Non-Ossifying Fibroma (NOF)

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