Fibrous dysplasia (FD) is a developmental benign medullary fibro-osseous process characterized by the failure to form mature lamellar bone and arrest as woven bone that can be multifocal. It can affect any bone and occur in a monostotic form involving only one bone or a polyostotic form involving multiple bones. Since the WHO classification of soft tissue and bone tumors (5^th edition) it has been titled a benign bony neoplasm.

Fibrous dysplasia accounts for the "F" in the popular mnemonic for lucent bone lesions FEGNOMASHIC.

This article is confined to the monostotic (involves a single bone) and polyostotic (multiple bones are involved) forms. Craniofacial fibrous dysplasia and cherubism are discussed in separate articles.

Terminology

Terms such as "liposclerosing myxofibrous tumor" and "fibrocartilaginous dysplasia" are no longer recommended ¹.

Epidemiology

Fibrous dysplasia is uncommon, occurs in children and adults and can affect all age groups ^1,2. It is usually first diagnosed in children and young adults. The true incidence is not known but it is estimated to make up for ~5% of benign bone lesions ^3,4. There is no gender predilection ¹. 

Associations

Although fibrous dysplasia is usually sporadic, a number of associations are well recognized ^4,5:

• McCune-Albright syndrome: in 2-3% of cases with the polyostotic form 

• isolated endocrinopathy without the full McCune-Albright syndrome precocious puberty in girls 

  • hyperthyroidism

  • hyperparathyroidism: renal stones, calcinosis

  • acromegaly

  • diabetes mellitus

  • Cushing syndrome: osteoporosis, acne

  • growth restriction

• Mazabraud syndrome: soft-tissue myxomas (rare); typically multiple intramuscular lesions in the vicinity of most severely affected bone

Diagnosis

The diagnosis of fibrous dysplasia is mainly based on clinical and typical radiographic features ¹ and if the imaging features are characteristic the lesion does not require histology ^5,6.

Histological confirmation is indicated in cases with atypical imaging appearance or in isolated monostotic lesions with clinical symptoms or other concerning features ^5,6. Typical asymptomatic lesions are followed-up with serial radiographs to rule out significant mechanical implications and assure biological inactivity ⁵.

Diagnostic criteria

Diagnostic criteria according to the WHO classification of soft tissue and bone tumors (5^th edition) ¹:

Essential features include ¹:

• a bone lesion with compatible imaging characteristics

• osseous part consisting of irregular curvilinear branching trabeculae of woven bone without apparent osteoblastic rimming

• fibrous part consisting of bland fibroblasts

The following additional criterion is desirable:

• evidence of GNAS activating missense mutations

Clinical presentation

The condition is often an incidental finding and is usually painless. Alternatively, it may present with bony expansion and remodeling or with pain ^1,2. Morbidity may arise from pathologic fracture ⁴ or compression and displacement of adjacent structures. The latter is particularly true in craniofacial fibrous dysplasia, where the content of the orbit or cranial nerves may be compressed resulting in loss of vision or hearing loss ⁴. 

Monostotic form

The monostotic form is far more common accounting for 70-80% of cases and is usually asymptomatic until the 2^nd to 3^rd decade but can be seen throughout adulthood ⁷. After puberty, the disease can become inactive. 

Polyostotic form

The polyostotic form accounts for 20-30% and presents earlier, typically in childhood with about 60% showing symptoms before the age of 10 years ².

Pathology

Fibrous dysplasia is characterized by altered osteogenesis leading to an intramedullary fibro-osseous proliferation with fibrous and osseous tissue components being present in varying degrees ¹. It comes in a monostotic or polyostotic form depending on whether only one single bone or multiple bones are affected. However, there is no progression from the monostotic to the polyostotic form ⁵.

Etiology

Fibrous dysplasia is linked to postzygotic activating missense GNAS mutations that encode the alpha subunit of the stimulatory G-protein ^1-5.

Location

Monostotic form

• ribs: 28%, most common ^7,8

• proximal femur: 23%

• tibia

• craniofacial bones: 10-25% ⁹

• humerus

Polyostotic form 

• often unilateral and monomelic: one limb ⁷

• femur: 91%

• tibia: 81%

• pelvis: 78%

• foot: 73%

• ribs

• skull and facial bones: 50% ⁹

• upper extremities

• lumbar spine: 14%

• clavicle: 10%

• cervical spine: 7%

Subtypes

There are no officially recognized subtypes ¹. 

Macroscopic appearance

Macroscopically, lesions are intramedullary, well-circumscribed, and often expansile with abnormal whitish or tannish-grey color and gritty consistency. Cystic changes might be present, especially in older lesions. Rarely cartilage might be found characterized by a blue-tinged translucent appearance ^1,2.

Microscopic appearance

Microscopically fibrous dysplasia is characterized by the following ^1,2,4,7:

• varying proportions of fibrous and osseous tissue

• fibrous tissue principally made up of bland spindle cells without conspicuous cellular atypia

• irregular curvilinear branching trabeculae of woven bone with a pattern that has been characterized as “looking like Chinese characters” ^2,4

• absence of osteoblastic rimming

• uncommon mitoses unless there is a fracture

Other possible histological features include ^1,2:

• cementum-like bone deposition

• rounded psammomatous calcifications

• islands of benign hyaline cartilage might rarely be seen

• possibly aneurysmal bone cyst-like changes

The absence of osteoblastic rimming aids in the differentiation from the cemento-ossifying fibroma.

Genetics

In about 50-70%, GNAS activating missense mutations can be detected in particular involving pArg201His and pArg201Cys ^1,4.

Radiographic features

General imaging features of fibrous dysplasia are ⁷:

• intramedullary, expansile lesion

• well-defined borders

• maintenance of a smooth cortical contour

• endosteal scalloping might be present

Plain radiograph

Fibrous dysplasia can generally display the following three main imaging features ⁵:

• cystic/lucent

• sclerotic

• mixed

Beyond that, appearances are usually smooth and homogeneous with endosteal scalloping and cortical thinning ⁵. The borders are well defined and the cortex is usually intact but thinned due to the expansive nature of the lesion ⁵. Other features include:

• ground-glass matrix

• no periosteal reaction

• rind sign

Pelvis and ribs

Ribs are the most common site of monostotic fibrous dysplasia. Fibrous dysplasia is the most common cause of a benign expansile lesion of a rib (see rib lesions)

• bubbly cystic lesions

• fusiform enlargement of ribs

• protrusio acetabuli

Extremities

• may lead to premature fusion of growth plates leading to short stature

• bowing deformities

• shepherd crook deformity of the femoral neck

• discrepant limb length

• Looser zones

CT

CT better delineates morphological osseous changes of bone and is considered the modality of choice in the evaluation of fibrous dysplasia, especially in the setting of craniofacial lesions ⁵. CT imaging features include:

• ground-glass opacities: 56% ⁹

• homogeneously sclerotic: 23%

• cystic: 21%

• well-defined borders

• expansion of the bone, with intact overlying bone

• endosteal scalloping may be seen ⁷

The attenuation of lesions usually ranges from 60-140 HU and they usually enhance after the application of contrast media ⁵.

MRI

MRI is not particularly useful in differentiating fibrous dysplasia from other entities as there is marked variability in the appearance of the bone lesions, and they can often resemble a tumor or more aggressive lesions. 

• T1: usually intermediate to low heterogeneous signal ⁵

• T2: variable signal ¹⁰

• T1 C+ (Gd): heterogeneous moderate to avid contrast enhancement ^9,10

Nuclear medicine

Demonstrates increased tracer uptake on Tc⁹⁹ bone scans (lesions remain metabolically active into adulthood).

Radiology report

The radiological report should include a description of the following ^5,6:

• location and size

• tumor margins and transition zone

• signs of benign matrix transformation ⁵:

  • aneurysmal bone cyst-like changes

  • myxoid changes

• concerning features suggestive of malignant matrix formation ⁵

  • pathologic fracture

  • cortical destruction

  • aggressive periosteal reaction

  • surrounding bone marrow edema

  • solid mass-like enhancement

  • soft tissue extension

• additional associated findings ⁵:

  • ovarian cysts

  • intraductal papillary mucinous neoplasm (IPMN)

If features are typical the lesion can be categorized as Bone-RADS 1 on CT or MRI ⁶.

Treatment and prognosis

Management aims to establish the extent of the disease and the maintenance of bone quality via dietary measures and exercise. The prognosis is excellent and usually, no other treatment is required ¹.

However monostotic fibrous dysplasia can lead to deformities leg-length differences and impingement or nerve compression syndromes ¹. If a mass effect is severe, then surgery excision may be considered ^4,5.

Complications

Not surprisingly, bone affected by fibrous dysplasia is weaker than normal and thus susceptible to pathological fractures.

Sarcomatous dedifferentiation (most commonly osteosarcoma ¹², fibrosarcoma, undifferentiated pleomorphic sarcoma, or rarely chondrosarcoma) is occasionally seen (<1%) and is more common in the polyostotic form. It should be noted that many reported cases may relate to previous treatment with radiation therapy ⁷.

History and etymology

Fibrous dysplasia was first described by the American bone pathologist Louis Lichtenstein in 1938 and the clinical, radiological and histological spectrum of findings were later characterized by him and his colleague Henry Louis Jaffe in 1942 ^13,14. 

Differential diagnosis

Due to the variability of the appearance of fibrous dysplasia the potential differential is very long but will be significantly influenced by the dominant pattern.

• Paget disease

  • mosaic pattern bone histologically

  • radiographically may be similar

  • different demographics

• neurofibromatosis type 1

  • osseous lesions are rare

  • the vertebral column is the primary target

  • ribbon ribs

  • other features of the disease usually present

• osteofibrous dysplasia

  • almost exclusively in the tibia with anterior bowing

  • the lesion begins in the cortex

  • usually seen in children <10 years

• adamantinoma

  • 80% seen in the tibia

  • may appear indistinguishable

• non-ossifying fibroma

• simple bone cyst

• giant cell tumor

• enchondromatosis

• hemangioma ¹¹