Fibrous dysplasia

Tumor biology and incidence

• Non-neoplastic, benign disorder of bone with latent, active or aggressive features
• Generally a disorder of growing bone
  • Lesion usually ceases to grow after adolescence
  • New lesions may develop after maturity, and pre-existing lesions can continue to grow
• Generally, the earlier the onset, the more progressive the disease
• Results in a haphazard mixture of immature fibrous tissue and small fragments of immature trabecular bone
• Caused by sporadic mutation of the GNAS1 gene that encodes the alpha subunit of the stimulatory G protein (G1)
• Accounts for approximately 15% of all benign bone tumors
  • 70% of cases are monostotic (involve one bone); often asymptomatic latent lesions
  • 25% of cases are polyostotic (involve more than one bone)
  • 2-5% of cases are diagnosed as McCune-Albright Syndrome
• Prevalence of malignant transformation (chondrosarcoma or osteosarcoma) approximately 0.4%

Age

• Monostotic lesions: Manifest from late childhood to adulthood
• Polyostotic lesions: Usually present at a younger age
• Polyostotic lesions and endocrine disorders: Present even earlier

Gender

• Monostotic: M:F = 1:1
• Polyostotic: M:F = 1:1
• McCune-Albright's: Females affected more than males

Presentation

• Pain may be present with complete pathologic fracture or micro-fracture
• With craniofacial involvement, patient may be somewhat disfigured or have hearing and visual disturbances 
• Deformity of long bones, especially proximal femur-varus deformity, may result in limp and restricted hip motion

Physical findings

• Patients may have a limb length discrepancy and skeletal deformity (especially with involvement of proximal femur)
• Severe varus deformity of the proximal femur (Shepherd's crook deformity) affects hip motion, especially abduction 
• Swelling may be present if pathologic fracture has occurred

Blood work

Some patients have elevated serum alkaline phosphatase

Plain films

• Appearance of lesions is variable
• Intramedullary diaphyseal lesion lends with thin, expanded cortex
• Hazy or ground glass lesion, which may occur with angular deformity

Figure 1. Typical ground glass appearance of fibrous dysplasia

• Angular deformity often present at the level of lesion
• Active lesion may progress in size and deformity
• Cystic lesion: Radiolucent with a reactive rim, no trabeculae, normal cortical thickness
• Pagetoid lesion: Trabecular pattern, which is denser than normal bone
• Shepherd's crook deformity: Extensive involvement of proximal femur results in a characteristic varus deformity that resembles a shepherd's crook

Monostotic lesions

Site

• Ribs, femur, tibia, maxilla, mandible, skull, and humerus
• Commonly affects proximal femur, particularly femoral neck, and intertrochanteric zone
• May be metaphyseal, meta-diaphyseal, diaphyseal, or extend through entire long bone
• Usually spare the epiphysis
• Lesion is centrally located, although small lesions are occasionally eccentric
• Tend to enlarge the medullary cavity with minimal periosteal new bone response

Size
Variable involvement of an area of bone: May be small latent lesions or involve entire long bone

Tumor effect on bone

• Lytic: Ground glass lesions
• Multiple fractures may occur with subsequent remodeling, giving rise to the Shepherd's crook deformity of proximal femur (varus deformity of neck and proximal femur)
• Lesion often expands the bone involved through a process of endosteal expansion (ie, endosteal erosion accompanied by minimal periosteal new bone formation)

Bone response to tumor

• Usually well-demarcated border, often with sclerotic rim
• Limited but well-ordered periosteal response to endosteal erosion
  • No acute periosteal reaction unless patient has pathologic fracture

Matrix

• Appearance depends on amount of osseous matrix present
  • With substantial osseous tissue, lesion will have classic "ground glass" appearance

Cortex

• Endosteal erosion usually present
• Cortex often markedly thinned with endosteal expansion in diaphyseal lesions

Soft tissue mass
None

Polyostotic lesions

Site
Femur, craniofacial bones, tibia, humerus, ribs and fibula (usually ipsilateral)

Size
Lesions may progress in size and number until skeletal maturity; occasionally afterwards as well

Tumor effect on bone

• Usually has defined geographic border
• More aggressive than the monostotic variant

Bone response to tumor
Endosteal expansion with periosteal new bone.

Matrix
May have lytic or ground glass appearance, depending on degree of internal ossification

Cortex

• Can have endosteal scalloping
• Can have fusiform expansion of cortex and gradual melding of lesion with normal bone over time

Soft tissue mass
None

Bone scan

Useful for detecting multiple lesions

Differential diagnosis

Monostotic lesions

• Unicameral bone cyst
• Nonossifying fibroma
• Solitary eosinophilic granuloma
• Aneurysmal bone cyst
• Giant cell tumor
• Hemangioma
• Infection
• Central low-grade osteosarcoma
• Fibrosarcoma

Polyostotic lesions

• Multiple enchondromatosis (Ollier's disease)
• Paget's disease
• Brown tumor of hyperparathyroidism
• Metastasis
• von Recklinghausen's disease
• Multiple myeloma
• Eosinophilic granuloma (Hand-Schuller-Christian disease)

Natural history

• Progression of disease often erratic
• Monostotic lesions: Good prognosis
• Polyostotic lesions: Tend to remain more active or aggressive, occasionally undergo malignant transformation to osteosarcoma or fibrosarcoma

Pathology

• Gross: Fibrous tissue with admixture of bony trabeculae
• Microscopic: Variably cellular fibrous tissue containing irregularly shaped trabeculae of woven bone
• Woven bone is immature bone that has not undergone remodelling into lamellar bone.
• Fibroblasts benign, with few mitoses.
• Bone appears to arise directly from fibrous tissue, not from osteoblasts; termed "Chinese characters" because of unusual shape.
• Central low-grade osteosarcoma may be difficult to differentiate from fibrous dysplasia histologically; correlation with radiological findings very important.

Diagnosis and treatment

• Biopsy may be required if lesion is monostotic; rarely needed for polyostotic lesions (diagnosed on radiographic appearance)
• Difficult to eradicate extensive lesions surgically without major bone resection
  • Usually not appropriate for dysplastic (as opposed to neoplastic) lesion
• Goal of therapy: Permit the patient to live in mechanical symbiosis with lesion
  • Therapy determined by patient's age, activity of lesion, extent of fracture risk, and mechanical deformity
    • Conservative therapy: Bracing and modification of activity
    • Surgical treatment: Replacement of dysplastic fibro-osseous tissue with autograft, cancellous allograft, and/or allograft cortical struts
    • Allograft cortical struts may be used as intramedullary splints or as onlay cortical struts
    • Internal fixation often necessary to supplement grafts
    • Consider correcting deformity to decrease risk of further fracture, such as valgus osteotomy of the proximal femur to correct progressive Shepherd's crook deformity

Complications

• Pathologic fracture
• Impaired mechanical structure of bone leads to micro-fractures and progressive deformity in weight-bearing bones
  • Painful stress fractures especially common in femoral neck
• Although dysplastic bone heals at normal rate after fracture, resulting callus also dysplastic and disease persists
• Lesion may transform to sarcoma (most commonly osteosarcoma, fibrosarcoma, or malignant fibrous histiocytoma of bone)
• Fibrous dysplasia third most common cause of osteosarcoma arising in diseased bone after Paget's and radiation-induced osteosarcoma