Practice Essentials
Hemangiomas are tumors identified by rapid endothelial cell proliferation in early infancy, followed by involution over time; all other abnormalities are malformations resulting from anomalous development of vascular plexuses. The malformations have a normal endothelial cell growth cycle that affects the veins, the capillaries, or the lymphatics, and they do not involute.
Hemangiomas are lesions that are not present at birth. They manifest within the first month of life, exhibit a rapid proliferative phase, and slowly involute to near complete resolution. Hemangiomas exhibit both a proliferating phase and an involuting phase, whereas vascular malformations are more stable and fail to regress. [1]
Hemangiomas of the oral cavity are not common pathologic entities, but, among hemangiomas, the head and the neck are common sites. Most true hemangiomas involute with time, but a certain small percentage do not, which may present with complications that require treatment (see Complications). An estimated 10-20% of true hemangiomas incompletely involute and require postadolescent ablative treatment. [2]
Hemangiomas are associated with the following syndromes:
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Rendu-Osler-Weber syndrome (autosomal dominant inheritance, multiple telangiectasias, occasional GI tract involvement, occasional CNS involvement)
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Sturge-Weber-Dimitri syndrome (noninherited and nonfamilial, port-wine stain, leptomeningeal angiomas)
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Kasabach-Merritt syndrome (thrombocytopenic purpura associated with hemangioma, consumptive coagulopathy, microangiopathic hemolysis, intralesional fibrinolysis)
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Maffucci syndrome (hemangiomas of the mucous membranes, dyschondroplasia)
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von Hippel-Lindau syndrome (genetic transmission variable, hemangiomas of the cerebellum or the retina, cysts of the viscera)
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Klippel-Trenaunay-Weber syndrome (port-wine stain, angiomatosis of the extremities)
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PHACE(S) (posterior fossa brain malformations, hemangiomas of the face [large or complex], arterial anomalies, cardiac anomalies, and eye abnormalities): The association is referred to as PHACE(S) when ventral developmental defects, such as sternal clefting or supraumbilical raphe, are present.
The term hemangioma has been commonly used to describe a large number of vasoformative tumors. Unfortunately, the nomenclature and the classification of these entities have been complex and not entirely consistent over time. The complexity and the inconsistency have led to a large number of terms and classification schemes being used, resulting in confusion in understanding the pathophysiology of these lesions and in comparing data from different periods. The nomenclature lends little insight into the natural history and the management of these lesions.
What was referred to as a hemangioma 30 years ago is not necessarily what a hemangioma would be referred to as today. The term hemangioma described many lesions that bore little relationship to each other apart from their being involved with vessels. With this concept in mind, this article discusses oral vasoformative tumors under the broad and not entirely correct term oral hemangiomas.
In 1982, Mulliken and Glowacki [1] described the classification scheme that is most accepted today. This scheme is straightforward and essentially divides the vasoformative tumors into 2 broad groups: hemangiomas and vascular malformations (see Table 1 below). The vascular malformations can be further subdivided into arterial, venous, capillary, and lymphatic malformations.
Table 1. Classification of Vasoformative Tumors (Open Table in a new window)
Vasoformative Tumor |
New Nomenclature |
Old Nomenclature |
Hemangiomas |
|
|
|
Capillary hemangioma |
Strawberry hemangioma |
|
|
Juvenile hemangioma |
|
Cavernous hemangioma |
|
|
Mixed hemangioma |
Parotid hemangioma |
Vascular malformations |
|
|
|
Venous malformation |
Cavernous hemangioma |
|
|
Hemangiomatosis |
|
Intramuscular venous malformation |
Intramuscular hemangioma |
|
Capillary malformation |
Capillary hemangioma |
|
|
Port-wine stain |
|
Arteriovenous malformation |
Arteriovenous hemangioma Arterial angioma Arteriovenous aneurysm Cirsoid angioma Red angioma Serpentine aneurysm |
|
Lymphatic malformation |
Capillary lymphangioma Cavernous lymphangioma Lymphangioma Cystic hygroma |
Signs and symptoms
On examination of the oral cavity, the vascular malformations of the mucosa and the adjacent soft tissues are usually readily apparent. The tissues have a slightly bluish hue and are soft. Venous channels become engorged when placed in a dependent position. They are readily compressible and fill slowly when released. They lack a prominent pulsation; if they represent an arteriovenous malformation, a thrill may be present.
Although the mucosal and soft tissue lesions are readily suspected by their appearance, the intrabony lesions may be difficult to distinguish on sight alone. Central jaw lesions can show hypermobility of the teeth and distortion of the arch form. [3] Severe hemorrhage following dental extraction is not an uncommon presentation of central hemangiomas of the maxilla and the mandible. [4] Common clinical findings in central hemangiomas of the jaws include gingival bleeding, postextraction bleeding, swelling, pain, mobility of the teeth, and bony expansion. [4] Root resorption of the teeth has been reported in 30% of cases, but the vitality of the teeth is usually not affected. [3]
Intramuscular vascular malformations represent a challenge on diagnosis because they exhibit few signs on clinical examination. Oftentimes, the extent of the lesion is not clinically apparent on examination, and imaging studies frequently define more extensive lesions than suspected.
Diagnostics
Usually, no laboratory studies are useful in the diagnosis or management of oral hemangiomas.
Workup of oral hemangiomas requires some form of imaging to determine their extent and flow characteristics.
Angiography is considered the most definitive of the studies, although the angiographic appearance of intraosseous lesions is less well defined than that of soft tissue lesions. [4]
Ultrasonography can be used to determine that a lesion is angiomatous in nature (ie, hemangioma, lymphangioma), but it cannot be used to differentiate a hemangioma from a lymphangioma.
Contrast-enhanced MRI can be used to differentiate a hemangioma from a lymphangioma in the oral cavity. [5] MRI appears to be highly reliable for lesions of either soft tissue or bone.
On plain films or panoramic radiographs, a central vascular malformation of the bone usually has a honeycombed appearance or cystic radiolucencies. [4] Intraosseous vascular malformations show a nonspecific reticulated or honeycombed pattern that is well demarcated from normal bone. A sunburst effect, created by spicules radiating from the center, is often present.
CT scans often show an expansile process with a high-density amorphous mass that may be suggestive of fibrous dysplasia.
Procedures other than a clinical history or examination, including aspiration of intraosseous lesions, that are used to diagnose oral hemangiomas readily produce frank blood. Performing a biopsy of oral hemangiomas can be potentially dangerous.
Also see Histologic Findings.
Management
For a full discussion, see Treatment.
Pathophysiology
Vascular malformations need to be understood in terms of their embryology and development. The classic sequence of events usually falls into 3 stages: (1) the undifferentiated capillary network stage, (2) the retiform developmental stage, and (3) the final developmental stage. In the undifferentiated capillary network stage, the primitive mesenchyme is nourished by an interlacing system of blood spaces without distinguishable arterial and venous channels. Separate venous and arterial stems appear on either side of the capillary network in the retiform developmental stage. The retiform developmental stage begins at about 48 days of embryonic development. The final developmental stage begins at 2 months' development and involves the gradual replacement of the immature plexiform network by the mature vascular channels.
The more common capillary hemangioma represents an arrest in the development of the mesenchyme primordia in the undifferentiated capillary network stage. As differentiation progresses, primitive vessels penetrate deeper into the subcutaneous layer, the muscle, or the bone tissue and give rise to capillary hemangiomas. Termination of development in the retiform developmental stage may produce venous, arterial, or capillary malformations because this stage is characterized by an established venous, arterial, and capillary system. In the final developmental stage, the maturation of the venous and lymphatic systems predominates. Aberrations in this mature stage of development result in venous malformations and lymphangiomas.
Proliferating hemangiomas have been shown to have estradiol-17 beta-receptors in the cytoplasm, [6] and corticosteroid treatment has been theorized to block these receptors. Lack of estradiol receptors in stable or involuting lesions has supported this theory, and steroid treatment has become a first line of treatment for proliferating lesions.
A number of growth factors, including vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), transforming growth factor-beta (TGF-beta), and interleukin 6 (IL-6), have been demonstrated as regulators of angiogenesis. [7] Takahashi et al [8] outlined a number of cellular markers that distinguish the phases of hemangiomas; these markers include tissue metalloproteinase (TIMP-1), bFGF, proliferating cell nuclear antigen, type IV collagenase, VEGF, and urokinase.
Another theory suggests that the endothelial cells of hemangiomas are derived from a distant population of endothelial precursors carried by existing vascular pathways to a receptive environment. Potential sources include the bone marrow and the placenta. A small embolic nidus of placental endothelial cells could reach fetal tissues through the permissive right-to-left fetal shunt of fetal circulation.
This occurrence could, in part, explain the 3-fold increased risk of hemangiomas observed in infants subjected in utero to chorionic villus sampling, because local placental injury might predispose the shedding of cells into the fetal circulation. At least 5 markers of hemangiomas are uniquely co-expressed in the placenta: GLUT1, merosin, Lewis Y antigen, Fc-R11b, and type III iodothyronine deiodinase. Recently, a comparison of the transcriptomes of the human placenta and infantile hemangiomas supported a placental origin of the tumors. [9]
Etiology
The causes of vasoformative tumors are unknown. One hypothesis postulates that placental cells, such as the trophoblast, may be the cell of origin for hemangiomas. Therefore, hemangiomas may arise secondary to some event in utero. However, conflicting evidence supports this hypothesis. One study found placenta-associated vascular antigens to be expressed by hemangiomas but not by other vascular malformations or tumors. On the other hand, a separate investigation found immunohistochemical staining of certain trophoblastic markers to be negative in all infantile hemangiomas that were examined. The relationship between hemangiomas and placental tissues needs further investigation.
Epidemiology
US frequency
Hemangiomas are the most common tumors of infancy, occurring in as many as 2.6% of neonates and 12% of children aged 1 year. [10, 11] Up to 30% of preterm infants with low birth weight (1000 g) may have hemangiomas. [12] Fifty percent of venous malformations occur in the head and the neck. [13]
In the oral cavity, the bones and the muscles are affected as well as the mucosa and the skin. The incidence of intraosseous hemangiomas varies from 0.5-1.0% of all intraosseous neoplasms. [14] The bones most frequently affected are the vertebral column and the calvaria. The most commonly affected facial bones are the mandible, the maxilla, and the nasal bones. Intraosseous lesions affect the mandible more often than the maxilla, with a ratio of 2:1 reported in one study. [3] Involvement of the zygoma is rare. [15]
Intramuscular hemangiomas in the oral region are most commonly seen in the masseter, compromising 5% of all intramuscular hemangiomas. [16]
Race
Hemangioma, the most common tumor of infancy, affects as many as 12% of whites, but it rarely occurs in darker-skinned individuals. Vascular malformations also more commonly occur in whites.
Sex
Hemangiomas are approximately 3-5 times more common in females than in males. [17] The male-to-female ratio for venous malformations is reported in one study [13] to be 1:1. Arteriovenous hemangiomas of the oral cavity have a predilection for females. [18] Intraosseous hemangiomas are about 3 times more common in females than in males. [3, 4]
The patient's sex does not influence the speed or the completeness of involution of hemangiomas. [19]
Age
By their definition, hemangiomas occur in infants and children. The incidence of hemangiomas increases to 23% in premature infants with a birthweight of less than 1000 g.
Vascular malformations have a much broader range of incidence. Barrett and Speight [18] observed 35 oral vascular malformations over a 48-year period at their institution. The mean age was 52.6 years, with a range of 12-90 years.
Intraosseous vascular malformations most commonly occur in the fourth decade of life but range from infancy to the eighth decade of life.
The peak incidence of central vascular malformations of the jaws is in the second decade of life. [4]
Intramuscular vascular malformation of the head and the neck most commonly present in the third decade of life. [16]
Prognosis
The morbidity of oral hemangiomas ranges from surface discoloration to life-threatening functional compromise of the airway or hemorrhage. Fatal spontaneous hemorrhage from jaw hemangiomas has been documented in 25 cases. [4] Significant morbidity can also occur from many of the treatments of hemangiomas, and biopsy of these lesions is also fraught with danger.
Tables
Vasoformative Tumor |
New Nomenclature |
Old Nomenclature |
Hemangiomas |
|
|
|
Capillary hemangioma |
Strawberry hemangioma |
|
|
Juvenile hemangioma |
|
Cavernous hemangioma |
|
|
Mixed hemangioma |
Parotid hemangioma |
Vascular malformations |
|
|
|
Venous malformation |
Cavernous hemangioma |
|
|
Hemangiomatosis |
|
Intramuscular venous malformation |
Intramuscular hemangioma |
|
Capillary malformation |
Capillary hemangioma |
|
|
Port-wine stain |
|
Arteriovenous malformation |
Arteriovenous hemangioma Arterial angioma Arteriovenous aneurysm Cirsoid angioma Red angioma Serpentine aneurysm |
|
Lymphatic malformation |
Capillary lymphangioma Cavernous lymphangioma Lymphangioma Cystic hygroma |
Complications |
Hemangiomas, % |
Vascular Malformations, % |
Immediate Complications |
||
Hemorrhage |
27 |
60 |
Airway compromise |
2 |
10 |
Hematoma |
14 |
14-30 |
Skin necrosis |
12 |
10-30 |
Coagulopathy |
7 |
14-20 |
Late Complications |
||
Restricted oral opening |
8 |
27-40 |
Malocclusion |
8 |
20-40 |
Drooling |
23 |
40-47 |
Dysphagia |
23 |
20-27 |
