Clinical Features

By definition, peripheral fibroma is a reactive hyperplastic mass that occurs on the gingiva and is believed to be derived from connective tissue of the submucosa or periodontal ligament (Figure 7-1). It may occur at any age, although it does have a predilection for young adults. Females develop these lesions more commonly than do males, and the gingiva anterior to the permanent molars is most often affected.

Peripheral fibroma may present clinically as a stalked (pedunculated) or a broad-based (sessile) mass that is similar in color to surrounding connective tissue. Ulceration may be noted over the summit of the lesion. It rarely causes erosion of subjacent alveolar bone.

Histopathology

Peripheral fibroma is a form of fibrous hyperplasia that may also be called hyperplastic scar. It is highly collagenous and relatively avascular, and it may contain a mild to moderate chronic inflammatory cell infiltrate. This lesion is basically the gingival counterpart to traumatic fibroma occurring in other mucosal regions.

Microscopically, several subtypes of this lesion have been identified. These are essentially of academic interest because the biological behavior and treatment of these microscopic variants are the same.

Peripheral ossifying fibroma is a gingival mass in which islands of woven (immature) bone and osteoid are seen. The bone is found within a lobular proliferation of plump, benign fibroblasts. Chronic inflammatory cells tend to be seen around the periphery of the lesion (Figure 7-2). The surface is typically ulcerated.

Peripheral odontogenic fibroma is a gingival mass composed of well-vascularized, nonencapsulated fibrous connective tissue. The distinguishing feature of this variant is the presence of strands of odontogenic epithelium, often abundant, throughout the connective tissue. Amorphous hard tissue resembling tertiary (reactive) dentin, so-called dentinoid, may also be present. The lesion is usually nonulcerated.

Giant cell fibroma is a fibrous hyperplasia in which many of the mesenchymal cells are relatively larger than normal fibroblasts (giant cells) and assume a stellate shape. Immunohistochemical studies have shown that most of these stellate cells are fibroblasts (a few factor XIIIa–positive dendritic cells are also typically present) (Figure 7-3). These same peculiar stellate cells can be found in focal fibrous hyperplastic lesions throughout the oral mucosa and occasionally on the skin (fibrous papule). One form of this lesion is known as retrocuspid papilla of the mandible.

Differential Diagnosis

Clinically, these lesions usually are not confused with anything else. However, some overlap may be noted with pyogenic granuloma and, rarely, peripheral giant cell granuloma, when these two lesions do not have a prominent vascular component.

Treatment

Peripheral fibroma should be treated by local excision, which should include the periodontal ligament, if involved. Also, any identifiable etiologic agent, such as calculus or other foreign material, should be removed. Recurrence may occasionally be associated with the microscopic subtype—peripheral ossifying fibroma. Re-excision to the periosteum or the periodontal ligament should prevent further recurrence.

Etiology

Focal fibrous hyperplasia is a reactive lesion usually caused by chronic trauma to oral mucous membranes. Overexuberant fibrous connective tissue repair results in a clinically evident submucosal mass. Although the terms traumatic fibroma and oral fibroma are often applied to these entities, they are misnomers because these lesions are not benign tumors of fibroblasts, as the term fibroma implies (Box 7-1).

Clinical Features

No gender or racial predilection for the development of this intraoral lesion has been noted. It is a very common reactive hyperplasia that is typically found in frequently traumatized areas, such as the buccal mucosa, the lateral border of the tongue, and the lower lip (Figure 7-4). It is a painless, broad-based swelling that is paler in color than the surrounding tissue because of its relative lack of vascular channels. The surface may occasionally be traumatically ulcerated, particularly in larger lesions. Lesions have limited growth potential and do not exceed 1 to 2 cm in diameter.

Multiple fibromas may be part of a rare autosomal-dominant syndrome known as Cowden’s syndrome or multiple hamartoma syndrome. Many organ systems, such as the mucosa, skin, breast, thyroid, and colon, may be affected. Frequently encountered abnormalities include numerous oral fibromas and papillomas; cutaneous papules, keratoses, and trichilemmomas; benign and malignant neoplasms of the breast and thyroid; and colonic polyps. The underlying genetic problem appears to be related to germline mutations of the tumor suppressor gene PTEN found on chromosome 10q23.

Histopathology

Collagen overproduction is the basic process that dominates the microscopy of this lesion. Fibroblasts are mature and widely scattered in a dense collagen matrix. Sparse chronic inflammatory cells may be seen, usually in a perivascular distribution (Figure 7-5). Overlying epithelium is often hyperkeratotic because of chronic low-grade friction.

Differential Diagnosis

This is a relatively trivial lesion that should be removed to rule out other pathologic processes. Depending on its location, several other entities might be included in a clinical differential diagnosis. Neurofibroma, Schwannoma, and granular cell tumor would be possibilities for masses in the tongue. In the lower lip and buccal mucosa, lipoma, mucocele, and salivary gland tumors might be considered. Although rare, benign neoplasms of mesenchymal origin could present as submucosal masses not unlike focal fibrous hyperplasia.

Treatment

Simple surgical excision is usually effective. Infrequently, recurrence may be caused by continued trauma to the involved area. These lesions have no malignant potential.

Etiology

Denture-induced fibrous hyperplasia of oral mucosa is related to the chronic trauma produced by an ill-fitting denture. The process is essentially the same as the one that leads to traumatic fibroma, except that a denture is specifically identified as the causative agent. This lesion has also been referred to by several older synonyms including inflammatory hyperplasia, denture hyperplasia, and epulis fissuratum.

Clinical Features

Denture-induced fibrous hyperplasia is a common lesion that occurs in the vestibular mucosa and less commonly along the mandibular lingual sulcus where the denture flange contacts tissue (Figures 7-6 and 7-7). As the bony ridges of the mandible and the maxilla resorb with long-term denture use, the flanges gradually extend farther into the vestibule. There, chronic irritation and trauma may incite an overexuberant fibrous connective tissue reparative response. The result is the appearance of painless folds of fibrous tissue surrounding the overextended denture flange.

Treatment

Some reduction in size of the lesion may follow prolonged removal of the denture. However, because the hyperplastic scar is relatively permanent, surgical excision is usually required. Construction of a new denture or relining of the old one is also required to prevent recurrence.

Etiology

In generalized gingival hyperplasia, overgrowth of the gingiva may vary from mild enlargement of the interdental papillae to such severe uniform enlargement that the crowns of the teeth may be covered by hyperplastic tissue (Box 7-2). Uniform or generalized gingival fibrous connective tissue hyperplasia may be due to one of several etiologic factors. Most cases are nonspecific and are the result of an unusual hyperplastic tissue response to chronic inflammation associated with local factors such as plaque, calculus, or bacteria. Why only some patients have a propensity for the development of connective tissue hyperplasia in response to local factors is unknown. Recent studies have reported a possible role for keratinocyte growth factor (a member of the fibroblast growth factor family) in this condition.

Other conditions such as hormonal changes and drugs can significantly potentiate or exaggerate the effects of local factors on gingival connective tissue. Hormonal changes that occur during pregnancy and puberty have long been known to be associated with generalized gingival hyperplasia. This hyperresponsiveness during pregnancy has led to the infrequently used and inappropriate term pregnancy gingivitis. Altered hormonal conditions act in concert with local irritants to produce the hyperplastic response. It is questionable whether significant gingival enlargement during periods of hormonal imbalance would occur in individuals with scrupulous oral hygiene.

Phenytoin (Dilantin), a drug used in the control of seizure disorders, is a well-known etiologic factor in generalized gingival enlargement. It is thought that phenytoin causes impaired collagen degradation through suppression of matrix metalloproteinases (MMPs)/tissue inhibitor of metalloproteinase-1 (TIMP-1) and α2β1-integrin–mediated endocytosis. The extent or severity of so-called Dilantin hyperplasia is dependent on the presence of local factors such as plaque and calculus. The effects of time and dose of the drug on gingival tissue are not clear. Reported prevalence has ranged from 0% to 80%, depending on the investigator’s clinical criteria and the number of patients observed. A value of 50% is generally accepted as the probable prevalence. In any event, the fact that not all patients taking phenytoin develop gingival hyperplasia indicates that some patients are predisposed to the development of this condition. It has only rarely been described in edentulous patients and in children before tooth eruption.

Cyclosporine, the immunosuppressant drug that is used to modulate T-lymphocyte function in transplant recipients and in patients with various autoimmune diseases, has also been linked to fibrous hyperplasia of the gingiva. The cause of this condition is not known, but edema secondary to increased sulfated-glycosaminoglycan synthesis by fibroblasts may play an important role. Not all patients are affected (10% to 70%), and local factors have a synergistic role. Unlike phenytoin-related hyperplasia, cyclosporine-induced hyperplasia has been reported to be a reversible process following cessation of drug use.

Nifedipine and other calcium channel blockers used in the treatment of cardiac angina, arrhythmias, and hypertension are known to contribute to gingival hyperplasia. The process mimics phenytoin-related hyperplasia but, similar to cyclosporine-induced gingival hyperplasia, appears to be reversible.

Gingival enlargement is also known to occur in patients with leukemia, especially those with the chronic monocytic form. This is believed to be a result of infiltration of the gingival soft tissues by malignant white blood cells. It may be modulated by local factors such as plaque and calculus; because of the bleeding tendency associated with leukemia, patients may be unable or reluctant to practice correct oral hygiene, resulting in the accumulation of plaque and debris. This accumulation may provide the inflammatory stimulus for connective tissue hyperplasia.

Some rare types of gingival hyperplasia that occur in early childhood have a hereditary basis. The best recognized is hereditary gingival fibromatosis, which clinically can resemble Dilantin-induced gingival hyperplasia. Patients with other rare syndromes such as Zimmerman-Laband, Cross’, Rutherfurd’s, Murray-Puretic-Drescher (juvenile hyaline fibromatosis), and Cowden’s syndromes can develop varying degrees of fibrous gingival hyperplasia.

Clinical Features

The clinical feature common to the variously caused gingival hyperplasias is an increase in bulk of the free and attached gingiva, especially the interdental papillae (Figures 7-8 to 7-10). Stippling is lost, and gingival margins become rolled and blunted. The consistency of the gingiva ranges from soft and spongy to firm and dense, depending directly on the density and amount of fibrosis. A range of color from red-blue to lighter than surrounding tissue is also seen; this varies with the severity of the inflammatory response as well. Generally, hyperplasias associated with nonspecific local factors and hormonal changes appear more inflamed clinically than drug-induced and idiopathic forms. The idiopathic type is particularly dense and fibrous, with relatively little inflammatory change.

Histopathology

An abundance of collagen is noted. Fibroblasts are increased in number, and various degrees of chronic inflammation are seen. In some cases, especially those in which hormonal changes are important, capillaries may be increased and prominent. The overlying epithelium usually exhibits some hyperplasia. Occasionally, plasma cells dominate the histologic picture. In leukemic enlargements, atypical and immature white blood cells, representing a malignant infiltrate, may be found.

Treatment

In all forms of generalized gingival hyperplasia, attentive oral hygiene is necessary to minimize the effects of inflammation on fibrous proliferation and the effects of systemic factors. Gingivoplasty or gingivectomy may be required but should be done in combination with prophylaxis, oral hygiene instruction, and a comprehensive home care program.

Giant Cell Angiofibroma

Myxoma

Nasopharyngeal Angiofibroma

Nodular Fasciitis