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 People’s 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 com-

mon 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 con-
troversies 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 Anoma-
lies formulated a treatment guideline for hemangiomas and
vascular malformations of the head and neck, which will be
modified and updated periodically based on new medical evi-
dence and research. V C 2009 Wiley Periodicals, Inc. Head
Neck 32: 1088–1098, 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
V
C 2009 Wiley Periodicals, Inc.
Mulliken and Glowacki1 in 1982 categorized
these lesions into 2 main categories: hemangi-
omas and vascular malformations. This classifi-
cation is, in general, correct and up-to-date and
has been widely accepted worldwide, but limita-
tions exist in which specific entities such as
tufted angiomas, hemangioendotheliomas, and
hemangiomas with segmental distribution pat-
terns are not included. In 1996, the Interna-
tional Society for the Study of Vascular
Anomalies (ISSVA) added the rapidly involuting
congenital hemangioma, noninvoluting congeni-
tal hemangioma, Kaposiform hemangioendothe-
lioma, tufted angioma, and pyogenic granuloma
to the list of vascular tumors. The subsequent
modified classification by Waner and Suen2 in
1999 is more practical and easily used clinically,
in which hemangiomas are subdivided into su-
perficial, deep-seated, and mixed type, and vas-
cular malformations are subdivided according to
the predominant channel anomaly into either
venular (capillary), arterial, venous, lymphatic,

1088 Treatment Guidelines for Hemangiomas and Vascular Malformations HEAD & NECK—DOI 10.1002/hed August 2010
or combinations. Arterial and arteriovenous
malformations (AVMs) are high-flow, whereas
venular, venous, and lymphatic malformations
are slow-flow. Hemangiomas and vascular mal-
formations are 2 different disease entities with
different histopathologic features, clinical char-
acteristics, and natural course. There are vari-
ous 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 scientific
research, and with reference to the latest inter-
national 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 chang-
ing, with new theories, views, diagnostic techni-
ques, and treatment procedures appearing
continuously. Therefore, this guideline will be
modified and updated periodically based on new
medical evidence and research.
TREATMENT OF HEMANGIOMAS
Characteristics and Treatment Principle. Heman-
giomas are common vascular tumors that occur
in as many as 2.5% of neonates4 and can be sep-
arated into congenital or infantile. Congenital
hemangiomas comprise the rapid involuting con-
genital hemangiomas (RICH) and the noninvo-
luting congenital hemangiomas (NICH), and are
much less common than those which happen
shortly after birth but occurs within the first
month of life. The RICH hemangiomas are pres-
ent at birth, involute over the first 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 he-
mangioma 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 (1–2 months after birth and 4–5 months
after birth). The growth of the hemangioma at
the early phase can be rapid and unpredictable;
early intervention may impede the progress into
Treatment Guidelines for Hemangiomas and Vascular Malformations
the rapid proliferation phase, preventing volu-
minous hemangiomas from developing.
The influence 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 impair-
ment such as amblyopia and refractive errors or
even blindness.
Massive hemangiomas can also lead to
ulceration, necrosis, and infection of important
structures.
Disfigurement can also lead to psychological
issues such as inferiority complex, unsociable,
stubbornness, and low self confidence.
With regard to the extent of final resolution
of the hemangioma, there is presently no objec-
tive assessment and predictability.
Principles of treatment selection.5 The treat-
ment of hemangiomas is dependent on the pri-
mary site and various stages of growth Early
treatment of even small hemangiomas of the
face is subject to controversy and must be crit-
ically 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
first choice of treatment. When the larynx or
trachea is involved, early intervention is usually
indicated to prevent airway obstruction. If eye-
lid involvement is threatening vision or if carti-
lage 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 immu-
nomodifier, which can be used for small and in-
termediate-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
superficial proliferating hemangiomas. This
mode of therapy may accelerate the regression
and reduce the size of the lesion, creating
HEAD & NECK—DOI 10.1002/hed August 2010 1089
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 lamp-
pumped pulsed dye laser has a wavelength of
585 nm or 595 nm, allowing selective destruc-
tion 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 superficial
hemangiomas and those at the involution stage.
However, this laser has little effect on subcuta-
neous 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. Per-
cutaneous laser therapy can be utilized for deep
hemangiomas. During the treatment process,
cooling devices should be used to lower the tem-
perature 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 superfi-
cial or deep hemangiomas, a systemic therapy
with steroids or b-blockers (still in clinical trials)
should be preferred as first-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 prolif-
erating hemangiomas is applied only in selected
cases,8 especially regarding modern treatment
concepts.
Drug therapy is indicated for mixed heman-
giomas, proliferative hemangiomas, and heman-
giomas that affect vital organs or are life-
threatening. Oral corticosteroid has been used
for more than 30 years, and has been the first-
line treatment for severe problematic heman-
giomas during the past years. The effective
rate is 84%,9 with a significant 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 methyl-
prednisolone. The regimen for oral corticos-
teroid10 is oral prednisolone (3.0–5.0 mg/kg)
1090 Treatment Guidelines for Hemangiomas and Vascular Malformations
every other morning for 6 to 8 weeks. The dos-
age 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 or-
bital 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 specifically 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 cu-
taneous hemangiomas13 and suitable for prolif-
erative hemangiomas which respond poorly to
steroids and/or laser therapy. Clinically, Pin-
gyangmycin hydrochloride (8 mg/syringe) is dis-
solved 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, infiltrates evenly within the
lesion via change of the injection direction until
the surface of the lesion appears pale. Compres-
sion is applied for 15 to 30 minutes after injec-
tion 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 (1/4–2/3). For cutaneous
superficial or mucosal hemangiomas, the con-
centration of Pingyangmycin is 1.0 mg/mL; for
subcutaneous or deep hemangiomas, the concen-
tration 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 Kasa-
bach–Merritt syndrome, which is caused by
Kaposiform hemangioendothelioma, have life-
threatening conditions and are best treated with
steroids and/or vincristine. In cases with fulmi-
nate life-threatening platelet consumptive coag-
ulapathy (platelet counts below 50
109/L),
which is more common in the trunk and extrem-
ities than the head and neck, diluted ethanol
embolotherapy was reported to be very effective.
Alpha-interferon has been shown to be effec-
tive15 but can have a serious side effect of spastic
diplegia, which is permanent and disabling. This
HEAD & NECK—DOI 10.1002/hed August 2010
drug is not recommended except in cases in
which other drugs have been ineffective.
Recently, 2 groups16,17 reported the use of b-
blockers such as propranolol for problematic he-
mangiomas 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 con-
ventional surgery is crucial in corrective meas-
urements and therapy of residual or remnant
disease. When resecting hemangiomas, the sur-
geon must decide whether the result from surgi-
cal 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 re-
sidual deformity, scar, hypertrophied abnormal-
ity, hyperpigmentation, or fibrofatty tissues to
improve cosmetics and function.
Local wound care is helpful to alleviate pain
and infection in ulcerated lesions.18 Wet com-
presses can be used to debride the ulcer in con-
junction with topical mupirocin, bacitracin, or
metronidazole.
TREATMENT OF VENULAR AND CAPILLARY
MALFORMATIONS
Characteristics and Treatment Principle. Venular
malformations include nevus flammeus 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 speci-
alized centers. Complete restitution and normal
Treatment Guidelines for Hemangiomas and Vascular Malformations
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 fine 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 flammeus or port wine
stain, there are 2 main types of treatment. The
first 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 scar-
ring. Another method is photodynamic therapy
(PDT). There are currently 2 types of laser: cop-
per 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 (hematoporphy-
rin monomethyl ether) for treatment, thus
avoiding damage to the superficial epidermis
and achieving the effect of selectively targeting
malformed venules and keeping the surrounding
epidermal tissue intact. This is presently the
first choice of treatment19 for venular malforma-
tions. The disadvantage is that with the use of a
photosensitizer, the patient should avoid expo-
sure of sunlight and direct strong light for
48 hours, causing a certain amount of
inconvenience.
Syndromes accompanying venular malforma-
tions should be treated with 2 or more of the
above-mentioned laser treatments interchange-
ably, for example, using the exfoliative lasers
(CO2 laser, Er:YAG laser) and PDL (585 nm,
595 nm) interchangeably, or using the exfolia-
tive laser and 1064 nm gentle YAG laser inter-
changeably, or the exfoliative lasers with
photodynamic laser interchangeably. For serious
HEAD & NECK—DOI 10.1002/hed August 2010 1091
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 vascu-
lar deformities of the head and neck region. They
are present from birth and, unlike hemangiomas,
they do not have a cycle of growth and subse-
quent spontaneous regression. They grow propor-
tionately during infancy and childhood. The
clinical features are bluish, compressible, and
nonpulsating masses, usually involving various
superficial 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 sur-
gery, a broad variety of techniques have been
described in the literature: irradiation, electro-
coagulation, cryotherapy, intravascular magne-
sium or copper needles, laser and
compression.20 A surgical approach is indicated
in well-circumscribed malformations of moder-
ate size, in which the possibilities of anatomic
and functional restoration are maximal. How-
ever, surgical treatment of more extensive
lesions can often lead to loss of motor function,
nerve damage, and massive bleeding. Sclero-
therapy is an alternative method of treatment
for venous malformations, and is used to reduce
the size of the lesion, or preoperatively as a sup-
port to surgery or as a postoperative comple-
ment.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 so-
dium, 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 veno-
grams before treatment through injection of con-
trast agent to understand the venous flow.
Contrast agent remaining in the veins after 5
minutes indicates a low-drainage venous malfor-
1092 Treatment Guidelines for Hemangiomas and Vascular Malformations
mation, whereas contrast agent disappearing
quickly in less than 5 minutes indicates a high-
drainage venous malformation. The status of
drainage in venous malformation provides im-
portant information for selection of different
sclerosing agents: for low-drainage venous mal-
formations, intralesional injection of Pinyang-
mycin (bleomycin A5) at a concentration of 1.5
to 2.0 mg/mL is sufficient 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, inflammatory reaction, formation of a
thrombus and fibrosis 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 flows away immediately after injection,
resulting in poor sclerosing effect. High-drain-
age venous malformations require an injection
of ethanol or 5% sodium morrhuate, as these
stronger sclerosing agents have intense destruc-
tive effects on the endothelial cells once within
the vessels and thus able to achieve the treat-
ment objective.
Sclerotherapy using sodium morrhuate has
definite 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, sur-
gical 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 fibrin glue23 can also be com-
bined with different sclerosing agents to aggre-
gate the drugs and increase the time of
pharmaceutical effect.
Ethanol is recognized as the most effective
sclerosing agent in the treatment of venous mal-
formation; 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 malforma-
tion, which is suitable for grade 2 and 3 (diame-
ter greater than 5 cm) facial and cervical venous
HEAD & NECK—DOI 10.1002/hed August 2010
malformations, according to the MRI classifica-
tion of Goyal et al25; grade 2A, well defined,
with a diameter greater than 5 cm; grade 2B, ill
defined, less than or equal to 5 cm in diameter;
grade 3, ill defined, greater than 5 cm in diame-
ter. 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, phar-
ynx, and larynx, it is suggested that a prophy-
lactic tracheotomy be performed. The treatment
should always be performed under the guidance
of DSA. If there is no DSA facility, it can be per-
formed under normal X-ray equipment to deter-
mine the extent of the lesion and the volume of
ethanol injection, and more important, to ensure
the injection is within the lesion. After disinfec-
tion of the surgical fields, a sterilized 21-gauge
butterfly needle is placed into the lesions,
adjusting the depth and direction until blood
flows through the connecting catheter. The con-
trast 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 admin-
istrated quickly into the lesions; the blood pres-
sure and heart rate of the patients are
monitored simultaneously. If the venous drain-
age is fast, the main reflux 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 Ringer’s
solution and sodium bicarbonate to prevent kid-
ney damage due to hemoglobinuria. Antibiotics
are prescribed to prevent infection post-treat-
ment 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 inflammatory reaction and formation of
blood clots, thrombosis, and fibrosis, eventually
leading to occlusion of the malformed veins and
resolution of the lesions. Clinical studies have
confirmed that ethanol injection is 1 of the effec-
tive modalities in the treatment of massive ve-
nous malformations. However, ethanol is an
irritating sclerosing agent, and severe complica-
tions will occur if flowing into the normal circu-
Treatment Guidelines for Hemangiomas and Vascular Malformations
lation in large amounts. Therefore, this
procedure should be done carefully by experi-
enced 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 ve-
nous malformations. Hemoglobinuria may occur
if the dosage exceeds 30 mL in a single injec-
tion, but no cases of renal impairment have
been reported when this has occurred. The he-
moglobinuria is a squeal of the ethanol admix-
ing with venous blood, crenating or destroying
red blood cells, releasing its hemoglobin, and
this being cleared by the kidneys. Prophylactic
Ringer’s 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 su-
perficial to prevent cutaneous or mucosal ulcera-
tion and/or necrosis. The vital signs, especially
the breathing and blood pressure of the
patients, should be monitored regularly after
treatment.25–28
Nd:YAG laser therapy has been proven to be
effective in the management of superficial ve-
nous malformations, but for deeper lesions,
especially those located in the parotid, masse-
teric, and deep facial areas, most of the laser
energy will be absorbed by the skin, resulting in
insufficient penetration of the laser beam; if the
power is increased, severe damage of the overly-
ing 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 avoid-
ing damage to the facial nerves.29 For larger
and thicker lesions, mucosal lesions of the phar-
ynx and larynx, application of low-power laser
at several times allows shrinkage of the malfor-
mations in layers from superficial 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 blu-
ish-purple in appearance. Histopathologically,
these lesions differ from the typical venous mal-
formation by the presence of numerous glomus
cells (abnormally formed smooth muscle cells).
HEAD & NECK—DOI 10.1002/hed August 2010 1093
From studying families with these lesions, the
gene is located on chromosome 1p, which is
called glomulin. The treatment of choice for iso-
lated cutaneous GVMs is surgical excision. How-
ever, this may be impractical in cases with
multiple or large segmental lesions. Sclerother-
apy 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 etha-
nol, 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 poten-
tial benefit for small, superficial lesions. Treat-
ment with the PDL may also help to flatten
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 appro-
priate modality is employed. But difficulties and
challenges still exist for lesions affecting the
glottis, pharynx, tongue, and floor 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 superficial ve-
nous malformation of the mucosal surface, such
as the oral tongue, oropharynx, or larynx,
Nd:YAG laser, intralesional injection of sclero-
sants such as Pinyangmycin and cosmetic sur-
gery can be used.
Patients with deep, localized, low-drain age
venous malformations are candidates for sclero-
therapy, especially Pingyangmycin injection.
Deep, high-drainage venous malformations
are preferably treated with ethanol emboliza-
tion, 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 þ surgery,
intralesional suture þ sclerotherapy, laser þ
surgery). In cases of extensive venous malforma-
tions, a calculation of therapeutic effect of scle-
rosing 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
1094 Treatment Guidelines for Hemangiomas and Vascular Malformations
underlying symptoms. Even in severe cases, a
conventional surgical therapy with inclusion of
perioperative safety measurements (like contin-
uous auto-transfusion systems, neuromoni-
toring, etc) is a more preferable approach as
sclerosing therapy with uncalculated local and
systemic side effects. Also minor surgical expo-
sures 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
fistula, whereas intraosseous AVMs used to be
called central hemangioma of the jaw. With pro-
found understanding of the pathogenesis of
AVMs, endovascular embolotherapy has become
the treatment of choice. Embolization and sur-
gery 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 benefit and should not be used.33
Choice of Treatment Methods. Once the diagno-
sis of AVM is confirmed, 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 sufficient 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 pul-
sation 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 hor-
monal changes during pregnancy may accelerate
the progress of AVMs.
Ethanol is probably the most effective scle-
rosing 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
HEAD & NECK—DOI 10.1002/hed August 2010
directly penetrate to the nidus of the malfor-
mation; (2) avoid injection of ethanol into nor-
mal tissues; (3) perform the procedure under
general anesthesia and monitor the vital signs
closely; (4) limit the dosage to 1 mL/kg for ev-
ery procedure; (5) ensure good postoperative
monitoring, intravenous infusion, and mini-
mize complications after treatment; (6) assure
regular revisits, and repeat embolization when
necessary. The use of tissue glue or coil to per-
form 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 pulmo-
nary arterial hypertension may occur. Utilizing
a Swan–Ganze catheter to monitor the changes
of the pulmonary arterial pressure can help
prevent cardiopulmonary sequelae.
Soft tissue AVMs can be divided into 3 types:
infiltrative, nidus, and fistula.24 For infiltrative
AVMs, it is suggested to use a mixture of etha-
nol and contrast at a ratio of 1:1 for emboliza-
tion, whereas nidus and arteriovenous fistula
require absolute alcohol for embolization.34 If
AVMs of the soft tissues affect important ana-
tomic structures with severe disfigurements, the
most effective treatment is preoperative emboli-
zation and radical resection.
Intraosseous high-flow vascular malforma-
tions include arterial malformation and arterio-
venous malformation. Varix is usually noted in
AVMs of the jaw. Successful intervention ther-
apy 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 collat-
eral 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 trans-
arterial embolization (which is called double
interventional therapy) is required in this cir-
cumstance to achieve cure. The embolizing
materials used for AVMs of the alveolar bone
include mainly fibered platinum coils and etha-
nol. The procedure is to deliver the coils into the
nidus first to decrease the blood flow within the
lesions, and then perform ethanol embolization
Treatment Guidelines for Hemangiomas and Vascular Malformations
either through the arteries or direct puncture.
Intraosseous arterial malformation of the jaw
has no varix, but infiltrative deformities in na-
ture; 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 possi-
ble. Surgery is very difficult because of the vas-
cularity, 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 experi-
enced with AVMs and the ability to reconstruct
immediately. It is common for AVMs to recur af-
ter 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 difficult to define 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 resec-
tion which is, in extended cases, possible only
after a preoperative angioembolization. In unre-
sectable cases, the value of angiogenesis-inhibi-
ting agents has to be discussed. Embolization
only can be performed on arteriovenous fistulas
or on selected otherwise not resectable cases,
but one has to point out the potential of collat-
eral vascular feeding and recurrences.
TREATMENT OF LYMPHATIC MALFORMATIONS
Characteristics and Treatment Principle. Lym-
phatic malformations can be divided into 2
types: macrocystic and microcystic. The treat-
ment options include surgery, sclerotherapy, and
laser therapy. Surgery used to be the mainstay
or even the only treatment choice and still
remains the first choice in the hands of many
surgeons. However, with technical advance-
ments and accumulation of clinical experience
in laser therapy and sclerotherapy, it is sug-
gested to decide the treatment plan on the basis
of location and type of lesion individually, rather
than doing surgery irrespective of the type of
HEAD & NECK—DOI 10.1002/hed August 2010 1095
lymphatic malformations. The close quarters of
the head and neck provide for a tedious dissec-
tion that often results in sacrificing vital struc-
tures and significant impairment after surgery.
In these cases, surgery may have to be avoided,
and an alternate therapy should be pursued.
Choice of Treatment Methods. Superficial 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 lym-
phatic malformations still presents great diffi-
culties; the results of surgical resection alone
are disappointing, and this approach may lead
to secondary oromaxillofacial deformities. In
selected cases, preoperative intralesional injec-
tion 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 com-
plementary means. Ethanol was the most com-
mon 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 malforma-
tions and is the first choice of treatment in
many institutions. Percutaneous sclerotherapy
with doxycycline is also a safe and effective
method for lymphatic malformations,42,43 espe-
cially 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 inflamma-
tory reactions, activating the white blood cells
which produce some kinds of cytokines to
increase the permeability of the lymphatic endo-
1096 Treatment Guidelines for Hemangiomas and Vascular Malformations
thelium, leading to fibrosis of the cystic linings,
and thus shrinkage of the cystic spaces. Before
injection, the fluid contents should be aspirated
as much as possible to ensure the sclerosant
infiltrating into the cystic walls.
Percutaneous sclerotherapy with Ethibloc
(alcoholic solution of zein) was another safe and
effective procedure in the treatment of macro-
cystic 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 trigger-
ing their clotting. These clots can obstruct ves-
sels and then reduce the volume of the
malformation, acting as an embolizing agent. In
addition, ethanol has a direct effect on the inter-
nal 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 per-
formed 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 fluoroscopy is per-
formed to document the native cyst volume, con-
tainment 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 macro-
cyst ablation of greater than 95% with the ma-
jority 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 floor 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
HEAD & NECK—DOI 10.1002/hed August 2010
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 malfor-
mations such as lymphatic-venous malformation
or lymphatic-venular malformation, an individu-
alized treatment protocol should be made based
on the condition of the patient and the technical
availability. Most often, application of a multi-
disciplinary approach will achieve the best
results when well planned and implemented.
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