= FIBROUS OSTEODYSTROPHY = OSTEODYSTROPHIA FIBROSA = OSTEITIS FIBROSA DISSEMINATA

= benign developmental anomaly of mesenchymal precursor of bone → slowly progressive replacement of normal bone marrow by immature fibroosseous tissue centered in medullary canal

Prevalence: 7% of benign bone tumors; 2.5% of all bone tumors; 1% of primary bone tumors at biopsy

Cause: probable gene mutation during embryogenesis manifested as defect in osteoblastic differentiation and maturation

Age: 1^st–2^nd decade (highest incidence between 3 and 15 years), 75% before age 30; progresses until growth ceases; M÷F = 1÷1 (range, 1÷1.2 to 2÷1)

Histo: spongiosa of medullary cavity replaced by

1. abnormal fibrous tissue = variable degree of immature collagen and myxoid component, and
2. osseous tissue containing poorly calcified + dysplastic + non–stress oriented + disorganized trabeculae of woven bone varying from solid round areas to curved / serpentine / curlicue shapes (= “Chinese characters” / alphabet soup); NO osteoblastic rimming of trabeculae (DDx from ossifying fibroma); cartilaginous islands present in 10% (DDx to chondrosarcoma)

Clinical Types:

1. Monostotic fibrous dysplasia (70–80%)
2. Polyostotic fibrous dysplasia (20–30%)
3. Craniofacial fibrous dysplasia = leontiasis ossea
   Variants: McCune-Albright syndrome (10%), Jaffé-Lichtenstein Disease (10%)
4. Cherubism (special variant)1

May be associated with:

1. endocrine disorders:
   • precocious puberty in girls
   • hyperthyroidism
   • hyperparathyroidism: renal stones, calcinosis
   • acromegaly
   • diabetes mellitus
   • Cushing syndrome: osteoporosis, acne
   • growth retardation
2. intramuscular soft-tissue myxoma (rare)
   = Mazabraud syndrome:
   [André Mazabraud (1921–2006), French rheumatologist and pathologist at Curie Institute, Paris]
   • typically multiple intramuscular myxomas in vicinity of most severely affected bone
   • polyostotic fibrous dysplasia (in 81%); M÷F = 1÷2
   • renal phosphate wasting
3. aneurysmal bone cyst

• swelling + tenderness; limp, pain (± pathologic fracture)
• increased alkaline phosphatase
• advanced skeletal + somatic maturation (early)

Common location: rib cage (30%), craniofacial bones [calvarium, mandible] (25%), femoral neck + tibia (25%), pelvis

Site: metaphysis is primary site with extension into diaphysis = expands along longitudinal axis of bone (rarely over entire length)

Radiography:

• lesions in medullary cavity: CHARACTERISTIC “ground-glass” / radiolucent appearance / increased density:
  • expansile remodeling:
    • HALLMARK endosteal scalloping with thinned / lost cortex (rib, long bone) and intervening normal cortex
    • expansion of cortices (rib, skull, long bone) with “blown-out” appearance (DDx from ossifying fibroma which is focally more altered)
  • trabeculated appearance ← reinforced subperiosteal bone ridges in wall of lesion
  • ill-defined wide zone of transition (DDx to ossifying fibroma)
• well-defined thick sclerotic margin of reactive bone = rind
• lesion may undergo calcification + enchondral bone formation = fibrocartilaginous dysplasia
• NO periosteal reaction unless fractured

CT (best technique for characterization):

• Most cases of monostotic fibrous dysplasia are incidental findings on (a cranial / other) CT examination!
• attenuation of typically 70–130 HU + intermixed areas of sclerosis with higher values:
  • pagetoid / ground glass appearance (53%) ← equal mixture of dense woven trabecular bone + radiolucent areas of fibrous tissue
  • homogeneously dense opaque sclerotic bone (23%) ← predominance of osseous elements
  • radiolucent cystic bone (21%) = spherical / ovoid density surrounded by dense bony shell ← abundance of fibrous elements
    DDx: central ossifying fibroma, central giant cell granuloma, aneurysmal bone cyst, osteomyelitis, early fibro-osseous lesion
• expansion of bone
• fibrous dysplasia enhances ← inherent vascularity

MR:

• MRI should not be used to differentiate fibrous dysplasia from other entities due to extreme variability in appearance of bone lesions (depending on ratio of fibrous tissue to mineralized matrix)!
• homogeneous / mildly heterogeneous marrow lesions:
  • low to intermediate SI on T1WI, typically hypointense to muscle
  • hyperintense to fat (63%) / low SI (18–38%) / intermediate SI (18%) on T2WI
• intense heterogeneous enhancement:
  1. centrally (73%) ← numerous small vessels
  2. peripherally (27%) ← large sinusoids

NUC:

• uptake on bone scan (lesions remain metabolically active into adulthood):
  1. intense activity on blood flow + blood pool images
  2. most intense activity on static delayed images

PET:

• marked radiotracer avidity (SUV of 3–19)
• Skull & facial bones
  • “blistering / bubbling” cystic calvarial lesions (CHARACTERISTIC), commonly crossing sutures:
    • widened diploic space displacing outer table + sparing inner table (DDx: Paget disease, inner table involved)
  • diffuse sclerosis of skull base obscuring ground-glass appearance:
    • sclerosis of orbital plate (DDx: Paget disease, meningioma en plaque)
    • occipital thickening
    • hypoplasia / obliteration of sphenoid + frontal sinuses ← encroachment by fibrous dysplastic bone
    • narrow neural foramina → visual + hearing loss
  • inferolateral displacement of small orbit
  • mandibular cystic lesion (very common) = osteocementoma, ossifying fibroma
• Ribs
  • bubbly cystic multiseptated lesion (extremely common)
  • fusiform enlargement of rib + loss of normal trabecular pattern + thin preserved cortex (in up to 30%)
    • Fibrous dysplasia is the most common cause of a benign expansile lesion of a rib!
    • A rib is the most common site of monostotic (6–20%) + polyostotic (55%) fibrous dysplasia!
• Pelvis
  • protrusio acetabuli
• Extremities
  • short stature as adult / dwarfism
  • premature fusion of ossification centers
  • epiphysis rarely affected before closure of growth plate
  • bowing deformities + discrepant limb length (tibia, femur) ← stress of normal weight bearing
  • “shepherd's crook” deformity of femoral neck = coxa vara
  • pseudarthrosis in infancy = osteofibrous dysplasia (DDx: neurofibromatosis)
  • premature onset of arthritis
• Spine
  • frequently asymptomatic / pain / fracture
  • mildly expansile lesion with “blown-out” cortical shell
  • lytic lesion with a sclerotic rim
  • common “ground-glass” matrix (CHARACTERISTIC)

Cx:

1. Dedifferentiation into osteo- / fibro- / (rarely) chondrosarcoma or malignant fibrous histiocytoma (0.4–1%; more often in polyostotic form)
   • increasing pain
   • enlarging soft-tissue mass
   • previously mineralized lesion turns lytic
2. Pathologic fractures: transformation of woven into lamellar bone may be seen, subperiosteal healing without endosteal healing

DDx:

1. Paget disease (older age group, mosaic pattern histologically, radiographically similar to monostotic cranial lesion, outer table involved, usually sparing of facial bones)
2. Ossifying fibroma (narrow zone of transition, displacement of teeth)
3. HPT (polyostotic, no bone expansion, chemical changes, generalized deossification, subperiosteal resorption)
4. Osteofibrous dysplasia (almost exclusively in tibia of children <10 years + anterior bowing, monostotic, lesion begins in cortex, spontaneous regression)
5. Neurofibromatosis (rarely osseous lesions, vertebral column is primary target, ribbon ribs, cystic intraosseous neurofibroma rare, café-au-lait spots smooth, familial disease)
6. Nonossifying fibroma = fibroxanthoma
7. Simple bone cyst (more lucent than fibrous dysplasia, not affecting growth plate, straw-colored fluid on aspiration)
8. Giant cell tumor (no well-defined sclerotic margin)
9. Enchondroma (often calcified chondroid matrix)
10. Eosinophilic granuloma = LCH
11. Osteoblastoma
12. Hemangioma
13. Meningioma
14. Low-grade osteosarcoma (invasion of surrounding soft tissues, osteolysis, cortical destruction)

Prognosis: bone lesions usually do not progress beyond puberty