Laboratory Studies
Molecular diagnosis using the techniques of polymerase chain reaction (PCR) analysis with peptide nucleic acid (PNA) has shown that fibrous dysplasia patients have blood cells with the G protein gene (GNAS) mutation. Diagnosis of fibrous dysplasia or McCune-Albright syndrome could be helped by identification of this mutation in the peripheral blood. [21] The utility of this technique is still being evaluated.
Serum alkaline phosphatase (ALP) levels are often elevated during active phases of this disease. This test could be useful to asses the evolution of disease in patients treated with bisphosphonates.
About 25% of patients may have a vitamin D deficiency. [22] Serum calcium, phosphate, and vitamin D levels are useful to exclude rickets. Pituitary gonadotropins and gonadosteroids are assessed to assist in the workup of precocious puberty.
Patients with the polyostotic form of fibrous dysplasia, particularly McCune-Albright syndrome, must be evaluated to exclude hyperthyroidism, pituitary gigantism, or hypercortisolism (possible autonomous endocrine hyperfunction).
Imaging Studies
Plain radiography
In both monostotic and polyostotic forms of fibrous dysplasia, the most common site of involvement is the femur. [12] Lesions in the long bones are medullary and usually affect the diaphysis and extend toward the metaphysis (see the image below).
Plain radiograph of a tibia in a patient who is skeletally mature, demonstrating expansion of the metaphysis and diaphysis, endosteal scalloping, and a ground-glass appearance of the matrix.
Typically, the matrix of the lesion has a ground-glass appearance. The lesion produces endosteal scalloping with a thin intact cortical shell. The contour of the bone may be expanded by the lesion. The classic deformity that results with involvement of the proximal femur is described as a shepherd's crook deformity on the basis of the deformation into varus.
Technetium-99m methylene diphosphonate bone scan
Increased uptake of the label that corresponds to osteoblastic activity is noted in the area of involvement seen on radiographs (see the image below). This study is useful in determining whether disease is monostotic or polyostotic.
Technetium-99m methylene diphosphonate (MDP) bone scan demonstrating increased uptake in the tibia corresponding to the radiographic margins.
Computed tomography
Computed tomography (CT) confirms a lesion confined to the interior of bone with no soft-tissue component. (See the image below.) It is helpful in distinguishing fibrous dysplasia from a malignancy. [23, 24] CT can show a homogeneous matrix. Single-photon emission CT (SPECT)/CT may be useful for the diagnosis of fibrous dysplasia. [25]
CT scan of the tibia demonstrating expansion of the tibia due to an expanding intramedullary lesion.
Magnetic resonance imaging
With magnetic resonance imaging (MRI), [24, 26, 27] intermediate signal intensity is present on T1-weighted images (see the first image below), and high signal intensity is present on T2-weighted images (see the second image below).
A T1-weighted MRI image demonstrating intermediate signal intensity and no soft tissue component.
A T2-weighted MRI image demonstrating increased signal intensity of the matrix of the lesion.
Diagnosis with imaging alone vs biopsy
Fusconi et al conducted a literary review to determine the feasibility of diagnosing fibrous dysplasia on the basis of imaging (CT and MRI with and without contrast) alone, without biopsy. [28] They concluded that it is not possible to make the diagnosis purely on the basis of imaging. A ground-glass appearance on radiography, though characteristic of fibrous dysplasia, is not pathognomonic. The authors recommended that histologic examination or follow-up imaging be conducted in cases of suspected fibrous dysplasia.
Radiographic classification
From an assessment of 227 femurs, Zhang et al suggested a radiographic classification for fibrous dysplasia of the proximal femur, [29] which included the following five types:
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Type 1 - Normal bone strength without angular deformity
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Type 2 - Decreased bone strength without angular deformity
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Type 3 - Isolated coxa vara with neck-shaft angle < 120°
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Type 4 - Isolated varus deformity in the proximal femoral shaft
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Type 5 - Coxa vara with varus deformity in the proximal femoral shaft
The authors found that this radiographic classification of fibrous dysplasia was reproducible and useful for evaluating fibrous dysplasia and that treatments based on it were effective.
Biopsy
Needle biopsy is used to establish the diagnosis of fibrous dysplasia, especially in monostotic cases. Open biopsy should be performed only as part of a multidisciplinary team approach, with personnel experienced in the management of both benign and malignant bone and soft-tissue sarcomas.
Histologic Findings
The gross findings of fibrous dysplasia include a centrally located, tan-to-gray-white, gritty-feeling lesion. The microscopic appearance shows a fibrous/collagenous matrix with randomly oriented bone or fiber trabeculae that are formed by osseous metaplasia of spindled stromal cells (see the image below).
Intermediate-power view of typical histology of fibrous dysplasia. Note the bland fibrous stromal tissue with islands of disorganized, immature osteoid. A key feature is the absence of rimming osteoblasts around the osteoid. While not present in this slide, foci of cartilage also may occasionally be present.
The spicules of immature bone that are produced are short and irregular and are not lined by osteoblasts. The appearance has been described as that of Chinese letters (see the image below). Small nodules of cartilage are found within the fibrous matrix in 10% of cases.
The metaplastic bone formed by fibrous dysplasia has the appearance of Chinese letters.
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Intermediate-power view of typical histology of fibrous dysplasia. Note the bland fibrous stromal tissue with islands of disorganized, immature osteoid. A key feature is the absence of rimming osteoblasts around the osteoid. While not present in this slide, foci of cartilage also may occasionally be present.
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Plain radiograph of a tibia in a patient who is skeletally mature, demonstrating expansion of the metaphysis and diaphysis, endosteal scalloping, and a ground-glass appearance of the matrix.
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Technetium-99m methylene diphosphonate (MDP) bone scan demonstrating increased uptake in the tibia corresponding to the radiographic margins.
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CT scan of the tibia demonstrating expansion of the tibia due to an expanding intramedullary lesion.
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A T1-weighted MRI image demonstrating intermediate signal intensity and no soft tissue component.
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A T2-weighted MRI image demonstrating increased signal intensity of the matrix of the lesion.
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The metaplastic bone formed by fibrous dysplasia has the appearance of Chinese letters.
