Joint Program in Nuclear Medicine
Kavitha Vadde, MD
David E. Drum, MD, PhD
April 18, 2000
A 46 year old female presented with right knee pain and a palpable mass
posterior to the knee.
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
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).
Fibrous dysplasia with sarcomatous degeneration in the tibia.
A CT guided biopsy of the lesion showed chondrosarcoma, grade 2 arising
within a pre-existing lesion.
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.
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).
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.
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.
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.
osteosarcoma (19/28 cases),
fibrosarcoma (5/28 cases),
chondrosarcoma (3/28 cases), and
malignant fibrohistiocytoma (1/28 case).
1. Murphy, M D: " Fibrous lesions of the Musculoskeletal System I &
II." Radiologic Pathology Course Syllabus, Armed Forces Institute of Pathology.
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