Hemangioma

It is confusing to attempt to classify hemangiomas on the basis of their histology. For example, the
histologic term capillary hemangioma is used for both the common involuting hemangioma of
childhood that disappears by age 7 and the port wine stain that persists into adulthood. The term
cavernous is used to designate several types of hemangiomas that behave quite differently. Some
hemangiomas are true neoplasms arising from endothelial cells and other vascular elements (such as
involuting hemangiomas of childhood, endotheliomas, and pericytomas). Others are not true
neoplasms but rather malformations of normal vascular structures (eg, port wine stains, cavernous
hemangiomas, and arteriovenous fistulas).

A simple classification based upon whether or not the hemangioma undergoes spontaneous
involution is proposed in Table 44-3.

A. Involuting Hemangioma

Involuting hemangiomas are the most common tumors that occur in childhood and constitute at
least 95% of all the hemangiomas that are seen in infancy and childhood. They are true neoplasms of
endothelial cells but are unique among neoplasms in that they undergo complete spontaneous
involution.

Typically, they are present shortly after birth or appear during the first 2-3 weeks of life. They grow
at a rather rapid rate for 4-6 months; then growth ceases and spontaneous involution begins.
Involution progresses slowly but is complete by 5-7 years of age.

Involuting hemangiomas appear on all body surfaces but are seen more often on the head and neck.
They are seen twice as often in girls as in boys and show a predisposition for fair-skinned individuals.

Three forms of involuting hemangioma are seen: (1) superficial, (2) combined superficial and deep,
and (3) deep. Superficial involuting hemangiomas appear as sharply demarcated, bright-red, slightly
raised lesions with an irregular surface that has been described as resembling a strawberry.
Combined superficial and deep involuting hemangiomas have the same surface characteristics, but
beneath the surface, a firm bluish tumor is present that may extend deeply into the subcutaneous
tissues. Deep involuting hemangiomas present as deep blue tumors covered by normal-appearing
skin.
The histologic findings in involuting hemangiomas are quite different from those seen in other types
of hemangiomas. There is a constant correlation between the histologic picture and the clinical
course. During the growth phase, the lesion is composed of solid fields of closely packed round or
oval endothelial cells. As would be expected during the growth phase, cellular division with mitotic
figures is seen, so that the lesion is sometimes called a hemangioendothelioma by the pathologist.
This term must not be used, however, since it is commonly used to denote the highly malignant
angiosarcoma that is seen in adults.

As the phase of involution progresses, the histologic picture changes, with the solid fields of
endothelial cells breaking up into closely packed, capillary-sized, vessel-like structures composed of
several layers of soft endothelial cells supported by a sparse fibrous stroma. These vascular
structures gradually become fewer and spaced more widely apart in a loose, edematous fibrous
stroma. The endothelial cells continue to disappear, so that by the time involution is complete the
histologic picture is entirely normal, with no trace of endothelial cells.

Treatment is not usually indicated, since the appearance following spontaneous regression is nearly
always superior to the scars that follow surgical excision. Complete surgical excision of lesions that
involve important structures such as the eyelids, nose, or lips results in unnecessary disfigurement
that is difficult to repair.

Partial resection of a portion of a hemangioma of the brow or eyelid is indicated when the lesion is
large enough to prevent light from entering the eye—a condition that will lead to blindness or
amblyopia. The same type of treatment may be necessary for lesions of the mucosal surfaces of the
lips when they project into the mouth and are traumatized by the teeth. In these cases, surgery
should be very conservative—only enough of the lesion should be resected to alleviate the problem,
and the remaining portions should be allowed to involute spontaneously.

In approximately 8% of cases, ulceration will occur. This may be accompanied by infection, which is
treated by the use of compresses of warm saline or potassium permanganate and by the application
of antibiotic powders and lotions. Bleeding from the ulcer is not common; when it does occur, it is
easily controlled by the application of pressure. In rare cases, the platelet trapping of these lesions
leads to the clinical picture of disseminated intravascular coagulopathy called Kasabach-Merritt
syndrome.

After involution of large lesions, superficial scarring may be present or the involved skin may be thin,
wrinkled, or redundant. These conditions may require conservative plastic surgery procedures.
The application of local agents such as dry ice to the surface of these lesions has been popular. This
type of treatment has no effect on the deep portions of the hemangioma. It will destroy superficial
lesions but results in severe scarring. Injections of sclerosing agents have minimal effect. There is no
place for radiation therapy in the treatment of these benign lesions. Corticosteroids given
systemically or intralesionally have been used with varying success. Anecdotal evidence exists in
favor of compression to speed up the involution process and give a better final result. Innovative
treatments have recently been proposed for the most serious hemangiomas. They include the
insertion of a laser probe deep into the lesion so that the heat generated by the laser produces
contracture of the hemangioma. Systemic interferon treatment of life-threatening hemangiomas of
the head and neck area obstructing the airway have produced varying results.

B. Noninvoluting Hemangioma

Most noninvoluting hemangiomas are present at birth. In contrast to involuting hemangiomas, they
do not undergo rapid growth during the first 4-6 months of life but grow in proportion to the growth
of the child. They persist into adulthood and may cause severe aesthetic and functional problems.
Some, such as arteriovenous fistulas, may cause death due to cardiac failure.

Unfortunately, treatment of noninvoluting hemangiomas is difficult and usually far from satisfactory.

Port wine stains are by far the most common of the noninvoluting hemangiomas. They may involve
any portion of the body but most commonly appear on the face as flat patchy lesions that are
reddish to purple in color. When present on the face, they are located in areas supplied by the
sensory branches of the fifth cranial nerve. The light-red lesions may fade to a varying degree but
persist into adulthood. Some of the deep red or purplish lesions that have a stippled appearance
show a propensity for growth later in life, in which case they become raised and thickened, with
nodules appearing on the surface.

Microscopically, port wine stains are made up of thin-walled capillaries that are arranged throughout
the dermis. The capillaries are lined with mature flat endothelial cells. In the lesions that produce
surface growth, groups of round proliferating endothelial cells and large venous sinuses are seen.

Results following treatment of the port wine stain have up to now been uniformly disappointing.
Since most lesions occur on the face or neck, patients seek treatment for aesthetic reasons. The
simplest and still most effective method of treatment is camouflaging. Unfortunately, this is difficult
because the port wine stain is darker than the surrounding lighter skin.
Tattooing with skin-colored pigments may offer some measure of disguise in the lighter lesions but
generally is unsatisfactory because the pigment deposited in the skin looks artificial and tends to be
absorbed unevenly, producing a mottled appearance.

Superficial methods of treatment such as dry ice, liquid nitrogen, electrocoagulation, and
dermabrasion are ineffective unless they destroy the upper layers of the skin, which produces severe
scarring.

Radiation therapy, including the use of x-rays, radium, thorium X, and grenz x-rays, is to be
condemned. If it is administered in doses high enough to destroy the vessels involved, it also
destroys the surrounding tissues and the overlying skin and the cancer incidence after radiotherapy
for skin hemangioma increases. The best treatment for early port-wine stains lighter red in color is
with the laser. The pulsed dye and Candela lasers are especially useful. The beam is selectively
absorbed by red-pigmented material such as hemoglobin, and the treated area becomes whiter.
Multiple treatments are necessary to obtain a satisfactory result. In darker and more advanced
nodular lesions, the laser is less effective and probably contraindicated because of the severe
scarring and hyperpigmentation that may develop.

If the lesion is small, surgical excision with primary closure is possible. Unfortunately, most lesions
are large. Sometimes the best choice is no treatment. Certain fast-growing capillary or primarily
arterialized hemangiomas have been managed successfully with superselective embolization, either
alone or in conjunction with surgery. This is performed under fluoroscopic control and with an
expert team. There have been reports of slough of large portions of the face as a result of
misdirected embolizations.

C. Cavernous Hemangioma

Cavernous hemangiomas are bluish or purplish lesions that are usually elevated. They may occur
anywhere on the body but, like other hemangiomas, are more common on the head and neck. They
are composed of mature, fully formed venous structures that are present in tortuous masses which
have been described as feeling like a bag of worms.

Cavernous hemangiomas are usually present at birth but do not usually grow except to keep pace
with normal body growth. In many cases, growth occurs later in life and may interfere with normal
function.
Microscopically, cavernous hemangiomas are made up of large dilated, closely packed vascular
sinuses that are engorged with blood. They are lined by flat endothelial cells and may have muscular
walls like normal veins.

Treatment is difficult. In only a few cases is the lesion small enough or superficial enough to permit
complete surgical excision. Most lesions involve deeper structures—including muscle and bone—so
that complete excision is impossible without radical surgery. Since most lesions are no more than
aesthetic problems, radical surgery is rarely indicated. Occasionally, the injection of sclerosing agents
directly into the venous channels may lead to some involution or may make surgical excision easier.
Great care must be used so that areas of overlying skin do not slough.

Mulliken JB, Fishman SJ, Burrows PE: Vascular anomalies. Curr Probl Surg 2000;37:517.

Hemangioma of Infancy

EPIDEMIOLOGY Hemangioma is the most common tumor of infancy. The incidence in the newborn
nursery is between 1.0 and 2.6 percent 3 , 4 in white, black 3 and Japanese infants. 5 An incidence of
10 to 12 percent has been reported in white children by 1 year of age. 6 Hemangiomas develop in
premature infants weighing between 1500 and 2500g at a frequency equal to that in full-term
babies, whereas 23 percent of premature infants weighing less than 1000 g manifest a hemangioma.
7 Females are affected more commonly than males in a 3:1 ratio. 8 Approximately 30 percent of
hemangiomas are nascent at birth; two-thirds become apparent during the first to fourth weeks of
life. A family history of hemangioma can be elicited in 10 percent of children, but this may be more
related to the frequency in whites rather than to an inheritable predisposition. 9 The hemangioma's
initial proliferative phase of rapid postnatal growth lasts for 3 to 9 months; rarely beyond 18 months
( Fig. 103-1 and Fig. 103-2). Proliferative-phase hemangiomas express high levels of angiogenic
molecules, specifically basic fibroblast growth factor (bFGF) and vascular endothelial growth
factor/vascular permeability factor (VEGF/VPF). Enzymes involved in remodeling of extracellular
matrix, e.g., type IV collagenase, urokinase, proteases, and metalloproteinases, are also present in
the proliferative phase. There is also evidence for diminished levels of an endogenous inhibitor of
angiogenesis, interferon-ß (IFN-ß). 10 Hemangiomas represent clonal expansions of endothelial cells
that may result from somatic mutations in one or more genes regulating endothelial cell
proliferation. 11
The phase of involution occurs gradually over 2 to 6 years and is complete by the age of 7 to 10 years
1 , 12 ( Fig. 103-2 and Fig. 103-3). The rate of involution varies greatly between children and does not
correlate with the size, location, or appearance of the lesion. An increase in cellular apoptosis during
the second year of life is associated with the initiation of the involuting phase. 13 During regression,
levels of IFN-ß return to normal. Mast cells are prominent in the involuting phase, along with
upregulation of tissue inhibitor of metalloproteinase (TIMP), clusterin, and mitochondrial
cytochrome. 14 About 50 percent of children have normal skin after involution, whereas the
remainder have variable telangiectasias, atrophy, fibrofatty residuum, or scarring (particularly if
there was ulceration during infancy).

DESCRIPTION The initial signs of a nascent hemangioma can be a hypopigmented blanched macule
with or without telangiectasia (similar in appearance to a nevus anemicus) or an erythematous to
ecchymotic patch that is superficial, 5 often with an irregular surface and borders. Several large
draining veins typically radiate from the tumor. Most hemangiomas grow to between 0.5 and 5.0 cm
in diameter, whereas some involve large areas of the face, trunk, or extremities (see Fig. 103-1 and
Fig. 103-3). Eighty percent of affected infants have a single lesion, most commonly located on the
head and neck (60 percent), followed by the trunk (25 percent), and the extremities (15 percent). 8
Multiple hemangiomas occur in 20 percent of affected infants. Often these cutaneous tumors are
tiny, dome-shaped lesions associated with hemangiomas in visceral organs such as the liver.

ATYPICAL PRESENTATIONS There are several unusual presentations, including deep (subcutaneous)
hemangioma, telangiectatic hemangioma, arteriovenous malformation (AVM)–like hemangioma,
multiple cutaneous hemangiomas, and congenital hemangioma.

Deep hemangioma Deep hemangiomas (old term, cavernous hemangioma) proliferate in the lower
dermis and subcutaneous tissue without penetration of the papillary dermis. They present as a
localized, firm, rubbery subcutaneous mass that can be slightly raised with a bluish color or with
telangiectasias involving the overlying skin, or they may be deep enough that the overlying skin is
completely flat and of normal hue ( Fig. 103-4). Hemangiomas that involve the papillary dermis, and
deeper tissues have the typical bright-red surface as well as a subcutaneous component and can be
called superficial and deep hemangiomas.

Telangiectatic hemangioma Telangiectatic hemangiomas are flat or slightly elevated and deep red
with an array of superficial dilated capillaries radiating over the surface ( Fig. 103-5). This tumor
resembles a port-wine stain but involutes spontaneously with the usual time course of all postnatal
hemangiomas, leaving telangiectasias and occasionally a minor fibrofatty residuum. Extensive
telangiectatic hemangiomas can be associated with fast flow, congestive heart failure, and
ulcerations.
AVM-like hemangioma There can be a localized hemangioma with shunting, sometimes referred to
as AVM-like hemangioma. Reported complications include episodic bleeding, venous thrombosis,
and increased cardiac output and failure. 15 Involution is slow, often these tumors can be resected.
Histologic examination reveals endothelial proliferation within arteries and venous walls indicative
of persistent fast flow.

Multiple infantile hemangiomas Hemangiomas also can present as multiple small (1 to 20 mm)
lesions involving the skin alone (called benign cutaneous hemangiomatosis) or involving both the
skin and viscera (called diffuse neonatal hemangiomatosis) ( Fig. 103-6). It is unknown whether
hemangiomatosis represents multifocal involvement or metastatic spread. Visceral hemangiomas
have been reported in the lymph nodes, liver, spleen, brain and meninges, iris, retina, salivary
glands, heart, thymus, gastrointestinal tract, lung, urinary bladder, kidney, gallbladder, pancreas, and
adrenal gland. 16 Hepatic hemangiomas can be solitary or multiple and can be associated with a
mortality as high as 30 to 40 percent because of high-output cardiac failure. Involution of multiple
cutaneous hemangiomas often begins after just 3 to 6 months and is complete within 1 to 2 years—
much sooner than with the more common solitary lesions. 16

Congenital hemangioma Hemangiomas can develop in fetal life, proliferate in utero and present as
fully formed tumors at birth. This is the definition of a congenital hemangioma. Congenital
hemangiomas can be subdivided according to natural history into rapidly involuting congenital
hemangiomas (RICH) and noninvoluting congenital hemangiomas (NICH). It is not clear whether or
not these two subtypes are really the same vascular tumor that behaves differently because of
prenatal and postnatal influences. The important observation is that there is no rapid proliferation in
the neonate. Curiously, neither RICH nor NICH have the marked female preponderance of common
infantile hemangiomas.

RAPIDLY INVOLUTING CONGENITAL HEMANGIOMAS RICH present as violaceous hemispheric

nodules with overlying telangiectasia, pale dusky borders, and large veins at the periphery (see Fig.
103-2). Alternatively, they may appear as firm, erythematous to violaceous plaques infiltrating the
dermis or subcutaneous tissue. Regression becomes obvious in early infancy, resulting in
disappearance of these lesions more rapidly than common hemangiomas that regress postnatally
(by 14 months versus 5 to 9 years). Approximately 50 percent of RICHs involute prior to 7 months of
age. 12

NONINVOLUTING CONGENITAL HEMANGIOMAS NICH are uncommon vascular lesions that grow
proportionately with the child and do not regress. NICH have many similar features to RICH in
appearance, size, and location. Characteristic features of NICH include coarse overlying
telangiectasia, pale halos at the rims, and intermingled areas of pallor ( Fig. 103-7). Lesions have an
average diameter of 5 cm and are located (in order of frequency) on the head/neck, extremities, and
trunk. Radiologic studies, specifically Doppler and arteriography, demonstrate fast flow.
Histologically, NICH differ from common involuting hemangiomas in several ways, including larger
and more irregular intralobular vessels, higher cellularity, and multiple microscopic arteriovenous
fistulas. Excision is generally the treatment of choice. 17
ASSOCIATED STRUCTURAL ANOMALIES Hemangiomas are rarely associated with underlying
anomalies, and in these unusual cases, a marked female preponderance has been documented.
Large cervicofacial hemangiomas may present with (1) ocular abnormalities such as microphthalmia,
congenital cataract, and optic nerve hypoplasia, (2) sternal nonunion and supraumbilical raphe, (3)
arterial abnormalities such as persistent embryonic intra- and extracranial embryonic arteries,
absence of ipsilateral carotid/vertebral vessels, and coarctation of a right-sided aortic arch, and (4)
posterior fossa malformations, including the Dandy-Walker malformation. The acronym PHACE has
been proposed as an mnemonic for these associations: posterior fossa malformations, hemangioma
(especially a segmental lesion), arterial abnormalities, coarctation of the aorta, and eye
abnormalities. 18 However, this term does not include other structural anomalies that can be
associated with hemangiomas. For example, lumbosacral hemangiomas may signal the presence of
spinal dysraphism and should be evaluated by magnetic resonance imaging (MRI). These
hemangiomas are often clinically distinctive, being telangiectatic, macular, or diffuse, sometimes
with an acrochordon. Pelvic and perineal hemangiomas may be associated with urogenital and
anorectal anomalies (e.g., anterior or vestibular anus, hemiclitoris, atrophy or absence of the labia
minora, and hypospadias).

DIAGNOSIS Hemangiomas almost always can be diagnosed accurately by clinical presentation and
history alone. The hemangioma is nonblanching and is firm to rubbery on palpation. In some infants
with ambiguous, atypical, or deep lesions, observation of change over time or radiologic
investigation is necessary to confirm the diagnosis. Biopsy of any vascular lesion is indicated
whenever there is the slightest suspicion of malignancy. Ultrasonography with color flow imaging is,
in experienced hands, a useful and cost-effective method, 19 but it does not portray the extent of
the lesion or its relation to adjacent structures. MRI provides the most useful information, including
exact localization, extent of involvement, and with midline lesions the presence of associated cranial
or spinal dysraphism. MRI is also useful for differential diagnosis of an atypical lesion, since
hemangiomas have an appearance on MRI distinct from vascular malformations, dermoid cysts,
meningoceles, and other benign and malignant infantile tumors. Computed tomography (CT) is less
informative than MRI because it cannot distinguish between fast-flow and slow-flow lesions,
although it does display skeletal abnormalities. These noninvasive imaging techniques have
essentially replaced arteriography. High endothelial immunoreactivity for the erythrocyte-type
glucose transporter protein GLUT1 is observed in hemangiomas of infancy in all phases as well as in
other microvessels of blood-tissue barrier function, including brain and placenta. Vascular
malformations do not exhibit any GLUT1 immunoreactivity. 20 GLUT1 may provide a diagnostic tool
to differentiate hemangioma from vascular malformation. RICH and NICH do not stain with
antibodies to GLUT1, however.

COMPLICATIONS Potential problems in the proliferative phase include ulceration; bleeding;

infection; distortion of the cornea; obstruction of the visual axis, nasal passages, larynx, or auditory
canals; congestive heart failure; skeletal distortion; and rarely, skeletal overgrowth. Spontaneous
ulceration, bleeding, and secondary infection occur in approximately 5 percent of superficial lesions
and are seen most often in hemangiomas involving the lips and genital areas, where abrasion is
common. Rarely, ulceration and subsequent infection can result in extensive necrosis and
destruction of facial soft tissues and the cartilaginous framework of the nose or ear. Hemangiomas in
the upper eyelid can obstruct the visual axis, resulting in deprivation amblyopia and failure to
develop binocular vision ( Fig. 103-8). Obstruction need be present for only 1 to 2 weeks to cause
blindness. More important, even a small hemangioma in the upper eyelid or supraorbital region can
distort the cornea, leading to refractive errors, both astigmatic and myopic. Periorbital
hemangiomas require prompt consultation with a pediatric ophthalmologist. Another ocular
complication is strabismus, an abnormal alignment of the eyes due to amblyopia or to infiltration of
the extraocular muscles by the hemangioma.

Blockage of the nasal passages typically develops so gradually that the infant adapts by breathing
through the mouth. However, subglottic obstruction can be life-threatening. It develops insidiously,
manifesting as biphasic stridor with or without respiratory distress. A child with a subglottic
hemangioma often presents with a mistaken diagnosis of laryngotracheitis or multiple episodes of
croup. Half of infants with subglottic hemangiomas have an associated cutaneous tumor in the
cervicofacial skin. 1 Furthermore, infants with a cutaneous hemangioma in a beard distribution
(preauricular areas, chin, anterior neck, and lower lip) are at increased risk for upper airway or
subglottic involvement. 21 High-output failure is another potentially life-threatening complication. It
is usually associated with multiple hepatic hemangiomas; however, it also can occur with a single
large cutaneous hemangioma. The proliferation of a hemangioma within the vascular hepatic
parenchyma produces the hemodynamic changes characteristic of a large left-to-right shunt. Hepatic
hemangiomas can be single or multiple; the latter are often associated with multiple small (2 to 15
mm in diameter) hemispherical cutaneous hemangiomas. Liver hemangiomas can also occur in the
absence of cutaneous lesions. Infants with multiple hepatic tumors present within the first 16 weeks
of life with a clinical triad of hepatomegaly, congestive heart failure, and anemia. 22 The rare infant
with a hepatic arteriovenous malformation or a single large hepatic hemangioma typically presents
at birth with the same triad.

TREATMENT The decision to treat a hemangioma is based on many factors, including size and
location of the lesion, psychosocial implications, and risks and benefits of the proposed therapy. For
the majority of small hemangiomas, active nonintervention is the most appropriate approach. This
does not mean doing nothing. The parents need a thorough explanation of the natural history of
their child's hemangioma, including photographs of the likely outcome for a similar lesion. The infant
should be seen frequently, and the parents must be reassured constantly. Over the past decade,
there has been an increase in parental pressure for intervention. Treatment is probably indicated in
about 25 percent of hemangiomas—the 5 percent that ulcerate; the 20 percent that compress,
distort, or obstruct vital structures such as the eyes, nose, ears, or larynx; and the less than 1 percent
of truly life-threatening tumors. Ulceration is managed with gentle cleansing and application of
topical antibiotics and barrier creams. Bioocclusive dressings may be helpful, especially in the
anogenital area, where the tumor is frequently contaminated. Systemic antibiotics are used for
infection. Other modalities for treatment of ulcerated hemangioma include intralesional and
systemic corticosteroids, excision, and interferon-a. Pain may be controlled with topical lidocaine
ointment and oral acetominophen with or without codeine. Ulcerations generally heal within 2 to 3
weeks with topical care, leaving a scar. Treatment with the pulsed-dye laser may reduce healing time
and pain; one study reported that 50 percent of ulcerated hemangiomas treated with pulsed-dye
laser showed a definite improvement, but 18 percent showed no change, and one hemangioma
showed definite worsening. 23

Pharmacologic therapy Intralesional glucocorticoids can be used for small hemangiomas (1 to 2 cm)
localized to critical sites such as the lip, nasal tip, cheek, or ear. Triamcinolone is injected slowly and
at low pressure at a dose of 3 to 5 mg/kg every 4 to 6 weeks for 1 to 5 total injections. Injection into
an upper eyelid hemangioma carries a slight risk of retrobulbar hematoma, and there are two case
reports of microvascular embolism causing blindness due to occlusion of the central retinal artery.
24 , 25 Glucocorticoid injections also can be effective in the treatment of minor ulceration. The
response rate for intralesional steroid injections is the same as for systemic steroid therapy. 26 The
high-potency topical steroid clobetasol propionate may be used to treat small superficial lesions. 27
Systemic glucocorticoids are the first-line pharmacologic treatment for deforming, endangering, or
life-threatening hemangiomas. Prednisone or prednisolone is given at a dose of 2 to 3 mg/kg per day
for 4 to 6 weeks, after which time the dosage is tapered gradually for several months. If the drug
dosage is lowered or stopped before the age of 8 to 10 months, rebound growth often occurs. The
response to oral glucocorticoids is excellent, with approximately 84 percent showing accelerated
involution or cessation of growth (response rate) with a mean prednisone equivalent daily dose of
2.9 mg/kg given over 1.8 months 28 (see Fig. 103-8). The optimal dosage is controversial. Response
is 75 percent with a dosage of prednisone between 2 and 3 mg/kg per day, whereas a dosage higher
than 3 mg/kg results in a response as high as 94 percent but greater adverse effects. Dosages lower
than 2 mg/kg per day result in a 69 percent response rate, but the rebound rate (enlargement after
tapering after response occurred) is 70 percent. If there is no response after 2 to 3 weeks of therapy,
the tumor is unlikely to respond to a higher dose, and the glucocorticoids should be discontinued.
Short-term complications of glucocorticoid therapy include cushingoid facies (71 percent),
personality changes (29 percent), gastric irritation (21 percent), fungal infection (oral or perineal, 6
percent), and diminished gain of height (35 percent) and weight (42 percent) during treatment. Over
90 percent of children with diminished gain of height return to their pretreatment growth curve for
height by 24 months of age. 29 Interferon-a2a and -2b are indicated in the treatment of endangering
and life-threatening hemangiomas, specifically for tumors unresponsive to glucocorticoids. The drug
is given subcutaneously at a dose of 3 million U/m 2 daily for 6 to 12 months. 30 , 31 Side effects
include transient fever, neutropenia, and minor elevations in liver enzymes. Spastic diplegia
develops in approximately 5 to 10 percent of infants treated with interferon. 32 The neurologic signs
are reversible after stopping the drug. Obviously, periodic neurologic examination is indicated during
treatment.

Laser therapy Treatment of hemangiomas with the flash-lamp pulsed-dye laser has been a subject of
considerable controversy over the past decade. This laser uses a wavelength of 585 nm, specific for
the absorption of oxyhemoglobin, the treatment target. In addition, the pulse duration is extremely
short (400 ms), allowing for effective coagulation of vessels without extensive thermal diffusion to
surrounding tissue that could result in scarring. Histologically, the flash-lamp pulsed-dye laser
produces selective intravascular and perivascular coagulation necrosis, seen clinically as purpura. On
resolution of the purpura, histologic examination shows an absence of dermal ectatic vessels and an
otherwise normal unaltered epidermis and dermis. With darker skin types, laser treatment can cause
damage to melanocytes in the basal cell layer, resulting in hypopigmentation. It is generally accepted
that the pulsed-dye laser is the treatment of choice for residual telangiectasias during or after
involution. More controversial is the treatment of a proliferating hemangioma or a precursor lesion
in an effort to prevent or diminish growth. Laser treatment of the superficial dermal component of
the tumor has no effect on proliferation of the deeper component. 33 Thus laser treatment is
ineffective in reducing the bulk of deep hemangiomas. 34 Some authors think that laser treatment
can accelerate involution and diminish the growth phase if therapy is begun early enough; however,
this has not been substantiated by controlled trials. Laser treatment is most effective in
telangiectatic-type hemangiomas, and it typically results in complete clearing of the lesion after a
mean of two laser sessions. 34 However, it is important to remember that telangiectatic
hemangiomas are generally macular or slightly elevated—the very tumors that tend to regress
spontaneously leaving minimal to no residua. 35 Potential side effects of pulsed-dye laser treatment
include ulceration with scarring and hypopigmentation that becomes evident only after regression.
The pulsed-dye laser should be considered in the treatment of ulcerated hemangiomas. One small
pilot study showed that 6 of 10 ulcerations healed after a single laser treatment, and pain was
subjectively decreased in all patients within 2 to 3 days after one treatment. 36 Controlled trials are
needed to confirm these findings.

Surgical therapy Surgical resection may be indicated at any time during the life cycle of a
hemangioma. Excision is often necessary for fibrofatty tissue and abnormal skin after involution
(when the child is 8 to 12 years old). Surgical intervention in early childhood should be considered
for special situations. For example, a localized pedunculated hemangioma on the upper eyelid
unresponsive to pharmacologic therapy sometimes can be totally excised, thereby quickly correcting
astigmatism. An ulcerated hemangioma that bleeds frequently and is largely necrotic can take as
long as 4 to 8 weeks to heal and is often associated with significant pain. Such tumors may be
excised, leaving a scar that is likely to be more cosmetically acceptable than the scar resulting from
natural regression. 35 Surgical excision should be considered during the preschool age, before the
child begins to manifest a facial or body image. A spheroidal hemangioma in the nasal tip usually
causes cutaneous expansion and splayed alar cartilages. For psychosocial reasons, subtotal excision
to improve nasal contour should be considered during early childhood. Hemangiomas of the
vermilion border, glabella, eyebrow, and eyelid ( Fig. 103-9) often are excised prior to the child's
entry into school. In some instances, it is best to wait until regression is nearly complete before
resecting the fibrofatty residuum or atrophic skin. In summary, excision in early childhood is
indicated (1) if it is obvious that resection is inevitable (because of postulcerative scarring
unalterably expanded skin, or likely fibrofatty residuum), (2) if the scar would be the same length or
appearance if excision were postponed, and (3) if the scar can be easily concealed. 35

PYOGENIC GRANULOMA

Clinical manifestations Pyogenic granuloma is a rapidly developing vascular lesion that often arises at
sites of minor trauma; it may represent a reactive phenomenon. Pyogenic granuloma is common.
Lesions are solitary, small (average size 6.5 mm), eroded papules or nodules that bleed
spontaneously or after trauma ( Fig. 103-11). Common locations include the face, fingers, toes, and
trunk. Pyogenic granuloma rarely appears prior to 6 months of age; mean age at presentation in
children is 6.7 years. 40 Pyogenic granuloma frequently presents in adults. The lesions can appear
within an existing capillary malformation (port-wine stain), but most commonly there is no history of
a preexisting dermatologic condition.
Pathology Histopathology reveals well-circumscribed lobular aggregates of proliferating capillaries
within an edematous stroma infiltrated by numerous neutrophils. The epidermis is often eroded.

Treatment Treatment is by surgical excision or curettage with electrodesiccation of the base. Smaller
lesions (<5mm) in cosmetically important areas can be treated with the pulsed-dye laser. Other rare
vascular proliferations 41 , 42 , 43 , 44 , 45 , 46 and 47 are summarized in Table 103-3.