatomic regions, with the residual

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lesions treated by sclerotherapy. If there is infection secondary to lymphatic malformations, the infection should be well controlled prior to operation. For complex, mixed types of vascular malformations such as lymphatic-venous malformation or lymphatic-venular malformation, an individualized treatment protocol should be made based on the condition of the patient and the technical availability. Most often, application of a multidisciplinary approach will achieve the best results when well planned and implemented.

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