Hemangioma

What is a hemangioma?
Right Align Classification of hemangioma
Epidemiology of hemangiomas
What is the underlying cause for hemangiomas?
When do hemangiomas arrise?
Where are the most common locations?
How does hemangioma look like?
Can hemangiomas be avoided?
When is it necessary to contact a specialist?
What are the possibvle complications of hemangiomas?
How to diagnose a hemangioma?
How to treat a hemangioma?

What is a hemangioma?

Today there is still a lot of confusion in the clinical practice, whether a lesion is a hemangioma or a vascular malformation. Hemangioma, the most common vascular tumor, occurs almost exclusively in infancy. Simplified one can say that hemangiomas are defined as vascular tumors, composed of hyperplastic endothelial cells, the type of cells lining all blood vessels in the human body, with the capacity for intensive proliferation.

The unique growth characteristics of hemangioma are a biphasic growth behavior, which can be divided into 3 phases: proliferation phase, involuting phase and involuted phase. The medium age of appearance of superficial hemangioma is about 2-4 weeks after birth. Deeper hemangiomas can remain unnoticed until a few months of age. A premonitory mark can be found at birth - this can be a barely visible pale spot, a telangiectatic or macula red stain or a pseudoecchymatic patch that mimics a bruise.

Right Align Hemangiomas have typical biphasic growth behavior. Their natural course is usually marked by a postnatal rapid proliferative phase, followed by a slow involution. The typical common hemangioma grows rapidly during the first year of life (proliferation phase), involutes slowly from 1 to 7 years (involuting phase), and completely regresses by 8 to 12 years of age (involuted phase) It is also important to know that there are hemangiomas with an “early proliferation growth pattern” and hemangiomas with a “late proliferation growth pattern”. Early proliferation is characterized by an earlier start of proliferation and proliferation essentially is complete after 5 months of age. The late proliferation growth pattern starts later and lasts longer. The phase of rapid growth is usually most pronounced during the first 3 to 6 months, but may be followed by a phase of slower growth. Regardless of subtype or depth, hemangiomas reach an average of 80% of their final size during the early proliferation stage, a stage that ended at a mean age of 3.2 months. [1]

Similarly, the time of onset of involution is somewhat unpredictable, in some cases it sets in at a few months, and in most cases by 12-18 months of age. But the change from proliferation to involution does not set in at specific point in the life cycle of a hemangioma; it is rather a floating process. While some superficial areas of the hemangioma are still in the proliferation phase, other parts can already be involuting. Clinical involution is identified by a color change from bright red to dull red to gray. The skin begins to pale and a patchy gray mantle forms. This process usually begins centrally and spreads out over the lesion by the time. Generally, involution takes place at an estimated rate of 10% per year, so that approximately 50% have involuted by 5 years of age, 70% by 7 years, and 90% by 9 years. [1]

After the involuting phase is completed, nearly normal skin is restored in only 50% of cases. In 50% of cases you can find mild residual changes, including telangiectasias, atrophic wrinkling, or yellowish discoloration. When the hemangioma was large and protuberant during proliferation, fibro-fatty residuum and redundant skin may remain. This phase is called "involuted hemangioma" The later a hemangioma starts to involute, the higher is their risk for residual changes after involution is completed. [1]

An involuted hemangioma will never stat to grow again - tumor growth is with completed involution phase always finished. So you can talk of a kind of predicted life circus, which is important for the therapy indication.

Beside the infantile hemangioma there is an other entity to discuss - congenital hemangiomas: The term “congenital hemangioma” was introduced to denote a vascular tumor that has grown to its maximum size at birth and does not exhibit accelerated postnatal growth. Congenital hemangiomas do not look like precursor (nascent) lesions of normal infantile hemangiomas, and also their behavior is different. There are 2 major subtypes of congenital hemangiomas: “rapidly involuting congenital hemangioma” (RICH) - hemangiomas full grown at birth, which starts immediately to involute - and “never involuting congenital hemangioma” (NICH) - hemangiomas fully grown at birth, which sty in shape an size an never start to involute. [1]

Classification of hemangioma:

Clinical appearance of hemangiomas is quite multifaceted. To make the requirements concerning diagnostic and therapy, a classification within the disease hemangioma was found. Every hemangioma is classified by size, dissemination and depth of penetration of the skin.
Concerning size and dissemination we have to differentiate between „localized hemangiomas“ (small and spatially confined laesions), and „segmental hemangiomas“ (hemangiomas covering a territory = a segment, or hemangiomas that are not spatially confined). Of course there are also lesions that are both localized and segmental and therefore called indeterminate.
Concerning the depth of penetration we have to differentiate 3 subtypes: „superficial hemangiomas“ (they are affecting only the superficial skin) „deep hemangiomas“ (they are only in the deep skin) and hemangiomas with superficial and deep parts, called „mixed hemangiomas“ Superficial and deep hemangiomas look quite different. This difference is going to be discussed in the chapter „ How does hemangiomas look like“. Generally you can say that 60% of hemangiomas are superficial, 15% are deep, and 25% are both deep and superficial. [1]

Focal, segmental, superficial, deep and mixed hemangiomas have got all the same typical biphasic growth pattern. Generally you have to say that deep an segmental hemangiomas proliferate longer, while superficial and focal hemangiomas start to involute 1 month earlier. [1]

Epidemiology of hemangiomas:

Hemangiomas of infancy are the most common benign tumors of childhood and their frequency is estimated to be as high as 10% to 12% within the first year of life. A higher prevalence can be found in premature neonates especially when their weight at birth is less than 1500 g. Female children are more likely affected than male children at rates of 3-5:1. Reasons for this circumstance are not really understood until today. There seem to be some ethnical and racial differences concerning the prevalence: They occur in children of all races, but may be less common in those of African or Asian origin, and more common in those of Caucasian origin. A 21% incidence of Hemangiomas in infants exposed to chorionic villus sampling at 9 to 12 weeks gestation has been reported. [2]

What is the underlying cause for hemangiomas?

Why hemangioma occur, and what leads to this typical biphasic growth pattern is not clearly understood now. Beside our interdisciplinary workgroup, several other workgroups all around the world are working to answer this basic questions concerning hemangiomas.
Although hemangiomas occur sporadically, an autosomal transmission of these tumors, with or without other vascular malformations, is persumed. [2]

When do hemangiomas arrise?

Normally first signs of a hemangioma are noticed within the first week of life. Hemangiomas never arrise in adults. In approximately 50% of neonates a premonitory mark can be found at birth. This can be a barely visible pale spot, a telangiectatic or macula red stain or a pseudoecchymatic patch that mimics a bruise. It is important to differentiate between this premonitory marks and congenital hemangiomas, which define a tumor, which is fully-grown at birth and was discussed in the chapter "What is a hemangioma".

Right Align

Where are the most common locations?

60% percent of hemangiomas are localized in the head and neck region, 25% are localized in the trunk area and 15% are localized on the extremities. 80% of the children with hemangiomas show only a singular lesion, while 20% show multiple hemangiomas. [2]

Most hemangiomas arise in the skin, but they can also grow in every internal organ as well, including the liver, the larynx, the lung or the gastrointestinal tract. There are also hemangiomas localized in the brain, although these hemangiomas are a really rare entity.

How does hemangioma look like?

Right Align The clinical appearance of proliferating hemangiomas depends on what kind of skin they affect. On the one hand, superficial hemangiomas are raised, lobulated and bright red lesions. Due to the color and shape, it is not wonder that words like “strawberry hemangioma” or “strawberry mark” are frequently used by patients and their families, although a right classification is important.

Deep hemangiomas, on the other hand, arise in the reticular dermis or subcutis and appear as raised soft masses, often with a bluish cast. The overlying epidermis usually appears normal, although dilated veins may be seen at the periphery of the lesion. But hemangiomas also can have both, superficial and deep parts, but without any histological differences. [2]

Right Align Clinical involution is identified by a color change from bright red to dull red to gray. The skin begins to pale and a patchy gray mantle forms. This process usually begins centrally and spreads out over the lesion by the time. Occasionally the superficial parts of the hemangioma are showing signs of involution, while deeper parts are still growing. With ongoing involution the tumor becomes softer and less tense by palpation, as fibro-fatty tissue replaces the endothelium. Deep hemangiomas, or deep parts of hemangiomas become less blue and get warmer. [2]

Congenital hemangiomas look quite different to the more frequently infantile hemangiomas.They are grown to their maximum size at birth, and have a grey pale color with prominent dilated veins, often surrounded by a pale ring.

Parents often feel anodyne when they see before/after pictures of other children with a hemangioma similar to the hemangioma their children is suffering from. This give them an idea of how the hemangioma will look like in each of the different growth phase and what they can expect of therapy. But parents should consider that every child is different and so are the outcome. The specialist for vascular anomalies is the best person to inform about the probable outcome. [2]

Can hemangiomas be avoided?

Hemangiomas can not be avoided. Nothing the mother can do during pregnancy or after birth will have influence whether her child develop a hemangioma or not.

When is it necessary to contact a specialist?

Right Align Clinical heterogeneity and the difficulty in predicting the course during early infancy make the management of hemangiomas during all growth phases quite difficult. A first step in management is to identify whether it is a low-risk/uncomplicated or high-risk/complicated hemangioma. A hemangioma that is asymptomatic, small in size, non-ulcerated and does not have the potential to impair a vital function is called low-risk or uncomplicated hemangioma. For these forms of lesion, it is generally enough to observe them. Lesions that do not qualify to require further intervention should be followed closely every 3 month, and if the lesion is in a cosmetically or functionally sensitive area, every 2 to 4 weeks if necessary to be able to determine its growth characteristics. Nevertheless, the parents require detailed information about the growth pattern, complications, and probably remaining residual skin lesions. In this case the optimal contact person is the normal pediatrician. [3]

A high-risk or complicated hemangioma is one that is symptomatic (e.g. ulcerated, painful, bleeding or infected), potentially function- or life-threatening (hemangiomas that cause ocular compromise, respiratory distress, congestive heart failure, gastrointestinal bleeding or extensive ulceration) or one that may lead to massive cosmetic disfigurement followed by subsequent social stigmatization (e.g. nasal hemangiomas, large segmental hemangiomas). The frequency with which these severe subset of hemangiomas occurs is estimated to be between 10% to 20% of all infantile hemangiomas. These hemangiomas should visit a specialist for vascular anomalies immediately. [3,4]

Children with multiple hemangiomas should also visit a specialist, because there is the risk that there are other vascular anomalies in other organ systems like the live or the gastrointestinal tract. This fact can be life threatening and have to be treated immediately. [3]

It is often difficult to predict the progress and prognosis of hemangioma during the first few months of life. Thus, a close monitoring within the first few weeks and months with measurements and photographic documentation is very important for the differentiation between high-risk and low-risk hemangiomas.

Due to the fact that 60% of hemangiomas are localized in the head an neck region, cosmetic problems of this tumors should also be considered and if it is necessary a specialist should be contacted.

What are the possible complications of hemangiomas?

Right Align Generally complications are a rare event. Complications are ulceration, bleeding, infection, deformation (for example deformation of the face), internal bleeding (for example in the gastrointestinal tract) and large hemangiomas can couse cardiac high output failure. Also pain shold be considured as a complication of hemangiomas. All this hemangiomas are among the „high risk“ hemangiomas. The frequency with which these severe subset of hemangiomas occurs is estimated to be between 10% to 20% of all infantile hemangiomas. [5]

Within 5-10% of the children with a hemangioma ulceration occour, mostly within hemangiomas of the lips or the ano-genital region. Treatment for ulceration is typically antibiotics to avoid infection, continuos cleaning and bandages. In some cases surgical intervention or laser treatment are necessary. Bleeding, a very rare event, can be treated with compression bandage. An ulcus normally heals within weeks, and is normally a single event.

Hemangiomas have the ability, depended on their size and localization, to deform facial features. To avoid such facial deformation and the resulting stigmatization, a treatment is necessary, to slow down the tumor growth. [5]

How to diagnose a hemangioma?

Most of infantile hemangiomas do not require special diagnostics. While clinical behavior and clinical examination usually provide enough information for diagnosis. Within 90% of cases clinical behavior provide enough information for a diagnose. A proper diagnose is important for therapy, because there are several differential diagnoses, that require a complete different diagnostic and therapy. The differential diagnoses include, but are not limited to: other vascular tumors e.g. pyogenic granuloma, tufted angioma, kaposiform hemangioendothelioma; vascular malformations e.g. port-wine stain, venous/lymphatic/arteriovenous malformation; non- vascular benign tumors e.g. nasal glioma, myofibromatosis, Spitz nevus, dermoid cyst. Differential diagnoses also contains non-vascular malignant tumors e.g. rhabdomyosarcoma, fibrosarcoma. If there is any suspicion of a malign tumor a biopsy is necessary. [3]

Some cases require a special diagnostic procedure for proper diagnosis. Especially visceral hemangiomas, e.g. with hepatic or cerebral localization, need special diagnostics for an accurate diagnosis, which is required for an optimal therapy. The most sufficient and low-risk method is ultrasonography imaging. Beside ultasonography imaging in some cases more detailed diagnostic is required. For those cases CT or MRI is an option. [2]

How to treat a hemangioma?

It is often difficult to predict the progress and prognosis of hemangioma during the first few months of life. Thus, a close monitoring within the first few weeks and months with measurements and photographic documentation is very important for the differentiation between high-risk and low-risk hemangiomas. After the decision to treat a high-risk hemangioma is taken, it is important to consider the medical status of the patient, the localization and size of the hemangioma, the urgency of treatment as well as the risks and benefits of the treatment modality. [3,5]
Frieden I.J. et al. defined 5 goals for treatment of hemangiomas in their guidlines: to prevent or reverse any threats to life or function, to prevent permanent disfigurement due to post-involution residual skin changes, to minimize psychosocial distress for patient and family, to prevent or treat ulcerated hemangiomas to reduce scarring, infection, bleeding or pain, to avoid aggressive treatment of hemangiomas that are likely to have an excellent prognosis if left alone. [3]
There are three main kinds of therapy available for the treatment of hemangiomas: pharmacotherapy, surgery/embolic therapy and laser therapy. The following list is a short overview over the most important therapy-strategies: pharmacotherapy, surgical therapy and laser or embolization.

The non selective Beta-Blocker is an effective therapy for infantile hemangiomas. The therapeutic effect of propranolol on infantile hemangiomas include vasoconstriction, which is immediately visible as a change in color, associated with a palpable softening of the hemangioma. Other pharmacotherapies as corticosteroides, interferon or vincristine are only necessary when there are contraindications for a Beta-Blocker. [6]

There are generally accepted indications for the excision of hemangiomas in proliferative phase, for example a well-localized or pedunculated lesion, particularly if ulcerated or bleeding repeatedly. Surgical therapy is also indicated for problematic hemangiomas that do not respond to pharmacologic therapy. Hemangiomas of the upper eyelid that do not or do only poorly respond to medical management can also be debulked or excised to minimize potential complication to the developing eye. Focal or multifocal gastrointestinal hemangiomas, which persist in bleeding despite pharmacotherapy, can be excised by an enterotomy or by endoscopic band ligation in selected patients. Staged or total excision of large or protuberant involuting-phase hemangiomas should be considered in the preschool period, because of psychosocial reasons and emotional distress of the child. Therefor the interdisciplinary work of pediatrician and plastic surgeons is very important. [2]

Pulsed-dye laser is accepted as an effective treatment of ulceration, although many would reserve its use for after occlusive dressings and topical therapies have failed. It is also widely accepted as a treatment for residual erythema or telangiectasias that may remain after involution. Its role in treating proliferating hemangiomas, however, is more controversial.

Hepatic hemangiomas with arteriovenous shunts, portovenous shunts, or both are highly associated with congestive heart failure as a result of high flow through these shunts. Early embolization is recommended for focal lesions with a direct shunt as a means of quickly controlling the heart failure. [2]

1. Chang LC, Haggstrom AN, Drolet BA, et al. Growth characteristics of infantile hemangiomas: implications for management. Pediatrics 2008;122:360-7
2. Mulliken JB, Fishman SJ, Burrows PE. Vascular anomalies. Curr Probl Surg 2000;37:517-84.
3. Frieden IJ, Eichenfield LF, Esterly NB, Geronemus R, Mallory SB. Guidelines of care for hemangiomas of infancy. American Academy of Dermatology Guidelines/Outcomes Committee. J Am Acad Dermatol 1997;37:631-7
4. Smith SP, Jr., Buckingham ED, Williams EF, 3rd. Management of cutaneous juvenile hemangiomas. Facial Plast Surg 2008;24:50-64
5. Roganovic J. An update on the treatment of high-risk hemangiomas in infants. Eur J Pediatr Surg 2007;17:147.
6. Leaute-Labreze C, Dumas de la Roque E, Hubiche T, Boralevi F, Thambo JB, Taieb A. Propranolol for severe hemangiomas of infancy. N Engl J Med 2008;358:2649-51