Etiology and Pathogenesis

Ossifying fibroma is of undetermined cause (Box 12-3). Although chromosome translocations have been identified in a few cases of ossifying fibroma, genetic studies have been insufficient to determine the molecular mechanisms that underlie the development of this tumor.

Clinical Features

Ossifying fibroma is an uncommon lesion that tends to occur during the third and fourth decades of life, and in women more than men. It is a slow-growing, asymptomatic, and expansile lesion. In the head and neck, ossifying fibroma may be seen in the jaws and craniofacial bones. Lesions of the jaws characteristically arise in the tooth-bearing regions, most often in the mandibular premolar-molar area (Figure 12-1). The slow but persistent growth of the tumor may ultimately produce expansion and thinning of the buccal and lingual cortical plates, although perforation and mucosal ulceration are rare (Figures 12-2 and 12-3). Most of these lesions are solitary, although instances of multiple synchronous lesions have been reported; a familial background for synchronous lesions is rare.

The most important radiographic feature of this lesion is the well-circumscribed, sharply defined border. Ossifying fibromas otherwise present a variable appearance, depending on the density of calcifications present. Lesions may be relatively radiolucent because of evenly dispersed, calcified new bone. Lesions may also appear as unilocular or multilocular radiolucencies that bear a resemblance to odontogenic lesions. A mixed radiolucent-radiopaque image is seen when islands of tumor bone are densely calcified. The roots of teeth may be displaced; less commonly, tooth resorption is seen.

The term juvenile (aggressive) ossifying fibroma was used in the literature to describe two variants of ossifying fibroma that occur in younger patients (Box 12-4). Currently these two entities are referred to as juvenile trabecular ossifying fibroma (JTOF) and juvenile psammomatoid ossifying fibroma (JPOF). Juvenile trabecular ossifying fibroma (JTOF) typically occurs in children and adolescents; only about 20% of cases occur in those older than 15 years. The lesion occurs almost exclusively in the maxilla and mandible and rarely in extragnathic locations. JTOF is characterized by progressive and sometimes rapid growth but rarely pain. Radiographically, the tumor has a defined border and can range from radiodense to radiolucent. Microscopically, JTOF is highly cellular and contains trabeculae or spheroids of new bone. Following complete excision, recurrences of JTOF are infrequent. By contrast, the juvenile psammomatoid ossifying fibroma (JPOF) occurs principally in the extragnathic craniofacial bones, particularly the paranasal sinuses and periorbital bones, where it may cause exophthalmos, proptosis, sinusitis, and nasal symptoms. JPOF occurs in a slightly older population compared with JTOF. Microscopically, JPOF is formed by relatively cellular stroma containing small, rounded calcifications (psammomatoid). Treatment consists of surgical excision, but up to 30% of cases will show recurrences, sometimes multiple and over a span of many years.

Cementifying fibroma and cemento-ossifying fibroma are terms occasionally used when the bony islands in these jaw tumors are round or spheroidal. These occur in similar age groups and locations, exhibit comparable clinical characteristics, and have the same biological behavior. They are, for all practical purposes, the same lesion as ossifying fibroma.

Histopathology

Ossifying fibroma is composed of fibrous connective tissue with well-differentiated spindled fibroblasts. Cellularity is uniform but may vary from one lesion to the next. Collagen fibers are arranged haphazardly, although a whorled, storiform pattern may be evident. Bony spheroids, trabeculae, or islands are evenly distributed throughout the fibrous stroma (Figures 12-4 to 12-6). Bone is immature and often is surrounded by osteoblasts. Osteoclasts are infrequently seen.

Differential Diagnosis

Distinguishing between ossifying fibroma and fibrous dysplasia is the primary diagnostic challenge. These lesions may exhibit similar clinical, radiographic, and microscopic features. The most helpful feature in distinguishing the two is the well-circumscribed radiographic appearance of ossifying fibroma and the ease with which it can be separated from normal bone. In most cases, the well-defined appearance of ossifying fibroma is evident radiographically. Historically, differentiating the two lesions was based primarily on histologic criteria. Fibrous dysplasia was reported to contain only woven bone, without evidence of osteoblastic rimming of bone. The presence of more mature lamellar bone was believed to be characteristic of ossifying fibroma. Most authorities now acknowledge that these criteria are unreliable, because both types of bone and cellular features may be found in either lesion.

Other differential considerations are osteoblastoma, focal cemento-osseous dysplasia, and focal osteomyelitis. Osteoblastoma is evident in a slightly younger age group and is often characterized by pain. In addition, osseous trabeculae in these lesions are rimmed by abundant plump osteoblasts, and a central nidus may be evident. Periapical cemento-osseous dysplasia in posterior teeth may appear radiographically similar and may require a biopsy to separate it from ossifying fibroma. Focal osteomyelitis is associated with a source of inflammation and may be accompanied by pain and swelling.

Treatment and Prognosis

Treatment of ossifying fibroma is most often accomplished by surgical removal using curettage or enucleation. The lesion can typically be separated easily from the surrounding normal bone. Recurrence is described only rarely after removal.

Etiology and Pathogenesis

The name given to fibrous dysplasia was originally intended to indicate that the condition represented a dysplastic growth resulting from deranged mesenchymal cell activity or a defect in the control of bone cell activity. Genetic studies, however, have provided evidence that it may be better classified as a neoplastic process. Mutations of the GNAS I gene encoding for the alpha subunit of a transmembrane-signaling G protein (Gsα) appear to be present in fibrous dysplasia. This genetic alteration may ultimately affect the proliferation and differentiation of fibroblasts/osteoblasts that make up these lesions.

Clinical Features

This disease most commonly presents as an asymptomatic, slow enlargement of involved bone. Fibrous dysplasia may involve a single bone or several bones concomitantly. Monostotic fibrous dysplasia is the designation used to describe the process in one bone. Polyostotic fibrous dysplasia applies to cases in which more than one bone is involved. McCune-Albright syndrome consists of polyostotic fibrous dysplasia, cutaneous melanotic pigmentations (café-au-lait macules), and endocrine abnormalities. The most commonly reported endocrine disorder consists of precocious sexual development in girls. Acromegaly, hyperthyroidism, hyperparathyroidism, and hyperprolactinemia have also been described. Jaffe-Lichtenstein syndrome is characterized by multiple bone lesions of fibrous dysplasia and skin pigmentations.

Monostotic fibrous dysplasia is much more common than the polyostotic form, accounting for as many as 80% of cases. Jaw involvement is common in this form of the disease. Other bones that are commonly affected are the ribs and the femur. Fibrous dysplasia occurs more often in the maxilla than in the mandible (Figure 12-7). Maxillary lesions may extend to involve the maxillary sinus, zygoma, sphenoid bone, and floor of the orbit. This form of the disease, with involvement of several adjacent bones, has been referred to as craniofacial fibrous dysplasia. The most common site of occurrence with mandibular involvement is in the body portion.

The slow, progressive enlargement of the affected jaw is usually painless and typically presents as a unilateral swelling. As the lesion grows, facial asymmetry becomes evident and may be the initial presenting complaint. The dental arch is generally maintained, although displacement of teeth, malocclusion, and interference with tooth eruption may occasionally occur. Tooth mobility is not seen.

This condition characteristically has its onset during the first or second decade of life. Rarely, the lesion presents later in life, although this may only reflect the insidious, asymptomatic nature of fibrous dysplasia. Monostotic fibrous dysplasia generally exhibits an equal gender distribution; the polyostotic form tends to occur more commonly in females.

Fibrous dysplasia has a variable radiographic appearance that ranges from a radiolucent lesion to a uniformly radiopaque mass (Figures 12-8 to 12-10). The classic lesion has been described as having a radiopaque change that imparts a “ground-glass” or “peau d’orange” effect. This characteristic image, which is most identifiable on intraoral radiographs, is not, however, pathognomonic. Lesions of fibrous dysplasia may also present as unilocular or multilocular radiolucencies, especially in long bones. A third pattern, most commonly seen in patients with long-standing disease, is a mottled radiolucent and radiopaque appearance. Additional radiographic features that have been described include a fingerprint bone pattern and superior displacement of the mandibular canal in mandibular lesions.

An important distinguishing feature of fibrous dysplasia is the poorly defined radiographic and clinical margins of the lesion. The process appears to blend into the surrounding normal bone without evidence of a circumscribed border. In addition, these lesions are often elliptic as opposed to spheric.

Laboratory values for patients with monostotic fibrous dysplasia, specifically, serum calcium, phosphorus, and alkaline phosphatase, are usually within normal ranges for patients with monostotic disease. However, these serum chemistry markers may be altered in patients with McCune-Albright syndrome.

Histopathology

Fibrous dysplasia consists of a slightly to moderately cellular fibrous connective tissue stroma that contains foci of irregularly shaped trabeculae of immature bone (Figures 12-11 and 12-12). A relatively constant ratio of fibrous tissue to bone throughout a given lesion is characteristic. The fibroblasts exhibit uniform spindle-shaped nuclei, and mitotic figures are not seen. The bony trabeculae assume irregular shapes likened to Chinese characters (the pictograms used in Chinese writing), and they do not display any functional orientation. The bone is predominantly woven in type and appears to arise directly from the collagenous stroma without prominent osteoblastic activity. In a mature fibrous dysplasia lesion, lamellar bone may be found. Capillaries typically are prominent and uniformly distributed.

Differential Diagnosis

The primary differential consideration for fibrous dysplasia of the jaws is ossifying fibroma. As previously noted, clinical, radiographic, and microscopic features must be considered together to distinguish these processes. The well-circumscribed ossifying fibroma as compared with the diffuse fibrous dysplasia often serves as the differentiating factor. Additional features that aid in distinguishing these processes are listed in Box 12-6.

Chronic osteomyelitis occasionally may mimic the radiographic appearance of fibrous dysplasia. Inflammation, often mild, is present in osteomyelitis and may be accompanied by symptoms that include tenderness, pain, or drainage. Periostitis is a radiographic feature of osteomyelitis. The slowly progressive, asymptomatic nature of fibrous dysplasia usually allows differentiation from malignant tumors of bone.

Treatment and Prognosis

After a variable period of prepubertal growth, fibrous dysplasia characteristically stabilizes, although a slow advance may be noted into adulthood. Small lesions therefore may require no treatment other than biopsy confirmation and periodic follow-up. Large lesions that have caused cosmetic or functional deformity may be treated by surgical recontouring. This procedure generally is deferred until after stabilization of the disease process. En bloc resections for complete removal are impractical and unnecessary because the lesions are relatively large and poorly delineated.

Medical management with bisphosphonates has been reported to improve symptoms of pain and bone density, but their long-term effects have yet to be determined. Whether other drugs that control osteoclast activity in use or in development will provide beneficial effects is speculative.

Malignant transformation is a rare complication of fibrous dysplasia (less than 1% of cases) that has been described usually in patients with the polyostotic type. Many of the reported patients were treated with radiation therapy, suggesting a role for radiation in the transformation process, although malignant change has been documented in the absence of radiation treatment.