Fibrous

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

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

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 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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