Excerpt from Fibrous Dysplasia

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Background

Fibrous dysplasia is a skeletal developmental anomaly of the bone-forming mesenchyme that manifests as a defect in osteoblastic differentiation and maturation. Virtually any bone in the body can be affected. It is a nonhereditary disorder of unknown cause.

Pathophysiology

In fibrous dysplasia, the medullary bone is replaced by fibrous tissue, which appears radiolucent on radiographs, with the classically described ground-glass appearance. Trabeculae of woven bone contain fluid-filled cysts that are embedded largely in collagenous fibrous matrix, which contributes to the generalized hazy appearance of the bone.

The following 4 disease patterns are recognized:

• Monostotic form

• Polyostotic form

• Craniofacial form

• Cherubism

Frequency

United States

The exact incidence is not clearly established.

International

The worldwide incidence is not exactly known.

Mortality/Morbidity

Usually, fibrous dysplasia is not a fatal disease. A small percentage of patients die when the bone lesion is complicated by malignant change.

Race

No specific racial predilection exists.

Sex

The incidence rates are equal in males and females.

Age

The initial manifestations of fibrous dysplasia are most commonly found in persons aged 3-15 years.

• Two thirds of patients with polyostotic disease are asymptomatic before they are aged 10 years.
• With monostotic disease, patients as old as 20 or 30 years are asymptomatic.

Clinical Details

Clinical findings of increasing pain and an enlarging soft tissue mass suggest malignant change. Clinical details of the 4 forms of fibrous dysplasia, as well as other features, are discussed below.

Monostotic form

Approximately 70-80% of fibrous dysplasias are monostotic. This form most frequently occurs in the rib (28%), femur (23%), tibia or craniofacial bones (10-25%), humerus, and vertebrae, in decreasing order of frequency.

This form may present with pain or a pathologic fracture in patients aged 10-70 years, but this form most frequently occurs in those aged 10-30 years. The degree of bone deformity of the monostotic form is relatively less severe than that of the polyostotic type. No clearly documented evidence supports conversion of the monostotic form to the polyostotic form.

Polyostotic form

Approximately 20-30% of fibrous dysplasias are polyostotic. Polyostotic fibrous dysplasia more frequently involves the skull and facial bones, pelvis, spine, and shoulder girdle. The sites of involvement are the femur (91%), tibia (81%), pelvis (78%), ribs, skull and facial bones (50%), upper extremities, lumbar spine, clavicle, and cervical spine, in decreasing order of frequency. The dysplasia may be unilateral or bilateral, and it may affect several bones of a single limb or both limbs with or without axial skeleton involvement. Although the polyostotic variety tends to occur in a unilateral distribution, involvement is asymmetric and generalized when disease is bilateral.

Two thirds of patients are symptomatic before they are 10 years of age. Often, the initial symptom is pain in the involved limb associated with a limp, a spontaneous fracture, or both. In one series, pathologic fracture was present in 85% of polyostotic fibrous dysplasias. Leg-length discrepancy of varying degrees occurs in about 70% of patients with limb involvement. The structural integrity of the bone is weakened, and the weight-bearing bones become bowed. The curvature of the femoral neck and proximal shaft of the femur markedly increase because a femoral lesion commonly causes a severe coxa vara abnormality, shepherd's-crook deformity, which is a characteristic sign of the disease. Overgrowth of adjacent soft tissues may be present.

Craniofacial form

This pattern of the disease occurs in 10-25% of patients with the monostotic form and in 50% with the polyostotic form. It also occurs in an isolated craniofacial form. In the isolated variety, no extracranial lesions are present. Sites of involvement most commonly include the frontal, sphenoid, maxillary, and ethmoidal bones. The occipital and temporal bones are less commonly affected.

Hypertelorism, cranial asymmetry, facial deformity (ie, leontiasis ossea), visual impairment, exophthalmos, and blindness may occur because of involvement of orbital and periorbital bones. Involvement of the sphenoid wing and temporal bones may result in vestibular dysfunction, tinnitus, and hearing loss. When the cribriform plate is involved, hyposmia or anosmia may result.

Cherubism

This special variant of fibrous dysplasia is an autosomal dominant disorder of variable penetrance. It occurs in children and is more severe in boys. Regression may occur after adolescence. The jaw is broad and protruding. Involvement of the maxilla and that of the mandible are symmetric.

Other features

Fibrous dysplasia may be associated with endocrinopathies in 2-3% of cases; these include precocious puberty in girls, hyperthyroidism, hyperparathyroidism, acromegaly, diabetes mellitus, and Cushing syndrome. McCune-Albright syndrome may be associated with hyperthyroidism and, hence, exophthalmos.

The prevalence rate of scoliosis in patients with polyostotic fibrous dysplasia is 40-52%. Most spinal lesions are located in the lumbar and thoracic spines, with very few located in the sacrum and cervical spine. The posterior elements of vertebrae are involved in 71%. In a series of 62 patients studied by Leet et al (2004), 40% had scoliosis and 48% had no scoliosis.

Sexual precocity in girls, with polyostotic fibrous dysplasia and cutaneous pigmentation, constitutes McCune-Albright syndrome. Cutaneous pigmentation is the most common extraskeletal manifestation in fibrous dysplasia. It occurs in more than 50% of cases of the polyostotic form. Cutaneous pigmentation in polyostotic fibrous dysplasia is ipsilateral to the side of bony lesions, a feature that differentiates this disease from pigmentation in neurofibromatosis.

The pigmented macules, or cafe-au-lait spots, are related to increased amounts of melanin in the basal cells of the epidermis. They tend be arranged in a linear or segmental pattern near the midline of the body, usually overlying the lower lumbar spine, sacrum, buttocks, upper back, neck, and shoulders. Similar lesions may occur on the lips and oral mucosa. Pigmentation may occur at birth, and in fact, it occasionally precedes the development of skeletal and endocrine abnormalities.

The only significant laboratory abnormality is an elevated alkaline phosphatase level.

Preferred Examination

Plain radiography is the first-line study. Usually, the diagnosis is straightforward when typical features are present. CT may be required to assess complex regions such as the spine, pelvis, chest, and facial skeleton. Bone scintigraphy has a limited role in the detection of subtle pathologic fractures. In fibrous dysplasia, the features on a bone scan are nonspecific for diagnostic purposes. MRI may be necessary to assess cord compression when the spine is involved.

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