Disclaimer: The information contained within the Grand Rounds Archive is intended for use by doctors and other health care professionals. These documents were prepared by resident physicians for presentation and discussion at a conference held at Baylor College of Medicine in Houston, Texas. No guarantees are made with respect to accuracy or timeliness of this material. This material should not be used as a basis for treatment decisions, and is not a substitute for professional consultation and/or peer-reviewed medical literature.

On physical examination it can be difficult to differentiate the different types of lesions and I will give a few examples to illustrate this.

This is a little infant with a red macular lesion on the right cheek, which could be consistent with a port wine stain, otherwise known as a venous malformation or superficial hemangioma.

This young boy has a bluish mass in his left cheek, which could be consistent with a subcutaneous hemangioma, a venous malformation or an AVM.

Then there are the masses that are deep, that do not have any discoloration and these could be either a deep hemangioma or a lymphatic malformation.

In the early 1980s researchers tried to distinguish between these different congenital vascular malformations. They came up with two distinct entities: hemangiomas and non-hemangiomas, what we call vascular malformations.

The difference between these two categories is that hemangiomas are usually (the key here is “usually”) not present at birth, whereas vascular malformations are always present at birth.

Hemangiomas proliferate during the first year of life, whereas vascular malformations never proliferate. Hemangiomas will eventually involute, whereas vascular malformations never involute.

They sub-classified vascular malformations as venous, venular, capillary, lymphatic (which we also know as cystic hygromas when they occur in the head and neck), and arterial venous malformations.

They classified hemangiomas into three groups, the first being superficial, which are also called strawberry or capillary hemangiomas. In this illustration, this baby has one in the V1 distribution of the trigeminal nerve and it is a bright red macular, papular lesion originating superficially in the papillary dermis. The second classification is deep hemangiomas, which are also coined cavernous hemangiomas. These originate within the subcutaneous tissue and commonly have a bluish hue. As the visible light enters the skin, the collagen absorbs the red light and reflects the blue light, so what we see is a blue lesion. If they are deep enough, these can also be colorless.The final classification is compound hemangiomas, which is a mixture of superficial and deep components, also called capillary cavernous hemangiomas in the literature. These are actually the same lesion, just at different depths of the skin.

In this illustration, the child has the red superficial hemangioma and then the underlying bluish hue, which tells you there is a deep component as well.

All hemangiomas, regardless of their color, constitute a single entity and they vary only by depth.

With regard to congenital vascular malformations, an accurate diagnosis is very important, since this changes the treatment plan, since hemangiomas involute, whereas vascular malformations do not. Since physical examination alone is difficult, it is important to get a good history. There are three key questions you must ask: 1) was this lesion present at birth? 2) has it increased in size? and, 3) has it decreased in size? Any one of these questions individually may not give you the answer or the diagnosis. It may require all three of questions plus the physical exam to get an accurate diagnosis.

We'll represent this with a little flow sheet and the first question "Was this lesion present at birth?” If it was present at birth, we know that vascular malformations are always present at birth; however, this can be confusing because sometimes hemangiomas can also be present at birth and sometimes vascular malformations are not noticed at birth. The next question is “Has the lesion increased in size?” We know that hemangiomas do increase in size via the process of hyperplasia. In other words, this actually divides and is a rapid process. Vascular malformations also increase in size, but they do so by hypertrophy: they don't divide, they just get bigger. Again, this can be a confusing situation, but it is important to note the rate of proliferation: a rapidly proliferating lesion is likely a hemangioma and a slowly growing lesion is likely a vascular malformation. Finally, the last question "Has this lesion decreased in size?” Again, only hemangiomas involute. However, again this can be confusing because vascular malformations, specifically lymphatic malformations, can change in size in the setting of URIs or hormonal influences.

Going back to the original case I presented earlier, here is a baby with a right macular lesion on the cheek. To answer the first question, this lesion was present at birth, which leads you to believe it may be a vascular malformation. However, this lesion increased in size rapidly and it's this rapid increase in size that gives the diagnosis of a hemangioma.

The second patient had the bluish mass in the cheek; this lesion again was present at birth. This lesion has increased in size but it has done so very slowly and it has not decreased in size. In addition, in the history, you find that the mass expands when the patient lies down. So this is consistent with a venous malformation.

Finally, this child with the colorless mass in the left cheek. This lesion was present at birth. It has increased in size, although the parents state that it changed in size during an upper respiratory tract infection and it has not decreased in size. The likely diagnosis is a lymphatic malformation.

Sometimes these lesions are diagnosed on plain film imaging when the patient is being worked up for symptoms. In our case, this patient was worked up for stridor and had a plain film x-ray, and here you can see an indentation of the trachea in the subglottic region that turned out to be a subglottic hemangioma.

Other possible films include computer tomography scans. These are good for evaluating lesions that are intraosseous, and they can be used when planning surgery for an extensive hemangioma that will include a surgical resection. This CT basically shows a mild bowing of the posterolateral wall of the maxillary sinus due to the pressure of the hemangioma. The best imaging is a MRI, which is the test of choice. Hemangiomas will give you an intermediate signal density on T1. They will be hyperintense on T2 and T1 with contrast they are very hyperintense. They do show high signal flow-voids and you can also see this with arterial venous malformations, but arterial venous malformations are not bright on T2’s because they do not have any parenchymal component. The MRI is very good: not only does it give you a information about the lesion, it can actually help differentiate between the different types of vascular malformations based on their T1 and T2 contrast enhancement.

Additional studies include colored-flow ultrasounds and time-of-flight MRA. Here is a time-of-flight MRA showing a feeding vessel into this lesion here on the cheek.

As to the epidemiology of hemangiomas, they occur in 10 to 12 percent of all white children. They are almost twice as common in pre-term infants weighing less than 1000 grams. Interestingly, they occur one-tenth as frequently in Asian and black children. They are not familial, but 10 percent of patients have a positive family history. Hemangiomas have a 6 to 1 female predominance versus vascular malformations, which have an equal incidence in both sexes.

As we said, hemangiomas are usually not present at birth, but up to 30 percent of lesions are present at birth. The majority of these lesions present during the first few weeks of life. Paradoxically, the earliest sign is actually a blanched lesion, which can often go unnoticed. This lesion is more apparent when the child cries because the skin around it becomes red, making the white or blanched area more noticeable. Following the blanched macule, you will get telangiectasia in a setting of the blanched macule. This will eventually form a red macule. Now, the reason that it is blanched and then becomes red is because in the blanched setting of the early growth of the hemangiomas, the endothelial cells are very big and plump and the lesion does not have a lot of red cells. As the lesion grows, the vessels dilate and become more filled with blood, ending up with a red macule.

Sixty percent of all hemangiomas occur in the head and neck region. There are two types of growths: a focal growth and a diffuse growth. This image shows the common locations including the lip, the tip of the nose and the periorbital region. The second pattern shown is diffuse. These typically occur in the distributions of the trigeminal nerve. Hemangiomas grow in phases: first they get big and then they go away. The first phase is proliferation, the second phase is involution. Commonly any one lesion will have these two phases going on at the same time. Some parts of the lesion will be in proliferation and other parts will be in involution. It is the balance of the two that determines if the lesion is actually getting bigger or starting to go away.

When do they proliferate? They proliferate for the first year of life, up to the first 18 months, and appear to have a bimodal growth distribution. They grow rapidly during the first one to three months and then again at four to six months and then typically taper off. But the rate of the growth and the timing vary from patient to patient and are not predictable.

Histologically, early proliferation includes these large, plump endothelial cells. There is just a little bit of blood, which is why these lesions actually appear blanched instead of red. If these are stained with a substance that stains reticula, you can see that this is not just a mass of endothelial cells. There are actually vessels here as evidenced by the circle of reticulum. As the lesion grows, it forms lobules with fibrous septa. There can be satellite nodules adjacent to the primary lesion. In addition, these can infiltrate adjacent structures, which can make them difficult to surgically resect. Although the infiltration of other tissues can complicate surgical excision, it is not invasive as in a cancer.

The second phase is the involution phase. The gradual transition from proliferation to involution begins after the first year of life and is signaled clinically by decrease in the overall growth rate of the lesion. The mechanism for involution is unknown but it can take several years for the involution to occur. There are no known characteristics which influence the rate or degree of completion of the involution. It is known, however, that in early involution there is an infiltration of mast cells. The mast cells, whose role is unknown, are known to secrete cytokines, which are involved in angiogenesis and chemotaxis. It is believed that these are playing a role in involution. As involution occurs, the cells, instead of being plump, start to become flat and the vessels start to dilate. In late involution these cells are very flat. There is no longer any mitotic activity and it is at this phase that the lesions can be confused with other vascular malformations, which is why we can't always rely on your pathology in making a diagnosis. Deeper hemangiomas can leave fibrofatty tissue, which can leave a cosmetic deformity to your patient. Grossly, involution begins as a blanched macule that typically starts in the center lesion and then occurs in a radial pattern toward the periphery.

What percentage of hemangiomas actually involute? It is a misconception that they all go away. Only 40% of hemangiomas will involute by the age of 5 and 70% of hemangiomas will involute by the age of 12.

In 1983, Finn reviewed 1998 cases of hemangiomas. He defined “excellent cosmetic result from involution” as the absence of residual scar, telangiectasia or redundant tissue, such as in a fibrofatty scar. He found that the rate of involution was directly related to how well the hemangioma goes away. Hemangiomas that involute by age 6 had a 60% percent chance of having a good cosmetic result. In the hemangiomas that took longer than six years to involute, 80% had a poor cosmetic result. Almost 60% of hemangiomas will leave a significant cosmetic deformity and these patients will benefit from corrective surgery.

So, the question is when should you intervene with a hemangioma? Any life-threatening or site-threatening hemangiomas should be dealt with on an as-needed basis, regardless of the stage of the lesion, as in subglottic hemangiomas causing airway compromise. Certain experts recommend active intervention for all obvious lesions, with the goal of preventing disfigurement and psychosocial trauma to the child. It is known that children at 18 to 24 months start to have an image of themselves, and know they look different, which affects them psychologically.

These experts recommend aggressive treatment during the first year of life, during the proliferative phase. The goal is to either completely get rid of the lesion or stunt the growth so that a much smaller lesion is left after the hemangioma has involuted. A patient already in the stage of involution can be watched and followed for a brief period to see what is happening with the hemangioma. As stated before, those hemangiomas that involute rapidly usually give a good cosmetic result, in which case you may elect to do nothing. But if the lesion appears to be slowly involuting, Intervention will give the best cosmetic result.

There are multiple treatment options. Since there are only a limited number of prospective randomized studies comparing one treatment modality versus the other, most physicians treat with the modality they are most comfortable with. A dermatologist will use medicines and lasers, while surgeons may use surgical excision or laser.

Treatment options include pharmacotherapy, lasers and surgical excision. Pharmacotherapy includes oral steroids and interferon. The use of oral steroids was first reported in the late 1960s by Dr.Katz. Throughout the years, prednisone and prednisolone have become a standard of care. The mechanism of steroids is actually unclear. It was thought that glucocorticoids potentiate actions on vasoconstrictors and on vascular smooth muscle and directly inhibit angiogenesis, but it has also been noted that dexamethasone, which is not really a glucocorticoid, also inhibits growth of hemangiomas, which contradicts this mechanism. The response rate to steroids varies from 30% to 93%, and varies with dose, the duration and the age of onset of treatment. The higher the dose, a longer treatment period, and the earlier start to treatment all give better results. Of course, all those things also result in more side effects from the steroids. The two factors must be balanced. Oral steroids only work during the proliferative phase, so cannot be used on lesions that have started to involute where they would have absolutely no effect. A recommended regimen would be to use steroids early, during the first six to eight months of life, which is the time of proliferation. Start with 5mg per kilo each morning, although some physicians use less. If there is no response after one week, stop the steroids; however, if a response is seen, continue the steroids for two to three weeks, followed by a long taper over two to two-and-a-half months. If you get a rebound effect during the taper, the dose may be increased, followed by taper again. Do not forget to give the patient antacids.

Regional and topical steroids have been tried, but neither has been found to give any benefits. With intralesional steroids, retinal artery occlusion, eyelid necrosis and more atrophic scarring can occur.

The second possible pharmacotherapeutic agent is interferon. Originally used as antiviral agent, it is known to inhibit endothelial cell migration, proliferation and angiogenesis in vitro. Interferon was found useful in hemangiomas while treating HIV patients who also had Kaposi's sarcoma. The Kaposi's sarcoma lesions would get better on interferon therapy. There have been prospective trials, which showed that interferon does work.

Why use interferon instead of steroids? Interferon does not have to be given during the proliferative phase. It works by a totally different mechanism than steroids. Therefore in patients who do not have good results with steroids, can be tried on interferon. Interferon does work much slower than steroids, requiring up to an average of eight months for effect. Side effects of interferon include low-grade fever, neutropenia, elevated liver enzymes and anemia. In addition, there have been reports of irreversible spastic diplegia in patients given interferon, which discourages some physicians from using it for their patients.

Moving on to laser therapy, for cutaneous lesions we recommend flash lamp pump dye lasers. These lasers allow photocoagulation of the attacked vessels while keeping the overlying skin and the oral mucosa intact. They have been found to give very reproducible and reliable results. These lasers were initially used in port wine stains. In the late 1980s and early 1990s, Sherwood, Gilchrest and Tan tried using it on hemangiomas and found it effective in these lesions. This laser only penetrates 1 to 2-mm, so can only be used in superficial hemangiomas. The wave length of this laser is around 580 or 585 nanometers, so the short wave length gives very little penetration. Lasers can be used during any phase of the hemangioma cycle and results are usually seen after only one or two treatments, although some reports relate up to six treatments. With laser treatment, the lesion goes from bright red to a dark, dusky.

There are complications of laser therapy, primarily hypopigmentation. It can cause atrophic scarring and, rarely, hypertrophic scarring.

There are newer flash and pulse dye lasers that allow the wave length to be varied. This allows them to go a little deeper, but the deeper they go, the more complications you have.

The CO2 laser can be used to treat the atrophic changes seen after involution of the superficial hemangioma. CO2 lasers have a wave length of 10,600 nanometers and this wave length is readily absorbed by water. Suture lasers work by blowing water and causing thermal damage in that way.

Usually two passes are required: the first pass vaporizes water off the epidermis, leaving behind a desiccate debris, which you wipe off. The second pass basically boils the water in the superficial tissue, deforming the collagen (not destroying it), causing it to shrink by as much as 20 percent. Over the next six months, as the skin heals, this layer will slough off, which basically serves as a scaffolding on which the new collagen forms.

Another treatment option is surgical excision. Surgery in hemangiomas is considered dangerous for the obvious reasons that these are blood vessels and bleed a lot. Also, hemangiomas can invade adjacent structures, which can make their dissection difficult. Surgical excision is primarily used for deep hemangiomas. If treating a compound hemangiomas, treat the superficial layer first. Let that heal. Then, when you do your surgery, you will have a flap that you can raise, remove the deep portion of the lesion, and lay the flap back down. There are several devices used to help with coagulation during surgery: the traditional unipolar or bipolar cautery, thermal scalpels and contact laser.

Complications of hemangiomas, the most common of which is ulceration, can occur up to 5% of lesions. These are usually seen in hemangiomas that are tense and rapidly proliferating. Also, certain anatomical sites seem to be prone to ulceration. These include the upper lip, upper chest and the genital region.

There are two possible mechanisms for ulceration. In the first, the lesion grows so fast that the skin can't grow and heal over the top resulting in an ulcer. In the second, the lesion grows so fast that it outgrows its own blood supply. All these lesions heal by secondary intention. They will always leave a scar, so these are the lesions which will require surgical intervention to get a good cosmetic result.

Additional complications include high output congestive heart failure. This is seen more with large lesions and also with multiple lesions, as in diffuse neonatal hemangiomatosis. In this disease process, you have multiple cutaneous hemangiomas and, in addition, multiple visceral hemangiomas, commonly located in the liver. These patients typically present with congestive heart failure, anemia and enlarged liver.

There may be additional complications due to location, including loss of sight if they are around the eye, loss of airway if they are in the subglottis and conductive hearing loss if they are around the ear.

A final complication can be hemorrhage, as seen with Kasabach-Merritt syndrome. Kasabach-Merritt syndrome is defined as profound thrombocytopenia in the setting of rapidly proliferating hemangiomas. The thrombocytopenia is thought to be caused by either an increased sequestration of platelets in the spleen, or by the hemangioma itself and a sequestration of the clotting factors. This usually occurs in the first few weeks of life. It occurs during the rapid proliferation of the hemangioma and will present with edema surrounding the tissue with overlying petechiae and ecchymoses. Thrombocytopenic hemorrhagic crisis can eventually occur if the platelet count gets too low and the clotting factors get too low. Treatment is basically supportive care.

In summary then, hemangiomas are benign tumors. They have three main characteristics. They are usually not present at birth although they can be in 30% of the cases. They have two phases, proliferation and involution, with involution occurring approximately 70% of the time by age 12. Sixty percent of these lesions will result in a poor cosmetic result after their involution has completed and therefore can benefit from corrective surgery.

Remember the three questions: was the lesion present at birth, has this lesion increased in size, and has this lesion decreased in size. Remember the caveats to each one of those questions, as well as the treatment options, which are steroids, interferon, lasers and surgery.

Case Presentation

M.M. is an 8-month-old baby boy, born full term without complications, who was initially referred to the pediatric otolaryngology department at Texas Children’s Hospital at 10 weeks of age for new onset stridor, which was steadily increasing in severity. The stridor was made worse when laying supine or with increased activity. The patient also has a history of multiple other cutaneous hemangiomas located on the leg, chest, scalp and buttucks. He has previously been treated with oral steroids. No other significant past medical history was present.

A flexible fiberoptic examination in the office revealed a reddish mass in the posterior L subglottis.

Treatment: The patient underwent MSDL with CO2 laser at 3, 4, 6 and 8 months of age with almost complete resolution of the lesion by his last treatment.

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