Etiology

The terms congenital, hemangioma, and congenital vascular malformation have been used as generic designations for many vascular proliferations, and they have been used interchangeably. Congenital hemangiomas and congenital vascular malformations appear at or around the time of birth and are more common in females. Because of the confusion surrounding the basic origin of many of these lesions, classification of clinical and microscopic varieties has been difficult. None of the numerous proposed classifications has had uniform acceptance, although there is merit in separating benign neoplasms from vascular malformations because of different clinical and behavioral characteristics (Table 4-1). The term congenital hemangioma is used to identify benign congenital neoplasms of proliferating endothelial cells. Congenital vascular malformations include lesions resulting from abnormal vessel morphogenesis. Separation of vascular lesions into these two groups can be of considerable significance relative to the treatment of patients. Unfortunately, in actual practice, some difficulty may be encountered in classifying lesions in this way because of overlapping clinical and histologic features.

In any event, congenital hemangiomas have traditionally been subdivided into two microscopic types—capillary and cavernous—essentially reflecting differences in vessel diameter. Vascular malformations may exhibit similar features but may also show vascular channels that represent arteries and veins.

Clinical Features

Congenital hemangioma, also known as strawberry nevus, usually appears around the time of birth but may not be apparent until early childhood (Fig. 4-1). This lesion may exhibit a rapid growth phase that is followed several years later by an involution phase. In contrast, congenital vascular malformations are generally persistent lesions that grow with the individual and do not involute (Figs. 4-2 to 4-6). They may represent arteriovenous shunts and exhibit a bruit or thrill on auscultation. Both types of lesions may range in color from red to blue, depending on the degree of congestion and their depth in tissue. When they are compressed, blanching occurs as blood is pressed peripherally from the central vascular spaces. This simple clinical test (diascopy) can be used to separate these lesions from hemorrhagic lesions in soft tissue (ecchymoses), where the blood is extravascular and cannot be displaced by pressure. Congenital hemangiomas and congenital vascular malformations may be flat, nodular, or bosselated. Other clinical signs include the presence of a bruit or thrill, features associated predominantly with congenital vascular malformations. Lesions are most commonly found on the lips, tongue, and buccal mucosa. Lesions that affect bone are probably congenital vascular malformations rather than congenital hemangiomas.

Vascular malformations are also a component of the rare condition termed blue rubber bleb nevus syndrome (Bean’s syndrome), in which multiple small and large cavernous hemangiomas are present on the skin and throughout the gastrointestinal tract, including the mouth. The condition is usually diagnosed in childhood or young adulthood. Recognition of this syndrome is significant because many of those afflicted may suffer overt life-threatening gastrointestinal bleeding or occult blood loss with severe anemia and iron deficiency.

Histopathology

Congenital hemangiomas are composed of abundant capillary spaces lined by endothelium without muscular support. Congenital vascular malformations may consist not only of capillaries, but also of venous, arteriolar, and lymphatic channels. Direct arteriovenous communications are typical. Lesions may be of purely one type of vessel, or they may consist of two or more vessels. Vascular morphology accounts for lesions exhibiting rapid flow versus those exhibiting slow flow.

Diagnosis

As a generic group, the diagnosis of congenital vascular lesions is usually self-evident on clinical examination. When they affect the mandible or the maxilla, a radiolucent lesion with a honeycomb pattern and distinct margins is expected. Differentiation between congenital hemangiomas and congenital vascular malformations can be difficult and occasionally impossible. When affecting a segmental portion of the face or oral cavity, facial hemangiomas may be associated with several syndromes, which may include the eye, heart, and posterior cranial fossa (PHACE syndrome). A complete history, a clinical examination, and angiography or angiographic magnetic resonance imaging should be definitive in lesion identification and characterization.

Treatment

Spontaneous involution during early childhood is likely for congenital hemangiomas. If these lesions persist into the later years of childhood, involution is improbable and definitive treatment may be required. Congenital vascular malformations generally do not involute, and they require intervention if eradication is the goal. Excellent results may be achieved with propranolol, a nonselective beta-adrenergic blocking agent. Adjuncts include selective arterial embolization and sclerosant therapy. Laser therapy is another accepted form of primary treatment of selected vascular lesions. Because the margins of these lesions are often ill defined, total elimination may not be practical or possible.

Encephalotrigeminal Angiomatosis (Sturge-Weber Syndrome)

Encephalotrigeminal angiomatosis, or Sturge-Weber syndrome, is a neurocutaneous syndrome that includes vascular malformations with characteristic distribution. In this syndrome, venous malformations involve the leptomeninges of the cerebral cortex, usually with similar vascular malformations of the face (Fig. 4-7). The associated facial lesion, also known as port-wine stain or nevus flammeus, involves the skin innervated by one or more branches of the trigeminal nerve. Port-wine stains may also occur as isolated lesions of the skin without the other stigmata of encephalotrigeminal angiomatosis. The vascular defect of encephalotrigeminal angiomatosis may extend intraorally to involve the buccal mucosa and the gingiva. Ocular lesions may appear.

Neurologic effects of encephalotrigeminal angiomatosis may include mental retardation, hemiparesis, and seizure disorders. Patients may be taking phenytoin (Dilantin) or similar drugs for control of the latter problem, with possible secondary development of drug-induced generalized gingival hyperplasia in relation to phenytoin. Calcification of the intracranial vascular lesion may provide radiologic evidence of the process in the leptomeninges.

A differential diagnosis would include Parkes-Weber syndrome and angio-osteohypertrophy (Klippel-Trenaunay) syndrome, the latter characterized by vascular malformations of the face (port-wine stains), varices, and hypertrophy of bone. The bony abnormality usually affects long bones but may also involve the mandible or maxilla, resulting in asymmetry, malocclusion, and an altered eruption pattern.

Hereditary Hemorrhagic Telangiectasia (Rendu-Osler-Weber Syndrome)

Hereditary hemorrhagic telangiectasia (HHT), or Rendu-Osler-Weber syndrome, is a rare condition, affecting 1 in 5000 to 8000 people, that is transmitted in an autosomal-dominant manner. Most cases are caused by mutations in two genes: endoglin on chromosome 9 (HHT type 1) and activin receptor–like kinase 1 (ALK 1) on chromosome 12 (HHT type 2). These genes are members of the transforming growth factor (TGF)-β signaling pathway and are implicated in vascular development and repair. HHT features abnormal and fragile vascular dilations of terminal vessels in skin and mucous membranes, as well as arteriovenous malformations of internal organs, particularly lungs, brain, and liver (Fig. 4-8). Telangiectatic vessels in this condition appear clinically as red macules or papules, typically on the face, chest, and oral mucosa. Lesions appear early in life, persist throughout adulthood, and often increase in number with aging.

Intranasal telangiectasias are responsible for epistaxis, the most common presenting sign of hereditary hemorrhagic telangiectasia. Bleeding from oral lesions is a common occurrence in affected patients. Occasionally, control of bleeding may be a difficult problem. Chronic low-level bleeding may also result in iron deficiency anemia.

Diagnosis of HHT is based on a history of spontaneous epistaxis, the presence of telangiectasias, arteriovenous malformations of internal organs, and family history. Another condition that might be considered in a differential diagnosis is CREST syndrome. This includes calcinosis cutis, Raynaud’s phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasia.

Clinical management includes follow-up examination and the use of antifibrinolytic drugs for those with frequent epistaxis.

Pyogenic Granuloma

Clinical Features

Pyogenic granulomas occur mostly in the second decade of life and are most commonly seen on the attached gingiva (75%), where they presumably are caused by the presence of calculus or foreign material within the gingival crevice (Figs. 4-13 to 4-15). The tongue, lower lip, and buccal mucosa are the next most common sites. Hormonal changes of puberty and pregnancy may modify the gingival reparative response to injury, producing what was once called a pregnancy tumor. Under these circumstances, multiple gingival lesions or generalized gingival hyperplasia may be seen.

Pyogenic granulomas are typically red and smooth or lobulated with hemorrhagic and compressible features. They characteristically become ulcerated because of secondary trauma. The ulcerated lesions may then become covered by a yellow, fibrinous membrane. They may be pedunculated or broad based and may range in size from a few millimeters to several centimeters. Older lesions become more pink and collagenized. These lesions may be seen at any age and tend to occur more commonly in females than in males; they are seen in up to 5% of pregnancies.

Histopathology

Microscopically, pyogenic granulomas are composed of lobular masses of hyperplastic granulation tissue (Fig. 4-16). Some scarring may be noted in some of these lesions, suggesting that occasionally maturation of the connective tissue repair process may occur. Variable numbers of chronic inflammatory cells may be seen. Neutrophils are present in the superficial zone of ulcerated pyogenic granulomas.

Peripheral Giant Cell Granuloma

Clinical Features

Peripheral giant cell granulomas are seen exclusively in gingiva, usually between the first permanent molars and the incisors (Fig. 4-17). They presumably arise from periodontal ligament or periosteum, and they cause, on occasion, resorption of alveolar bone. When this process occurs on the edentulous ridge, a superficial, cup-shaped radiolucency may be seen. Peripheral giant cell granulomas typically appear as red to blue, broad-based masses. Secondary ulceration caused by trauma may result in the formation of a fibrin clot over the ulcer. These lesions, most of which are about 1 cm in diameter, may occur at any age and tend to be seen more commonly in females than in males.

Histopathology

Fibroblasts are the basic element of peripheral giant cell granulomas (Fig. 4-18). Scattered throughout the fibroblasts are abundant multinucleated giant cells believed to be related to osteoclasts. The giant cells appear to be nonfunctional in the usual sense of phagocytosis and bone resorption.

Islands of metaplastic bone occasionally may be seen in these lesions. This finding has no clinical significance. Chronic inflammatory cells are present, and neutrophils are found in ulcer bases.

Scarlet Fever

Scarlet fever is an acute exanthematous condition caused by any of three exotoxin-producing, antigenically dissimilar streptococcal strains (A, B, or C), most commonly seen between 1 and 10 years of age. The characteristic effects of scarlet fever, a systemic bacterial infection, are the result of an erythrogenic toxin that causes capillary damage and that is produced most commonly by some strains of group A streptococci. Other strains of group A streptococci that are unable to produce the toxin can cause pharyngitis and all the attendant features of infection, but without the red skin rash and oral signs of scarlet fever. All group A streptococcal infections are generally spread through droplets from contact with an infected individual or, less likely, a carrier. Crowded living conditions promote the spread of streptococcal infections, with the upper respiratory tract representing the most common portal of entry.

Clinically, children are typically affected after an incubation period of several days. In addition to the usual symptoms of all group A streptococcal infections—pharyngitis, tonsillitis, fever, lymphadenopathy, malaise, and headache—the child exhibits a red skin rash that starts on the chest and spreads to other surfaces. The face is flushed except for a zone of circumoral pallor. The palate may show nonspecific inflammatory changes, and the tongue may become covered with a white coat in which fungiform papillae are enlarged and reddened (strawberry tongue). Later, the coat is lost, leaving a beefy red tongue (red strawberry tongue or raspberry tongue). In untreated and uncomplicated cases, the disease subsides in a matter of days.

Penicillin is the drug of choice for the treatment of group A streptococcal infections. Erythromycin should be used in patients allergic to penicillin. The rationale for antibiotic treatment of this short-lived, self-limited disease is the prevention of complications, particularly rheumatic fever and glomerulonephritis.

Etiology

Erythroplakia is a clinical term that refers to a red patch on oral mucous membranes. It does not indicate a particular microscopic diagnosis, although after a biopsy most cases are found to be severe dysplasia or carcinoma. The causes of this lesion are believed to be similar to those responsible for oral cancer. Therefore tobacco use probably has a significant role in the induction of many of these lesions, as does heavy alcohol consumption. Nutritional deficits and other factors may have modifying roles.

Clinical Features

Erythroplakia is seen much less commonly than its white lesion counterpart, leukoplakia. A strong association with tobacco consumption and use of alcohol has been noted. In comparison with leukoplakia, it should, however, be viewed as a more serious lesion because of the significantly higher percentage of malignancies associated with it (Box 4-1). The lesion appears as a velvety red patch with well-defined margins (Figs. 4-19 and 4-20). Common sites of involvement include the floor of the mouth, the tongue, retromolar mucosa, and the soft palate. Individuals between 50 and 70 years of age are usually affected, and no gender predilection is apparent. Focal white areas representing keratosis may be seen in some lesions (erythroleukoplakia). Erythroplakia is usually supple to the touch unless the lesion is invasive, in which case induration may be noted.

Histopathology

Approximately 40% of erythroplakias show severe dysplastic change; about 50% are squamous cell carcinoma and 9% mild or moderate dysplasia. A relative reduction in keratin production and a relative increase in vascularity account for the clinical color of these lesions.

A histologic variant of carcinoma in situ exhibits changes analogous to the skin lesion called Bowen’s disease. Microscopic features that sep/>