Fibrous Dysplasia of Bone and Albright’s Syndrome

Fibrous dysplasia of bone results from an abnormality in the development of bone-forming mesenchyme.This is manifested by the replacement of spongy bone by a peculiar fibrous tissue, within which trabeculae or spherules of poorly calcified nonlamellar bone are formed by osseous metaplasia. Histologically, a given lesion may show a great variability of pattern,with some fields that are predominantly collagenous, some that are osteoid, and others that are fully ossified and calcified. Radiographically, the lesion will usually present varying degrees of radiopacity and lucency; some

areas will resemble compact bone, and others will be cystic areas. Surgical exploration of such cystic areas usually reveals either a soft fibrous tissue or (more characteristically) a tissue that is gritty on section or curettage. Because these lesions often develop to quite a large size with few symptoms other than a slowly developing asymmetry of the bone, they may exhibit a quite dramatic deformity and apparent bony destruction upon radiographic examination. Patients may have a small solitary focus (monostotic form) or may have many bones affected with multiple lesions (polyostotic form). Rare cases exist in which the lesions of fibrous dysplasia coexist with other developmental bony defects or with extraskeletal changes, notably a blotchy cutaneous hyperpigmentation and precocious puberty. The term “McCune-Albright syndrome” (or simply “Albright’s syndrome”) has been used to describe these more dramatic cases occurring in children (see “Syndromes with Benign Oral Neoplastic or Hamartomatous Components,” below). Recently, the lesional tissues taken from patients with Albright’s syndrome have revealed a mutation in the G protein of the internal signaling pathways. Solitary foci are far more common than multiple lesions, particularly in the jaw bone. Other than the greater variety of histologic patterns and sizes of lesions seen in the polyostotic form, there is no essential difference between the two lesions.The hamartomatous nature of the condition is exemplified by (1) the existence of congenital forms of the disease, (2) the association of fibrous dysplasia with other developmental bone problems in the same patient, (3) the frequency with which increasing size of the lesion correlates with periods of increased skeletal growth rate, (4) the association of endocrine abnormalities with bony lesions in patients with Albright’s syndrome, and (5) the rarity of malignant transformation of these lesions (considering the frequency with which fibrous dysplasia is seen). Recent reviews have stressed that malignant transformation of these lesions probably occurs more frequently than is usually believed because small foci of fibrous dysplasia are often overlooked in the examination of a patient with a malignant bone lesion. In most cases, fibrous dysplasia can be safely handled as a benign developmental anomaly, and superficial recontouring of the lesion or curettage of a large cystic lesion remains appropriate management, provided that an adequate and representative bone biopsy specimen has been obtained.Radiotherapy is contraindicated in the treatment of fibrous dysplasia. Radiotherapy administered in earlier decades of the twentieth century may have played a role in the rare cases of malignant transformation to fibrosarcoma or osteogenic sarcoma.
The extensive size and the nonuniform radiographic appearance of some lesions of fibrous dysplasia pose a problem to the surgeon who needs to obtain representative biopsy specimens with minimal disturbance of the lesion. Biopsy specimens of these lesions, as do other bone biopsy specimens, frequently reveal nothing more than superficial layers of reactive normal bone formation. Curettage of one of the cystic cavities usually provides material of more diagnostic value. At times, the hypercellularity, pleomorphism, and aggressiveness
of the fibrous tissue in these lesions will lead the pathologist to suspect a fibrosarcoma or an osteogenic sarcoma; consideration of both the clinical behavior and the histologic appearance of the lesion is needed to arrive at a diagnosis. Fibrous dysplasia has been described in association with giant cell reparative granuloma of bone, aneurysmal bone cyst, and a number of other fibro-osseous lesions, and the coexistence of different histologic pictures in one lesion or in one patient can provide added diagnostic difficulties.
The clinical problems associated with fibrous dysplasia of bone are related to the site and extent of involvement. Many small foci probably remain unrecognized throughout life. In the long bones, deformity and fractures are common complications that often lead to the initial diagnosis of the lesion. In the jaws and other parts of the craniofacial skeleton, involvement of adjacent structures such as the cranial sinuses, cranial nerves, and ocular contents can lead to serious complications in addition to cosmetic and functional problems. Intracranial lesions arising from the cranial bones may produce seizures and electroencephalographic changes. Extension into and occlusion of the maxillary and ethmoid sinuses and mastoid air spaces is common.Proptosis, diplopia, and interference with jaw function also often prompt surgical intervention.
Computed tomography and technetium (Tc)-99m bone scans have proved to be of great help in the diagnosis of lesions of fibrous dysplasia.Trimming and surface contouring of the affected bone, curettage of bony cavities, and packing with bone chips remain the recommended treatments. Surgical interventions before the patient has reached puberty may actually activate these fibro-osseous lesions and should be avoided except in cases of the more disfiguring lesions. Attempts at treating advanced cases of the polyostotic form with calcitonin have not been greatly successful. There is laboratory evidence of increased bone turnover, increased alkaline phosphatase, and high urinary hydroxyproline levels with normal serum calcium and phosphate levels in large monostotic lesions of fibrous dysplasia and in the polyostotic form.
Opinions differ as to whether pain is a common feature of fibrous dysplasia. In the general skeleton, small lesions are undoubtedly often asymptomatic. Larger lesions associated with cortical fractures are painful and incapacitating and lead to extreme degrees of deformity in many cases. Pain is not a feature of craniofacial lesions. The extent of the deformity may be as great as that associated with untreated von Recklinghausen’s disease of bone due to hyperparathyroidism, and in the early part of this century, fibrous dysplasia was often confused with this metabolic bone disorder.