Key Points
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Vascular anomalies are divided into vascular malformations and vascular tumors .
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The molecular mechanisms that give rise to vascular anomalies result from disordered angiogenesis and vasculogenesis. The most common type of vascular tumor is hemangioma of infancy.
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The most common type of vascular malformation that involves the head and neck is a lymphatic malformation.
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Hemangiomas of infancy are absent at birth, occur in infancy, proliferate for up to 9 to 10 months of age, and invariably involute or shrink over years.
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Endothelium from hemangiomas of infancy have unique properties that distinguish them from other types of vascular tumors and malformations.
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Lymphatic malformation endothelium has unique staining properties that distinguish it from other types of vascular endothelium.
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Hemangiomas of infancy occur in characteristic places in the head, neck, and face. These lesions are termed segmental, focal, superficial, deep, and mixed.
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PHACES syndrome is associated with large hemangiomas of infancy. This is a description of hemangiomas of infancy associated with ventral clefting, congenital cardiac malformations, intracranial malformations, and ocular abnormalities.
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Periocular hemangiomas of infancy can cause deprivation amblyopia and astigmatic amblyopia.
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Superficial hemangiomas of infancy and other red, cutaneous vascular lesions can be treated with a pulsed-dye laser, which preserves epithelium while reducing lesion redness.
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Surgical excision of focal hemangiomas can be done to both prevent complications of hemangiomas and improve treatment outcomes.
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Vascular malformations commonly occur in the neck; most frequently, these are lymphatic.
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Lymphatic malformations are classified by stage and by radiographic appearance as macrocystic, microcystic, or a combination of the two.
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Lymphatic malformations are low-flow vascular malformations that occur in utero and manifest at birth or in association with an infection or trauma later in life. Most malformations that present at birth or later in life are associated with a normal karyotype.
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Low-stage macrocystic lymphatic malformations can resolve spontaneously or can be treated successfully with either surgery or sclerotherapy. In contrast, high-stage suprahyoid lymphatic malformations are difficult to treat with any modality and frequently cause macroglossia. Suprahyoid microcystic malformations that involve oral and oral-pharyngeal mucosa have been associated with lymphocytopenia and recurring inflammation.
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Venous malformations are associated with tyrosine-kinase type 2 receptor dysfunction, which causes abnormal venous structure. Histologically, venous malformations can be a combination of both blood vasculature and lymphatic vasculature.
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Kasabach-Merritt phenomenon is most commonly associated with the vascular tumors kaposiform hemangioendothelioma and tufted angioma.
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Arteriovenous malformations are high-flow malformations that can occur in any area of the head and neck; they are treated with a combination of embolization and surgical therapy.
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Rapidly involuting congenital hemangiomas and noninvoluting congenital hemangiomas are described. These lesions are histologically identical to hemangiomas of infancy but lack glucose transporter-1 endothelial staining.
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Hemangiomas of infancy have unique endothelium that stains with glucose transporter-1 immunostain, which distinguishes them from other vascular tumors. Treatment for hemangioma of infancy has been dramatically changed by propranolol.
Vascular anomalies have abnormal blood and lymphatic vasculature and occur frequently in the head and neck. Usually, clinical and radiographic findings, and occasionally histologic evidence, are used to distinguish between various vascular anomaly subtypes. A vascular anomaly classification system has been developed based on these factors ( Box 20-1 ). In this classification scheme, vascular anomalies are separated into vascular tumors and vascular malformations . The initial division into these categories reflects the careful analysis of the natural clinical history of cutaneous hemangiomas of infancy (HOIs), which that are absent at birth, appear during infancy, and grow rapidly within the first year of life. Following this proliferative phase, a variable period of shrinkage or involution occurs. This clinical behavior is distinct from that of vascular malformations. These astute clinical observations have opened the possibility of further separating blood and lymphatic-derived tumors into individual groups to allow more accurate diagnosis and treatment. Numerous recent discoveries have further solidified the distinction between vascular tumors and vascular malformations.
Vascular Malformation
Single-Vessel Type
Capillary
Venous
Lymphatic
Arteriovenous
Combined and Complex Malformations
Lymphaticovenous
Capillary venous
Capillary lymphaticovenous
Capillary arteriovenous
Vascular Tumor
Hemangioma
Hemangioma of infancy
Congenital hemangioma
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Rapidly involuting congenital hemangioma
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Noninvoluting congenital hemangioma
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Lobular hemangioma (pyogenic granuloma)
Vascular Neoplasm
Kaposiform hemangioendothelioma
Angiosarcoma
Hemangiopericytoma
Miscellaneous
Tufted angioma
Currently, vascular tumors are thought to represent disordered vascular development and demonstrate certain neoplastic characteristics. Most vascular tumors are benign, but some can be malignant. Radiographically these tumors can be characterized by describing the lesion size, blood flow, and location ( Fig. 20-1 ). Certain conditions are associated with vascular tumors but not vascular malformations. The prime example is profound thrombocytopenia (i.e., Kasabach-Merritt phenomenon). Additionally, some vascular tumors are associated with known syndromes, such as PHACES ( p osterior fossa intracranial abnormalities, h emangiomas, a rterial abnormalities, c ardiac defects and coarctation of the aorta, e ye abnormalities, and s ternal clefting).
Vascular malformations have been described in lesions that contain all vessel types: arterial, venous, and lymphatic. It remains to be proven that vascular malformations represent an early embryonic disorder in vasculogenesis. Some vascular malformations have been associated with genetic defects, especially those with tissue overgrowth. In contrast to vascular tumors, most vascular malformations are present at birth and demonstrate growth parallel to the individual’s growth. These lesions have a distinct radiographic appearance in their location, size, and intralesional blood flow. Additionally, certain types of vascular malformations are characterized by radiographic architecture. This has been most useful in evaluating lymphatic malformations, which are also associated with either local tissue or bony overgrowth ( Fig. 20-2 ). Since the original distinction of HOI from other types of vascular tumors and malformations, molecular characteristics and radiographic features of individual vascular anomaly subtypes have allowed further distinction between various types of vascular anomalies. This chapter outlines these distinctions and explains how they have led to treatment improvements that can in turn lead to better treatment outcomes.
Genetic and molecular bases for some vascular anomalies are being investigated. The most apparent link between a genetic defect and disease is seen in inherited venous malformations, in which a mutation is found in the protein receptor for tyrosine kinase (Tie2), which normally allows endothelial–smooth muscle communication essential for venous morphogenesis. Defects in the smooth muscle layer of vessels within venous malformations are thought to result from this mutation. Similarly, vascular anomalies that occur in hereditary hemorrhagic telangiectasia types 1 through 3 have been associated with gene mutations that adversely affect endothelial function. Familial HOIs have been linked to regions of the fifth chromosome. Glomangiomas are associated with defective function of glomulin, which distinguishes them from other venous malformations. Arteriovenous malformations (AVMs) that occur in conjunction with atypical capillary malformations have been linked to a potential candidate gene, RASA1 . Hypertrophy of tissues near vascular malformations has been linked in certain syndromes to a mutation in the PTEN tumor suppressor gene and in other novel genes. This information creates a basis for understanding the mechanisms behind the pathogenesis of vascular anomalies and opens the door for new treatment options.
Vascular anomalies involve the head and neck 70% to 80% of the time. These lesions have varied presentations and can cause unique effects both systemically and locally. Since HOIs were originally distinguished from vascular malformations, a number of treatment and diagnostic changes have occurred that will be discussed based on lesion type.
Vascular Tumors
Hemangiomas of Infancy
HOIs are absent at birth and appear in infancy; then they proliferate for 6 to 9 months and involute partially or completely over several years ( Fig. 20-3 ). Vascular lesions that do not follow this pattern should be considered for alternative diagnoses. In addition to the clinical diagnosis, HOI can be further confirmed through molecular staining and sophisticated imaging characteristics. HOI endothelium has several unique surface markers that can be detected by immunohistochemistry. The first marker described for HOI was glucose transporter 1 (GLUT-1); others have since been described. Detection of GLUT-1 in HOI endothelium distinguishes them from other vascular anomalies. Improvements in image acquisition with both computed tomography (CT) and magnetic resonance imaging (MRI) allow differentiation between HOIs and other vascular anomalies ( Fig. 20-4 ).
Clinical Presentation
At birth, HOIs can be completely absent or present as a slight redness or pallor, where an HOI subsequently appears. In the first several months of life, the hemangioma grows rapidly and can involve any area of the head and neck or body. Two thirds of such lesions occur in girls, and HOIs are more prevalent in premature infants and in those born to mothers of advanced maternal age and with a history of chorionic villous sampling. Terminology to describe HOIs and their location are illustrated ( Fig. 20-5 ). Segmental HOIs are usually superficial, variably involve cutaneous dermatomes, and have more associated morbidity than focal HOI. Head and neck segmental lesions are thought to occur in embryologic prominences related to neural crest cells and their influence on vascular development. Head and neck focal HOIs occur in identifiable patterns thought to be associated with lines of embryonic tissue fusion. Building on the concept of embryonic fusion planes, several groups have observed that midface HOIs do not predictably involute. It is thought that the HOI “footprint” is set by 4 months of life and that residual growth occurs in lesion thickness, not size.
PHACES Syndrome
An association between some HOIs and ventral clefting, congenital cardiac malformations, intracranial malformations, and ocular abnormalities has been described ( Fig. 20-6 ). PHACES stands for p osterior fossa intracranial abnormalities, h emangiomas, a rterial abnormalities, c ardiac defects and coarctation of the aorta, e ye abnormalities, and s ternal clefting (and sometimes with other ventral clefting abnormalities). Central nervous system symptoms include developmental delays, seizures, and congenital stroke. Suspected PHACES patients should undergo head imaging, ophthalmologic exam, and cardiac evaluation. Some recommend antiplatelet therapy for patients with abnormal cerebral vasculature to prevent congenital stroke. Further analysis of HOI biology is necessary to understand these associations. Of note a significant number of PHACES patients have airway HOI.
Other Types of Vascular Tumors
Congenital Hemangioma
High-flow vascular tumors that present at birth and are histologically identical to HOI except for positive GLUT-1 staining are called congenital hemangiomas . There are two types of congenital hemangiomas: those that rapidly resolve over the span of a year and those that persist. For this reason they are named rapidly involuting congenital hemangioma or noninvoluting congenital hemangioma , respectively. These lesions are often difficult to distinguish from HOI unless a careful history is taken and histologic analysis performed. Often the diagnosis remains uncertain until the clinical behavior of a given lesion is observed ( Fig. 20-7 ). Medical therapy is ineffective for congenital hemangiomas. Treatment for rapidly involuting congenital hemangiomas is usually observation, whereas noninvoluting congenital hemangiomas may require laser or surgical therapy.
Kaposiform Hemangioendothelioma and Tufted Angioma
Most nonhemangioma vascular tumors are benign and rarely occur in the head and neck. The two most common are kaposiform hemangioendothelioma (KHE) and tufted angioma (TA). KHE occurs anywhere in the head and neck and has a significant lymphatic component in addition to blood vascular endothelium. Clinically, KHE appears as violaceous cutaneous nodules that extend into deep tissues ( Fig. 20-8 ). Their radiographic appearance is one of a diffuse infiltrative vascular process (see Fig. 20-8 ). Careful assessment through imaging and diagnostic biopsy should guide KHE therapy. TAs are more localized and may or may not involve the skin. Treatment of both KHE and TA is centered on proper diagnosis, prevention of complications, and tumor control. Diagnosis requires an incisional biopsy with possible immunohistochemical staining. Curative surgical resection is possible and is advisable in some localized tumors, but for large lesions, surgery may not be curative. In extensive KHE or TA that causes pain, loss of function, or significant disfigurement, antiangiogenic chemotherapy may be necessary. The natural history of these lesions is often unclear; therefore, treatment needs to be individualized.
Common Complications of Vascular Tumors
Because most vascular tumors are HOIs, and these lesions proliferate rapidly, complications occur most frequently in HOI and are discussed first. HOI complications occur from lesion-induced functional compromise and cutaneous ulceration. Breathing can become compromised and obstructed from airway HOI, which causes biphasic stridor by narrowing the infant’s airway ( Fig. 20-9 ). Visual axis obstruction by proliferating HOI occurs with eyelid lesions and induces deprivation amblyopia ( Fig. 20-10 ). Eye deformation from lesion compression or periocular tissue distortion before 6 months of age induces astigmatic amblyopia. Proliferating HOI in places of repetitive skin trauma, such as the lips and neck skin folds, can ulcerate and can result in scarring ( Fig. 20-11 ). The reasons for ulceration are unclear, but when present, ulcerations begin as brown crusts that become painful and bleed, and they require local wound care for healing. Extensive HOI ulcerations can become infected and result in tissue loss, which further complicates healing and treatment ( Fig. 20-12 ). Lip ulceration makes oral feeding challenging because of pain and HOI-induced lip distortion. Large head and neck HOIs that involve the parapharyngeal and scalp regions are often associated with high-output cardiac failure from increased blood flow in these vascular lesions. The psychosocial consequences of HOI on the family and patient are important to consider in treatment planning.
Unusual Conditions Associated with Vascular Tumors
Kasabach-Merritt Phenomenon
For unknown reasons, KHE and TA—not HOI—are the vascular tumors most frequently associated with Kasabach-Merritt phenomenon. This occurs in infancy and requires extensive chemotherapy to reduce the risk of bleeding associated with thrombocytopenia. The mechanisms that lead to thrombocytopenia are unknown. Prior to the capability of histologically distinguishing between the endothelium of KHE, TA, and HOI, many vascular tumors were simply called hemangiomas, and Kasabach-Merritt phenomenon was associated erroneously with HOI. Rarely, vascular entities that are not classified as vascular tumors are also associated with thrombocytopenia, and the spectrum of this phenomenon as it relates to vascular anomalies is being defined.
Bone Resorption
Bone resorption can occur in association with some KHE and lymphatic malformations and can result in localized osteopenia. Gorham syndrome, otherwise known as disappearing bone disease, is the most striking manifestation of lymphatic vessels overtaking bony structures. The mechanisms for bone resorption are unknown. When bone loss occurs, chemotherapy has not been shown to change the outcome.
Hemangioma of Infancy: Treatment Overview
Analysis and Treatment of Facial Hemangiomas
It is beyond the scope of this chapter to fully discuss all aspects of facial hemangioma treatment, although general principles that surround decision making will be outlined. Societal attitudes and recognition of treatment possibilities for facial HOIs are changing. Lesions that formerly were allowed to involute and undergo delayed treatment of residual skin changes are being managed more aggressively in early childhood ( Fig. 20-13 ). HOIs in certain areas of the face are prone to complications and noninvolution; this is especially true of midface lesions. Recognition of the varied natural history of facial HOIs is essential to treatment planning and family counseling. HOIs distort involved tissue by creating tissue excess and sometimes inducing adjacent bone and soft tissue hypertrophy ( Fig. 20-14 ). This creates surgical and reconstructive challenges that differ from the usual tissue deficits associated with facial tumor resection. Large facial HOIs require more intensive monitoring and treatment planning than smaller lesions. Often the treatment of these lesions requires combined modalities and occurs in multiple stages over several years ( Figs. 20-15 and 20-16 ). Understanding the medical, laser, and surgical treatment options and implications associated with HOI type and facial location is essential in planning treatment of these lesions.
Medical Therapy
Medical therapy for proliferating HOI is directed at stopping angiogenesis and has radically changed in the past 5 years. Until 2008, the mainstay of medical therapy was systemic corticosteroids, which are antiangiogenic. The major indication for corticosteroid use was the presence of HOI complications or the attempt to prevent such complications, which occur more frequently in extensive segmental lesions. Prednisolone was given orally with 1 to 5 mg/kg in treatment courses that began with a high dose followed by a slow tapering off of the medication over 4 to 6 weeks. In theory this minimized the systemic side effects of steroid usage, but no long-term efficacy studies have been done. The effectiveness of therapy was monitored, live vaccine administrations were avoided, and the blood pressure was monitored. Focal HOI of the head and neck can be injected with corticosteroids to localize drug delivery. This practice is controversial and specialty specific because of the risk of blindness, training differences, and uncertain efficacy. Despite this, for eyelid hemangioma, steroid injection is frequently done under general anesthesia, while directly visualizing the retina. In this location, steroids are very effective in reducing the size of the HOI, thereby decreasing the risk of HOI-induced visual impairment; however, even these small doses can induce measurable adrenal suppression. The role of topical medications to treat hemangiomas is being defined. Other antiangiogenic chemotherapy agents, such as interferon and vincristine, have been used to treat HOI. Interferon is an effective treatment for extensive HOI, but in patients less than 1 year of age, the central nervous system is sensitive to this medication, and frequent neurologic complications, such as spastic diplegia, occur. For this reason, it is not routinely used. Some think interferon-associated complications were from inappropriately high interferon dosing. Vincristine has also been used for extensive HOI, but it also can induce neurologic deficits in young children.
Since the initial report of propranolol’s dramatic effect on some HOIs and the surrounding skin, medical therapy for these lesions has changed ( Fig. 20-17 ). Currently this is the first-line therapy for HOIs that impair function. It can be safely initiated as outpatient therapy with appropriate education and monitoring. Inpatient initiation is reserved for patients with airway lesions, young patients, and patients with abnormal cerebral vasculature associated with PHACES syndrome. The usual dose is 2 mg/kg/day divided into three doses. The safety profile for this medication is excellent, with hypoglycemia being associated with prolonged fasting. Because the medication affects cardiac function, it is advisable to have pretherapy cardiology evaluation. Successful therapy with propranolol is associated with decreased blood vessel density in the HOI. Long-term studies are necessary to determine the exact way in which propranolol has changed HOI therapy.
Laser Therapy
Superficial HOIs are red; the pulsed-dye laser with a cooling device can reduce and even remove this skin redness while preserving the overlying epidermis without causing scarring. The pulsed-dye laser does not reduce HOI volume ( Fig. 20-18 ). Care must be exercised when using this device in HOI patients under 6 months of age because it can induce epithelial disruption, ulceration, and scarring in proliferating HOI.
Surgical Therapy
During proliferation, when HOI causes functional compromise of vision or breathing or is unresponsive to medical therapy, surgical excision may be necessary. After proliferation, partially involuted HOIs may leave significantly abnormal fibrofatty skin changes, which are amenable to surgical resection. HOI that occurs on the face can be significantly disfiguring and may be best treated with surgical excision. When this type of lesion is mixed with a larger superficial component, staged treatment with the pulsed-dye laser induces skin and dermal thickening to allow HOI excision with minimal skin loss and tension-free closure of the defect ( Fig. 20-19 ). A variety of techniques for HOI removal and reconstruction have been described. In most cases, waiting until the HOI has stopped proliferating is advisable.
Assessment and Treatment of Airway Hemangiomas
Otolaryngologists treat HOI that involves the airway. HOI can occur anywhere in the upper and lower airway, it has the same histologic characteristics as cutaneous lesions, and it is asymptomatic when limited to the superficial mucosa. Large parapharyngeal HOI that abuts the pharynx can create extrinsic upper-airway compression, particularly during sleep. Laryngeal HOI frequently presents in infancy during proliferation in association with an upper respiratory infection. Because the subglottic airway is the narrowest portion of the pediatric airway, HOI in this area induces the most respiratory embarrassment. Assessment of a stridulous infant must include the possibility of an airway hemangioma, especially if a cutaneous HOI is present. Patients with segmental HOI in the lower face or those with PHACES have airway HOI in at least 50% of cases. Stridor in association with segmental HOI should prompt hospital admission, fiberoptic laryngoscopy, and even operative endoscopy if the initial evaluation is nondiagnostic ( Fig. 20-20 ). Advances in CT imaging techniques enable accurate assessment of HOI extent, and this can be applied to airway lesions. This imaging along with careful endoscopy reveals a pattern of HOI in the airway. Focal HOI can be located in one area of the airway, or transglottic segmental HOI can extend into the soft tissues that surround the airway. Airway HOI treatment is geared at preventing the need for a tracheotomy. Empiric use of high-dose corticosteroids in an infant with cutaneous HOI and new-onset stridor usually improves the respiratory status and can be used as a diagnostic assessment. Rapid improvement in stridor usually means an airway HOI is present. When the infant has severe respiratory compromise, airway protection can be accomplished with endotracheal intubation using a small uncuffed endotracheal tube. This allows safe transfer to a facility capable of comprehensive HOI care and avoids using a tracheotomy for airway protection.
