This group of conditions, which can affect infants, children, and adults, continues to be a source of concern and confusion for patients and their families, despite having been described for hundreds of years. One of the principal problems is in making the proper diagnosis, which then dictates which tests and procedures should be done. Most medical practitioners see these problems so infrequently that they are unsure as to the best course of action. In many cases, once the proper diagnosis is made, nothing more need be done beyond assuring the patient and family that the condition will follow a benign course.
A look through the medical literature (and now the internet) will reveal a wide range of terminology, including hemangioma, vascular birthmark, port wine stain, vascular malformation, arteriovenous malformation, venous malformation, cavernous venous malformation, Klippel Trenaunay Syndrome, Parkes Weber Syndrome, hemangioendothelioma, and lymphatic malformation, among many others. Many of these terms are equivalent or are no longer considered accurate. After 25 years of dealing with these problems, I find that it is helpful to simplify things by dividing these conditions into only five groups: Hemangioma, Arteriovenous Malformation, Arteriovenous Fistula, Venous Malformation, and Lymphatic Malformation. Each of these conditions is distinct in terms of diagnosis, prognosis, and treatment. Let’s consider each of these individually.
This term is commonly (and mistakenly) applied to all vascular lesions, but it actually describes a very distinct condition which is confined to infants and children. This is the lesion commonly seen in infants and referred to as a “strawberry birthmark”. It is quite common in the general population, occurring in up to 12% of infants. It is significantly more common in premature infants, females and in the Caucasian population, and may be present at birth or appear shortly thereafter. It is a single lesion in most infants, but can be multiple on occasion. This is not a malformation or “birthmark” per se, but a benign tumor of endothelial cells (the cells which normally form the walls of blood vessels). What makes these conditions unique is their characteristic of going through three distinct stages: appearance (at birth or shortly thereafter), the proliferative stage (weeks to months) and the involution stage (the lesion spontaneously resolves by itself, usually by the age 7 or 8 years). This course of events is quite unique biologically, making hemangiomas a subject of intense interest to researchers in conditions where blood vessel development plays a major role, ranging from atherosclerosis to cancer.
Diagnostically, most hemangiomas have such a typical appearance and follow such a predictable chronological course that the diagnosis is easily made clinically and no further diagnostic testing is required. On occasion, a lesion located more deeply and appearing as just a soft tissue mass may require imaging studies (CT, MRI) or rarely a biopsy to confirm the diagnosis. While CT and MRI scans are “non-invasive” tests, they will generally require sedation or anesthesia in infants and children, so that their use is reserved for lesions which are of indeterminate nature clinically or when treatment is required. When would treatment be required in this condition? This is a controversial area, but most experts would agree that those hemangiomas which interfere with breathing, feeding, or visual development should undergo treatment. There are also hemangiomas which grow so rapidly during the proliferative stage that they can present with painful ulceration and bleeding requiring intervention. On occasion, hemangiomas can occur in the liver, where they can be so large and have such high flow that they put a strain on the heart; these lesions will also require more aggressive treatment. Finally, there is a rare variant called Kaposiform Hemangioendothelioma, which tends to occur over the trunk, thigh, or shoulder, and has an unusual diffuse reddish or purple color with thickening of the skin which resembles inflammation. This specific type of hemangioma has a tendency to consume platelets from the blood (the cells which are part of the normal clotting mechanism), which can in turn lead to bleeding complications (referred to as Kasabach-Merritt Syndrome).
If treatment is required for hemangiomas, it usually consists of a combination of local care (topical treatment) combined with systemic therapy, generally oral steroids. Steroids have been used for decades in treating hemangiomas and are still considered the mainstay of therapy when it is required. Steroids should be administered by pediatricians with specific expertise in treating hemangiomas, as dosage, timing, and duration of therapy must be judged and monitored closely, due to potential side effects, including suppression of the immune system. Other drugs, including interferon and cytotoxic drugs, are used less frequently now due to their much greater potential toxicity. Radiation treatment was used in the past but has no current role in the management of hemangiomas due to the risks of local tissue damage as well as the potential for long term carcinogenesis (tumor formation).
Until very recently, surgery was felt to play little role in the treatment of hemangiomas, due to their tendency to resolve spontaneously over time. Aside from the unusual situation where surgery is required for hemangiomas involving respiratory, digestive, or visual structures, there has been a resurgence of interest in lesions causing cosmetic deformity, particularly on the face. While it is true that small lesions will disappear over time leaving almost no trace, extensive lesions may leave behind pale, atrophic skin after involution, in some cases requiring plastic surgery to achieve an acceptable cosmetic appearance. Some plastic and head and neck surgeons feel that earlier surgical removal in these cases may be preferable, not only achieving an immediate improvement in
appearance but also avoiding the psychosocial difficulties which may be encountered by patients (especially children) with a cosmetically disfiguring condition.
In summary, hemangiomas are benign blood vessel tumors which occur in infants and children. They typically progress through a proliferative stage where they may show rapid growth, and then tend to involute (or resolve) spontaneously in early childhood without treatment. Due to this typical benign, self-limited history, management is conservative in most patients. When treatment is required, it should be under the care of physicians with specific expertise in this area.
Arteriovenous malformations, also referred to as vascular malformations or AVMs, are congenital abnormalities in the local development of the blood vessels, usually confined to a single anatomic area. In the normal development of the circulatory system, there is initially a primitive system with poorly defined vascular “lakes”. As the embryo and fetus develop, there is a progressive complex process of refinement (still not completely understood) where these primitive structures develop an organization into arteries (carrying oxygenated blood away from the heart), capillaries (tiny networks where the oxygen is actually delivered to the tissues), and veins (which carry the deoxygenated blood back to the heart). A vascular malformation represents the localized failure of this process, resulting in a disorganized structure where arteries and veins connect without the normal tapering of vessels into a capillary bed. The size of the abnormal direct connection between arteries and veins will determine the amount of flow “short-circuited” through the malformation. If the malformation is small or deeply located, it may be of little or no clinical significance. If the malformation is larger or in a more critical location, it can have significant effects locally or even on the entire body.
Since these are not tumors but just abnormal areas of tissue development, they tend to grow along with the individual. Unlike hemangiomas, they do not resolve spontaneously; this is why it is critically important to make the specific diagnosis and not lump all vascular lesions under the term “hemangioma”.
Depending on where they are located and the amount of abnormal flow through them, they may show up at any time in life from infancy to adulthood. One common but poorly understood aspect of vascular malformations in female patients is their apparent increase in size and symptoms at times of increased hormonal activity, specifically puberty and during pregnancy. We commonly see the first complaints related to the malformation when a young girl reaches puberty or is in her early teens; these patients may also note that symptoms are worse at certain points in the menstrual cycle.
Arteriovenous malformations can occur anywhere in the body and are usually isolated abnormalities in otherwise normal, healthy individuals. They are congenital but not genetic (with rare exceptions), meaning that there is little likelihood of passing them on to one’s children, little likelihood of siblings having the same problem, and rarely any family history of vascular malformation. There are rare genetically transmitted familial syndromes (such as Rendu Osler Weber Syndrome) where multiple family members will have multiple AVMs, but most affected families will already be aware of this condition. Unlike hemangiomas, there is no tendency for them to occur in females and they seem to occur with equal frequency in all races and ethnic groups.
Depending on where in the body they are located, their size, and the amount of abnormal flow through them, AVMs can range from being asymptomatic lesions requiring no treatment to life-threatening problems in rare cases. If they are near a skin surface they may present as a soft tissue mass with or without changes in the overlying skin. If the flow is rapid enough, a pulsation may be felt over the area, and the blood vessels leading to and way from the malformation may be enlarged and pulsatile. They usually cause no pain and are not tender to the touch. If the flow is very rapid, it may cause blood to flow through the short-circuit, where the pressure is lower, rather than to the normal tissues in the area. This can lead to the seemingly paradoxical situation of having excessive blood flow to the general region but signs and symptoms related to the lack of flow to the normal structures beyond the malformation (localized ischemia). When the malformation is located in an extremity, this may be manifest by pain on exercise, atrophy of tissues in the hand or foot, or even breakdown of the skin integrity (ischemic ulceration). In some patients, their major presenting problem is this distal ischemia, rather than at the site of the malformation itself. The veins draining the malformation are also subjected to flow and pressure they were not designed to handle, resulting in dilation and thickening of the veins, eventually leading to secondary changes of “venous hypertension”. The veins under pressure can cause localized thickening and eventual deterioration of the overlying skin similar to that seen in patients with severe varicose veins, sometimes resulting in ulceration. Treating the underlying vascular malformation will usually reverse these changes to a great extent.
If the abnormal flow through an arteriovenous malformation is extremely high, there can be generalized effects on the entire cardiovascular system. These effects can include increased blood volume, elevated heart rate, and in rare cases, heart failure. These changes, while mentioned in every text book and often mentioned by pediatricians and internists as a concern, are actually quite rare in practice. Out of over a thousand patients treated with vascular malformations in 25 years, I have seen only a handful of patients with this problem. It is generally seen in the setting of a small child with a very large shunt (short circuit) or in the rare adult with an extremely high flow AVM. In these cases, treatment of the malformation can be life-saving.
Another concern is that of bleeding or hemorrhage related to the malformation. Major bleeding is exceedingly rare, and is usually associated with ulceration of the skin or internal involvement of the gastrointestinal or urinary tracts. The risk in other patients is so low that I never limit a patient’s activities, whether child or adult, with the possible exception of such activities as swordfighting.
When vascular malformations are located in certain parts of the body, specific issues and concerns arise. Vascular malformations in the pelvis can involve the bladder, colon, or uterus, potentially causing bleeding from any of these organs. I have treated many women with pelvic AVMs, and the question of fertility and risk of pregnancy is always raised. The normal changes which occur during pregnancy cause enlargement of the AVM and an increase in flow through it, sometimes increasing symptoms. Unless the AVM involves the uterus itself, fertility is generally not adversely affected and a normal delivery is possible in most patients, although involvement of a specialist in high-risk pregnancy is advised.
Two other anatomic locations which pose unique problems are pulmonary AVMs and those involving the central nervous system (brain and spinal cord). Pulmonary AVMs are unusual in that they represent a short circuit in the lung blood vessels where blood from the veins is directly shunted into the arterial circulation. This has two potential effects – the oxygen level in the blood may be reduced, causing shortness of breath and decreased exercise tolerance, and the filtering function of the lung is partly lost, allowing blood clots from the venous system to reach the arterial circulation. This can result in a condition called paradoxical embolism, with the possibility of stroke. Vascular malformations involving the brain or spinal cord are complex management problems; they may be asymptomatic but can cause bleeding or a mass effect (like a tumor) in the closed space of the skull. Vascular malformations involving the nervous system should be managed by physicians with highly specialized expertise in this area (certain neurosurgeons and interventional neuroradiologists).
The treatment of arteriovenous malformations depends on the size, location, and clinical problem resulting from the lesion. Small, asymptomatic lesions which are discovered incidentally do not require specific treatment once the diagnosis has been confirmed by imaging studies or angiography. In the majority of patients, the diagnosis can be confirmed on non-invasive imaging studies – ultrasound, CT, or MRI scans – and angiography is only performed if the diagnosis is in doubt or if endovascular (embolization) treatment is planned (see below).
When treating vascular malformations, two things must be kept in mind – first, they are generally benign conditions which show little or no progression once growth stops, and two, it is difficult or impossible to “cure” or eradicate them completely, as they have a strong tendency to recur regardless of the type of treatment performed. Therefore treatment should be directed at eliminating symptoms with a minimal degree of risk and
invasiveness. Surgical removal is generally not possible except in very localized malformations; since these are benign lesions, heroic “cancer type” surgery is inadvisable, as it is not necessary and may replace a relatively minor problem with significant scarring or disability.
Embolization treatment has assumed a major role in treating vascular malformations, as it combines minimal invasiveness with a significant reduction in symptoms. The principle involves passing a small catheter through the arterial system into the specific arterial branch supplying the malformation; an embolic agent is then injected through the catheter under fluoroscopic (x-ray) guidance into the center of the malformation (the nidus). A range of materials has been specifically developed for this purpose, including certain polymers, acrylic adhesives, microspheres, ethanol, and platinum coils. Each embolic agent has advantages and disadvantages, the choice being made on the basis of the type of malformation and the experience and preference of the physician performing the procedure. The procedure is performed under IV sedation or general anesthesia; there is no incision – the only entry point is a needle puncture in the femoral artery at the top of the leg. The patient is generally observed overnight and goes home the following morning. Depending on the size and location of the malformation, one or a series of treatments may be required.
In terms of treatment results, approximately 80% of patients can expect marked improvement or elimination of symptoms following treatment; 15% of patients can be “cured” completely, meaning there is no evidence either clinically or radiologically that there is any residual malformation. Again, as these are benign conditions, resolution of symptoms rather than complete eradication should be the goal. Potential complications of embolization treatment are of two types – those occurring at the arterial entry site (bleeding, hematoma or bruise, damage to the artery), and those related to the actual embolization, where too much blood flow is stopped, the wrong artery is blocked, or the embolic agent passes through the malformation completely and reaches the vein or pulmonary circulation. In experienced hands, the significant complication rate should be less than 1%.
An arteriovenous fistula is a direct abnormal connection between an artery and a vein, allowing blood to shunt directly from the high pressure artery to the low pressure vein. This problem is usually related to a penetrating injury, which can be traumatic or iatrogenic (the result of a medical procedure). A small fistula may close by itself without treatment, but larger ones will enlarge over time, eventually resulting in the same kinds of problems seen with congenital vascular malformations (increased flow, enlarged vessels in the area, stealing of flow away from normal tissues, and increased cardiac work).
Fistulas have been described since antiquity, usually related to war-related injuries. If treated early, before the surrounding blood vessels become abnormally enlarged, arteriovenous fistulas can usually be completely cured by either surgery or embolization. It is essential that the actual point of connection between the artery and vein be closed, or other blood vessels in the region (collaterals) will be drawn into the process, making subsequent treatment more difficult. Since the anatomy of a fistula is much simpler than a congenital malformation (single hole versus tangle of abnormal connections), the likelihood of complete cure is much greater.
Congenital fistulas (present at birth) are rare but do occur, both in the brain and elsewhere in the body, such as the lung and kidney. Due to the very high flow through these vessels, treatment can be technically difficult but a complete cure is possible in most cases.
Venous malformations are the commonest type of malformation occurring in the general population, probably five times more common than arteriovenous malformations. Other terms applied to this condition are cavernous venous malformation and cavernous hemangioma (the latter a misnomer, as hemangioma should refer only to the benign vascular tumor of infancy). These malformations can range from a superficial skin lesion, sometimes referred to as a “port wine stain”, to abnormal development of the entire deep venous system of an extremity. Like congenital arteriovenous malformations, these are problems of vascular development present from birth, congenital but not genetically transmitted. By definition, they are purely venous with no arterial component, meaning they are slow-flow, low pressure venous spaces. If they are in an area which is near the surface, they will present as a soft fluid-filled mass which can be emptied by manually compressing it or, if it is in an extremity, elevating the extremity above the level of the heart. In infants and children, the lesion may change in size or shape depending on position or even when the child is crying, which increases venous pressure. Since they are low flow, they will not have pulsation, nor will they show enlargement of the vessels in the area. They are nearly always painless to the touch, although when they become distended with blood following activity or when in dependent position, aching, heaviness, or a feeling of pressure may be experienced.
When a cavernous venous malformation is accessible to physical examination, the diagnosis is usually obvious. Ultrasound examination will show fluid-filled spaces with little or no flow, while CT and particularly MRI can confirm the diagnosis with certainty.
As in arteriovenous malformations, these lesions will grow along with the child until maturity; unlike hemangiomas, they will not go away by themselves. If symptoms are absent or minimal, treatment is not required, nor is any limitation of normal activities. The patient may periodically experience episodes of localized pain in the malformation with associated signs of inflammation (redness, swelling, warmth); this is nearly always due to localized clotting (thrombosis) within these slow-flow spaces (blood tends to clot when it is not flowing). These are benign localized clots, not the type of blood clot which put the patient at risk for pulmonary embolism or stroke; treatment consists of warm soaks and anti-inflammatory medication. The symptoms can be expected to resolve in one or two weeks.
Treatment should be directed at relief of symptoms, rather than complete eradication of the malformation, which is often not possible without disfiguring (and unnecessary) surgery. Local measures such as support stockings, ace bandages, or elastic sleeves may show a significant reduction in venous distention and pain when used during strenuous activity. Surgical removal may be indicated when the malformation is localized and accessible without excessive loss of normal tissue; it is essential for detailed imaging studies (CT, MRI) to be obtained prior to any planned surgery, as the visible or palpable mass may be the “tip of the iceberg”, and a simple operation can quickly become
Direct embolization, a form of sclerotherapy, can be effective at shrinking these venous malformations and reducing or eliminating symptoms. Under sedation or anesthesia, the malformation is entered directly with a small catheter and radiographic contrast (x-ray dye) is injected while observing under fluoroscopy. This will show the true extent of the lesion and whether it connects to the normal veins in the region, an important piece of information for planning a safe procedure. Once the size and volume of the malformation is determined, the embolic agent (ethanol or sodium tetradecyl sulfate are the commonest) is directly injected, again under visual x-ray guidance. Often a venogram, or radiologic study of the normal veins in the region, will be performed prior to the embolization. In some patients with venous malformations, an associated congenital abnormality is an absence or underdevelopment of the normal venous system in the area, meaning that the only route for blood draining from the extremity is through the malformation. Blocking off the malformation with embolization would then make the symptoms much worse.
Following a direct embolization procedure, the area will likely appear enlarged and possibly more uncomfortable for a period of two to three weeks. This is due to the inflammatory process deliberately caused in order to clot the abnormal venous spaces.
As the clot is reabsorbed and replaced with connective tissue, the malformation will typically show shrinkage over a period of six to eight weeks. It is common for multiple procedures to be required to achieve a maximum effect in shrinking the malformation and
eliminating symptoms of pain and swelling. In certain parts of the body, particularly the calf and forearm, treatment must be staged in order to avoid excessively increasing pressure in the closed tissue compartments found in these locations (compartment syndrome). Other possible problems following direct embolization include skin ulceration and bleeding, both usually minor and controlled with topical treatment.
One of the commonest forms of venous malformation, despite its exotic-sounding name, is Klippel-Trenaunay Syndrome, which generally involves a singe extremity (usually the leg), and includes over- or undergrowth of the involved limb, varicose veins, and a port wine stain (capillary venous malformation) over the involved part. There is a wide range of signs and symptoms ranging from minimal, with unilateral mild varicose veins, to severe forms which can cause significant disability. Like the other malformations, this condition is congenital but not genetically transmitted, and is rarely seen in other family members. Treatment is usually for symptoms only, and usually includes support stockings and local skin care over large superficial veins. In some children with significant limb length discrepancy, carefully timed fusion of the growth plate (epiphysis) at the knee is performed in order to minimize the length discrepancy when full growth is attained. One important caution in treating patients with this syndrome is to determine the status of the deep venous system either by MR venography or contrast venography prior to considering the stripping, removal, or ablation of symptomatic veins. Approximately one third of patients with this syndrome will have abnormalities of the deep veins which would make vein stripping inadvisable or even dangerous. An unusual variant of Klippel Trenaunay Syndrome is one in which there is an arterial component to the malformation; this is termed Parkes Weber Syndrome, and these patients may benefit from arterial embolization to reduce the pressure in the abnormal veins. MRI studies will generally allow this diagnosis to be made accurately.
The lymphatic system is part of the body’s circulatory system, but rather than carrying blood, it picks up the tissue fluid that normally escapes into the tissues and returns it to the general circulation through a series of tiny channels. In addition to scavenging this fluid, it serves an important immunologic function by delivering bacteria and other pathogenic agents to the lymph nodes, where the cellular immune response is initiated
Lymphatic malformations may occur alone or in combination with venous malformations. The three broad categories of lymphatic malformation are the cystic type (cystic hygroma), usually seen in infants and children, more diffuse malformations which often have superficial skin involvement, and syndromes involving underdevelopment of the lymphatic system in an anatomic region (congenital lymphedema syndromes). The cystic malformations usually occur in the neck and present as a soft tissue mass;
treatment is by excision or by drainage and injection of a sclerosing agent. The more diffuse form is more commonly seen in adults, who develop small blister-like lesions (vesicles) which can leak clear lymphatic fluid and tend to develop multiple episodes of infection and inflammation (cellulitis). Treatment is difficult and consists of sclerotherapy, local care, and in some cases surgical removal. Congenital lymphedema syndromes are uncommon, but may be seen in association with some genetic abnormalities such as Turner’s Syndrome. There is no specific treatment other than compression garments and lymphatic massage.
If you’ve read this far, you now know more about hemangiomas and vascular malformations than 95% of practicing physicians. As you have seen, these represent a wide range of conditions which can affect all age groups and range in severity from trivial to extremely serious. The key points to remember are that proper diagnosis is essential, treatment should be by individuals with specific expertise in this field, and that these are generally benign conditions in otherwise healthy individuals, so that any proposed treatment should be directed at treating symptoms with a minimal degree of risk and discomfort.
If you have any questions regarding these conditions in general or about yourself or a family member, please feel free to contact me:
Robert J. Rosen, M.D.
Lenox Hill Heart and Vascular Institute
130 East 77th Street
New York, N.Y. 10021