The hallmark of FD is the appearance of painless enlargement of bone usually before the end of the second decade of life. It may involve one bone (monostotic) or many bones (polyostotic). Polyostotic FD occurring with cutaneous cafe au lait pigmentation and endocrinopathy constitute the McCune-Albright syndrome. The cause of FD has been a mystery since its recognition more than a half century ago. The discovery of a gain-in-function mutation in the gene encoding the signal transducing G protein has provided new insight. Cells with this mutation have a proliferation advantage over those that do not. The extent of the disease is determined by the time in life when the activating mutation occurs.
Mutation early in embryogenesis accounts for the mosaic distribution of skeletal lesions resulting in polyostotic disease. If the mutation is confined to osteoprogenitor cells, the phenotype is skeletal disease only, the Jaffe phenotype. Appearance of the mutating event earlier in embryogenesis and ostensibly involving a cell ancestral to osteoprogenitor, endocrine, and pigment cell lineages results in the full McCune-Albright syndrome. Somatic mutation later in life accounts for more common monostotic presentation that accounts for approximately 70% of all cases. The fact that the lesions appear to grow without purpose and are attributed to gene mutations that have oncogene-like function suggests a neoplastic disease. However, the observation that lesions of FD eventually decrease proliferation and that growth of the lesion is arrested as the skeleton matures indicates a developmental abnormality. There is lack of agreement regarding the radiographic appearance of FD. Some authors accept a radiolucent lesion with well-defined borders as within the range of FD. The prevailing view is the FD appears as a fine-grain (ground glass), radiodense lesion with indistinct borders that blends imperceptibly with adjacent normal bone. The two views are not mutually exclusive. FD may evolve as the disease progresses, changing radiographically along the way similar to Paget's disease of bone and florid osseous dysplasia. The bone lesions of FD are characterized by the proliferation of spindle mesenchymal cells that replace and fill the normal marrow, cause resorption of native bone matrix, expand the bone and thin the cortex, and eventually replace the normal lamellated bone with new, structurally unsound woven bone. Unrestrained activity enlarges the bone and betrays the presence of the disease. Because the histopathologic features of FD are similar to other fibro-osseous lesions, microscopy alone is often insufficient for diagnosis.
It is useful to determine if there is osteoblastic rimming, a term that describes an orderly row of osteoblasts bordering newly formed bone. The absence of rimming is widely accepted as a feature of FD that helps to separate it from other lesions; however, published accounts of inherited craniofacial lesions of FD show osteoblas-tic rimming. The shape of the newly deposited bone trabeculae has been described as being curvilinear, an unreliable feature. The spindle cells that constitute the parenchyma are osteoprogenitor cells that resemble ordinary fibroblasts, and the nuclei are uniform in size and shape. The appearance of nuclear pleomorphism or atypical mitoses suggests the diagnosis of FD may be wrong as FD is not neoplastic. Rather, it forms a mass that may clinically and radiographically resemble a neoplasm but with time, growth ceases. A similar unexplained phenomenon occurs in other jaw disease such as cherubism. Treatment planning should take the limited growth potential into account. Surgery is the only option and should be reserved for those cases that exceed acceptable functional and cosmetic limits. The conversion of FD to osteogenic sarcoma has been reported but it is a rare event.
Was this article helpful?