Published October 18, 2004Orhan Konez, MD |
Birthmarks include benign erythamatous patches, hemangiomas and various forms of vascular malformations. Vascular malformations are grouped as high- and low-flow malformations based on the flow dynamics within the lesion. If the lesion has arteriovenous shunting, it is considered to be a high-flow malformation; otherwise, it is considered to be a low-flow malformation. Most birthmarks are small and harmless, and require no additional testing or treatment. However, treatment may be imperative for some birthmarks. For many patients, particularly teenagers, discolorations of the skin or cosmetic disfigurations are a major concern. Many birthmarks may not be easily noticeable but may cause significant discomfort and pain despite their benign nature. Other birthmarks can grow rapidly and cause significant health problems (eg, heart failure), requiring intense medical care and therapeutic intervention such as embolization or sclerotherapy. See Table 1 for the tabulation of the vascular anomalies. |
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DefinitionPrevalencePathophysiologySigns
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The exact prevalence is very difficult to assess since most birthmarks are harmless benign lesions and many are deep in the tissues. Also, despite the name, many birthmarks are not present at birth. Erythamatous skin patches in newborns are very common; however, most disappear. Capillary malformations (CMs; slightly raised skin discolorations), commonly called "port-wine stains," are less common, appearing probably in 3 of every 1,000 infants.2 It is generally said that 1 in every 10 children develops a hemangioma, most of which are on the head or neck and most of which occur in females.3,4 Other forms of hemangioma are much less common. Venous malformations (VMs), commonly and erroneously called "cavernous hemangiomas," probably exist in as much as 30% to 50% of the general population. Most of them are unrecognized mostly because of their deep locations in the body. Other forms of vascular malformations are less common. Overall, if all the above-mentioned birthmarks are included, they are present in more than 50% of the general population. Obviously, only a small percentage of this population seeks medical care; many forms of newborn birthmarks disappear, and most people never know they have a birthmark or simply ignore it. |
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Hemangiomas are benign tumors of infancy and are grouped (Table 1) as infantile hemangiomas, rapidly involuting congenital hemangiomas, noninvoluting hemangiomas, and intramuscular hemangiomas. Although Kaposiform hemangioendothelioma (KHE) is generally more aggressive and may be associated with life threatening Kasabach-Merritt syndrome, KHE is also considered to be in this group. Infantile hemangioma is a relatively common, benign neoplasm that usually develops in neonates within their first few months of life. Most infantile hemangiomas undergo rapid initial proliferation, with a subsequent plateau in infants aged 9 to 10 months. The plateau phase may last for several years. Finally, the hemangiomas become involuted, usually between age 1 year and 5 to 7 years.1 The rapidly involuting congenital hemangioma is a similar benign tumor, but it differs from infantile hemangioma in that it has a fully developed presentation at birth, with rapid involution and regression.5-7 Intramuscular hemangioma and noninvoluting congenital hemangioma are rare entities; they differ from infantile hemangioma simply because they do not regress and extend into adulthood. Kaposiform hemangioendothelioma (KHE) is a hemangioma-like tumor in infancy, but usually presents as a more aggressive tumor than infantile hemangioma, and there is a well-known association between KHE and Kasabach-Merritt syndrome (severe coagulopathy caused by platelet trapping, resulting in spontaneous hemorrhage). Kaposiform hemangioendotheliomas are histopathologically distinct from the common hemangiomas of infancy. Kaposiform hemangioendothelioma is characterized by irregular lobules, spindled or less rounded endothelial cells that form slit-like or crescenting vessels containing microthrombi, hemosiderin and fragmented erythrocytes, whereas infantile hemangioma is characterized by well-formed capillaries.8 Vascular Malformations: High-flow
Vascular Malformations
Arteriovenous malformations are considered to be congenital vascular anomalies, but are usually first noted several years after birth or after certain triggering changes such as trauma or the hormonal changes of puberty or pregnancy. Arteriovenous malformations generally enlarge in size and number (eg, a single nidus may become multiple) and may cause significant health problems as a result of progressive arteriovenous shunting resulting in high-output cardiac failure, ischemia or bleeding. Arteriovenous fistulas (AVFs) are simple arteriovenous connections. Most AVFs are secondary to penetrating injuries after birth, although some are believed to be congenital. Low-Flow
Vascular Malformations
Lymphatic malformations are congenital abnormalities of the lymphatic system. Lymphatic malformations are usually classified as microcystic, macrocystic, or mixed. Microcystic lymphatic malformations consist of masslike soft-tissue abnormalities, although abnormal lymphatic channels are generally present in the abnormal tissue. Macrocystic lymphatic malformations consist of visible cystic spaces that contain lymphatic fluid. The term "cystic hygroma," which was previously and commonly used for macrocystic lymphatic malformations in the neck, is no longer used in modern medical terminology. Mixed lymphatic malformations consist of mass-like solid-appearing lesions accompanied by cystic lesions. Lymphatic venous malformations are a combination of abnormal lymphatic and venous channels. Abnormal venous structures gradually develop in association with most lymphatic malformations, and these lesions are considered to be lymphatic venous malformations rather than a completely separate histopathologic entity. Capillary malformations (port-wine stains) are common birthmarks and involve only the superficial tissues (skin) and do not extend into the deep tissues. Although they have a significant psychosocial impact, most capillary malformations do not cause health problems and are generally treated for cosmetic reasons. Overgrowth Syndromes: These conditions are generally characterized by the overgrowth of involved body parts. The typical condition in this group is Klippel-Trénaunay syndrome, which is a low-flow combined vascular anomaly (capillary-lymphatic-venous malformation) usually associated with marked overgrowth of the leg and capillary stains. The condition may rarely be associated with hypotrophy. Anomalous lateral veins, which are typically on the lateral aspect of the thigh, become prominent because of incompetent valves and deep venous anomalies. The main features of Proteus syndrome include verrucous nevus, lipomas and/or lipomatosis, macrocephaly, asymmetric limbs with partial gigantism of the hands and feet, and cerebriform plantar thickening. In Maffucci's syndrome, low-flow vascular malformations, similar to venous malformations, are associated with bony exostoses and enchondromas. The osseous lesions usually appear in children, whereas the vascular lesions usually manifest in adulthood. Bony and vascular lesions may be unilateral or bilateral. Patients typically have spindle-cell hemangioendotheliomas, ie, a reactive vascular proliferation within a preexisting vascular malformation. Malignant transformation, most commonly to chondrosarcoma, occurs in 15% to 30% of patients.11 Parkes-Weber syndrome consists of an AVM-like high-flow malformation that involves the entire extremity (usually a lower limb), and it is usually associated with a capillary malformation over the enlarged limb. Cobb syndrome (cutaneomenengial angiomatosis) consists of a capillary malformation that is high-flow in nature and located on the posterior thorax in association with spinal involvement. Sturge-Weber syndrome is a neurocutaneous condition characterized by "angiomas" (capillary malformation) of the leptomeningies (typically in the parietooccipital region) and face. |
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Hemangiomas usually first appear a few weeks after birth and affect the head and neck in most patients. The trunk and extremities are less commonly involved. Hemangiomas look like red, flat or raised, patches or plaques with or without a cluster of superficial veins (Figures 3, 4, 5). Deep hemangiomas can cause skin discoloration. Hemangiomas are generally firm and rubbery to the touch. In the shrinkage (involution) phase, hemangiomas get darker. The color gradually turns to a light flesh color. With completion of the shrinkage phase, the lesion may leave a wrinkled crepe-paperlike appearance on the skin, which is believed to be secondary to the loss of collagen and elastin in the skin. If ulceration occurs over the lesion, a scar develops where the ulceration occurred. Rapidly involuting congenital hematomas usually present at birth and usually appear to be aggressive lesions, although their progress into the involution phase is generally much faster than that of infantile hemangiomas (Figures 6A, and 6B). Because of their aggressive appearance with possible skin ulcerations, aggressive diagnostic and therapeutic means may be suggested but are generally unnecessary in most patients with these lesions. A thrill due to rapid arteriovenous shunting, similar to that of arteriovenous malformations, may also be noted in some patients and usually raises false concern about a congenital arteriovenous malformation or a congenital sarcoma. Other forms of hemangiomas (noninvoluting hemangiomas and intramuscular hemangiomas) do not regress in early childhood and are commonly encountered in early adulthood. Kaposiform hemangioendotheliomas may be present at birth in neonates or they can develop in infants within the first few months after birth. The trunk is the most common location. An ill-defined purpuric mass is a common presentation in kaposiform hemangioendothelioma (Figure 7). Patients with kaposiform hemangioendothelioma typically present with an ecchymotic hemangiomalike mass with scattered bruising and petechiae. The tumor is associated with extremely low platelet counts and markedly decreased fibrinogen levels (Kasabach-Merritt syndrome). Kaposiform hemangioendothelioma has a mortality rate of 24%, which is caused by coagulopathy or complications of local tumor infiltration.12 Arteriovenous malformations (AVMs) are generally present in neonates at birth, but they often suddenly become obvious when the patient is older because of various stimuli such as trauma, pregnancy, or puberty. Progression may also occur after iatrogenic trauma, such as a biopsy, proximal ligation, or subtotal surgical excision. Although the overlying skin may be normal, these malformations can be easily recognized at clinical examination by the presence of a pulsatile mass, thrills, increased warmth, and redness. (Figures 8 and 9). Focal or diffuse enlargement of the involved extremity is also a common clinical finding. Common symptoms of AVM include pain and skin changes related to ischemia. AVMs in the extremities are relatively common. They may be single or multifocal in the extremity, or they may be diffuse and involve the entire extremity and adjacent trunk. Head and neck arteriovenous malformations differ somewhat because of their catastrophic complications, which include bleeding from dental manipulation (common in dental arcade AVMs) and the potential risk of stroke when they are embolized. Pulmonary arteriovenous malformations and arteriovenous fistulas usually cause cyanosis, clubbing, and polycythemia, as well as cerebral infarcts and abscesses due to loss of the normal filtering function of the pulmonary vasculature.13 There are four recognized stages of AVMs:14 A stage I lesion has a pinkish-bluish stain and warmth. In stage II, the lesion has pulsations, thrill, and bruit. In stage III, the patient has dystrophic skin changes, ulceration, bleeding, and pain. Finally, in stage IV, the patient has high-output cardiac failure. Arteriovenous malformations involving the lungs and/or gastrointestinal system are common in Rendu-Osler-Weber syndrome (hereditary hemorrhagic telangiectasia). In this syndrome, the bowel lesions are small hemangioma-like abnormalities without angiographically demonstrable arteriovenous shunting.13 Hepatic involvement shows increased hepatic arterial vascularity, giving the appearance of a dirty hepatic arteriogram, and may cause significant arteriovenous shunting.13 Venous malformations are congenital lesions but usually become symptomatic in older children or young adults, with bluish skin discoloration, local swelling, and pain (Figures 10, 11, 12). These lesions are commonly (and erroneously) referred to as "hemangiomas." The characteristic physical finding is a soft and easily compressible soft-tissue mass or swelling associated with bluish skin discoloration. Increasing engorgement with dependency is typical. These lesions can be small and localized or extensive and involving the entire extremity or body part. Although venous malformations are considered benign entities, some extensive venous malformations can result in significant morbidity, particularly those in the head and neck (eg, with airway involvement). Several syndromes, such as Klippel-Trénaunay, Maffucci, and blue rubber bleb nevus, are characterized by VM-like slow-flow vascular anomalies. Some large venous malformations are associated with sinus pericranii (abnormal communication between intracranial and extracranial circulations) and developmental intracranial venous anomalies when located in the head and neck.9 Large pharyngeal, laryngeal, and deep cervical-oropharyngeal venous malformations can expand to compress the airway and cause significant deviation that requires tracheostomy in most cases. Extremity venous malformations may be associated with a limb-length discrepancy, particularly if the malformation is large. Intraosseous venous malformations can cause structural weakening of the osseous shaft and pathologic fractures. Involvement of a joint by venous malformation may result in hemosiderin arthropathy caused by repeated intraarticular bleeding, which is typically seen in the knee. Venous malformations of the gastrointestinal tract most commonly cause chronic bleeding and anemia, and they may be part of blue rubber bleb nevus syndrome. Lesions that involve the foregut can be associated with portal venous anomalies such as absence of the portal vein, portal hypertension, and so on. Glomangioma, or glomovenous malformation, is an autosomal dominant disorder that is characterized by multiple, often tender, blue, nodular skin venous malformations.10 Although this entity differs from typical venous malformation because of the presence of numerous glomus cells (immature smooth muscle cells) that line the ectatic vascular channels at histopathologic study, whether the images of typical venous malformations and glomangiomas differ has not yet been determined. Another familial condition associated with multiple venous malformations is the familial cutaneous mucosal venous malformation, in which dome-shaped cutaneous lesions of various sizes develop progressively over time. Lymphatic malformations commonly occur in the cervicofacial region (approximately 75% of lymphatic malformations). Most lymphatic malformations are apparent in young children. These malformations appear in various forms, such as localized small lesions or in the diffuse involvement of an extremity or particular body part or organ system. There are three forms of lymphatic malformation: microcystic lymphatic malformation (no cystic lesion on magnetic resonance imaging [MRI]); macrocystic lymphatic malformation (cysts on MRI); and mixed lymphatic malformation (cystic and solid tissue on MRI). The overlying skin can be normal, or it may have tiny characteristic vesicles. Cervicofacial lymphatic malformations may be associated with the overgrowth of the mandibular body. Lymphatic malformations of the floor of the mouth and tongue are usually characterized by vesicles, swelling, and bleeding. In most cases, the airway is involved to some degree. Lymphatic malformations of the orbit typically cause proptosis (sudden proptosis is usually due to intralesional bleeding), which may require surgical or interventional decompression to save the optic nerve. Lymphatic malformations in an extremity can cause diffuse or localized swelling with soft-tissue and skeletal overgrowth (Figures 13 and 14). When a lymphatic malformation is located in the pelvis, it is usually associated with bladder outlet obstruction, constipation, or recurrent infection. Disappearing bone disease (Gorham-Stout syndrome) is a rare disease entity with progressive osteolysis that is considered an lymphatic malformation.
Lymphatic venous malformations (LVMs) consist of mixed clinical and imaging findings of lymphatic malformations and venous malformations (Figure 15). Capillary malformations are common form of vascular anomalies. They are usually easily recognized by general practitioners and do not require additional testing (Figure 16). Most patients seek medical help because of concern about a suspected significant, underlying condition, or more commonly for cosmetic reasons. Klippel-Trénaunay syndrome usually presents with low-flow anomalies (venous malformation and/or lymphatic malformation) and varicoid superficial veins. The involved extremity (usually the leg) is larger than the other, with a geographic skin discoloration/capillary stain (Figure 17). Lateral venous anomaly is known as marginal vein of Servelle. Parkes-Weber syndrome usually presents with cutaneous warmth and a bruit or thrill on clinical examination, all of which are more suggestive of a complex vascular malformation than a simple capillary malformation. Proteus syndrome consists of complex congenital vascular, skeletal, and soft-tissue anomalies. The vascular anomalies in this entity include both fast-flow malformations such as arteriovenous malformation and low-flow malformations such as lymphatic malformations and/or venous malformations. Maffucci's syndrome is a rare anomaly combining multiple enchondromas (benign bone tumors) with soft-tissue, low-flow malformations similar to venous malformations. Patients with Maffucci syndrome are usually symptomatic because of a growth disturbance of the affected bones; also, the vascular malformations may be painful. Sturge-Weber syndrome is usually characterized by facial capillary malformations (port-wine stain) located in the distribution of the trigeminal nerve. The neurological manifestation of this syndrome varies depending on the location of leptomeningeal angiomas. Patients with Sturge-Weber syndrome may develop seizures, hemiparesis, developmental delay or glaucoma. |
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Most vascular anomalies, particularly the superficial anomalies (eg, capillary malformations port-wine stains) are recognized by simple clinical history and clinical assessment and do not require any imaging studies. However, most anomalies extending into the deep tissues require imaging studies to confirm the initial diagnosis, to determine the extent of the malformation and to plan treatment despite the fact that an experienced physician can easily recognize most vascular anomalies accurately. The most common misdiagnosis or misconception is referring to venous malformations as "hemangiomas." This misconception can easily lead to incorrect triaging and mistreatment. In addition, venous malformations are often called arteriovenous malformations although all clinical and radiologic findings are characteristic of a low-flow vascular anomaly. Because of this, many patients undergo conventional arteriography unnecessarily. Unnecessary embolization procedures may also be performed in some of these patients. Therefore, recognizing a vascular malformation and appropriately classifying the malformation is essential for optimal patient care and requires solid knowledge and experience. MRI is the imaging modality most commonly used today to assess these anomalies.15 MRI should include T1- and T2-weighted spin-echo imaging in multiple planes, fat-saturated T1-weighted imaging with the intravenous administration of a gadolinium-based contrast agent, and gradient-recalled echo (GRE) imaging. T2-weighted images are used mainly to evaluate the extent of the abnormality; GRE images are used to identify the hemodynamic nature of the condition (high- vs low-flow lesions); and contrast-enhanced images are used to determine the extent of the malformation and to distinguish low-flow vascular anomalies (venous malformation versus lymphatic malformation). For any vascular anomaly, the basic approach is first, to evaluate fat-suppressed T2-weighted images to determine the extent of the anomaly, and second, to evaluate the GRE images to decide whether the anomaly is a high-flow lesion. If the anomaly is a low-flow lesion, arteriovenous malformation, arteriovenous fistula, and hemangioma can be excluded from the differential diagnosis. Low-flow vascular anomalies (venous malformation, lymphatic malformation, capillary-lymphatic-venous malformation, and combined overgrowth syndromes) can be further differentiated on the basis of their morphologic appearances and contrast-enhancement patterns. If the anomaly has no contrast enhancement or a minimal degree of peripheral contrast enhancement (rings and arcs), lymphatic malformation should be considered foremost in the differential diagnosis (Figure 18). If the anomaly has easily noticeable patchy areas of contrast enhancement, venous malformation should be suspected (Figure 19). If the lesion is a high-flow anomaly, the differential is limited to arteriovenous malformation, arteriovenous fistula, and hemangioma. In patients aged 8 years and older, hemangioma can be excluded in the majority of patients. Noninvoluting hemangiomas and intramuscular hemangiomas may be encountered in adults, but they are rare. When a high-flow anomaly is found, a malignant tumoral mass should also be considered in the differential diagnosis. In hemangiomas, fast-flow vessels are usually at the periphery of the mass, and the mass usually enhances homogeneously (Figure 20), whereas in a malignant tumoral mass, vessels have a random distribution and enhancement is usually inhomogeneous. A mass lesion is not expected in an arteriovenous malformation, although some arteriovenous malformations, particularly those encapsulated by the muscle fascias, may have masslike enhancement; these can be confused with tumoral masses. If there are any remaining questions, the high-flow nature of an arteriovenous malformation can be easily confirmed with Doppler examination, which reveals high-flow, low-resistance arteries and an arterialized waveform in the draining veins. Although the gold standard for high-flow anomalies is conventional arteriography, the new noninvasive angiographic techniques such as magnetic resonance angiography or computed tomographic angiography offer noninvasive assessment of the flow dynamics and vasculature of high-flow anomalies (eg, arteriovenous malformation, arteriovenous fistula). Portability and availability are the main advantages of ultrasonography compared with MRI. Ultrasonography is commonly used to quickly evaluate anomalies during the patient's initial visit to confirm the suspected diagnosis. It is also used to triage patients and schedule them for appropriate treatment. For example, if the mass is a suspected hemangioma, it can be easily confirmed by ultrasonography without additional tests. Duplex ultrasonography, continuous-wave Doppler ultrasonography, color Doppler ultrasonography, and Doppler spectral analyses are all useful in evaluating vascular malformations. Additionally, Doppler spectral analysis can be used to differentiate arterial from venous flow. An experienced sonographer or radiologist is needed for appropriate sonographic evaluation. CT is particularly useful in detecting phleboliths in venous malformations and in evaluating bone overgrowth or lysis that may accompany vascular anomalies. |
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Treatment varies according to the nature of the vascular anomaly. Capillary malformations are either isolated anomalies or part of more complicated syndromes (Parkes-Weber syndrome, Klippel-Trenaunay syndrome, Sturge-Weber syndrome) and can be managed by laser treatment. Also, laser treatment can be used for ulcerated hemangiomas quite effectively. Other birthmarks generally require more invasive imaging-guided procedures (embolization or sclerotherapy) and multidisciplinary management to obtain a satisfactory outcome. The treatment options and strategies based on the particular type of vascular anomalies follow. Hemangiomas: Most hemangiomas regress gradually and require no treatment. However, some require treatment because of endangering forms or locations (eg, airway or ocular) or associated coagulopathy, ulceration, or cardiac failure. The leading pharmacologic agents used for hemangiomas are steroids, either by systemic use or intralesional injection. Angiogenesis inhibitors such as interferon, vincristine, radiotherapy, and arterial embolization can be used in selected cases. Arterial embolization is rarely needed in patients with significant heart failure (usually because of a large hepatic hemangioma) or with bleeding that is unresponsive to medical management. Kaposiform hemangioendothelioma should be followed closely to rule out severe coagulopathy (Kasabach-Merritt syndrome). Most kaposiform hemangioendotheliomas require pharmacologic intervention, and arterial embolization is more commonly used in this particular tumor as an adjunct to drug treatment than it is in common hemangiomas. Low-flow Malformations: Venous
Malformations Lymphatic
Malformations Lymphatic
Venous Malformations High-flow Malformations: Most AVMs enlarge and increasingly involve more nearby soft tissues. These arteriovenous malformations require therapeutic intervention. Small, superficial arteriovenous malformations can be removed surgically. However, embolization has been the only feasible treatment option for most arteriovenous malformations. Embolization, which closes off the arterial feeders of the malformation, is generally effective in arteriovenous malformations to stabilize the malformation. In some patients, AVMs can be cured with repetitive embolizations. Most AVMs require several sessions, generally 2 months apart, with regular follow-ups. Also, with successful embolization, a surgical excision can become feasible in some AVMs. Embolotherapy should be performed only by an interventional radiologist who has adequate training and enough experience in these malformations to improve effectiveness and lower the procedure-related potential complications, such as skin necrosis or nerve damage. Moreover, in rare instances, although rarely, embolotherapy can be fatal, particularly when absolute alcohol is used. Currently, the most commonly used embolization agents are absolute alcohol and N-butyl-2-cyanoacrylate. During the embolization procedure, the nidus needs to be embolized, and the large arterial feeders should not be embolized. Similarly, surgical ligation of the arterial feeders should not be performed. If the arterial feeders are embolized percutaneously or ligated surgically, the arteriovenous malformation nidus recruits new smaller arterial feeders, which then can not be accessed for nidus embolization and makes AVM management very difficult. Unlike AVMs, arteriovenous fistulas are generally cured by coil embolization of the arteriovenous connection. Overgrowth Syndromes: In Klippel-Trénaunay syndrome, thrombophlebitis and pulmonary embolism are the main complications and require careful surveillance. If a patient with Klippel-Trénaunay syndrome has a patent and adequate deep venous system, abnormal varicoid veins (usually painful) and/or low-flow malformations can be treated by sclerotherapy or surgical excision. Embolotherapy is the primary mode of treatment in patients with Parkes-Weber syndrome. The therapeutic approach in Proteus syndrome depends on the nature of the vascular malformation. |
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Although they often cause significant psychosocial stress for parents and potentially for children, most vascular anomalies are benign conditions and do not require invasive diagnostic tests or treatments. However, some (eg, arteriovenous malformations or large venous malformations) are quite problematic, causing significant discomfort or disability, and they may worsen. Unfortunately, misclassifications or incorrect diagnoses are common and usually a result of the limited experience of the clinicians or radiologists involved in the diagnosis and management. Use of an inappropriate imaging modality (eg, CT instead of MRI) and poor image quality can also contribute to this clinical difficulty. With the appropriate diagnostic workup and therapeutic management, even rapidly progressing malformations can be managed successfully. |
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