Hemangiomas of Infancy: Clinical and

Biological Characteristics
Kara N. Smolinski, MD, PhD
Albert C. Yan, MD

Summary: Hemangiomas of infancy are common in the general pediatric population, are usually
easily diagnosed, and generally do not require treatment. However, a small but significant
percentage of hemangiomas of infancy may develop complications, including infection or
ulceration. In addition, hemangiomas located in some anatomic regions may be associated with
other anomalies and therefore require more careful monitoring and earlier intervention to
prevent permanent sequelae. This review focuses on distinguishing hemangiomas from vascular
malformations and delineates the natural history of hemangiomas of infancy, with an emphasis on
identifying those hemangiomas that require additional evaluation and closer follow-up. Current
treatment modalities, including the use of systemic steroids and the pulsed-dye laser, are discussed.
In addition, several conditions that often present with cutaneous hemangiomas are described,
including PHACES syndrome and neonatal hemangiomatosis. Finally, an assessment is made of the
current understanding of the biology of hemangioma proliferation and involution, including
the role of endothelial growth factors and GLUT1, a new marker for hemangiomas of infancy.
Clin Pediatr. 2005;44:747-766

Introduction fants and children. They are pre- African-American, Hispanic, or

sent in approximately 2% to 3% Asian descent. They are also more

H emangiomas are benign

congenital vascular neo-
plasms composed of vas-
cular endothelial cells that have
the capacity for excessive prolifer-
ation and represent one of the
most common birthmarks in in-
of neonates and in 10% of all in-
fants by 12 months of age.1-4 For
reasons that are not clear, heman-
giomas are approximately 3 times
more common in female infants
common in premature infants,
and are seen in approximately
20% of premature infants with a
birth weight of less than 1000 g.5,6
There are also reports of families
and are also more common in in whom the development of he-
white infants than in those of mangiomas appears to be inher-
ited as an autosomal dominant
trait.7

Classification
Section of Pediatric Dermatology, Children’s Hospital of Philadelphia. Historically, the nomenclature
of hemangiomas and other vascu-
Reprint requests and correspondence to: Albert C. Yan, MD, Director, Pediatric Dermatology, lar birthmarks has been confus-
Children’s Hospital of Philadelphia, 34th and Civic Center Blvd, Philadelphia, PA 19104.
ing. Currently, the classification
© 2005 Westminster Publications, Inc., 708 Glen Cove Avenue, Glen Head, NY 11545, U.S.A. system devised by Mulliken and

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Glowacki and recently refined in
1997 by the International Society
for the Study of Vascular Anom-
alies provides the best framework
for understanding vascular anom-
alies in infants and children. 8,9
Hemangiomas are more properly
classified as vascular tumors com-
posed of hyperplastic vascular en-
dothelial cells that have the ca-
pacity for excessive proliferation
but normally undergo eventual
regression and involution. This is
in contradistinction to vascular
malformations, which are hamar-
tomas of mature endothelial cells
(Table 1). Vascular malformations
result from structural abnormali-
ties of endothelial cells that are
usually present at birth, are rela-
tively mature at presentation, and
do not exhibit a tendency to-
wards hyperplasia with rapid pro-
liferation; rather, they display a
normal pattern of growth and
only enlarge proportionally as
the child grows. Furthermore,
they do not spontaneously re-
solve. Clinically, the distinction
between a port wine stain and he-
mangioma of infancy is usually
straightforward but may be diffi-
cult during the first few weeks of
life until the natural history of
the lesion declares itself.
Natural History
On clinical examination, he-
mangiomas may display a super-
ficial component, a deep com-
ponent, or both. Super f icial
hemangiomas are composed of
collections of telangiectatic mac-
ules and papules located in the su-
perficial dermis that form raised,
well-def ined, non-blanchable
plaques. A surrounding zone of
pallor may be appreciated during
the active proliferative phase.
Deep hemangiomas, in contrast,
consist of collections of dilated
vascular channels located in the
deeper dermis and subcutaneous
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S m o l i n s k i , Ya n
Table 1
COMPARISONS OF HEMANGIOMAS OF INFANCY
VS. VASCULAR MALFORMATIONS
Vascular Malformations
Hemangiomas of Infancy (capillary, venous, lymphatic, mixed)
Endothelial cell hyperplasia Hamartoma of normal endothelial cells
Spontaneous involution Do not involute
Present during early infancy Present at birth
tissue with little involvement of oration with softening and flat-
the overlying skin. They appear as tening of the hemangioma is ob-
compressible, rubbery, poorly-de- served as the blood vessels invo-
fined bluish nodules and may lute and f ibrosis and fatty
demonstrate visible draining su- infiltration occurs. Involution
perficial veins. Mixed heman- proceeds slowly over many years,
giomas contain both superficial with approximately 50% of he-
and deep components. mangiomas having reached the
Most hemangiomas are not point of maximal involution by
identified at birth, but often a age 5 years and 90% having
precursor lesion that appears as a reached maximal regression by 9
pale bluish-grey macule or a small years of age, although in some
cluster of telangiectasias may be children involution may be com-
visible. They are most commonly plete by 2 or 3 years of age.10-12
located on the head and neck The majority of hemangiomas will
(60%), followed by the trunk involute with minimal or no
(25%), and the extremities residua; however, an estimated
(15%).10 Most hemangiomas be- 20–50% will leave areas of scar-
come clinically evident within the ring, residual fibrofatty tissue, at-
first few weeks to months of life as rophy, hypopigmentation, or
a result of extensive proliferation residual telangiectasias, which
of vascular endothelial cells. The may be visibly conspicuous (Fig-
growth rate of hemangiomas is ure 1).13,14 Patients with suspected
highest during the first 3 to 6 congenital hemangiomas which
months of life during the prolifer- are atypical in appearance or that
ative phase. The growth rate then do not follow the expected clini-
begins to slow between ages 6 to 9 cal course should be referred to a
months of life, and by 12 months pediatric dermatologist for evalu-
of age most hemangiomas have ation, as there are a number of
reached their maximal size. Be- rare malignant vascular tumors of
ginning at approximately 12 to 18 infancy that may mimic the ap-
months of age, hemangiomas en- pearance of an infantile heman-
ter a gradual regression or involu- gioma, including Kaposiform he-
tional phase. During the involu- mangioendothelioma, tufted
tional phase, the development of angioma, and infantile fibrosar-
a super f icial, grayish discol- coma. In these cases, skin biopsy,
NOVEMBER/DECEMBER 2005

Figure 1. Involuting hemangioma with residual telangiectasias.
magnetic resonance imaging, and
angiography will aid in the cor-
rect diagnosis, and prompt refer-
ral to addditional pediatric sub-
specialists, including pediatric
surgery and pediatric oncology,
may be facilitated.
Special Circumstances
Hemangiomas of infancy that
are present in certain locations
may be associated with other
anomalies or may have an in-
creased risk of developing partic-
ular complications (Table 2).
Most complications arise during
the proliferative phase of growth,
and prompt recognition and in-
tervention may be required in or-
der to prevent permanent seque-
lae. Hemangiomas that are
present in the following areas are
of particular concern and require
closer follow-up, additional evalu-
ation, specialized therapy, or re-
ferral to pediatric subspecialists
for further management: perior-
bital, pelvic and perineal, lum-
bosacral, and facial. In addition,
ulcerated hemangiomas require
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Hemangiomas of Infancy
orbits are an ophthalmologic
emergency, because they may
compromise the developing vi-
sual system and cause a range of
sequelae, including refractive er-
rors, astigmatism, strabismus, pto-
sis, and stimulus deprivation am-
blyopia if untreated (Figure
2).15,16 Referral for urgent oph-
thalmologic evaluation may be
necessary to preserve vision and is
mandatory if the hemangioma is
rapidly growing or if there is a risk
of obstructing the visual fields or
compressing vital introrbital
str uctures. Per manent visual
deficits may result from a period
of ocular compromise as short as
2 weeks. Inter ventions include
patching of the unaffected eye,
use of topical constrictive drops to
meticulous attention to wound the unaffected eye, systemic or in-
care and may benefit from addi- tralesional steroids, and surgical
tional therapies, including use of debulking of the affected eye.17
the pulsed dye laser.
Pelvic and Perineal
Periorbital Hemangiomas Hemangiomas
Rapidly growing heman- Rarely, pelvic and perineal he-
giomas that are located near the mangiomas are associated with
Table 2
WHEN TO WORRY: LOCATION AND HEMANGIOMA RISK
Location Complication Risk
Beard distribution Laryngeal or subglottic hemangioma and risk
of stridor, obstruction, respiratory failure
Anogenital, oropharynx, lip Ulceration, infection, scarring
Cervicofacial PHACES syndrome
Midline lumbosacral Spinal dysraphism, tethered cord
Periorbital Strabismus, amblyopia, astigmatism
Nose, lip, parotid Poor spontaneous involution, scarring
Multiple cutaneous Visceral hemangiomas (most commonly liver,
gastrointestinal tract, lung, brain and
meninges)
Hepatic and large
cutaneous hemangiomas Thyroid dysfunction
CLINICAL PEDIATRICS 749
 S m o l i n s k i , Ya n

urogenital and anorectal anom-

alies such as hypospadias, anterior
or vestibular anus, imperforate
anus, and atrophy or absence of
the labia minora.18 Perineal he-
mangiomas are prone to ulcera-
tion and infection as a result of
frictional and chemical trauma
(Figure 3).

Figure 2. Periorbital hemangioma. Hemangiomas in this location may compress the globe
or cause obstruction of the visual field, impairing the developing visual system.
Figure 3. Perineal heman-
gioma. Hemangiomas in this
location are prone to ulcera-
tion and infection.
Lumbosacral Hemangiomas
A definite correlation exists
between lumbosacral heman-
giomas and underlying spinal
anomalies, including occult spinal
dysraphism, tethered spinal cord,
and lipomeningomyelocele (Fig-
ure 4). A thorough neurologic ex-
amination and spinal imaging by
ultrasound (appropriate in very
young infants) or magnetic reso-
nance imaging (MRI) (for older
infants or children) is recom-
mended for all infants with a he-
mangioma overlying the midline
lumbosacral region.19-22 The inci-
dence of occult spinal dysraphism
was 17.5% in one large case series
involving 120 patients with a su-
perficial hemangioma even with-
out other stigmata overlying the
midline lumbosacral area. 23
Prompt neurosurgical consulta-
tion is indicated for any infant
with a clincally abnormal neuro-
logic examination with an accom-
panying midline lumbosacral he-
mangioma. In addition, close
neurologic follow-up is important,
because some infants who do not
manifest any initial neurologic
deficits will later develop perma-
nent neurologic sequelae that
may have been prevented by early
surgical intervention.

Facial Hemangiomas
The head and neck is the most
common location for heman-
giomas of infancy, accounting for
60% in one large series.10 Specific
Figure 4. Partially involuted lumbosacral hemangioma. Hemangiomas involving the lum- areas of concern on the face in-
bosacral area are associated with underlying spinal cord anomalies, including tethered cord. clude the preauricular area, the

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 Hemangiomas of Infancy

parotid, the nasal tip, the lips and

orophayrnx, and the ears. In gen-
eral, hemangiomas involving the
lips and orophar ynx, the nasal
tip, and ears may incompletely in-
volute and may require surgical
intevention to minimize residual
scarring and deformity (Figures
5, 6). Preauricular hemangiomas
may be associated with heman-
giomas involving the parotid, but
do not usually compromise the fa-
cial nerve. Parotid hemangiomas
are rarely associated with conduc-
tive hearing loss and bony distor-
tion of the mandible and tend to
heal slowly and with scarring.
Figure 5. Nasal tip hemangioma. Hemangiomas involving the nose often leave residual
Rarely, hemangiomas that ob-
scarring and deformity after involution.
struct the external auditory canal
may result in hearing loss if per-
sistent and bilateral.
Recently, facial hemangiomas
have been further charcterized
based on their growth pattern
and on their anatomic location
as related to structural and devel-
opmental landmarks.24 The ma-
jority of hemangiomas, over
76%, are characterized as focal
lesions, which are localized and
tumorlike and appear to segre-
gate along putative lines of em-
bryonic fusion of the primitive
mesenchyme and ectoder m
that form the developing head
and neck str uctures. The re-
maining hemangiomas have a
Figure 6. Hemangioma involving the lower lip. Hemangiomas involving the beard distrib-
more diffuse, plate-like appear-
ution, which includes the preauricular area, the lower lip, and the chin, are associated with
ance and appear to localize to
laryngeal and subglottic hemangiomas.
more segmental distributions
within the frontonasal, maxillary,
or mandibular facial areas, al- giomas, most commonly involv- Hemangiomas located on the
though not correlating exactly ing the liver, gastrointestinal face in the beard distribution
with the dermatomal distrubu- tract, and brain.25 A significant (preauricular, chin, lower lip, an-
tion of the branches of the number of infants with facial seg- terior neck) raise concern due to
trigeminal nerve. Diffuse facial mental hemangiomas in associa- an association with laryngeal or
hemangiomas are more likely to tion with visceral hemangiomato- subglottic hemangiomas that may
be associated with complications, sis meet criteria for PHACES rapidly compromise the air way
including ulceration. Recent re- syndrome (posterior fossa abnor- during the proliferative growth
ports suggest that facial segmen- mality, hemangioma, arterial phase (Figure 6).26,27 Laryngeal
tal hemangiomas are also associ- anomaly, cardiac defects, coarc- and subglottic hemangiomas may
ated with an increased incidence tation of the aorta, eye/ocular cause stridor, persistent cough,
of associated visceral heman- abnormality, sternal defect).25 hoarseness, respiratory distress,

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 S m o l i n s k i , Ya n

or cyanosis, and many infants will

present with respirator y symp-
toms between 6 to 12 weeks of life.
Evaluation by imaging with lateral
neck radiographs, MRI scan, or di-
rect laryngoscopic visualization
will aid in defining the extent of in-
volvement. In infants with exten-
sive involvement, tracheostomy
may be required if local measures,
which include corticosteroids, irra-
diation, surgical excision, and
laser ablation, fail to adequately
control the airway.28-32

Ulcerated Hemangiomas Figure 7. Ulcerated hemangioma.

Genital and orophar yngeal
hemangiomas are particularly sus-
ceptible to ulceration and infec-
tion as a result of chronic irrita-
tion (Figures 7, 8). Common
organisms isolated from infected
hemangiomas include Staphylo-
coccus aureus, group A beta-
hemolytic streptococci, and
Enterobacteriaceae, although
anaerobic and mixed infections
are also seen frequently.33 Treat-
ment of ulcerated hemangiomas
includes meticulous attention to
wound care, with gentle cleans-
ing, application of topical antibi-
otics and the use of barrier oint-
ments such as zinc oxide and
occlusive dressings such as Duo-
Derm or petroleum gauze. The
use of superabsorbent diapers, as
well as frequent diaper changes to
minimize exposure to irritants, is
an important adjunct to therapy.
To minimize the risk of infection, Figure 8. Ulcerated perineal hemangioma.
topical mupirocin ointment is
recommended for ulcerated he- form of recombinant human mon in ulcerated hemangiomas
mangiomas involving the lips or platelt-derived growth factor that is or those involving the scalp, and
oropharynx, while topical metro- currently approved for use in the can usually be easily controlled
nidazole gel is efficacious for ul- treatment of diabetic ulcers, has with pressure and occasional use
cerated anogenital heman- shown potential in the treatment of of gel-foam. Adequate pain con-
giomas.34 Systemic antibiotics are ulcerated hemangiomas that are trol is an important component of
indicated in any child with an ul- refractory to standard therapy.35 treatment as ulcerated heman-
cerated hemangioma that shows Despite the fears of many par- giomas can be quite painful, with
signs of wound infection, such as ents, hemangiomas rarely cause infants often manifesting irritabil-
fever or cellulitis. Recently, the significant or life-threatening ity, behavioral changes, and sleep
use of becaplermin gel, a topical bleeding. Bleeding is more com- disturbances. Administration of

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 Hemangiomas of Infancy

oral analgesics is often required,
and may include acetaminophen
or codeine products. Topical
agents, such as 2.5% lidocaine
ointment, can provide prompt
pain relief when used judiciously;
however, prolonged use of topical
anesthetics which contain prilo-
caine, such as EMLA, is not rec-
ommended due to the risk of
methemoglobinemia.
Ulcerated hemangiomas heal
more slowly that those that have
not ulcerated and are more likely
to heal with scarring. Pulsed dye
laser treatments have been shown
to be of benefit in treating ulcer-
ated hemangiomas by hastening
healing and reducing pain; how-
ever, the laser may also cause ulcer-
ation, scarring, and hypopigmenta-
tion. 34,36-38 On rare occasions,
surgical excision may be required
for ulcerated hemangiomas that
have not responded to more con-
servative wound care, topical and
systemic antibiotic administration,
or pulsed dye laser therapy.
type of these congenital heman- mations (including Dandy-Walker
giomas is the rapidly involuting malformation, cerebellar atrophy,
congenital hemangioma (RICH); agenesis of the corpus callosum),
the second type is the noninvolut- hemangiomas, arterial anomalies
ing congenital hemangioma (persistent embryonic intra- and
(NICH). Another condition of extracranial arteries, aneurysmal
special interest, although not as- dilatations and anomalous
sociated with benign heman- branches of the internal carotid
giomas of infancy, is Kasabach- artery, and absence of ipsilateral
Merritt phenomenon, which is a carotid or cerebral vessels have
potentially fatal complication of been reported), cardiac defects
other vascular tumors, in particu- and coarctation of the aorta (in-
lar Kaposifor m hemangioen- cluding patent ductus arteriosis
dothelioma and tufted angioma. and ventricular septal defects), eye
abnormalities (including microph-
PHACES Syndrome thalmia, congenital cataracts,
The presence of a large, glaucoma, and optic ner ve hy-
plaque-like segmental cervicofa- poplasia), and midline sternal
cial hemangioma is one defining malformations (most commonly
component of PHACES syn- supraumbilical raphae and ster-
drome (Figure 9). This multisys- nal clefts) (Table 3).39-41
temic constellation of associations A review of cases reported in
includes posterior fossa malfor- the literature reveals that the ma-

Special Circumstances
Certain presentations of he-
mangiomas of infancy are indica-
tors of possible systemic or syn-
dromic manifestations. Although
rare, clinicians should be aware of
these associations in order to as-
sure prompt recognition and
evaluation. Two well-defined con-
ditions associated with heman-
giomas of infancy are PHACES
syndrome, one component of
which is a large facial segmental
hemangioma, and neonatal he-
mangiomatosis, in which multiple
small focal hemangiomas are pre-
sent, usually distributed diffusely.
There are also two rare presenta-
tions of hemangiomas that are
present at birth and do not ex-
hibit the typical growth pattern of Figure 9. Large facial segmental hemangioma in PHACES
hemangiomas of infancy. One syndrome.

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Table 3
Criterion
P—posterior fossa abnormality
H—hemangioma
A—arterial anomaly
C—cardiac defects, coarctation of the aorta
E—eye/ocular abnormality
S—sternal defect
jority of affected patients (70%)
possess only one extracutaneous
manifestation in addition to the
cervicofacial hemangioma; how-
ever, reported cases are found pre-
dominantly in the dermatology lit-
erature and are therefore biased
towards the recognition of the fa-
cial hemangioma as a defining
characteristic of the syndrome.
The most common reported ex-
tracutaneous manifestation in in-
fants with PHACES syndrome is
structural and arterial brain mal-
formations, which are present in
71% of affected infants.40 These
anomalies place infants at high
risk for neurologic sequelae, in-
cluding developmental delay and
seizures. Congenital heart disease
was reported in over one-third of
cases reported in the literature
and in 21% of cases in one small
case series.40 One recent case se-
ries of infants with PHACES syn-
drome and aortic arch anomalies
demonstrated that there appears
to be a strong correlation be-
tween the laterality of the facial
hemangioma and the underlying
cerebrovascular and aortic arch
anomalies, leading the authors to
suggest vascular imaging studies
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PHACES CRITERIA
Examples
Dandy-Walker malformation, agenesis of the corpus callosum,
cerebellar atrophy
Cervicofacial location
Aneurysms and anomalies of internal carotid arteries
Coarctation of the aorta, ventricular septal defect, patent ductus arteriosus
Cataracts, microphthalmia, optic nerve hypoplasia, glaucoma
Supraumbilical raphae, sternal cleft
prior to surgical repair in any in- neonatal hemangiomatosis (Fig-
fant with PHACES syndrome and ure 10). In general, these heman-
an aortic anomaly.42 giomas are benign and involute
The association of large cervi- within the first 2 years of life.43-47
cofacial hemangiomas with other However, multiple, progressive,
significant comorbidities indi- rapidly growing cutaneous he-
cates that any infant who presents mangiomas may be associated
with a cervicofacial hemangioma with widespread visceral heman-
should be considered at risk for giomas in the liver, lungs, gas-
PHACES syndrome. They should trointestinal tract, brain and
undergo careful neurologic meninges. This presentation, re-
evaluation and should be re- ferred to as diffuse neonatal he-
ferred for ophthalmologic evalu- mangiomatosis, carries the risk of
ation, brain MRI/magnetic reso- systemic complications, including
nance angiography (MRA), and high-output cardiac failure, hem-
cardiac evaluation. In addition, orrhage, and neurologic defects,
cervicofacial hemangiomas in the with an attendent high mortality
beard distribution are also associ- rate (Table 4).48-52
ated with laryngeal and subglottic Infants who present with mul-
hemangiomas, and infants with tiple cutaneous hemangiomas
hemangiomas in this location should be evaluated for the in-
should also be monitored care- volvement of other organ systems
fully for respiratory distress with with close follow-up. An abdomi-
otolar yngologic consultation nal ultrasound with Doppler is
where appropriate. recommended in all symptomatic
infants presenting with multiple
Neonatal Hemangiomatosis hemangiomas. Hepatic involve-
Hemangiomas usually occur ment represents the most com-
as isolated lesions. Multiple scat- mon site of extracutaneous dis-
tered, small, dome-shaped he- ease and greatest cause of
mangiomas that present at birth morbidity and mortality in infants
or during the first few weeks of with systemic involvement. He-
life are referred to as benign patic hemangiomas commonly
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 Hemangiomas of Infancy

complete blood cell counts, an

ophthalmologic examination,
urinalysis, and stool guaiacs. Of
note, the development of hy-
pothyroidism as a result of in-
creased type 3 iodothyronine
deiodinase activity has been re-
ported among infants with he-
patic hemangiomas.53

Congenital Hemangiomas
Rarely, fully developed vascu-
lar tumors that clinically resemble
hemangiomas may present at
birth. These congenital heman-
giomas are believed to result from
the in utero development of he-
Figure 10. Neonatal hemangiomatosis. The presence of multiple hemangiomas may be mangiomas with a proliferative
associated with internal hemangiomas involving the gastrointestinal tract, the lungs, and phase. They differ clinically from
the central nervous system. common hemangiomas of infancy
in appearance, natural history, and
biologic origins. They present at
Table 4 birth as raised violaceous-grey tu-
mors with overlying telangiectasias
and a peripheral rim of pallor, and
BENIGN NEONATAL HEMANGIOMATOSIS VS are often quite large, averaging sev-
DIFFUSE NEONATAL HEMANGIOMATOSIS eral centimeters in diameter (Fig-
ure 11). They may also demon-
Benign Neonatal Diffuse Neonatal strate warmth and a palpable bruit
Hemangiomatosis Hemangiomatosis as the result of high-flow vascula-
ture. Some of these hemangiomas
Multiple cutaneous hemangiomas Yes Yes will begin to involute early in in-
Systemic involvement Infrequent Yes fancy and will have regressed com-
pletely by 12 to 18 months of age.
Requires therapy No Yes
These rapidly involuting congeni-
Requires close follow-up Yes Yes tal hemangiomas (RICH) require
Prognosis Excellent Poor no intervention unless complica-
tions occur.54-56 Histopathologic
evaluation demonstrates capillary
lobules in a dense, fibrotic stroma
present within the f irst few temic complications and who fail with focal thrombosis and sclerosis
months of life with hepatomegaly, to respond to systemic steroids. of capillary lobules and associated
congestive heart failure, and ane- Interferon-alpha, vincristine, he- thin-walled vessels in the absence
mia as a result of a large arteri- patic arter y embolization, and of normal tissue elements.54 On
ovenous shunt and high-output partial hepatectomy have all been angiography, RICH demonstrate
cardiac failure. Early consultation used with variable success. Fre- proliferating vascular lobules
with a pediatric cardiologist and quent monitoring of infants at composed of proliferating capil-
initiation of systemic corticos- risk for diffuse neonatal heman- laries and thin-walled vessels set
teroids is essential in infants with giomatosis to evaluate for involve- in a fibrous stroma; large, irregu-
hepatic involvement and conges- ment of other organ systems lar, disorganized feeding arteries
tive heart failure. More aggressive should include a thorough physi- with arterial aneurysms; arteri-
therapy may be indicated for in- cal examination as well as tar- ovenous shuts; and intravascular
fants who have developed sys- geted screening tests, including thrombi.54,57

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Figure 11. Rapidly involuting congenital hemangioma.
Figure 12. Noninvoluting congenital hemangioma.
In contrast, some congenital
hemangiomas do not involute but
continue to proliferate. These
noninvoluting congenital heman-
giomas (NICH) also manifest as
purplish nodules and plaques
with overlying telangiectasias and
central or peripheral pallor, and
may also demonstrate palpable
warmth and a bruit (Figure 12).58
They have been reported more
commonly in males and are
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S m o l i n s k i , Ya n
RICH and NICH lesions are
distinct clinical entities and differ
from hemangiomas of infancy in
their various surface markers as
well as in their histology. Neither
RICH nor NICH express GLUT1,
a vascular marker for heman-
giomas of infancy. 54,58 The ap-
pearance of RICH and NICH on
MRI and ultrasound also show dis-
tinctive patterns, and can help to
differentiate these atypical vascu-
lar tumors from benign heman-
giomas of infancy. Rarely, chil-
dren may present with a RICH or
a NICH in association with a he-
mangioma of infancy, or may pre-
sent with a lesion initially diag-
nosed as a RICH that fails to
undergo complete involution and
persists as a lesion more compati-
ble with a NICH.59 Clearly, our un-
derstanding of the biology of he-
mangiomas remains incomplete
and continues to evolve.
Kasabach-Merritt Phenomenon
Kasabach-Merritt phenome-
non indicates a consumptive coag-
ulopathy that manifests as severe
thrombocytopenia, hemolytic
anemia, and disseminated in-
travascular coagulation occuring
in the setting of a rapidly growing
vascular tumor (Table 5). Despite
prior reports in the literature, he-
mangiomas of infancy are not as-
sociated with Kasabach-Merritt
phenomenon.60-64 Large venous
or mixed vascular malformations
may rarely be associated with a
found most frequently on the consumptive coagulopathy that is
head and neck. On Doppler ultra- milder than that seen with
sound, NICH demonstrate persis- Kasabach-Merritt phenomenon;
tant fast arterial flow. Histopatho- significant coagulopathy is not as-
logic examination shows small, sociated with hemangiomas of in-
thin-walled vessels arranged into fancy. Kasabach-Merritt phenom-
lobules with dilated, dysplastic in- enon has been associated
terlobular veins and small arteries primarily with Kaposiform he-
that shunt into lobular vessels.58 mangioendotheliomas, but has
NICH are treated with surgical ex- also been reported to occur with
cision and exhibit no tendency to tufted angiomas, congenital he-
recurrence. mangiopericytomas, and certain
NOVEMBER/DECEMBER 2005

Table 5
KASABACH-MERRITT PHENOMENON
Associated vascular malformations
Hematologic manifestations
Risks
Treatment
lymphatic malformations. 8 Ka-
posifor m hemangioendothe-
lioma is a rare vascular tumor that
presents at birth or within the first
year of life and clinically appears
as a rapidly growing, purplish, in-
durated, compressible tumor. It
occurs most commonly in the
retroperitoneum and on the ex-
tremities. The tumor is locally ag-
gressive, and complications may
include life-threatening hemor-
rhage, compression of vital struc-
tures, infection, and respiratory
distress. There is a high mortality
rate in affected infants. MRI,
Doppler ultrasound, and histol-
ogy are useful in diagnosing Ka-
posifor m hemangioendothe-
lioma. Coagulation studies and
complete blood cell counts
should be followed carefully. Ag-
gressive therapy is indicated and
may include systemic corticos-
teroids, cytotoxic medications
such as cyclophosphamide and
vincristine, antiplatelet agents, ε-
aminocaproic acid, transexamic
acid, selective embolization, and
transfusion of blood components.
Surgical resection may be indi-
cated in selected cases. Manage-
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Hemangiomas of Infancy
recommended during early in-
fancy, when the rapid growth
phase predominates. When the
growth rate slows and the heman-
gioma is stable in size, less fre-
quent monitoring is necessar y
Kaposiform hemangioepithelioma, tufted and annual evaluations are usu-
angioma, congenital hemangiopericytoma, ally sufficient for involuting he-
lymphatic malformations mangiomas, unless families re-
Thrombocytopenia, hemolytic anemia, quire more frequent evaluations
coagulopathy in order to receive psychological
Severe hemorrhage, infection, locally support. In addition, photo-
aggressive with obstruction of vital graphic documentation may be a
structures useful adjunct to expectant man-
agement, allowing physicians and
Combination therapy—corticosteroids,
families to record the progression
chemotherapy, antiplatelet medications,
transfusions and involution of the heman-
gioma over time.
Hemangiomas located near vi-
tal structures and those that cause
obstruction or compression or
ment requires a multidisciplinary that have developed complica-
approach that includes dermatol- tions such as ulceration require
ogy, oncology, and pediatric surgi- additional evaluation and man-
cal subspecialties. In patients who agement. Approximately 5% of
do not succumb to complications, hemangiomas will ulcerate dur-
spontaneous, often incomplete, ing the proliferative phase, and a
resolution usually occurs.60 significant proportion of heman-
giomas (20%) interfere with vital
Treatment structures.66,67 Intervention may
The majority of hemangiomas also be indicated for a heman-
require no intervention and in gioma present in any location that
general the ultimate cosmetic out- demonstrates a very rapid growth
come is usually better in heman- rate with tripling or quadrupling
giomas that are allowed involute in size within weeks in order to
spontaneously.65 It is imperative slow progression. Certain heman-
to educate parents and caregivers giomas, particularly those occur-
on the natural history of heman- ring on the nasal tip, the lip, and
giomas of infancy, particularly as perhaps some parotid lesions,
some parents are quite distressed characeristically show poor or in-
by the physical appearance of the complete involution. Heman-
hemangioma, especially during giomas present in these locations
the phase of rapid growth or with benefit from early intervention
hemangiomas located on the with systemic corticosteroids and
face. Sensitivity to these psychoso- with elective surgical intervention
cial issues is an integral part of the before school age.
routine management of heman- The mainstay of treatment for
giomas. Regular evaluations to symptomatic hemangiomas in-
provide parental reassurance and volves the judicious administra-
to monitor growth, regression, tion of oral corticosteroids, which
and the potential development of through mechanisms that remain
complications are essential. More poorly characterized, help to pro-
frequent clinical evaluations are mote stabilization or regression of
CLINICAL PEDIATRICS 757

most hemangiomas.68-70 A starting
dose of 2 to 3 mg/kg per day of
prednisone or prednisolone as a
single morning dose is commonly
used, and the dose is increased as
needed to achieve a clinical re-
sponse. A decrease in the growth
rate, softening of the lesion, or
the development of bluish-gray
discoloration should be apparent
within 1 to 2 weeks of initiating
therapy. Although various ap-
proaches have been used, therapy
is typically maintained for 1 to 2
months, after which time the dose
is slowly tapered over several
weeks to months. The use of high-
potency topical steroids has been
of limited benefit for small super-
ficial hemangiomas and currently
is used infrequently.71,72 Intrale-
sional corticosteroids can be use-
ful for selected small heman-
giomas involving the lips, ears,
nose, and eyes. Small, superficial
hemangiomas and those involv-
ing the perioral area appear to
have the best response rate; how-
ever, there is a small but signifi-
cant risk of complications, includ-
ing atrophy, skin necrosis, and
adrenal suppression.73 Periorbital
intralesional injections are best
performed by ophthalmologists,
as there is a small but finite risk of
central retinal artery occlusion
and subsequent blindness. As in-
tralesional corticosteroids require
expertise and patience during ad-
ministration to minimize the risk
of complications, many dermatol-
ogists prefer to administer sys-
temic corticosteroids.
Although uncommon during
short-term therapy, the use of cor-
ticosteroids can have several ad-
verse effects. Infants and children
must be monitored for side ef-
fects such as hypertension, im-
munosuppression, irritability, gas-
tritis, weight gain or loss, and
temporar y growth retardation
(through transitory inhibition of
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S m o l i n s k i , Ya n
bone lengthening).74,75 Of note, tive necrosis with the production
adrenal suppression has been re- of self-limited post-laser purpura.
ported to occur in a significant Clinical improvement may be
percentage of infants who have seen after the first treatment, al-
received intralesional or perile- though several treatments may be
sionsl steroid injections for the required to produce the desired
treatment of periorbital heman- clinical results. The pulsed-dye
giomas. 74,75 Administration of laser is most effective on superfi-
stress-dose steroids following cial hemangiomas and remains
completion of corticosteroid ther- ineffective in addressing the sig-
apy should be considered under nificant dermal component of
appropriate circumstances in chil- deep hemangiomas. Pulsed dye
dren who have chronically re- laser therapy works optimally on
ceived systemic steroids due to fair skin types, as hypopigmenta-
concerns for adrenal suppression. tion may result when treating
It should be recognized that in in- darker skin types as a result of in-
fants who develop growth delay cidental damage to melanocytes.
while on short courses of systemic In addition, hyperpigmentation,
steroids, catch-up growth is gener- scarring, and atrophy are poten-
ally seen after discontinuation.75 tial complications of pulsed dye
To minimize the risk of gastritis, laser therapy. Although many par-
prophylactic administration of an ents pressure clinicians to initiate
oral H2 antihistamine may be pulsed-dye laser treatments for
helpful. In addition, it is recom- otherwise uncomplicated heman-
mended that children not receive giomas to hasten regression, sev-
live virus vaccines such as the oral eral studies have suggested that
polio and varicella vaccines dur- the final cosmetic outcome when
ing systemic steroid therapy. using the pulsed dye laser to treat
For life-threatening heman- uncomplicated hemangiomas is
giomas that have failed to re- not improved when compared to
spond to systemic corticosteroids, the results after natural regres-
interferon-alpha, pulsed dye laser, sion. 88,90,94 However, heman-
surgery, and sclerotherapy have giomas on the nose, lips, or ears
been employed. Interferon alpha often heal poorly with scarring af-
therapy, although efficacious, is ter natural regression; therefore,
limited by an adverse effect pro- selected patients with superficial
file that includes fever, myalgias, hemangiomas in these locations
transaminase elevations, neu- might benefit from early inter-
tropenia, anemia, and both re- vention with pulsed dye laser ther-
versible and irreversible neuro- apy in an effort to provide a better
logic sequelae such as spastic cosmetic outcome. In addition,
diplegia.76-86 children with telangiectatic re-
The use of the flash-lamp mants of facial hemangiomas may
pulsed-dye laser has gained popu- also benefit from pulsed dye laser
larity for the treatment of residual therapy prior to enrolling in
telangiectasias in involuted he- school if they are self-conscious of
mangiomas as well as in the treat- their appearance.
ment of proliferating or ulcerated Surgical excision is indicated
hemangiomas. 66,87-95 In current for localized hemangiomas on the
usage, the pulsed dye laser emits a face that are unresponsive to sys-
585- to 595-nm wavelength that temic glucocorticoids and that
targets oxyhemoglobin and re- are causing obstruction or com-
sults in selective vascular coagula- pression of vital structures such as
NOVEMBER/DECEMBER 2005

the ear or eye; excision is also ben-
eficial for ulcerated or bleeding
hemangiomas that have not re-
sponded to more conser vative
treatment. 96-100 Some pediatric
plastic surgeons also recommend
early excision of pedunculated
hemangiomas predicted to invo-
lute with residual fibrofatty tissue
that would require subsequent
surgical resection. Hemangiomas
on the ears and those on the tip of
the nose (“Cyrano nose”) also
tend to heal poorly as a result of
damage to underlying cartilage,
and cosmetic outcome may be im-
proved by early treatment with
pulsed-dye laser or surgical exci-
sion.101-106 Some psychologically
distressing hemangiomas on the
face, in particular those on the
ears, lips, and in the periorbital
region, may be removed during
the preschool years before school
entry if involution is incomplete.
In addition, surgical excision to
improve final cosmetic outcome
may be indicated in those heman-
giomas that involute with residual
scarring, cutaneous redundancy,
areas of alopecia on the scalp, or
atrophy. Rarely, sclerotherapy has
been used, either alone or as an
adjunct therapy, for the treatment
of rapidly growing hemangiomas
in cosmetically sensitive areas or
hemangiomas that have not fully
involuted.107-111 While generally
favorable results can be achieved,
there is small complication risk
of cutaneous ulceration at the in-
jection site. Recently, MR-guided
sclerotherapy has been studied
as a technique to target heman-
giomas more effectively with the
use of a minimum amount of
sclerosant.112
Current therapies for treating
life-threatening or complicated
hemangiomas are often limited
by adverse effects and delays in
therapeutic effects. Recently, the
use of imiquimod, a topical im-
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Hemangiomas of Infancy
mune-modulator, was shown to be about their biology on a cellular
efficacious in the treatment of or molecular level. The identifica-
two infants with uncomplicated tion of the progenitor cell that
hemangiomas.113 In both cases, gives rise to hemangiomas of in-
treatment was complicated by the fancy remains controverial; how-
development of significant local ever, several cell markers for he-
inflammation and crusting, which mangiomas have been recognized,
resolved after a 2-week drug holi- including GLUT1, FcgammaRII,
day. Both infants showed com- merosin, and Lewis Y antigen.116
plete resolution of the heman- Recently, several growth factors
gioma after 2 treatment courses have been identified that are asso-
of 3 to 6 weeks each, with no evi- ciated with the proliferation and
dence of recurrence at 1 to 4 involution of hemangiomas. In-
months after treatment. Im- vestigations into the pathogenesis
iquimod is US Food and Drug Ad- of hemangiomas of infancy are
ministration–approved for the closely correlated with studies in-
treatment of genital warts and volving angiogenesis, and en-
basal cell carcinoma, but has been dothelial growth factors such as
used extensively as an off-label vascular endothelial growth factor
treatment for a variety of other cu- (VEGF) are are believed to play
taneous diseases, including com- an important role in the develop-
mon warts, actinic keratoses, and ment of hemangiomas. As the ma-
alopecia areata. Imiquimod stim- jority of hemangiomas occur spo-
ulates innate and acquired immu- radically, genetic linkage studies
nity through a variety of mecha- have provided only limited infor-
nisms, including the activation of mation on other candidate genes
toll-like receptor-7 and the pro- to date.
duction of a variety of cytokines,
including interferon alpha (IFN-α) Histopathology
and IL-12.114 Other investigators, The histopathology of heman-
using a mouse hemangioendothe- giomas varies depending on the
lioma model, have demonstrated clincal stage. During the prolifer-
that application of imiqimod to ative stage of superficial heman-
implanted tumors results in de- giomas, proliferating lobules of
creased tumor growth and in- endothelial cells arranged in
creased survival, with decreased strands and masses with few capil-
tumor cell proliferation, in- lary lumens are seen in the super-
creased tumor cell apoptosis, and ficial dermis. As the hemangioma
increased expression of tissue in- matures to the involutional stage,
hibitor of metalloproteinase-1 the capillary lumens enlarge and
(TIMP-1).115 Further controlled the endothelial cells flatten; even-
trials are indicated in order to val- tually, fibrosis ensues with obliter-
idate use of imiquimod in the ation of the blood vessel lumens.
treatment of hemangiomas of in- Deep (cavernous) hemangiomas,
fancy, both complicated and un- by contrast, may manifest larger,
complicated. irregular vascular spaces lined
with flattened endothelial cells
present in the deeper dermis and
Pathogenesis subcutaneous tissue.117
Mast cells, pericytes, intersti-
Despite the common occur- tial cells, and fibroblasts are pre-
rence of hemangiomas of infancy, sent in hemangiomas in all stages,
until recently little was known although mast cells may be more
CLINICAL PEDIATRICS 759

prominent in involuting heman-
giomas.118-120 Recently, a role for
mast cells in the involution of he-
mangiomas was proposed based
on the observation that expres-
sion of clusterin/apoJ, a glycopro-
tein involved in cell apoptosis, is
increased in involuting heman-
giomas and localizes to mast cell
granules. 120,121 Endothelial cell
apoptosis is increased in involut-
ing hemangiomas, and is postu-
lated to play a major role in the in-
volutional process, although the
triggers for induction of apoptosis
remain unknown.122,123 A CD68(+)
population of cells with dendritic
cell morphology have also been
shown to occur in proximity to the
vascular endothelial cells that com-
prise infantile hemangiomas.124
Endothelial Cell Origins
The origin of the endothelial
cells that comprise hemangiomas
of infancy remains controversial.
Some investigators have sug-
gested a placental origin, either
involving embolic endothelial
cells or the differentiation of
progenitor endothelial cells to-
wards a placental phenotype dur-
ing gestation.116 The normal invo-
lution of hemangiomas during
infancy may result from the loss of
angiogenic stimuli previously pre-
sent during gestation, or alterna-
tively, the rapid growth of heman-
giomas during the proliferative
phase in early infancy may result
from the loss of inhibitors of an-
giogenesis that maintain the pla-
centa during pregnancy.125
Hemangioma-derived en-
dothelial cells are clonal, and un-
like normal endothelial cells, are
stimulated to migrate in response
to the angiogenesis inhibitor en-
dostatin.126 Evidence supporting
a clonal etiology for the endothe-
lial cells in hemangiomas include
genetic studies that have revealed
loss of heterozygosity involving
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chromosome 5q in both spo- mal developmental continuum,
radic hemangiomas and in sev- or whether these cells represent a
eral hemangioma kindreds.127,128 subset of intially more mature en-
Nonrandom X-inactivation has dothelial cells that have regressed
also been demonstrated in he- to a more embryonic state as a re-
mangioma-derived endothelial sult of some environmental or ge-
cells.126,129 This population of “an- netic insult.
gioblastic” endothelial cells be-
haves more like embryonic en- Growth Factors
dothelial cells as opposed to The VEGF family, which in-
neonatal endothelial cells, and cluded the ligands VEGF-A,
may represent a clonal popula- VEGF-B, VEGF-C, VGF-D, and
tion of cells derived from en- VEGF-E, and the angiopoietin
dothelial progenitor cells. Expres- family are well-characterized
sion of the human stem cell/ growth factor families that regu-
progenitor cell marker CD133 has late endothelial cell proliferation
been demonstrated to occur in a and angiogenesis. 132,133 The
small percentage of endothelial VEGF receptor family includes
cells derived from hemangiomas, VEGFR-1 (also known as fms-re-
some of which also co-expressed lated tyrosine kinase-1 [Flt-1]),
the endothelial cell marker kinase VEGFR-2 (also known as kinase
insert domain-containing recep- insert domain-containing recep-
tor (KDR), which mediates VEGF- tor [KDR] or fetal liver kinase-1
mediated endothelial cell prolif- [Flk-1]) and VEGFR-3 (also
eration.130 Endothelial cells from known as Flt-4). The angiopoi-
primary cultures of hemangiomas etins Ang-1 and Ang-4 (stimula-
of infancy, similar to fetal en- tory) and Ang-2 and Ang-3 (in-
dothelial cells, express lower lev- hibitor y) bind to the tunica
els of von Willebrand factor (vWF) interna endothelial cell kinase-2
and platelet-endothelial cell ad- (Tie-2) receptor; a Tie-1 receptor
hesion molecule-1 (PECAM-1).131 also exists, although its ligand is
In addition, these cultured hu- unknown. Flk-1/KDR, Flt-1, Tie-1,
man endothelial cells assume a Tie-2, and Ang-2 are strongly ex-
spindled morphology more char- pressed in cultured hemangioma-
acteristic of embryonic endothe- derived endothelial cells and in
lial cells. Hemangioma-derived hemangioma tissue, while there is
endothelial cells also express in- minimal expression of Ang-1.134
terstitial-collagen types I, III, and VEGF expression may be reduced
V in all stages but predominantly in involuting hemangiomas, but
during involution; in contrast, conflicting data exists. 118,134-137
neonatal endothelial cells express Mutations in the VEGF receptors
epithelial-specific type IV colla- Flk-1/KDR and Flt-4 have been
gen.118,131 Taken together, these demonstrated in two clonal he-
findings suggest that the endothe- mangioma cell populations.129
lial cells that constitute heman- In addition to VEGF, prolifer-
giomas of infancy represent a dis- ating hemangiomas express high
tinct population of endothelial levels of several cellular markers,
cells that appear to express an em- including proliferating cell nu-
bryonic phenotype. It is unclear clear antigen (PCNA), type IV col-
whether these hemangioma-spe- lagenase (a metalloproteinase), E-
cific endothelial cells represent a selectin, and basic f ibroblast
clonal cell population that has growth factor (b-FGF), that are
failed to progress along the nor- not expressed in vascular malfor-
NOVEMBER/DECEMBER 2005

mations. 118,138,139 PCNA is a
marker for cell proliferation,
while bFGF is a potent angiogenic
growth factor. Expression of al-
pha-smooth musle actin (alpha-
SMA), another vascular endothe-
lial marker, is highly expressed in
both proliferating and involuting
hemangiomas but is rare in
RICH, providing further evi-
dence that congenital heman-
giomas, or at least RICH, are de-
rived from a phenotypically
distinct endothelial cell popula-
tion. 122 In involuting heman-
giomas, expression of the growth
inhibitor transforming growth
factor-beta (TGF-β) in increased,
as is expression of placental
growth factor (PlGF).118,122,137
Other growth factors have
been implicated in the heman-
gioma growth and involution. Ex-
pression of IL-6, platelet-derived
growth factor-A (PDGF-A), PDGF-
B, TGF-β1, and TGF-β3 are de-
creased in involuting heman-
giomas, including those treated
with steroids, while expression of
bFGF, remains unchanged.135,136
DNA microarray analysis of gene
expression in proliferating and in-
voluting hemangiomas indicates
that insulin-like growth factor-2
(IGF-2) expression is upregulated
in proliferating hemangiomas,
suggesting a role for IGF-2 in he-
mangioma growth.140 In addition,
several interferon-induced genes
are expressed in involuting he-
mangiomas, indicating that inter-
feron may also play a role in the
natural course of hemangioma
resolution.
Apoptosis is believed to be a
critical component of the involu-
tional pathway of hemangiomas
of infancy. Expression of clus-
terin/apoJ, a marker of apopto-
sis, and mitochondrial cy-
tochrome b, which is also
involved in apoptosis, is in-
creased in spontaneously involut-
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Hemangiomas of Infancy
ing hemangiomas, as well as in in- Endothelial cells from both
voluting hemangiomas that have proliferating and involuting he-
been treated with steroids.121,141 mangiomas express CD31 and
Further studies are needed to elu- von Willebrand factor, two en-
cidate the factors responsible for dothelial cell markers.118,138 Ex-
the induction of apoptosis in in- pression of the cell surface adhe-
voluting hemangiomas. sion molecule CD 146, another
endothelial cell marker, is not ex-
Cellular Markers pressed in hemangioma-derived
The placental-associated vas- endothelial cells, although ex-
cular antigens GLUT1, an er y- pression is present in surround-
throcyte-type glucose transporter ing pericytes. 144 Involuting he-
whose expression is restricted to mangiomas also express the
tissues with blood-tissue barrier angiogenesis inhibitor tissue in-
function; merosin; FcgammaRII; hibitor of metalloproteinase-1
and Lewis Y antigen (LeY) are (TIMP-1). 138 A switch from ex-
strongly expressed in heman- pression of beta(3) integrin to
giomas of infancy; other vascular beta(4) intergrin also accompa-
lesions, including vascular malfor- nies the progression from the pro-
mations and Kaposiform heman- liferative phase to the involu-
gioendotheliomas, fail to demon- tional phase.124
strate expression of these
markers. 116,142 Kaposiform he-
mangioendotheliomas express Conclusions
the endothelial cell markers
CD31, CD34, and Friend Hemangiomas of infancy are
leukemia vir us integration-1 common, benign, vascular tu-
(FLI1), further confirming that mors that express specific cellular
these markers can help to differ- markers that distinguish them
entiate benign hemangiomas of from other vascular tumors and
infancy from vascular tumors with malformations. The natural his-
malignant potential.143 This ob- tory of these lesions includes an
servation suggests a critical dis- inital proliferative phase during
tinction between the origin of he- the first 6 to 9 months of life, fol-
mangiomas of infancy as opposed lowed by a slow involutional phase
to other vascular lesions, and fur- that begins after the first year of
ther implicates a cell phenotype life and progresses over several
similar to placental-derived en- years. Most hemangiomas do not
dothelial cells as the progenitor of require intervention and regress
hemangiomas of infancy. Con- spontaneously over several years.
genital nonprogressive heman- However, treatment is indicated
giomas (RICH), in contrast to for hemangiomas which obstruct
common hemangiomas of infancy, or interfere with vital structures or
fail to express GLUT1 and LeY.54 are complicated by ulceration , in-
NICH are also negative for GLUT1 fection, or systemic involvement.
expression.58 The congenital he- First-line therapy is administration
mangiomas NICH and RICH, of systemic or, less commonly, in-
therefore, represent a phenotypi- tralesional corticosteroids. The
cally distinct subtype of vascular tu- most common complication of
mor that may represent the end hemangiomas is ulceration,
result of a different developmental which can be initially treated con-
pathway along the spectrum of en- servatively with topical therapy;
dothelial cell maturation. pulsed dye laser treatments are in-
CLINICAL PEDIATRICS 761

dicated for severe, non-healing ul-
cerations. Early pulsed dye laser
therapy and surgical excision are
reserved for hemangiomas which
are life-threatening or have devel-
oped complications and are not
responding to more conservative
management. Hemangiomas lo-
cated in certain areas, including
the midline lumbosacral area, the
beard area of the face and neck,
and the periorbital area, may be as-
sociated with other anomalies, and
these children require appropriate
and timely evaluation . In addition,
infants with facial segmental he-
mangiomas or the presence of
multiple cutaneous hemangiomas
are at risk for potentially devastat-
ing systemic manifestations, and
should also receive further evalua-
tion as indicated.
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