Joint Program in Nuclear Medicine

Fibrous Dysplasia

Kavitha Vadde, MD
David E. Drum, MD, PhD

April 18, 2000

Presentation

A 46 year old female presented with right knee pain and a palpable mass posterior to the knee.

Imaging Findings

Radiographs

Radiographs of the right knee and femur revealed foci of increased density in the proximal, lateral tibial plateau without evidence of a fracture. Foci of increased density leading to a ground glass appearance throughout the femur with expansion of the femoral neck consistent with fibrous dysplasia.

Magnetic Resonance Imaging

MRI of the right knee showed a mass in the lateral aspect of the proximal tibia that breeches the osseous cortex and extends into the muscles of the anterior compartment. A narrow zone of transition is seen between the mass and surrounding tissues. Marginal enhancement of the lesion is seen. There is no surrounding edema or evidence of vascular invasion.

Bone Scan

Whole body bone scan and spot views of the legs show focal very avid uptake in the proximal right tibia and fibula (shown by arrows). There are foci of abnormal uptake throughout the right femoral diaphysis, metaphysis and head with expansion of the intertrochanteric region. Abnormal increased uptake in the L4 vertebra, left 8th rib, right 11th rib, distal right humerus and skull base (shown by arrowheads).

Diagnosis

Radiographic Diagnosis

Fibrous dysplasia with sarcomatous degeneration in the tibia.

Pathologic Diagnosis

A CT guided biopsy of the lesion showed chondrosarcoma, grade 2 arising within a pre-existing lesion.

Follow up

A CT of the Chest showed no evidence of pulmonary metastases. The patient underwent resection of the right proximal tibia and fibula followed by placement of a knee prosthesis.

Discussion

Fibrous Dysplasia

Fibrous dysplasia is a congenital, non-hereditary skeletal disorder that occurs with equal frequency in males and females. It is a developmental anomaly of bone formation in which the marrow is replaced by fibrous tissue. One percent of biopsied bone lesions are due to fibrous dysplasia. Monostotic disease is more common than polyostotic disease. When polyostotic, all the lesions tend to occur on one side of the body. The bones most frequently involved are the long bones: femur (most common), skull, and the ribs.

Polyostotic disease can be associated with abnormal skin pigmentation (ipsilateral to the osseous lesions) and endocrinopathies. The constellation of polyostotic fibrous dysplasia, skin pigmentation and precocious puberty has the eponym McCune Albright Syndrome. Mazabraud Syndrome is fibrous dysplasia associated with soft tissue myxomas (1).

Pathology / Pathophysiology

Fibrous dysplasia is characterized by fibrous stroma in which spicules of disconnected woven bone are seen, resembling letters of the alphabet. The conversion of the fibrous tissue to bone is thought to result from fibro-osseous metaplasia. Few mature osteoblasts and osteoclasts are seen.

Recently, gene mutations have been delineated that cause inappropriate proliferation and differentiation of osteoblasts resulting in the production of the fibrotic bone matrix seen in both monostotic and polyostotic fibrous dysplasia. The cells and matrix of fibrous dysplasia lesions have been shown to produce an abnormal complement of bone matrix proteins. In light of these developments, dysplastic lesions are thought to consist of an excess of pre-osteogenic cells producing a disorganized collagenous matrix. The few mature osteoblasts present create abnormal bone matrix. This matrix is rich in anti-adhesion molecules and poor in pro-adhesion molecules, in direct contrast to normal lamellar bone (2).

Radiology

The radiographic findings of fibrous dysplasia can be distinctive. Individual lesions can appear as a lucent area with a sclerotic rim. Medullary lesions may have a "milky" or "ground glass" appearance with a lack of normal trabeculation. The affected bone can be locally expanded. Rib lesions are usually expansile with a "ground glass" appearance. Calavarial lesions are usually lytic and multilocular with sclerotic margins. In the skull base and facial bones, fibrous dysplasia manifests as marked sclerosis and bony thickening. The sinuses may be obliterated.

Long standing disease can result in bowed and deformed bones. The proximal femur develops a characteristic shape referred to as a "shepherd’s crook" deformity associated with coxa vara and anterolateral bowing of the diaphysis. Pathologic fractures are seen.

Scintigraphy

The majority of lesions in fibrous dysplasia are tracer avid on Tc-99m MDP bone scans. Machida et al(3) analyzed 59 lesions in 26 patients with fibrous dysplasia. Four (14%) of 29 cystic lesion and two (7%) of 30 "ground glass" lesions had radiotracer uptake equivalent to normal bone. The remainder showed supra-normal tracer uptake. Bone scanning can be helpful in conjunction with radiography to detect polyostotic involvement. Intense uptake of gallium is seen in the dysplastic bone. No preferential uptake of thallium or indium-labeled leukocytes is seen.

Natural History

A variable clinical course is seen. Patients are often asymptomatic. Others experience pain, pathologic fractures and bone deformity. Craniofacial fibrous dysplasias can result in impingement of the cranial nerves. An increased incidence of sarcomas is seen in dysplastic lesions, unattributable to prior radiation therapy. Ruggieri et al (4) in a review of 1122 cases of fibrous dysplasia and found 28 cases of sarcoma. Prior radiation of the dysplastic bone occurred in 13 of the 28 cases (46%). The histologic subtypes seen in descending order of frequency were: The incidence of sarcomatous degeneration is approximately 1%. Associated symptoms include pain and swelling. Clinical mimics of sarcomatous degeneration are the coexistence of a secondary aneurysmal bone cyst and cystic degeneration of fibrous dysplasia. The most constant radiographic feature of malignant degeneration is extension of the lesion through the bone cortex into the surrounding soft tissues. The prognosis for these secondary sarcomas is poor and similar to that for their primary counterparts.

References

1. Murphy, M D: " Fibrous lesions of the Musculoskeletal System I & II." Radiologic Pathology Course Syllabus, Armed Forces Institute of Pathology. 1997.

2. Singer F R: Fibrous dysplasia of bone: the bone lesion unmasked. Am J Pathol 1997 Dec;151(6):1511-5.

3. Macida K et al: Scintigraphic manifestation of fibrous dysplasia. Clin Nucl Med 1986 Jun; 11(6):426-29.

4. Ruggieri P et al: Malignancies in fibrous dysplasia. Cancer 1994 Mar 1;73(5): 1411-24

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J. Anthony Parker, MD PhD, Tony_Parker@CareGroup.Harvard.edu