Non-Ossifying Fibroma (NOF)

Non-Ossifying Fibroma (NOF)

Prepared by Dr. Enes KANAY

Non-ossifying fibroma (NOF) is a benign, non-osteogenic bone lesion composed of fibroblastic cells, typically located in the metaphysis of long bones during childhood and adolescence.
It is usually asymptomatic and detected incidentally on radiographs obtained for other reasons.

1.Synonyms

• Fibrous      cortical defect (for smaller lesions)
• Metaphyseal      fibrous defect
• Fibroxanthoma
• Nonosteogenic      fibroma
• Fibrous      histiocytoma of bone
• Sometimes      confused with “cortical desmoid” (different localization)

2. Associated Conditions / Syndromes

NOF can be an isolated finding but may also be associated with certain systemic syndromes:

• Neurofibromatosis      type 1 (NF1)
• Jaffe-Campanacci      syndrome: Multiple NOFs + café-au-lait macules + mental retardation +      hypogonadism + cardiac anomalies

3. Epidemiology

• Age:      Common between 5–20 years
• Sex:      Slight male predominance (~1.6:1)
• Prevalence:      Seen radiographically in 30–40% of children
• Most      frequent locations: Distal femur, proximal tibia, distal tibia, proximal fibula

4. Pathogenesis and Genetics

Previously thought to be a reactive process; current DNA analyses have revealed KRAS, FGFR1, and NF1mutations → suggesting a neoplastic process related to RAS-MAPK pathway activation.
Typically eccentric in location, adjacent to the cortex.

5. Clinical Features

• Usually      asymptomatic
• Large      lesions:
  • Mechanical       weakness → risk of pathological fracture
  • May       cause pain
• Diagnosis      is often facilitated if a pathological fracture is present

6. Imaging

• Radiograph:      Eccentric, metaphyseal, cortically based, well-defined, lobulated      radiolucent lesion with internal septations
  • Often       1–3 cm (fibrous cortical defect) or larger (NOF)
• CT:      Demonstrates cortical thinning and intracortical location
• MRI:      Hyperintense on T2; hypointense on T1 if hemosiderin present
• Periosteal      reaction is typically absent

7. Histology

Gross:

• Well-circumscribed,      soft, yellow-brown fibrous tissue
• Cut      surface may show small foci of hemorrhage and hemosiderin deposits

Microscopic:

• Well-vascularized      fibrous stroma with haphazardly arranged spindle-shaped fibroblasts
• Interspersed      lipid-laden foam cells (xanthomatous histiocytes)
• Focal      multinucleated giant cells
• Frequent      hemosiderin pigment deposition
• Minimal      cellular atypia, rare mitotic figures
• Occasional      ossification or bone trabeculae within fibrous stroma
• Sclerotic      bony rim may be present at the periphery

Differential Diagnosis: Aneurysmal bone cyst, fibrous dysplasia, giant cell tumor

8. Treatment and Natural History

• Small/asymptomatic:      Observation (most regress and sclerose spontaneously by late adolescence)
• Large/high      fracture risk: Curettage + bone grafting
• Prophylactic      fixation may be considered
• Recurrence      after surgery is rare