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VASCULAR TUMORS
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Hemangiomas and vascular malformations are the most common congenital lesions
noted in infancy.
Definitions
Hemangiomas - a vascular tumour with increased endothelial turnover during the
proliferative phase of development that may involute by progressive cellular death and
fibrosis
Vascular malformations - errors in morphogenesis populated by a stable, mature
vascular endothelium. Divided into subtypes based on their flow characteristic and
also on the constituent vessel. They are present at birth and grow commensurately with
the child and don’t involute
Classification International Society for the Study of Vascular Anomalies
1) Vascular tumors
a. Hemangioma
b. kaposiform hemangioendothelioma,
c. tufted angioma.
d. Hemangiopericytomas
e. Malignant - angiosarcoma
2) Vascular malformations
a. capillary,
b. venous
c. lymphatic
d. arteriovenous malformations (AVM).
e. Mixed
Also high vs low flow; diffuse vs localised
Hemangiomas
Definition
 Hemangiomas are proliferative lesions characterized by increased endothelial
turnover
 Tumours usually appear after birth grow rapidly and involute over years
Types
1. congenital hemangioma (Mulliken Clinics 2005)
 rare, present at birth
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Two subtypes – rapidly involuting and noninvoluting
Noninvoluting grows commensurate with child, does not proliferate or involute
and may be mistaken for a AVM
2. Infantile hemangioma
 majority of hemangiomas
 appear in the first 3 months of life.
 exhibit the classic stages of early, rapid proliferation followed by slow
involution over 5 to 7 years.
Incidence
 Most common tumour in infancy
 2-3% of all neonates, Affects 12% of white kids before age of 1 yr
 Less common in Asians and blacks with incidence of approx 1%
 high incidence in premature births - 23% of infants <1000g
 F>M 2-5:1 (in comparison to 1:1 seen in congenital hemangiomas, kaposiform
hemangioendotheliomas, and vascular malformations)
 Even higher female preponderance for problematic hemangiomas
 majority sporadic
 Small group of familial hemangiomas that follow autosomal dominant inheritance
with locus on 5q
Presentation
 tend to be rubbery, firm, well-circumscribed lesions.
 Telangiectases and large superficial veins radiating from the hemangioma often are
associated.
 As hemangiomas proliferate, depending on their size and depth, their morphology and
texture may be dome-shaped, bosselated, plaquelike, tumoral, or any combination of
these morphologies
 The telangiectatic variant may be confused with a capillary malformation; however,
the rapid growth characteristics assist in differentiation..
 When they develop in the superficial dermis, the proliferation of cells causes the
skin to become raised and bright red.
 In contrast, lesions in the deeper dermis or subcutaneous tissues may be less
demarcated, and they may have a bluish hue.
 Historically, these were thought to be different lesions and thus were termed capillary
or capillary-cavernous hemangiomas, reflecting supposedly different histology.
 Histologic evaluation has revealed considerable consistency in endothelial cell
proliferation, regardless of tumor depth. Therefore, hue is more indicative of lesion
depth than histology.
Distribution
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Hemangiomas can be superficial, deep or visceral in location
Skin most common site
80% have 1 lesion; 20% have >1 lesion
60% occur in head and neck; 25% on the trunk, and 15% on the extremities
Superficial lesions exhibit a classic crimson colour -strawberry hemangioma
Those within the deep dermis or sub cut tissue often present as pale blue or purple
masses that may be confused with venous malformations
Visceral lesion are not apparent on physical exam - 50% of cases have no cutaneous
hemangiomas and only suggested by signs of hepatomegaly.
o Large cutaneous or visceral hemangiomas (particularly liver) can result in
high-output cardiac failure due to increased vascular flow.
Disseminated neonatal hemangiomatosis
o Widely disseminated, 2 to 15 mm, red to blue-black papular hemangiomas
present at birth
o Gastrointestinal, hepatic, central nervous system and pulmonary visceral
hemangiomas may be present, and high-output cardiac failure may occur by
two to nine weeks of age
o Treatment includes hepatic lobectomy (if the liver is involved), vessel ligation
or embolization, high-dose corticosteroids (2 to 4 mg per kg per day),
interferon alfa-2a and treatment for high-output cardiac failure. Lesions
spontaneously involute in some patients.
o child with multiple miliary haemangiomas need to be screened early and often
for the development of visceral lesions (especially liver)
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Lumbosacral hemangiomas
o cutaneomeningospinal angiomatosus
o associated with tethered spinal cord or abnormalities of the anorectal or
urogenital regions.
o hemangiomas are flat and span the midline.
o Radiographic imaging of the pelvis should be obtained to identify associated
anomalies
o Neurologic symptoms usually develop in later childhood or adolescence, but
early spinal angiography may detect spinal angiomas, which may be
surgically excised more easily before they have enlarged.
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Beard area hemangiomas
o Infants with large V3 dermatomal hemangiomas (beard area hemangiomas)
have a higher incidence of upper airway hemangiomas,
o consultation for mild signs or symptoms (noisy breathing or stridor) may
prevent possible future complications.
(Above) Proliferating hemangioma obstructing the visual axis at 2 months of age. (Center) Rapid
improvement with oral and intralesional steroid therapy. (Below) At 1 year of age, there is a residual
subcutaneous mass, atrophy, and telangiectasia.
Natural history
1. Herald spot
o Occurs in 30-50%
o Typically appear within the first 2 months of life
o small, well demarcated pale patch, an erythematous macular patch, or a small
area of telangiectasia surrounded by a pale halo.
2. Proliferative phase (<1 year)
o rapid enlargement out paces the growth of the child.
o characterized by bright crimson coloration that gives rise to strawberry
appellation
o Palpation at this stage reveals a tense non compressible mass with draining
veins frequently seen around the periphery
o Expansile growth starts at 3 months and continues for 4-8 months before
plateauing
3. Involuting phase(1-6 years)
o begins at 12 months and continues over the next 5-7 years
o characterized by a decrease in cellularity and tumour size, formation of larger
vascular channels, fibrofatty replacement and the development of a lobular
architecture with septae.
o One of the first signs of involution is the changing of the bright red color to
a darker red. The may be followed by a gray appearance to the surface
with small white spots appearing, process called ‘graying’. Colour change
may be difficult to appreciate in deeply seated heamangiomas
o hemangioma shrinks centrifugally from the center of the lesion
o The skin becomes less tense with wrinkling as the lesion involutes.
o Involution and proliferation may be seen simultaneously within different part
of a given lesion or among hemangiomas in children with multiple lesions
4. Involuted phase (>6years)
o 50% of hemangiomas involuted by age 5
o 70% of hemangiomas involuted by age 7
o The remainder tend to improve until the age of 12
o Even with complete involution signs of hemangiomas may persist as residual
tumour, telangiectases, superficial dilated veins, stippled scarring, anetoderma
or epidermal atrophy (particularly with superficial lesions), hypopigmentation,
and/or redundant skin with fibro-fatty residua (especially with subcutaneous
lesions).
o Rate or completeness of involution is not influenced by lesion size, location,
ulceration, depth, sex or age of presentation
o An early onset of involution is the only factor associated with improved
outcome. Of lesions that have involuted by age 6 years, 38% will have
residual evidence with scar formation, telangiectasia, or redundant or
anetodermic(cutaneous laxity) skin.
Associated conditions
PHACES
 Large cervicofacial hemangiomas have been associated with other malformations
in 10% of cases
o P - Post cranial fossa malformation
o H – Hemangioma (large segmental plaque-like hemangioma on face)
o A - Arterial anomalies
o C - Cardiac anomaly (coarctation
o E - Eye anomalies (choroidal hemangiomas, cryptophthalmos,
exophthalmos, colobomas, posterior embryotoxon, optic atrophy,
microphthalmos, strabismus, and optic nerve hypoplasia, glaucoma)
o S - Sternal cleft
 The majority of patients are girls and are prone to occlusive cerebrovascular
accidents at early stage
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Should be evaluated for CNS, arterial, cardiac and ocular abnormalities in the first
weeks of life. Head MRI and MRA, Chest MRI, cardiac ultrasound and head
sonogram should be considered for all such infants.
Multidisciplinary team
Facial hemangioma responds to high dose oral steroids but regrowth after tapering
of dose is common.
Combination of laser and interferon alpha-2a has been successful
Maffucci Syndrome
 Features:
o Enchondroma (30% risk of chondrosarcoma)
o Hemangiomas -manifest as blue subcutaneous nodules that can be emptied
by pressure. The hemangiomas can be unilateral or bilateral and are
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usually asymmetric. Thrombi often form within vessels and develop into
phleboliths. These phleboliths appear as calcified vessels under
microscopic examination.
o Venous-lymphatic malformations can occur but are much less common.
Rare – 160 case reports (but may be under-reported as Ollier’s disease)
No racial or sexual predilection is apparent.
No familial pattern of inheritance has been shown
The disease appears to develop from mesodermal dysplasia early in life.
Patients apparently are of average intelligence, and no associated mental or
psychiatric abnormalities seem to be present
Histology
proliferative phase
 nonencapsulated masses and dense cords of mitotically active, plump
endothelial cells in close association with pericytes
 thickened, multilaminated basement membranes
 elevated mast cell concentrations - proliferating-phase hemangiomas display a
10-fold increase in mast cell concentration over involuting lesions and normal
tissue.
 Elevated urinary markers of angiogenesis – bFGF and high molecular weight
matrix metalloproteinases
Involuting phase
 increase of apoptotic endothelial cells and a decrease in plump, mitotically
active endothelial cells herald the involution phase.
 cellular parenchyma is replaced by fibrofatty tissue.
Involuted phase
 few tiny capillary-like feeding vessels and draining veins surrounded by island of
fibrofatty tissue admixed with dense collagen and reticular fibers.
 Multilaminated basement membranes persists around the residual tiny capillary
vessels
Summary
 Proliferation is characterized by increased levels of basic fibroblast growth
factor and vascular endothelial growth factor.
 Involution is characterized by endothelial apoptosis and the downregulation of
angiogenesis and is correlated with the accumulation of mast cells and the
increase of the tissue inhibitor metalloproteinase
Pathogenesis
Theories
1. Nonendothelial cells
 Stromal cells - release vascular endothelial growth factor (VEGF).
 Dendritic cells – cytokines
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2.
3.
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6.
Mast cells – express fibroblast growth factor 2 (FGF2), a potent
angiogenic polypeptide and VEGF. Probably play a complex role
involving stimulation of angiogenesis in the proliferative phase and
inhibition of angiogenesis in the involuting phase
Angioblast theory
 hemangiomas develop from embryonic sequestrations of omnipotent
angioblastic cells.
 angioblastic cells form an anlage that fails to connect to the normal
vascular system and develops into a hemangioma
Developmental field defect
 From observations of striking segmental patterns for facial hemangiomas
with a predilection for regions of embryological fusion
 Also association with other defects as in bearded distribution, lumbosacral
hemangioma or PHACES
Placental origin
 Sharing of several immunological markers (GLUT-1, Lewis Y antigen)
has prompted the suggestion that hemangiomas may originate from
embolization of placental cells
 expression of the erythrocyte-type glucose transporter molecule GLUT1 –
normally found only in the microvascular endothelia of blood tissue
barriers of the central nervous system and the placental trophoblast. It is
not present in the vasculature of normal skin and subcutis, but it is highly
expressed in the capillary endothelium of hemangiomas.
 No other benign vascular tumors, reactive vascular proliferations, or
vascular malformations show GLUT1 expression
 universal trait of hemangiomas, irrespective of mitotic activity, phase, or
anatomical location
 chorionic villus sampling is associated with a three- to fourfold increased
incidence of hemangiomas in children born to women who underwent this
procedure vs amniocentesis, which does not involve a placental disruption
and does not influence the risk for hemangiomas
Derangement of angiogenesis
 caused by unregulated angiogenesis or an imbalance between angiogenic
and angiostatic factors.
 Key growth factors in angiogenesis include VEGF and basic fibroblast
growth factor (bFGF).
 Tissue inhibitor of metalloproteinase 1 is an inhibitor of angiogenesis expressed in involuting hemangiomas but not in proliferating
hemangiomas
Mutation in cytokine regulatory pathway
 hemangioma proliferation is caused by aberrant upregulation of VEGF
and bFGF pathways
Diagnostic imaging
 Hemangiomas can be differentiated from other vasc malformations by CT, MRI, and
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angiography
Although hemangiomas can be diagnosed on clinical ground in over 93 % of cases
diag imaging can be useful:
1. difficult lesions and in preoperative planning
2. visceral involvement
3. assess treatment efficiency
4. define associated anomalies
MRI with and without intravenous gadolinium
 imaging modality of choice
 delineates the location and extent of both cutaneous and extracutaneous
hemangiomas.
 helps in differentiating other high-flow vascular lesions (eg, arteriovenous
malformations vs proliferating hemangiomas).
 Involuting hemangiomas have features that resemble low-flow lesions (eg, venous
malformations).
 On T1 images hemangiomas are iso and hypo intense to muscle
 With T2 images they are hyper intense
 Hemangiomas demonstrate intense homogenous contrast enhancement with IV
gadolinium
Ultrasound
 useful in differentiating hemangiomas from other deep dermal or subcutaneous
structures, such as cysts or lymph nodes.
CT
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demonstrate a distinctive soft tissue mass that enhances with contrast
Angiography
 reserved for equivocal cases or in pts undergoing therapeutic embolization
 They appear as well described masses with persistent, intense parenchymal
staining.
 Equatorial vessels are also seen and represent feeding arteries and draining veins
 During the proliferative phase hemangiomas appear as high flow lesions which
gradually diminish with involution
Differential diagnosis
1. Macular stains
2. Vascular malformations
3. Other vascular tumours of infancy
Diagnosis obvious in 93% of case on clinical basis but occasionally biopsy and
radiology tests may be needed
Macular stains (angel’s kiss, salmon patch, stork bite)
 The most common birth mark is the macular stain
 flat lesions ranging from pink to red
 40% of newborns
 Typical in the neck, glabella eyelid and forehead
 These are thought to be physiological phenomena that resolve with time
 If don’t resolve yellow green laser treatment is effective for lesions that persist
Vascular malformations
 Vascular malformations are a result of errors of morphogenesis and may be
categorized based on the constituent vessel ie
1. capillary
2. venous
3. Arterial
4. Lymphatic
5. And combined
They may be further categorized based on the flow characteristics into
1. High flow
2. Low flow malformations
Distinguishing features
 Males and females equally affected
 All present at birth as errors in morphogenesis
 May not be recognized at birth
 The appearance depends on the vessel involved
 Grow commensurately with the child and don’t undergo the rapid proliferative phase
of hemangiomas
 Sensitive to hormonal modulation and may show rapid enlargement in pregnancy and
puberty
 Infection and trauma can cause rapid periods of enlargement
 They don’t spontaneously involute
 Malformation do not show the parenchymal staining seen with hemangiomas on CT
scan and MRI and are less distinct and consist of multiple ectatic channels
 Histological exam- vascular channels with normal endothelium
 Mast cells, growth factors and cellular markers are present in normal numbers and
distribution
 Treatment is different as they are not proliferative lesions and the antiangiogenic
agents such as corticosteroids and interferon are ineffective
 Sclerosis and embolization are curative or may control some malformations
Other vascular tumours of infancy
Pyogenic granuloma (Lobular Capillary Hemangioma)
 Acquired vascular lesion that closely resembles a hemangioma clinically and
histologically
Incidence
 Occur in the skin and mucosa of older children and young adults with a mean
age of 6.7 years.
 F>M.
 Common in pregnancy particularly on the gingiva or elsewhere in the oral
mucosa, and then is termed the "pregnancy tumor." (up to 5% of pregnancies)
 Other pyogenic granuloma variants include the disseminated, subcutaneous,
intravenous, and systemic medication (retinoid and protease inhibitor; OCP)induced subtypes.
Aetiology
 Arise suddenly and usually without history of trauma.
 precise mechanism for the development of pyogenic granuloma is unknown.
 Trauma, hormonal influences, viral oncogenes, underlying microscopic
arteriovenous malformations, and the production of angiogenic growth factors
have all been postulated to play a role.
 A nitric oxide synthase–dependent mechanism is thought to contribute to
angiogenesis and the rapid growth of PGs
Location
 most often on the head/neck(62%), upper trunk(20%), upper extremities(13%),
and lower extremities (5%)
 can occur within capillary malformations(port wine stains)
 Aside from cutaneous(88%) and oral lesions, pyogenic granuloma has been
reported throughout the gastrointestinal tract, the nasal mucosa, the larynx, and
the conjunctiva and cornea.
Macro
 May be sessile or pedunculated with narrow stalk
 Prone to bleeding or ulceration
Histologic Findings
 The histopathologic findings in all variants of pyogenic granuloma are similar.
 Early lesions resemble granulation tissue - numerous capillaries and venules with
plump endothelial cells arrayed radially toward the skin surface amidst an
edematous stroma containing a mixed inflammatory infiltrate
 There often is overlying erosive or ulcerative change.
 The matured polypoid lesion exhibits a fibromyxoid stroma separating the lesion into
lobules. Reepithelialization of the surface and a peripheral hyperplastic adnexal
epithelioid collarette may be noted, and less inflammatory infiltrate is present.
 regressing pyogenic granuloma displays extensive fibrosis.
 The intravenous variant has less lobulation and is connected to the wall of a vein by a
stalk.
Clinical
 Grows rapidly over several weeks then stops (average size 6.5mm)
 May have a history of trauma
 Course marked by superficial ulceration ad repetitive episodes of bleeding thus called
the band aid diagnosis
 5% of pregnant women; usually 2nd or 3rd trimester – often along maxillary buccal
surface
Treatment
 Stop offending medication
 Silver nitrate (small lesions only – high recurrence rate)
 Electrocautery
 Laser ablation - pulsed-dye laser at vascular-specific 585 nm is very selective,
 Excision – shave, punch, excise
o If shave biopsy,curettage with electrodessication to the base decreases the
likelihood of recurrence
o Full thickness skin excision gives the lowest chance of recurrence
 Many lesions occurring in pregnancy resolve with parturition; because recurrences
are higher during pregnancy, postpone removal until after delivery.
 Recurrence rate 40-50%
Kaposiform hemangioendothelioma
 Aggressive vascular tumour of infancy that
is frequently associated with severe
thrombocytopenia, petechia and bleeding –
known as Kasabach-Merritt syndrome
 Kasabach merritt originally described this
bleeding disorder in conjunction with a
giant hemangioma but it has recently been
recognized that this coagulopathy does not
occur with the common hemangioma of
infancy but accompanies kaposiform
hemangioendothelioma or tufted angioma
(PRS 1997 Mulliken)
Clinical
 50% present at birth
 equal gender distribution
 Predilection for trunk, extremities and
retroperitoneum, rarely in cervicofacial
region
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Undergoes slow regression
Distribution - Trunk, extremity, and retroperitoneum
Lesions show rapid expansion
May appear as a bruise
Macro
 Cutaneous form often has a purple, indurated appearance
Histological appearance
 characterized by poorly formed slit-like vascular channels lined by irregular
spindled or less rounded endothelial cells.
 Channels contain microthrombi, hemosiderin and fragmented erythrocytes.
Pathophysiology
 triggers
1. intravascular coagulation with platelet trapping and activation
2. consumption of coagulation factors
 Platelet consumption early in life
 Mortality is high with retroperitoneal tumours or when complicated by K-M
syndrome (10-40%)
 The chronic consumptive coagulopathy seen in low flow vascular malformation is
different – this leads to consumption of coag factors but platelets remain normal.
Heparin is used to treat this unlike in KM syndrome.
Treatment methods
 Need involvement of haematologist, neonatal intensivist, pediatrician
1. Corticosteroids
o 1st line treatment. Variable success; oral or IV
2. Alpha interferon
o Second line
o Risk of spastic diplegia
3. Chemotherapy
o Second line
o Vincristine
4. Embolization
5. Ticlopidine
6. Aspirin
7. Radiation
o Abandoned due to lack of success and late sequelae
8. Excision
9. Often combination treatment used
Heparin should not be used for thrombocytopenia of K-M syndrome as it can cause
release of fibroblasts growth factor and may be associated with accelerated tumour
growth
Tufted angioma
 May represent a pathological spectrum with kaposiform hemangioendothelioma
 Both may be found in the same patient
 Associated with development of K-M syndrome.
Congenital hemangiopericytoma
 Rare vascular tumour consisting of benign pericytes typically located in the extremity
of new born and young
 biopsy may be required for diagnosis
 Excision is indicated if the lesion does not spontaneously involute
Angiosarcoma
 Vascular tumours that are uncommon in children
 Usually arise in the liver and frequently mets to lung
 Poor prognosis
Complications
Ulceration
 Most common complication - occurs in 5-15% of cases
 often involves perioral and perineal lesion
 inevitably leads to scarring, also pain, infection, bleeding
 superficial ulceration usually respond to wound care, duoderm over topical
lignocaine, compression, pain relief and topical antibiotics ointment
 Deeper ulcerations may require steroids
 Excision of ulcerated lesions may be indicated if painful and lesion small
 BJPS 2003 - found the pulse dye laser effective for the alleviation of pain,
decreasing infection, and decreasing bleeding by promoting the epithelialisation of
the ulcer. There were no long-term complications.
Infection
 May develop in the presence of ulceration
 Local wound care
 Topical antibiotics
 Systemic antibiotics reserved for cellulitis
Visual impairment
 Periorbital hemangiomas may cause visual impairment by
1. obstructing the visual axis
2. distorting the cornea - astigmatism
 Optic cortex extremely sensitive to stimulus deprivation and during the first year of
life
1. ptotic eyelid closure may cause amblyopia
2. Anisometropia (differential refractive power) due to astigmatism will also
lead to moderate amblyopia
3. Proptosis may occur from intraconal lesions
4. Strabismus may occur through the involvement of the extraocular muscles
5. exposure keratitis (4%)
6. optic nerve atrophy due to compression (2%)
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Lesions that compromise vision should be treated urgently
Patch unaffected eye if there is a delay in treatment
Corticosteroids are used initially
Direct injection does not have a faster onset of action and requires a GA and in the
periorbital region has been associated with specific complications which include
blindness, globe penetration and eyelid necrosis
Recent use of laser (neodymium:yttrium-aluminium garnet lasers)report significant
regression of the hemangiomas but high incidence of ulceration thus must use in
combo with steroids
Airway obstruction
 Infants are obligate nose breathers thus intranasal hemangiomas may cause insidious
airway obstruction
 50% have cutaneous hemangioma usually in beard distribution
 Usually occurs between 4-12 weeks of age
 Sub glottic lesions often present with stridor and cause life threatening obstruction beware a beard cutaneous distribution
 Intranasal lesion may be treated with corticosteroids
 Submucosal resection is reserved for cases unresponsive to medical management
Subglotic hemangiomas’ may be treated with steroids if airway obstruction is not severe
 Lesions causing severe obstruction or those unresponsive to initial management may
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be treated with CO2 laser ablation
Because circumferential laser ablation can cause subglotic stenosis interferon should
be considered as an alternative for extensive laryngeal involvement
Tracheostomy may be required if the above is not successful
Auditory canal obstruction
 Parotid hemangiomas may cause obstruction of the external auditory canal
 Obstruction produces a conductive hearing loss that may affect speech development
 Bilateral involvement that persists greater than one year of age should be treated to
prevent hearing loss
Congestive heart failure
Usually occurs in one of two settings
1) diffuse neonatal hemangiomatosis
2) large visceral hemangiomas(usually hepatic lesions that create AV fistulas and
cardiac decompensation
Medical management of the CCF in combination with steroids, interferon and
embolization
Management
 Accurate diagnosis
 In majority of cases parental education and reassurance will suffice
 20% of all hemangiomas will require treatment for either deformation, destruction,
obstruction, ulceration or life threatening complications
Treatment indications
1. Ulceration and Bleeding that has failed conservative treatment
2. Airway obstruction
3. Visual obstruction
4. Auditory obstruction
5. CCF
6. large lesion associated with thrombocytopenia
7. Psychological effect on the patient and the parents should also be considered
8. Certain anatomic sites eg nasal tip may warrant early treatment
 must be mindful that lesions that do not fully involute may leave
unacceptable scars
Medical treatments
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Corticosteroids are the first line of treatments and may be used for massive life
threatening hemangiomas
Steroids
 Mechanism: antiangiogenic
 Intralesional
o Useful for localised lesions
o Triamcinolone or betamethasone injections repeated in 6-8 week
o A mixture of triamcinolone acetonide (2-100 mg per injection) and
betamethasone acetate (0.3-15 mg per injection) is preferred to injection of a
single agent. It is injected directly into the hemangioma in different directions
through the same needle hole. Direct pressure is applied for 2-10 minutes to
prevent bleeding.
o 3-5 injections required to have same effects as oral steroid
o Is used for periorbital hemangiomas but be aware of risks:
1. central retinal artery occlusion through emboli
2. perforation of globe
3. infection
4. fat atrophy
5. pigmentation changes
6. skin atrophy
7. bleeding
8. eyelid necrosis
9. adrenal suppression
 Systemic dose
o 2-3mg /kg of body wt rapidly induces involution on hemangiomas
o 5mg/kg dose did not give additional benefit
 In general the lowest dose administered for the shortest duration possible is used
 Muliken suggest that initial 2 weeks of therapy if successful should be continued and
slowly tapered over several months
 PMH dermatologists give full dose over a 2-4 weeks then taper over 1-2 months
 Clinical response usually within 7 days
 As majority of hemangiomas involute at 10 -12 months treatment is usually
discontinued before one year of age
 Response rates are said to be around 90% for true hemangiomas
 Consider antiacid medications
 Rebound growth may occur and if it does then reinstitution of therapy may be
warranted
Adverse effects
 most are minor and usually temporary (Mulliken PRS 1999)
 no evidence of immunologic suppression (ie no increase in infections)
 Include
1. Cushingoid facies (71%)
2. Mental status changes such as irritability, depressed mood, euphoria (29%)
3. Gastric upset (21%) – resolved with antacids
4. Candida infection (6%)
5. Growth retardation(35%)
a. Due to inhibition of somatomedin activity and by directly inhibiting
synthesis of type 1 procollagen
b. catch up growth is usually seen within cessation of the steroids
6. hypertension, avascular necrosis and steroid proximal myopathy are rare –
not observed in Mulliken’s series.
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All adverse effects are temporary and occur with increasing frequency with increased
duration of treatment
Delay live virus vaccination until the end of treatment (but immunosupp not
demonstrated)
Intra lesion steroids may be advocated for certain lesions (eg eyelids)(triamcinolone
or betamethasone)
Rapid regression shown over 1-2 weeks followed by gradual improvement over next
6-8 weeks
But note same complications may occur with steroid injections
Interferon Alpha
 cytokines produced by monocytes and dendritic cells
 Alpha interferon has 22 subtypes
 effects of alpha interferon two-fold:
1) antiangiogenic
2) antiproliferative
 Appears to induce involution of hemangiomas in a dose dependent increase in
endothelial cell apoptosis or programmed cell death
 used in cases where steroid are contraindicated or failed or have had significant
complications
 In patients with Kasabach-Merritt syndrome, INF appears to have additional
beneficial effects of decreasing platelet adherence, improving flow, and facilitating
prostacyclin-mediated protection of the endothelium. The hematologic response
seems to be distinct from the antiproliferative response because hematologic profiles
(eg, platelets, prothrombin time/activated partial thromboplastin time, fibrinogen
levels) often normalize prior to regression of the lesion.
 reserved for 1) functional and life-threatening hemangiomas, 2) contraindication,
complication, or nonresponders to prolonged systemic corticosteroid, and 3) failure of
other conventional treatments
Treatment regimen
 1-3million units/m2/day of alpha 2a interferon or alpha2b interferon
 For emergent treatment, given once daily subcutaneously for 2 weeks together with
steroids
 Treatment continued until the tumour has stabilized - averages 20 months but may
take up to 3 years
 Accelerates involution in 80% of cases with complete resolution in as many as 42%

In rare cases antibodies to the alpha interferon may develop and cause rebound
growth during treatment
Adverse effects (usually transient)
1) flu like illness and fever
2) chronic neutropenia may persist for the length of the treatment – need to monitor
FBC
3) hepatic enzyme abnormality
4) spastic diplegia develop in up to 25% of patients with long term interferon
o Affected children tend to treated at an early age and some demonstrate
central nervous system demyelination on MRI. Not all children fully
recover though myelination does return to normal after treatment
o Thus neuro developmental testing should be undertaken before initiating
and then during interferon treatment

Need admission and close blood and neurological monitoring if children are given
interferon.
Intralesional bleomycin (PRS Jan 2006)
 Can be used at any age and at any stage
 2/3rd of children can expect tumor to involute by >75%
 complete response is seen in 49% of lesions.
 Complications – hyperpigmentation (40%), pulmonary fibrosis
Surgical excision
 Most hemangiomas are small and inconsequential and should be observed
 Some involute so completely that the scar will be better than any surgical scar
 Broad principles:
o Surgery for congenital vascular anomalies should generally be considered as
a last resort, if intervention is necessary and other treatment modalities have
failed or are considered inappropriate or contra-indicated.
o Wherever possible, surgery should be combined with non-surgical treatment
modalities. Patients with lesions requiring intervention should therefore be
assessed in the context of a multi-disciplinary unit
 In proliferative phase
o reserved for obstruction, deformation, ulceration or large hemangiomas
unresponsive to drug treatment
o ulcerations
1. often slow to heal and cause pain, so if tumor is small then resection is
a quick solution.
2. when anticipated scar from ulceration is more pronounced than after
surgery
3. ulcerated scalp hemangiomas lead to alopecia – scalp is lax in an
infant facilitatind direct closure.
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During Involuting phase
o Some advocate early excision of facial lesions that may interfere with the
development of the childs self image but most consider excision during the
involuting phase, usually before entering school.
o Relative indications for early excision
1. obvious that resection is inevitable (postulcer scarring, high chance of
fibrofatty residuum)
2. scar would be same length or appearance as excision performed later
3. scar would be easily concealed
4. staged resection/reconstruction required
During Involuted phase
o Ideally delayed to this phase
o Most do not need surgery unless require surgical revision for residual tumour
or skin atrophy
PRS 2002 (Mulliken) – hemangiomas tissue expand the skin thus consider closure in
a purse-string method. Can be used at any phase.
Liposuction
 Has been used for involuted large fatty lesions
Laser
 May arrest growth or induce involution
 Several different types of LASER may be used
1. Argon
o Penetrates deeper than pulse dye laser
2. Flash lamp pumped Pulse dyed
o Shown to be effective for ulceration
3. Neodymium:yttrium aluminium garnet
o Associated with higher complication rate of bleeding and scarring
4. CO2
5. Potassium titanyl phosphate (KTP)
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Superficial hemangiomas can be treated by delivering laser energy to the skin surface
Bulky lesions – intralesional delivery of laser energy which is accomplished by
percutaneous placement of bare KTP laser fibre within the tumour mass (PRS 1998
Achaeur )
Laser treatment is predicated on the principle of selective photo thermolysis
Yellow green lasers emit light of 532 to 585 nm that corresponds to one of the
oxyhemoglobin absorption peaks. This makes well vascularised tissue such as
hemangiomas susceptible to their effects
The response of the flash lamp pulse dyed and other lasers is limited by their shallow
depth of penetration (approx 1mm)
The inability of lasers to penetrate more than 1.5 mm is prompted the use of
intralesional [percutaneously placed fibre of Neodymium:yttrium aluminium garnet
orpotasium titanyl phosphate(83% improvement in 8months)
Embolization
 Selective embolization of hemangiomas may be indicated for lesions associated with
life threatening coagulopathy, CCF, airway and ocular obstructive lesions refractory
to treatment or as an adjunct to excision
Chemotherapy
 Antineoplastic agents are successful in the treatment of hemangiomas because of their
proliferative nature
 Cyplophosphamide and vincristine have been used successfully in the treatment of
K-M phenomenon
 Vincristine has recently become the second line medical management of lifethreatening hemangioma
o inhibits mitotic spindle microtubules by binding to tubulin, resulting in
inhibition of mitosis.
o appears to be well tolerated; however, neurotoxicity is the most common
reported complication.
o indications for use of vincristine are 1) functional and life-threatening
hemangiomas, 2) contraindication, complication, or nonresponders to
prolonged systemic corticosteroids, and 3) failure of other conventional
treatments.
Radiation
 Hemangiomas are very susceptible top radiation due to their rapid cellular turnover
 Small doses of 400 centigray are used
 Due to long term sequelae, radiation is reserved for severe life threatening lesions
refractory to other treatments
Cryotherapy
 Topical liquid nitrogen and CO2 have been used in the of superficial hemangiomas
 Unacceptable scarring and hypopigmentation
Compression
 Compression used on extremity hemangiomas for lesions exhibiting symptomatic
platelet trapping
Special Sites
Parotid Hemangioma (PRS 2004, Mulliken)
 Most common tumor of the parotid gland in children
 90% of salivary gland hemangiomas arise in parotid; 10% in submandibular
 Treatment indicated for
o Ulceration
Respiratory distress – due to subglottic narrowing by tumor
Impairment of visual axis
Congestive cardiac failure
Obstruction of auditory canal – leads to minor-moderate conductive hearing
loss, not a concern unless it is bilateral and persists beyond 1 year old
Steroids first line with interferon given for failure
Parotidectomy rarely indicated for proliferating parotid hemangiomas
Surgery often required in the involuted phase for excision of redundant fibrofaty
tissue, excision of scar or auricular revision.
Reinisch (PRS 2004) recommend early parotidectomy for large deforming parotid
tumors by an experienced surgeon as feels that drug treatment will not prevent
disfigurement – Muliken strongly disagrees with this
o
o
o
o
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Intramuscular hemangiomas
 Masseter muscle most common site of involvement in head and neck (36%), trapezius
(24%), periorbital muscles (12%)
 Equal sex distribution
 If the intramuscular hemangioma is compressible, a Valsalva manoeuvre, prolonged
recumbency or jugular vein compression may cause tumor to increase in size.
 Regression of intramuscular hemangiomas has not been described
 Differentials for masseter swelling include – lymphadenopathy, sialoceles, salivary
gland tumors, congenital cyst, sarcomas, benign muscle hypertrophy, myositis
ossificans.
 Treatment individualised according to tumor location, extent, rate of growth,
anatomic accessibility and aesthetics.
 Best treatment is surgical excision – recurrence rate of 18%
Hemangiomas of the eye lid
 Initial treatment should be systemic steroids (intralesional steroids used in some
centres but risk blindness)
 Interferon as second line
 Achauer (PRS 1999) has used intralesional laser photocoagulation (ulceration rate of
17%)
 If requires surgical debulking, incision thru tarsal crease
Subglottic hemangiomas
 rare condition with the potential to cause life-threatening complications in the
newborn period.
 Cutaneous hemangioma is present in approximately 50% of affected children
 63% association between the presence of cutaneous hemangiomas distributed in the
“beard pattern” (preauricular, chin, lower lip, neck) and the presence of symptomatic
hemangioma in the upper airway or subglottis
 The most common presenting symptom is biphasic stridor, which is often exacerbated
by crying and upper respiratory tract infection.
 Symptoms frequently present before 6 months of age.
 The natural history of this entity is characterized by progressive airway obstruction
during the proliferative phase followed by resolution of symptoms during the
involution phase.
 Treatment
1. conservative
a. indications: mild stridor without any evidence of apnea, cyanosis, or
feeding difficulty.
2. systemic corticosteroid
a. successful as the only treatment modality in 25% of patients
3. trachestomy
a. mortality rate of 40% to 60% has been reported because of tracheotomy
tube plugging and accidental decannulation.
b. Indicated when the airway is compromised because of hemangioma in the
area of 1) glottis and supraglottic, 2) multiple lesions of subglottis and
trachea, and 3) a contraindication to another treatment modality
c. When considering tracheotomy as a treatment option, factors such as
adequate family teaching, availability of nursing and medical care, and
communication and speech development must be taken into account.
4. laser
a. Effective when used in combination with systemic steroids
b. Options: CO2, potassium-titanyl-phosphate (KTP) and neodymium:
yttrium-aluminum-garnet (Nd:YAG) laser has also been reported with
good success.
c. The KTP laser (wavelength of 532 nm) and Nd:YAG laser (wavelength of
1064 nm) are preferentially absorbed by hemoglobin, making them
applicable to the treatment of hemangioma and other vascular tumors.
5. Interferon
6. Open excision
a. Complications such as subglottic stenosis and recurrent laryngeal nerve
injury are of concern
Hemangiomas of the lip
 Zide PRS 1997 – recommends early excision before school age to prevent
psychosocial distress
 Principles
1. early treatment should be conservative to realise the advantages of involution
2. avoid aggressive muscle resection as this causes overreduction deformity
3. reductions should be done in a central or paracentral fashion to avoid denervation
4. revisions frequently required – central wedge excisions, fascial grafts and
vermillion flaps
5. laser to address surface telangiectasias
Nasal tip hemangiomas (Cyrano/Pinocchio nose)
 more than any site cause visible distortion
 Incisions described
1. low flying bird (Rethi incision)
o visible scar
2. bilateral rim-transcolumella (open rhinoplasty)
3. vertical midline
4. Rotterdam nasomaxillary extended L
o Does not directly address excess skin tip problems
5. Subunit incision
o Favored by Zide PRS Jan 2002 – direct approach and leaves good scars

Open rhinoplasty used by McCarthy (PRS Jan 2002)
o Offer operation to patients over 3 years of age, where after a period of
involution, there are no further signs of regression for at least 6 months
Open rhinoplasty technique – no skin excision
Open rhinoplasty with skin excision
Cleft lip and hemangioma
 Rare
 May be seen in Maffucci, Wolf-Hirschhorn (4p deletion), trisomy 13, Dandy-Walker
 One strategy is:
o Intralesional steroid to accelerate involution
o Lip adhesion 4-5 weeks after 1st steroid injection
o Waiting 3-4months before definitive lip repair