Adamantinoma

Adamantinoma is a rare, low grade malignant bone tumour made of epithelial cells in a fibrous or osteofibrous stroma. It accounts for under 0.5% of primary malignant bone tumours.

It has a strong predilection for the diaphysis of the tibia (80 to 90%, usually the anterior cortex of the middle third), and about 10 to 20% of cases involve the ipsilateral fibula. It occurs between 10 and 50 years of age (the peak is in the 20s to 30s), with a slight male predominance. It is slow growing, and symptoms may be present for years.

Two histological forms exist. Classic adamantinoma is a biphasic tumour of epithelial nests in a fibrous stroma, with a risk of local recurrence and metastasis. Differentiated (osteofibrous dysplasia like) adamantinoma has little epithelium, and an osteofibrous background that resembles osteofibrous dysplasia, with a more indolent course. Local recurrence is 20 to 30% after marginal excision, and metastasis (lungs, regional lymph nodes, and bone) develops in 15 to 30%, often years after treatment.

Pathophysiology.

The tumour cells express cytokeratins (keratin 5, 14 and 19, and epithelial markers), and their origin is debated: basal cell, synovial, or an epithelial rest. Adamantinoma and osteofibrous dysplasia are thought to be a spectrum, with the latter a possible precursor, and trisomy 7, 8, 12, 19 and 21 are described. The tumour is not sensitive to conventional chemotherapy or radiotherapy.

Local pain (insidious, sometimes for years), swelling over the anterior tibia, a palpable bony mass, anterior bowing of the tibia, or a pathological fracture (in about 15 to 20%). Systemic symptoms are absent. Cough or chest pain suggests lung metastasis.

Examine the tibia for tenderness, swelling, deformity (anterior bowing), limb length, joint motion, neurovascular state, and regional lymph nodes.

• Radiographs: multiple, well defined, eccentric lytic lesions in the anterior cortex of the mid-tibia with a sclerotic, "soap bubble" appearance, separated by sclerotic bone, with cortical expansion, which may involve the full length of the diaphysis. Fibular lesions are common.
• MRI: defines intramedullary and soft tissue extent, and skip lesions, with heterogeneous enhancement.
• CT: delineates cortical destruction and fracture risk; CT chest for metastases (staging).
• Biopsy: open or CT-directed (core), in the line of the planned surgical incision; immunohistochemistry (keratin positive in epithelial cells) differentiates it from fibrous dysplasia, osteofibrous dysplasia and metastatic carcinoma.
• Bone scan or positron emission tomography for staging.

Differential diagnosis.

• Osteofibrous dysplasia (younger children, under 10 years, keratin positive cells in small numbers) and fibrous dysplasia.
• Non-ossifying fibroma and chronic osteomyelitis (Brodie abscess).
• Metastatic carcinoma and Ewing sarcoma variants.
• Congenital pseudarthrosis of the tibia and stress fracture.

Surgery is the only curative treatment. The aim is complete excision with a wide margin.

Surgery.

• Wide en bloc resection of the involved segment, including the biopsy tract, with reconstruction. Intralesional or marginal excision gives recurrence in up to 90% in some series and a higher metastatic risk.
• Reconstruction options: vascularised fibular graft (contralateral), massive allograft, intercalary allograft with plate, bone transport with a ring fixator, or a tumour endoprosthesis.
• Amputation (transtibial) for extensive disease, soft tissue involvement, nonreconstructable limbs or recurrence after limb salvage.
• Metastases: surgical removal (lung metastasectomy, lymph node dissection) improves survival where the disease is resectable.
• Chemotherapy and radiotherapy have no proven benefit, and are reserved for palliation in unresectable disease. Systemic therapies are selected by a sarcoma team.

Operative antibiotic prophylaxis.

• Cefazolin 2 g intravenously (3 g when weight is 120 kg or over) within 60 minutes before incision as a single dose. Repeat after 4 hours or blood loss over 1500 mL.
• With severe penicillin allergy, give vancomycin 15 mg/kg intravenously starting 90 to 120 minutes before incision as a single dose. In prolonged cases, check levels and creatinine.

Thromboprophylaxis.

• Enoxaparin 40 mg subcutaneously once daily, started 6 to 12 hours after surgery. Continue for 28 to 35 days after major limb reconstruction or when mobility is reduced.
• Use 20 mg once daily at creatinine clearance under 30 mL/min. Adjust by anti-Xa level in obesity and renal impairment.
• Check the platelet count on days 5 to 14 for heparin induced thrombocytopenia.
• Use mechanical prophylaxis until then.

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).
• 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.
• Avoid NSAIDs while union of a graft or fracture is awaited.

Monitoring. Clinical review and radiographs of the limb at 3 months, 6 months and 12 months, then every 6 months for 3 years and yearly afterwards. Chest CT every 6 months for 2 years, then yearly for at least 10 years, since late recurrence and metastasis occur up to 20 years later. MRI for suspected local recurrence. Graft union and limb function.

Referral and escalation. Refer every suspected adamantinoma to a sarcoma centre before biopsy or surgery. Urgent referral for a pathological fracture, rapid growth, soft tissue mass or suspected metastases.

Special groups.

• Children: osteofibrous dysplasia is more likely; observe and avoid unnecessary resection, with biopsy for keratin positive cells.
• Pathological fracture: allow treatment planning; avoid early fixation that spreads tumour.
• Reconstructed limbs: long term review for graft failure, nonunion and infection.
• Kidney impairment: avoid NSAIDs and reduce morphine doses.