Fibrous Dysplasia - Pathology

summary
- Fibrous Dysplasia is a developmental abnormality caused by a GS alpha protein mutation that leads to failure of the production of normal lamellar bone.
- The condition usually presents in patients who are less than 30 years of age with an asymptomatic lesion that is found incidentally on radiographs.
- Diagnosis is made with radiographs showing a lesion with ground glass appearance or a "punched-out" lesion with a well-defined margin of sclerotic bone.
- Treatment is usually nonoperative with bisphosphonates for pain control. Surgical management is indicated for lesions that lead to bone deformities such as scoliosis or coxa vara.

Epidemiology
- Demographics
  - male:female ratio
    
    females > males
  - age bracket
    
    found in any and all ages
    
    onset for 75% of patients at <30 years of age
- Anatomic location
  - any bone can be involved
  - the proximal femur is most common site, followed by rib, maxilla, and tibia

Etiology
- Genetics
  - associated with GNAS mutation
    
    GS alpha protein (chromosome 20q13) activating mutation (affects cAMP signaling pathway leading to increased production of cAMP)
  - high production of FGF-23 which may lead to hypophosphatemia
- Associated conditions
  - orthopedic manifestations
    
    McCune Albright syndrome
    
    condition defined by the presence of
    
    skin abnormalities (cafe au lait spots in coast of Maine pattern)
    
    endocrine abnormalities (precocious puberty)
    
    renal phosphate wasting due to FGF-23 (oncogenic osteomalacia)
    
    unilateral polyostotic fibrous dysplasia
    
    obtain AP spine radiographs to look for scoliosis
    
    Mazabraud syndrome
    
    polyostotic fibrous dysplasia
    
    soft-tissue intramuscular myxomas
    
    Osteofibrous dysplasia
    
    rare form that primarily affects the tibia and is confined to the cortices
  - nonorthopedic manifestations
    
    severe cranial deformities with blindness

Presentation
- Symptoms
  - usually asymptomatic and discovered as an incidental finding
  - may have swelling or deformity
  - bone lesions may be monostotic (80%) or polystotic (20%)
  - pain from stress fractures
- Physical exam
  - inspection
    
    cafe au lait spots
    
    larger and more irregular borders ("coast of Maine") than neurofibromatosis
    
    may or may not be present with fibrous dysplasia
    
    by definition present with McCune-Albright syndrome
    
    swelling around lesion
    
    scoliosis

Imaging
- Radiographs
  - hip/pelvis radiograph
    
    central lytic lesions in medullary canal (diaphysis or metaphysis)
    
    may have cortical thinning with expansile lesion
    
    highly lytic lesions or a ground glass appearance
    
    "punched-out" lesion with well-defined margin of sclerotic bone is common
    
    modest expansion of bone
    
    Shepherd's crook deformity
  - AP spine radiograph
    
    vertebral collapse
    
    kyphoscoliosis
- Bone scan
  - usually warm

Studies
- Gross - yellow-white gritty tissue
- Histology
  - characteristic look of "alphabet soup" or "chinese letters"
  - fibroblast proliferation surrounding islands of woven bone
    
    woven bone lacks osteoblastic rimming (osteofibrous dysplasia has osteoblastic rimming)
  - trabeculae of osteoid and bone in fibrous stroma with metaplastic cartilage or areas of cyst degeneration
  - mitotic figures are common

Treatment
- Nonoperative
  - observation
    
    indications
    
    asymptomatic patients
  - bisphosphonate therapy
    
    indications
    
    symptomatic polyostotic fibrous dysplasia
    
    effective in decreasing pain and reducing bone turnover
- Operative
  - internal fixation and bone grafting
    
    indications
    
    symptomatic lesions
    
    impending/actual fractures through lesions in areas of high stress (femoral neck)
    
    severe deformity
    
    neurologic compromise in the spine
    
    technique
    
    never use autogenous cancellous bone, as the transplanted bone will quickly turn into fibrous dysplastic woven bone
    
    use cortical or cancellous allografts
    
    intramedullary device more effective than a plate in the lower extremity
  - osteotomies
    
    indications
    
    coxa vara deformity
    
    intertrochanteric osteotomy

                        Differential
                    
                                            Fibrous Dysplasia Differential 
                                        
                                            Multiple lesions in young patients
                                        
                                            Treatment is Observation alone
                                        
                                            Benefits from Bisphonate therapy
                                        
                                            Fibrous Dysplasia 
                                        
                                            •
                                        
                                            •
                                        
                                            •
                                        
                                            Eosinophilic granuloma
                                        
                                            •
                                        
                                            •
                                        
                                            Lymphoma
                                        
                                            •
                                        
                                            Leukemia
                                        
                                            •
                                        
                                            Enchondroma / Olliers / Maffucci's
                                        
                                            •
                                        
                                            •
                                        
                                            Osteochondroma / MHE
                                        
                                            •
                                        
                                            •
                                        
                                            NOF /Jaffe-Campanacci syndrome
                                        
                                            •
                                        
                                            •
                                        
                                            Hemangioendothelioma
                                        
                                            •
                                        
                                            Paget's
                                        
                                            •
                                        
                                            •
                                        
                                            Metastatic Disease
                                        
                                            •
                                        
                                            Myeloma
                                        
                                            •

Prognosis
- 1% risk of malignant transformation to osteosarcoma, fibrosarcoma, or malignant fibrous histiocytoma
  - poor prognosis

Action	Numeric Key	Letter Key	Function Key
Show Bullets		S	Enter (frontside only)
20%	1	N
40%	2	H
60%	3	F	Enter (backside only)
80%	4	E
100%	5	M
Toss	0	T

Fibrous Dysplasia Differential
	Multiple lesions in young patients	Treatment is Observation alone	Benefits from Bisphonate therapy
Fibrous Dysplasia	•	•	•
Eosinophilic granuloma	•	•
Lymphoma	•
Leukemia	•
Enchondroma / Olliers / Maffucci's	•	•
Osteochondroma / MHE	•	•
NOF /Jaffe-Campanacci syndrome	•	•
Hemangioendothelioma	•
Paget's		•	•
Metastatic Disease			•
Myeloma			•