VASCULAR TUMORSLiterature Revision

DR. LEONARDO BALLESTAS MALDONADOGENERAL SURGERY RESIDENT

UNIVERSIDAD DEL VALLE

DR. RENE TIMARANVASCULAR SURGERY TEACHER

HOSPITAL SAN VICENTE DE PAULUNIVERSIDAD DE ANTIOQUIA

Clinic case• Female

• 2 weeks after birth

• Premature antecedent

• GLUT-1 positive

DIAGNOSIS

“Not every skin lesion looking like a strawberry is a hemangioma; not all

hemangiomas look like strawberries”

J.B. Mulliken, MD

Evidence

• A search of the evidence in the database: Medline, Embase, Cohcrane, Tripdatabase, Scielo

• Key words: Hemangioma, vascular anomalies, kaposiform hemangioendothelioma, infantile hemangioma, pyogenic granuloma, congenital hemangioma

Introduction

• Vascular anomalies are the most common skin and soft tissue lesions observed in infants and children

• Older nomenclature continues to cause confusion, misunderstood diagnoses, and potencial mismagement

• In 1982, Milliken and Glowacki proposed a classification system for vascular anomalies based on their clinical behavior and endothelial cell characteristic

Kilcline C, Frieden IJ. Infantile hemangiomas: how common are they? A systematic review of the medical literature. Pediatr Dermatol 2008;25(2):168–

73.

ISSVA ClassificationSociety for the Study of Vascular Anomalies

Vascular tumors Vascular malformation

Vascular anomaliesVascular Tumors Vascular malformaciones

Infantilehemangioma

Congenitalhemangioma

NICH RICH

• Capillary malformation • Venous malformation• Lymphatic malformation

• Arterial malformation • Arteriovenous fistula• Arteriovenous malformation

Combined types

Slow flow Fast flow

Differentiating Features

TUMOR• True tumors, with

proliferation of the vascular endothelium

• >3:1 female : male• Small or absent at birth• Rapid growth during infancy • Self-limited• Diagnosis: Clinical +

appearence

MALFORMATION• No tumor, comprised of

dysplastic vessels• 1:1 female : male• Present at birth• Growth proportional to

child• Never disappear• Diagnosis: MRI, Doppler

ultrasonography, angiography

Vascular tumors

• Infantile Hemangioma

• Congenital Hemangioma

• Kaposiform Hemangioendothelioma

• Pyogenic Granuloma

Infantile Hemangioma (IH)

• Bening endothelial cell tumor

• Most common tumor of infancy/childhood

• Incidence of 4.5% overall

• It is more frequent in caucasian, premature infants and females (3:1 to 5:1)

• Perinatal characteristics associated with a higher risk of IH include preeclampsia, multiple gestation, and low birth weight

Hemangioma Investigator Group, Haggstrom AN, Drolet BA, Baselga E, et al. Prospective study of infan- tile hemangiomas: demographic, prenatal,

and peri- natal characteristics. J Pediatr 2007;150(3):291–4.

Pathogenesis

• Despite the frequency of this tumor, understanding of the pathogenetic mechanisms

• Generally believed to be a complex interaction of both genetic and environmental factors

• Histologically, have markedly increased cellularity with clusters of plump cells that are positive for markers of immature endothelial cells

Drolet BA, Swanson EA, Frieden IJ, et al. Infantile hemangiomas: an emerging health issue linked to an increased rate of low birth weight infants. J

Pediatr 2008;153(5):712 No-715.

Pathogenesis

• Endothelial-like cells of the hemangioma expressed GLUT-1, the erythrocyte-type glucose transporter protein that has been shown to be upregulated in zones of hypoxia

• GLUT-1 seems to be an exclusive marker for IH and is an invaluable tool used to distinguish hemangiomas from other vascular lesions.

NorthPE,WanerM,MizerackiA,etal.GLUT1:anewly discovered immunohistochemical marker for juvenile hemangiomas. Hum Pathol 2000;31(1):11–22

Diagnosis

• History and physical examination

• Radiographic imaging

• Histopathology – GLUT-1

History

• The diagnosis is typically made clinically based on its appearance and characteristic behavior

• Between 30% and 50% of lesions are visible at birth as a small, pale spot, telangiectatic stain or ecchymotic area

• Appears weeks/months afther birth (the median age appearance is 2 weeks)

Localitation

• Most hemangiomas are single (80%)

Head an neck 60%

Trunk 25%

Extremities 15%

Age (Years) 1 2 3 4 5 6 7 8

Gro

wth ■ Proliferating

■ Involuting■ Involuted

Natural growth infantile hemangioma

Proliferation stage

Involution stage

Residual changes

classified by their depth of soft tissue involvement

Classification based on morphology

• Localized or segmental or indeterminate

• Segmental hemangiomas are at higher risk of complications and associated anomalies

•Connors III JP, Mulliken JB. Vascular Tumors and Malformations in Childhood. Vascular Surgery 6 th ed 2005

Ultrasound

• Differentiate deep hemangiomas to venous malformations

• To evaluate the response to drug treatment

• Findings

Dense parenchyma rapid flow Minor arterial resistance Increased venous velocity Effect of soft tissue mass

•Connors III JP, Mulliken JB. Vascular Tumors and Malformations in Childhood. Vascular Surgery 6 th ed 2005

Magnetic resonance

• Test "reference”

• Findings

Intermediate intensity parenchymal tissue (T1), and moderate hyperintensity (T2)

Empty Flow (arteriovenous shunts) Glasses high flow or low flow Reducing the size and number of vessels irrigating / draining lobularity Body fat avascular

Complications

• Although most IHs are uncomplicated and do not require treatment

• 24% of those referred to tertiary institutions had complications

• Size, location, and subtype (localized vs segmental) are major factors to consider in evaluating an infant’s risk

Haggstrom AN, Drolet BA, Baselga E, et al. Prospective study of infantile hemangiomas: clinical characteristics predicting complications and treat-

ment. Pediatrics 2006;118(3):882–7.

Ulceration

• Is the most common complication and can result in pain, infection, bleeding, and permanent scarring

• Larger in size or of the segmental subtype are more likely to develop ulceration

• The cause of ulceration is not well understood, but maceration and friction are likely contributing factors given the higher frequency in locations prone to this

Chamlin SL, Haggstrom AN, Drolet BA, et al. Multi- center prospective study of ulcerated hemangi- omas. J Pediatr 2007;151(6):684–9, 689-e1.

Ulceration

Visual compromise

• Threat to vision is a common reason for treatment in the IH population

• Infants are at particular risk because stimulus deprivation for as little as 1 week can interrupt visual development and result in permanent visual impairment

• Periocular IH may cause ptosis, strabismus, and anisometropia, each of which may result in astigmatism, amblyopia, or blindness

Al Dhaybi R, Superstein R, Milet A, et al. Treatment of periocular infantile hemangiomas with propranolol: case series of 18 children. Ophthalmology

2011; 118(6):1184–8.

Visceral involvement and complications

• Hemangiomatosis – 30%

• The lesions are usually less than 5 mm in diameter and domelike

• Are recognized to have a higher risk of visceral hemangiomas, with liver and gastrointestinal involvement being most common

• Should be screened with ultrasound to rule out lesions in internal organs

Anomalies associated with anatomic localization of HI

• The presence of IH in particular locations can be a marker for underlying or associated anomalies

• The “beard” distribution has been associated with the presence of airway hemangiomas

Orlow SJ, Isakoff MS, Blei F. Increased risk of symp- tomatic hemangiomas of the airway in association with cutaneous hemangiomas in a “beard”

distribution. J Pediatr 1997;131(4):643–6.

In the lumbosacral area have also been reported in

association with occult spinal dysraphism

Anomalies associated with anatomic localization of HI

Girard C, Bigorre M, Guillot B, et al. PELVIS syndrome. Arch Dermatol 2006;142(7):884–8.

PHACE syndrome

The neurocutaneous disorder characterized by

posterior fossa abnormalities [P], large facial hemangiomas [H], arterial anomalies [A], cardiac defects [C], and

eye anomalies [E]

Frieden IJ, Reese V, Cohen D. PHACE syndrome. The association of posterior fossa brain malforma- tions, hemangiomas, arterial anomalies,

coarctation of the aorta and cardiac defects, and eye abnormal- ities. Arch Dermatol 1996;132(3):307–11.

• Prevent or reverse the life-threatening complications or function

• Prevent or minimize disfigurement

• Minimize psychosocial stress for the patient and family

• Properly treat ulceration to minimize scarring, bleeding, infection and pain

Treatment Objetives

Conservative treatment

• Observation is the mainstay of management because 90% of IHs are small and localized and do not involve aesthetically or functionally important areas

• Up to 38% of hemangiomas referred to tertiary care specialists require systemic treatment because of complications

B-Blockers

• The use of propranolol for IH quickly gained favor, because it has been perceived to have a lower side-effect profile than other systemic therapies

• Its mechanism of action in the treatment of IH is unknown

• Possible mechanisms of action purported include vasocon- striction, inhibition of angiogenesis, and induction of apoptosis

Leaute-Labreze C, Dumas de la Roque E, Hubiche T, et al. Propranolol for severe hemangiomas of infancy. N Engl J Med 2008;358(24):2649–51

Systemic Corticosteroids

• Response to treatment is variable, regression in one third of cases, stabilization of growth in another third of cases, and minimal to no response in the final third of cases

• Adverse effects are common and include irritability, gastrointestinal upset, sleep disturbance, cushingoid facies, adrenal suppression, immunosuppression, hypertension, bone demineralization, cardiomyopathy, and growth retardation

• The duration of treatment is variableBarrio VR, Drolet BA. Treatment of hemangiomas of infancy. Dermatol Ther 2005;18(2):151–9.

Intralesional and topical corticosteroids

• Reported to decrease the size or slow growth

• Are most effective for small and localized cutaneous hemangiomas

• The efficacy is limited by the depth of its penetration compared with the depth of hemangioma involvement

Barrio VR, Drolet BA. Treatment of hemangiomas of infancy. Dermatol Ther 2005;18(2):151–9.

Vincristine

• Effective in the treatment of IH and has historically been reserved for those IHs resistant to corticosteroids or in patients intolerant of corticosteroids

• Constipation is the most common side effect, but neuromyopathy, most commonly presenting as foot drop, is a potentially serious side effect

• Administration of vincristine requires placement of a central line; therefore, risks associated with this must be considered as well

Barrio VR, Drolet BA. Treatment of hemangiomas of infancy. Dermatol Ther 2005;18(2):151–9.

Interferon

• Recombinant interferon-a an inhibitor of angiogenesis, administered as a subcutaneous injection

• Side effects include flulike symptoms of fever, irritability, and malaise

• Its use is not recommended in earlier age

Laser therapy

• The mechanism for this is not well understood

• Controversy exists surrounding its use for the treatment of proliferating IH as adverse outcomes including ulceration and scarring have been described

• Tuse of laser for intact IH is limited by the depth of the laser’s penetration (1 mm)

• A few studies describing its benefit in the treatment of ulcerated hemangiomas in terms of both increasing reepithelialization and decreasing painWitman PM, Wagner AM, Scherer K, et al. Complica- tions following pulsed dye laser treatment of super- ficial hemangiomas. Lasers Surg Med

2006;38(2): 116–23.

Surgery

• Surgical excision may be an option for function- threatening or life-threatening hemangiomas when medical therapy fails or is not tolerated

• More commonly its role is for removal of residual fibrofatty tissue or correction of scarring after involution

Congenital Hemangioma (CH)• Unlike IH, CH is fully developed

at birth and does not undergo postnatal growth

• Rare (compared to infantile)

• Blue/gray hue, pale halo (skin)

• Is more common in the extremities and has an equal sex distribution

• 2 typesNon Involuting Congenital Hemangioma

(NICH) – persistentRapidly Involuting Congenital Hemangioma

(RICH) – resolved by 1 – 2 years

Treatment

• Most CHs are managed by observation

• RICHs begin to involute shortly after birth, and most have resolved by 12 months of age

• NICH is a stable lesion that does not involute or respond to pharmac logic treatment. Thus, NICH causing disfigurement or functional problems is treated by excision

Kaposiform Hemangioendothelioma

• Rare vascular neoplasm that is locally aggressive but does not metastasize

• Fifty percent of lesions are present at birth and are diagnosed during infancy (58%), early childhood (1 to 10 years; 32%), or late child hood (10 to 20 years; 10%)

• Has an equal sex distribution, is solitary, and affects the head or neck (40%), trunk (30%), or extremity (30%)

Kasabach-Merritt phenomenon

• "Giant Hemangioma”

• Thrombocytopenia (typically <10,000 mm3)

• Petechiae

• bleeding

• A localized tumor can be resected, depending on its location

• Patients with KMP require systemic treatment to prevent life threatening complications

• Responds best to vincristine (90%), followed by IFN (50%) and corticosteroid (10%)

Treatment

Pyogenic granuloma• Is a solitary a small red papule that grows rapidly, forming a stalk

• The male female ratio is 2 : 1

• It is commonly complicated by bleeding (64.2%) and epidermal ulceration (36.3%)

• The presentation is inversely correlated with age

• They are distributed on the head or neck (62%), trunk (19%), upper extremity (13%), or lower extremity (5%)

• Twenty five percent of patients have a history of trauma or an underlying cutaneous condition (including capillary malformation, dermatologic disorder, viral infection, or insect bite).

• Numerous treatment methods have been described: curettage, shave excision, laser therapy, and excision

• These modalities have a recurrence rate of 43.5%

• Definitive treatment requires full thickness skin excision, which has an approximately 100% cure rate

Treatment

Clinic case

• Female

• 2 weeks after birth

• Premature antecedent

INFANTILE HEMANGIOMA

THANKS