Fibrous Dysplasia - Pathology

Introduction

Overview
- fibrous dysplasia ia a developmental abnormality caused by failure of the production of normal lamellar bone leading to areas of the skeleton with poorly mineralized trabeculae.
- treatment is usually nonoperative with bisphosphonates for pain control unless there are bone deformities like scoliosis or coxa vara that require surgical alignment
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
- location
  - any bone can be involved
  - the proximal femur is most common site, followed by rib, maxilla, and tibia
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
Prognosis
- 1% risk of malignant transformation to osteosarcoma, fibrosarcoma, or malignant fibrous histiocytoma
  - poor prognosis

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 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

Differentials & Groups

	Multiple lesions in young patients (1)	Treatment is Observation alone (2)	Benefits from Bisphonate therapy
Fibrous dysplasia	•	•	•
Eosinophilic granuloma	•	•
Lymphoma	•
Leukemia	•
Enchondroma / Olliers / Marfucci's	•	•
Osteochondroma / MHE	•	•
NOF / Jaffe-Campanacci syndrome	•	•
Hemangioendothelioma	•
Paget's		•	•
Metastatic Disease			•
Myeloma			•
ASSUMPTIONS: (1) Younger patient is < 40 yrs; (2) assuming aymptomatic and no impending fracture

IBank

	Location	Age	Xray	Xray	CT	B. Scan	MRI	MRI	Histo(1)
Case A	fibula	10 yrs.
Case A	spine
Case B	radius
Case C	humerus
Case D	skull

(1) - histology does not always correspond to clinical case