FIBROUS DYSPLASIA – A REVIEW
Dr. Nimish Agarwal
Abstract Fibrous dysplasia is a common benign skeletal lesion that may involve one bone (monostotic) or multiple bones (polyostotic) and occurs throughout the skeleton with a predilection for the long bones, ribs, and craniofacial bones and is equally found in both genders and is not inherited. Most lesions are monostotic, asymptomatic, and identified incidentally and can be treated with clinical observation and patient education. Its etiology has been linked to an activating mutation of Gsa and the downstream effects of the resultant increase in Camp. Fibrous dysplasia may occur as a component of McCune-Albright syndrome or the rare Mazabraud syndrome. The radiological picture is somewhat variable, including a ground-glass appearance, expansion of the bone, and sclerosis surrounding the lesion. Histologically, fibrous dysplasia shows irregularly-shaped trabeculae of immature, woven bone in a background of variably cellular, loosely arranged fibrous stroma. It may be complicated by pathologic fracture, and rarely by malignant transformation. This review examines interesting issues surrounding the etiology of fibrous dysplasia, its clinical and laboratory manifestations, radiological picture, utility of bone biopsy, gross and microscopic pathology, complications, and its differential diagnostic considerations.
Introduction
Fibrous dysplasia a developmental tumour-like condition still remains as a clinico-pathologic challenge for many reasons. Although usually easily diagnosed, fibrous dysplasia may present with clinical and radiographic features that may border with other benign fibro-osseous lesions of the skeleton and (although rarely) may be confused with certain elusive types of malignancies. 1.2 Mention of fibrous dysplasia first appeared in the literature in 1937 when Albright and co-workers reported a disease showing cutaneous pigmentation and endocrine disorder in addition to fibrous dysplasia.³
The term fibrous dysplasia of bone was first used by Lichtenstein in 1938 to describe a condition to which attention had been drawn by Hunter and Turnbull (1931). Fibrous dysplasia is a rare benign intramedullary fibro-osseous lesion, which may present in either monostotic or polyostotic forms.45 It is a genetic non-inherited condition caused by missense mutation in the GNASI gene on chromosome 20. Fibrous dysplasia is characterized by abnormal proliferation of fibrous tissue interspersed with
to mature lamellar bone and a failure of the bone to realign in response to mechanical stress. Failure of maturation leaves a mass of immature isolated trabeculae enmeshed in dysplastic fibrous tissue that are turning over constantly but never (or very, very slowly) completing the remodelling process. 12 In addition, the immature matrix does not mineralize normally. The combination of a lack of stress alignment and insufficient mineralization results in substantial loss of mechanical strength, leading to the development of pain, deformity, and pathologic fractures. 13
The etiology of fibrous dysplasia has been linked with a mutation in the GNASI gene that encodes the alpha subunit of the stimulatory G protein-coupled receptor, Gsa, and is located at chromosome 20q13.2-13.3.13,14 The activating mutations occur post-zygotically, replacing the arginine residue amino acid with either a cysteine or a histidine amino acid. All cells that derive from the mutated cells manifest the dysplastic features. The clinical presentation varies, depending on the location of the mutation in the cell mass and the size of the cell mass during embryogenesis when the mutation occurs. 15 Severe disease
normal or immature bone, and may be associated with endocrine dysfunction, abnormal pigmentation, and precocious puberty in girls. It occurs in equal proportions in males and females, most often during the first two decades of life. The abnormal skin pigmentation also tends to be present on the same side. The initial clinical sign is usually a painless enlargement of the affected bone. Other signs and symptoms include bone pain, pathologic fractures, and bone deformities. 9.10 Malignant transformation is rare, and is usually precipitated by radiation therapy
Etiology and Pathophysiology
Fibrous dysplasia is postulated to occur as a result of a developmental failure in the remodelling of primitive bone
associated with an earlier mutational event that leads to a larger number or a more widespread distribution of mutant cells. The sporadic occurrence of these diseases and the characteristic lateralized pattern of skin and bone involvement in the polyostotic forms of fibrous dysplasia suggest this mosaic distribution of abnormal cells. The Gsa mutation was first identified in patients with McCune-Albright syndrome, and the Gsa gene has also been linked to other endocrine tumours and human diseases. 15 The strongest evidence to support a genetic link to the etiology of fibrous dysplasia was found in an experimental study by Bianco et al who isolated Gsa genes from patients with McCune-Albright syndrome, transplanted them into immunocompromised mice, and induced dysplastic bone production. 16