Non-Ossifying Fibroma

Non-ossifying fibroma is a benign, fibrous bone lesion of the metaphysis in children and adolescents, consisting of spindle cells in a storiform pattern with giant cells and foamy histiocytes. It is larger than a fibrous cortical defect (over 3 cm long, or over 50% of the transverse width of the bone) and extends into the medullary cavity.

It is found in up to 30 to 40% of children during growth, with a peak between 10 and 20 years of age, and a male predominance. The usual sites are the distal femur, the proximal and distal tibia, and the fibula, with about half in the knee region. Lesions are often multiple (in 40%) and bilateral.

Most are asymptomatic and found incidentally. Complications are:

• Pathological fracture (about 5%, mostly in lesions over 33 mm in length and over 50% of the width of the bone).
• Rarely, multiple lesions with café-au-lait spots, intellectual disability, hypogonadism, and eye and heart anomalies (Jaffe-Campanacci syndrome, linked to neurofibromatosis type 1).
• Hypophosphataemic osteomalacia in the very rare patient with a large burden of lesions.

Malignant change does not occur.

Pathophysiology.

Activating variants in the MAPK signalling cascade (KRAS in about 45%, FGFR1 in about 15%, and NF1) are found in most lesions, so it is regarded as a true neoplasm. The lesion starts near the physis and moves into the diaphysis as the child grows, then fills in with bone from the margin, showing sclerosis, and resolves by skeletal maturity in most. Rarely a lesion produces fibroblast growth factor 23.

Often none. Mild pain after activity, or a pathological fracture after minor injury (sudden pain and swelling). Swelling is unusual. Multiple lesions with pigmented skin patches, short stature, or learning difficulty suggest a syndrome.

Examine the limb for tenderness, deformity, range, gait, alignment, café-au-lait spots, axillary freckling and neurofibromas.

• Radiographs: an eccentric, multiloculated, well defined lucent lesion in the metaphyseal cortex extending into the medulla, with a scalloped sclerotic margin and thinned cortex, without periosteal reaction or soft tissue mass. Healing lesions are sclerotic. The Arata classification grades the stage and the risk of fracture.
• MRI or CT for large, atypical or symptomatic lesions: low to intermediate signal on T1 and heterogeneous signal on T2, with a low signal rim.
• Biopsy is not needed for typical lesions; it is used for atypical lesions with histology of storiform spindle cells and giant cells.
• Blood tests when lesions are multiple and large: calcium, phosphate, alkaline phosphatase, parathyroid hormone, and fibroblast growth factor 23 if phosphate is low.

Differential diagnosis.

• Fibrous cortical defect and fibrous dysplasia.
• Giant cell tumour and aneurysmal bone cyst.
• Chondromyxoid fibroma and unicameral bone cyst.
• Brodie abscess, osteofibrous dysplasia and desmoplastic fibroma.

Observation. Most lesions need no treatment. Explain that they regress and heal by skeletal maturity. Activity can be continued with caution for lesions at risk of fracture, and contact sports are limited when a lesion is large.

Follow up. Radiographs at 6 to 12 months for lesions at risk of fracture (over 33 mm, or over 50% of the transverse width), with discharge when the lesion is sclerotic and shrinking.

Surgery.

• Indications: a pathological fracture through a large lesion that has healed, symptomatic lesions with high fracture risk (over 50% of the width and over 33 mm), progression, or diagnostic uncertainty.
• Curettage with bone graft or bone substitute, with a high speed burr; internal fixation is added for lesions in the weight bearing femur or tibia. Recurrence is under 5%.
• Fracture: treat by cast or fixation, allow the fracture to heal (often the lesion fills in), then curettage and graft if the lesion persists.

Operative antibiotic prophylaxis. Cefazolin 30 mg/kg to a maximum of 2 g intravenously (2 g in adults; 3 g when weight is 120 kg or over) within 60 minutes before incision as a single dose. With severe penicillin allergy, clindamycin 10 mg/kg (maximum 900 mg) intravenously or vancomycin 15 mg/kg intravenously starting 90 to 120 minutes before incision as a single dose.

Analgesia.

• Children: paracetamol 15 mg/kg orally every 4 to 6 hours (maximum 75 mg/kg daily and not exceeding 4 g daily).
• Children: ibuprofen 10 mg/kg orally every 6 to 8 hours with food (maximum 40 mg/kg daily and not exceeding 2400 mg daily); both drugs for up to 5 days. Avoid ibuprofen with kidney impairment, dehydration or active bleeding.
• Adolescents and adults: paracetamol 1 g orally every 6 hours as needed (maximum 4 g daily; 3 g daily when weight is under 50 kg, with chronic alcohol use or hepatic impairment).
• Adolescents and adults: ibuprofen 400 mg orally every 8 hours with food for up to 5 days (maximum 1200 mg daily).

Monitoring. Radiographs at 6 to 12 months for observed lesions, and at 6 weeks, 3 months and 6 months after surgery to check graft incorporation. Growth and alignment until skeletal maturity. Phosphate when lesions are multiple.

Referral and escalation. Refer large (over 33 mm or over 50% of the width), symptomatic, atypical or fractured lesions to paediatric orthopaedics. Urgent referral for rapid growth, a soft tissue mass, periosteal reaction, or a lesion in an adult that looks different from before.

Special groups.

• Children: observe; most lesions heal. Limit sport only when the fracture risk is high.
• Multiple lesions with café-au-lait spots: assess for neurofibromatosis type 1 and Jaffe-Campanacci syndrome (clinical genetics, eye and cardiac review).
• Hypophosphataemia: investigate for a phosphaturic tumour and treat osteomalacia.
• Adults: a persistent or new lesion should be reassessed for other diagnoses with MRI.