Fibrous

Dysplasia

http://www.emedicine.com/RADIO/topic284.htm

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Author: Mahesh Kumar Neelala Anand, MBBS, DNB, FRCR, Clinical Director, Consultant Radiologist, Department of Radiology, Pennine Acute Hospitals NHS Trust, Manchester, UK

Fibrous Dysplasia

Background

Fibrous dysplasia is a skeletal developmental anomaly of the bone-forming mesenchyme that manifests as a defect in osteoblastic differentiation and maturation. Virtually any bone in the body can be affected. It is a nonhereditary disorder of unknown cause.

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Pathophysiology

In fibrous dysplasia, the medullary bone is replaced by fibrous tissue, which appears radiolucent on radiographs, with the classically described ground-glass appearance. Trabeculae of woven bone contain fluid-filled cysts that are embedded largely in collagenous fibrous matrix, which contributes to the generalized hazy appearance of the bone

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The following 4 disease patterns are recognized:

 

Monostotic form

Polyostotic form

Craniofacial form

Cherubism

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Frequency

United States

The exact incidence is not clearly established.

International

The worldwide incidence is not exactly known.

Mortality/Morbidity

Usually, fibrous dysplasia is not a fatal disease. A small percentage of patients die when the bone lesion is complicated by malignant change.

Race

No specific racial predilection exists.

 

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Sex

The incidence rates are equal in males and females.

Age

The initial manifestations of fibrous dysplasia are most commonly found in persons aged 3-15 years. 

Two thirds of patients with polyostotic disease are asymptomatic before they are aged 10 years. 

With monostotic disease, patients as old as 20 or 30 years are asymptomatic.

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Clinical Details

Clinical findings of increasing pain and an enlarging soft tissue mass suggest malignant change

Monostotic form

Approximately 70-80% of fibrous dysplasias are monostotic. This form most frequently occurs in the rib (28%), femur (23%), tibia or craniofacial bones (10-25%), humerus, and vertebrae, in decreasing order of frequency.

This form may present with pain or a pathologic fracture in patients aged 10-70 years, but this form most frequently occurs in those aged 10-30 years. The degree of bone deformity of the monostotic form is relatively less severe than that of the polyostotic type. No clearly documented evidence supports conversion of the monostotic form to the polyostotic form.

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Polyostotic form

Approximately 20-30% of fibrous dysplasias are polyostotic. Polyostotic fibrous dysplasia more frequently involves the skull and facial bones, pelvis, spine, and shoulder girdle. The sites of involvement are the femur (91%), tibia (81%), pelvis (78%), ribs, skull and facial bones (50%), upper extremities, lumbar spine, clavicle, and cervical spine, in decreasing order of frequency

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The dysplasia may be unilateral or bilateral, and it may affect several bones of a single limb or both limbs with or without axial skeleton involvement. Although the polyostotic variety tends to occur in a unilateral distribution, involvement is asymmetric and generalized when disease is bilateral.

Two thirds of patients are symptomatic before they are 10 years of age. Often, the initial symptom is pain in the involved limb associated with a limp, a spontaneous fracture, or both. In one series, pathologic fracture was present in 85% of polyostotic fibrous dysplasias. Leg-length discrepancy of varying degrees occurs in about 70% of patients with limb involvement. The structural integrity of the bone is weakened, and the weight-bearing bones become bowed. The curvature of the femoral neck and proximal shaft of the femur markedly increase because a femoral lesion commonly causes a severe coxa vara abnormality, shepherd's-crook deformity, which is a characteristic sign of the disease. Overgrowth of adjacent soft tissues may be present.

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Craniofacial form

This pattern of the disease occurs in 10-25% of patients with the monostotic form and in 50% with the polyostotic form. It also occurs in an isolated craniofacial form. In the isolated variety, no extracranial lesions are present. Sites of involvement most commonly include the frontal, sphenoid, maxillary, and ethmoidal bones. The occipital and temporal bones are less commonly affected.

Hypertelorism, cranial asymmetry, facial deformity (ie, leontiasis ossea), visual impairment, exophthalmos, and blindness may occur because of involvement of orbital and periorbital bones. Involvement of the sphenoid wing and temporal bones may result in vestibular dysfunction, tinnitus, and hearing loss. When the cribriform plate is involved, hyposmia or anosmia may result

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Cherubism

This special variant of fibrous dysplasia is an autosomal dominant disorder of variable penetrance. It occurs in children and is more severe in boys. Regression may occur after adolescence. The jaw is broad and protruding. Involvement of the maxilla and that of the mandible are symmetric.

Other features

Fibrous dysplasia may be associated with endocrinopathies in 2-3% of cases; these include precocious puberty in girls, hyperthyroidism, hyperparathyroidism, acromegaly, diabetes mellitus, and Cushing syndrome. McCune-Albright syndrome may be associated with hyperthyroidism and, hence, exophthalmos.

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The prevalence rate of scoliosis in patients with polyostotic fibrous dysplasia is 40-52%. Most spinal lesions are located in the lumbar and thoracic spines, with very few located in the sacrum and cervical spine. The posterior elements of vertebrae are involved in 71%. In a series of 62 patients studied by Leet et al (2004), 40% had scoliosis and 48% had no scoliosis.

Sexual precocity in girls, with polyostotic fibrous dysplasia and cutaneous pigmentation, constitutes McCune-Albright syndrome. Cutaneous pigmentation is the most common extraskeletal manifestation in fibrous dysplasia. It occurs in more than 50% of cases of the polyostotic form. Cutaneous pigmentation in polyostotic fibrous dysplasia is ipsilateral to the side of bony lesions, a feature that differentiates this disease from pigmentation in neurofibromatosis.

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The pigmented macules, or cafe-au-lait spots, are related to increased amounts of melanin in the basal cells of the epidermis. They tend be arranged in a linear or segmental pattern near the midline of the body, usually overlying the lower lumbar spine, sacrum, buttocks, upper back, neck, and shoulders. Similar lesions may occur on the lips and oral mucosa. Pigmentation may occur at birth, and in fact, it occasionally precedes the development of skeletal and endocrine abnormalities.

The only significant laboratory abnormality is an elevated alkaline phosphatase level.

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Preferred Examination

Plain radiography is the first-line study. Usually, the diagnosis is straightforward when typical features are present. CT may be required to assess complex regions such as the spine, pelvis, chest, and facial skeleton. Bone scintigraphy has a limited role in the detection of subtle pathologic fractures. In fibrous dysplasia, the features on a bone scan are nonspecific for diagnostic purposes. MRI may be necessary to assess cord compression when the spine is involved.

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DIFFRENTIALS

Enchondroma and Enchondromatosis

Eosinophilic Granuloma, Skeletal

Fibrous Cortical Defect and Nonossifying Fibroma

Giant Cell Tumor

Hemangioma, Bone

Hyperparathyroidism, Primary

Neurofibromatosis Type 1

Paget Disease

Other Problems to Be Considered

Metastases

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RADIOGRAPH

Findings Common locations for lesions are the ribs, craniofacial

bones, femoral neck, tibia, and pelvis. Radiographic findings in these and other structures are discussed below.

Long and short tubular bones The usual appearance of fibrous dysplasia includes a lucent

lesion in the diaphysis or metaphysis, with endosteal scalloping and with or without bone expansion and the absence of periosteal reaction. Usually, the matrix of the lucency is smooth and relatively homogeneous; classically, this finding is described as a ground-glass appearance. Irregular areas of sclerosis may be present with or without calcification. The lucent lesion has a thick sclerotic border and is called the rind sign.

The lesion may extend into the epiphysis only after fusion. Premature fusion of the ossification centers may occur, resulting in adult dwarfism. The dysplastic bone may undergo calcification and enchondral bone formation

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Skull and facial bones

The frontal bone is involved more frequently than the sphenoid, with obliteration of the sphenoid and frontal sinuses. The skull base may be sclerotic. Single or multiple, symmetric or asymmetric, radiolucent or sclerotic lesions in the skull or facial bones may be present. The external occipital protuberance may be prominent; however, these features are less common in Paget disease, neurofibromatosis, and meningioma.

Most commonly, maxillary and mandibular involvement has a mixed radiolucent and radiopaque pattern, with displacement of the teeth and distortion of the nasal cavities. The diploic space is widened, with displacement of the outer table. The inner table of the skull is spared in fibrous dysplasia, unlike in Paget disease. Cystic calvarial lucencies, which commonly cross the sutures with sclerotic margins, may have a doughnut configuration.

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Pelvis and ribs

These bones have lucencies, with a diffuse ground-glass appearance and rind lesions. Cystic lesions are common. Protrusio acetabuli is a feature on the pelvic radiograph.

Spine

Spinal involvement is common in polyostotic disease and rare in monostotic disease. Well-defined, expansile, radiolucent lesions with multiple internal septa or striations involve the vertebral body and, occasionally, the pedicles and arches. Paraspinal soft-tissue extension and vertebral collapse are rare. Kyphotic deformity and spinal cord compression may occur.

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Degree of Confidence

Plain radiographs are highly specific when characteristic features are present in a lesion. However, the specificity decreases when the lesion occurs at more complex sites such as the spine, the skull, and, sometimes, the pelvis. The identification of malignant change and soft-tissue extension on plain radiographs may be difficult; cross-sectional imaging may be required.

Radiographic features suggestive of malignant degeneration include a rapid increase in the size of the lesion and a change from a previously mineralized bony lesion to a lytic lesion.

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CT SCAN

Findings

CT is not often required for diagnosis. CT demonstrates the nature of the lesion better by characterizing the matrix of the lesion. It also depicts expansion of the affected bone and its subtle mineral contents. It can demonstrate subtle nondisplaced pathologic fractures. CT is extremely useful in evaluating the extent of disease in complex locations such as the facial bones, pelvis, chest wall, and spine. Usually, attenuation is in the range of 70-130 HU (Hounsfield unit).

In the skull, the outer table always expands outward. Therefore, the lesion is invariably convex; both tables are intact, although they are thinner. In the spine, CT can demonstrate the extent of bony disease and compromise of the spinal canal space. Paraspinal soft-tissue extension can be demonstrated at CT. CT scans may suggest malignant transformation, with the definition of an extraosseous soft-tissue mass and bone destruction.

 

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Degree of Confidence

CT is not optimal for the differentiation of fibrous dysplasia from other lesions that mimic it. CT findings complement plain radiographic findings.

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MRI

Findings

On T1-weighted MRIs, the lesion has low-to-intermediate signal intensity equal to that of muscle. T2-weighted images also show low signal intensity owing to the high content of collagen and bone. Cartilaginous islands may be present in some lesions, and they appear as areas of high signal intensity on T2-weighted images. In children, T2-weighted images show hyperintense signal greater than that of subcutaneous fat; this finding is characteristic of fibrous dysplasia.

Also, fluid-fluid levels are reported in fibrous dysplasia. On short–inversion time inversion-recovery (STIR) images, the signal intensity of the lesion may be very high. MRI may be useful in assessing malignant change and demonstrating extension of the tumor into the surrounding soft tissues.

For postoperative follow-up, gadolinium-enhanced MRI is useful in demonstrating the proliferation of fibrocellular tissue.

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Gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK], gadoteridol [ProHance]) have recently been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). For more information, see the eMedicine topic Nephrogenic Fibrosing Dermopathy. The disease has occurred in patients with moderate to end-stage renal disease after being given a gadolinium-based contrast agent to enhance MRI or MRA scans. As of late December 2006, the FDA had received reports of 90 such cases. Worldwide, over 200 cases have been reported, according to the FDA. NSF/NFD is a debilitating and sometimes fatal disease. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of the eyes; joint stiffness with trouble moving or straightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs; and muscle weakness. For more information, see the FDA Public Health Advisory or Medscape

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ULTRASONOGRAPHY 

Findings

Ultrasonography has no significant role in the diagnosis or management of fibrous dysplasia.

NUCLEAR MEDICINE

Findings

In fibrous dysplasia, accumulation of isotope increases because of the lesion's hypervascularity. Hot spots or increased uptake of the radioisotope tracer technetium-99m methylene diphosphonate (99mTc MDP) occurs in the spine, pelvis, ribs, and appendicular skeleton. Pathologic or stress fractures also can increase isotopic activity in the lesions. The features on the bone scan are nonspecific for a conclusive diagnosis based solely on the distribution of the isotope.

Degree of Confidence

The technique is not specific for a firm diagnosis based on the imaging characteristics. The specificity is relatively poor.

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ANGIOGRAPHY 

Findings

Angiography is not used as a diagnostic tool to characterize fibrous dysplasia.

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Special Concerns 

Malignant degeneration The estimated frequency is 0.4-1% in fewer than

50 reported cases.   The interval from the diagnosis of fibrous

dysplasia to the development of malignancy varies and is usually years or decades.

  Most often, skull and facial bones undergo

malignant change in monostotic disease, whereas femoral and facial bones undergo malignant change in polyostotic disease.

 

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Osteosarcoma and fibrosarcoma are the most common tumors. Chondrosarcomas occur less frequently.

  Radiographic features suggestive of malignant

degeneration include a rapid increase in the size of the lesion and a change from a previously mineralized bony lesion to a lytic lesion. Clinical findings of increasing pain and an enlarging soft-tissue mass suggest malignant change.

Metabolic changes Hypophosphatemic rickets and osteomalacia have

been noted in patients with fibrous dysplasia.   One hypothesis to explain the associated metabolic

disorder suggests that lesions such as fibrous dysplasia synthesize phosphaturic hormone.

 

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REFERENCES

Daffner RH, Kirks DR, Gehweiler JA Jr, Heaston DK. Computed tomography of fibrous dysplasia. AJR Am J Roentgenol. Nov 1982;139(5):943-8. [Medline].

De Smet A, Travers H, Neff JR. Chondrosarcoma occurring in a patient with polyostotic fibrous dysplasia. Skeletal Radiol. 1981;7:197.

Harris WH, Dudley HR, Barry RJ. The natural history of fibrous dysplasia. An orthopaedic, pathological, and roentgenographic study. J Bone Joint Surg Am. Mar 1962;44-A:207-33.

King RM, Payne WS, Olafsson S, Unni KK. Surgical palliation of respiratory insufficiency secondary to massive exuberant polyostotic fibrous dysplasia of the ribs. Ann Thorac Surg. Feb 1985;39(2):185-7.

Leet AI, Magur E, Lee JS, et al. Fibrous dysplasia in the spine: prevalence of lesions and association with scoliosis. J Bone Joint Surg Am. Mar 2004;86-A(3):531-7.

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Lichenstein L, Jaffe HL. Fibrous dysplasia of bone: a condition affecting one, several or many bones, the graver cases of which may present abnormal pigmentation of skin, premature sexual development, hyperthyroidism or still other extraskeletal abnormalities. Arch Pathol. 1942;33:777.

National Institutes of Health. Osteoporosis and Related Bone Disorders-National Resource Center Web site. Fast Facts on Fibrous Dysplasia page. Available at: http://www.osteo.org/default.asp. Washington, DC: National Institutes of Health;2001. [Full Text].

Resnick D, Niwayama G. Diagnosis of Bone and Joint Disorders. 2nd ed. Philadelphia, Pa: WB Saunders;. 1988: 4057-70.

Schwartz DT, Alpert M. The malignant transformation of fibrous dysplasia. Am J Med Sci. Jan 1964;247:1-20. [Medline].

 

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