Chondromyxoid Fibroma

Chondromyxoid fibroma is a rare, benign, cartilage forming tumour with lobules of myxoid and chondroid tissue separated by cellular spindle cell zones. It is the rarest cartilage tumour, accounting for under 0.5% of all bone tumours and about 2% of benign bone tumours.

It occurs mainly in adolescents and young adults (10 to 30 years), with a slight male predominance. About half arise around the knee (proximal tibia and distal femur), and the others in the bones of the foot, pelvis (ilium), fibula, ribs and small bones of the hand. It lies eccentrically in the metaphysis, and may extend to the epiphysis after physeal closure.

Complications are pain, local expansion, pathological fracture (uncommon), local recurrence (15 to 25%), rare malignant transformation, and growth disturbance if the lesion lies near an open physis.

Pathophysiology.

The tumour carries rearrangements that upregulate the glutamate receptor gene GRM1 (about 90% of cases), through promoter swapping. Histology shows lobules of myxoid and chondroid matrix with stellate and spindle cells, with hypercellular peripheral zones with giant cells and a fibrous septa pattern. Cellular atypia is minimal, and the pattern must be separated from chondrosarcoma and chondroblastoma.

Mild to moderate pain that has been present for months, local swelling and tenderness, and sometimes a limp or reduced motion. Some are found incidentally. Pathological fracture is uncommon. A lesion in the foot may cause pain with walking.

Examine the site for tenderness, swelling, joint range and gait, neurovascular state, and the contralateral limb.

• Radiographs: an eccentric, well defined, lobulated or scalloped lytic metaphyseal lesion (often oval and elongated along the long axis), with a sclerotic, geographic margin, a buttress of thinned expanded cortex, and rarely matrix calcification (in about 10 to 15%).
• MRI: low to intermediate signal on T1, and heterogeneous high signal on T2 with enhancement; identifies soft tissue extension and the relationship to the physis.
• CT: defines the cortical shell, calcification and extent.
• Biopsy: required before definitive treatment in most cases, since the findings overlap with chondrosarcoma, chondroblastoma and aneurysmal bone cyst. Immunohistochemistry (S100, SOX9) and GRM1 testing can assist.

Differential diagnosis.

• Chondroblastoma and non-ossifying fibroma.
• Aneurysmal bone cyst and giant cell tumour.
• Chondrosarcoma and fibrous dysplasia.
• Osteoblastoma, unicameral bone cyst and infection.

Surgery.

• Extended intralesional curettage with high speed burring (with an adjuvant such as phenol, cryotherapy or argon beam where the site allows) and filling with bone graft, bone substitute or cement. Recurrence is 15 to 25% after simple curettage, and lower with extended curettage.
• En bloc (marginal) resection for expendable bones (fibula, rib, small bones of the foot or hand), or for recurrence, with reconstruction as required.
• Observation is accepted for small, asymptomatic lesions found incidentally with typical imaging, with follow up imaging at 6 months and 12 months.
• Radiotherapy has no role, and chemotherapy is not used.

Operative antibiotic prophylaxis. Cefazolin 2 g intravenously (3 g when weight is 120 kg or over; 30 mg/kg to a maximum of 2 g in children) within 60 minutes before incision as a single dose (repeat after 4 hours or blood loss over 1500 mL); with severe penicillin allergy, vancomycin 15 mg/kg intravenously starting 90 to 120 minutes before incision as a single dose, with levels and creatinine checked in prolonged cases.

Analgesia.

• Paracetamol 1 g orally every 6 hours as needed for up to 5 to 7 days (maximum 4 g daily; 3 g daily when weight is under 50 kg, with chronic alcohol use or hepatic impairment).
• Ibuprofen 400 mg orally every 8 hours with food for up to 5 days (maximum 1200 mg daily); avoid with eGFR under 30 mL/min/1.73 m2, peptic ulcer, heart failure or anticoagulant use.
• Oral morphine 5 to 10 mg every 4 hours as needed for severe pain for up to 3 days (start 2.5 to 5 mg with age over 75 or eGFR under 30 mL/min/1.73 m2; avoid exceeding 60 mg in 24 hours without senior review); monitor sedation and respiration and prescribe a laxative.

Monitoring. Clinical review and radiographs at 6 weeks, 3 months, 6 months and 12 months, then yearly for 3 to 5 years, since recurrence is usually within 2 years. MRI for suspected recurrence. Growth and alignment in children until skeletal maturity.

Referral and escalation. Refer every suspected chondromyxoid fibroma to a bone tumour service for biopsy, because of the overlap with malignant cartilage tumours. Urgent referral for rapid growth, a soft tissue mass or a pathological fracture.

Special groups.

• Children: protect the physis and monitor growth.
• Recurrent lesions: wider excision; reassess the diagnosis for chondrosarcoma.
• Pregnancy: avoid NSAIDs in the third trimester; defer non-urgent surgery.
• Kidney impairment: avoid NSAIDs and reduce morphine doses.