Parosteal Osteosarcoma

Parosteal osteosarcoma is a low grade, bone forming malignant tumour that arises on the surface of a bone from the outer layer of the periosteum, and grows as a dense, lobulated mass attached to the cortex. It is the commonest surface osteosarcoma, and accounts for about 4% of all osteosarcomas.

It occurs between 20 and 40 years of age, a decade later than conventional osteosarcoma, with a slight female predominance. About 65 to 70% arise on the posterior surface of the distal femoral metaphysis (popliteal region), and the rest in the proximal tibia, proximal humerus and, less often, the fibula and the bones of the hand. It grows slowly, and many patients have symptoms for 1 to 3 years before diagnosis.

Invasion of the medullary canal occurs in 20 to 30%. Dedifferentiation to a high grade sarcoma occurs in 15 to 25% (at presentation or at recurrence), and it changes the prognosis. With wide resection, 5-year survival is over 90%; incomplete excision causes recurrence, which is often higher grade. Complications are knee stiffness, local recurrence, dedifferentiation, lung metastasis (mainly with dedifferentiation), and reconstruction failure.

Pathophysiology.

The tumour carries amplification of MDM2 and CDK4 from 12q13 to 15, often as a supernumerary ring chromosome, and this is useful to separate it from osteochondroma and myositis ossificans. Histology shows a well differentiated fibrous stroma with long, parallel, well formed bone trabeculae, and cartilage in some cases. A dedifferentiated area has high grade spindle cell features. The tumour grows around the bone and extends along the cortex before invading the marrow.

A slowly growing, hard, painless or mildly painful mass, most often behind the knee, with knee stiffness (loss of flexion) and a limp. Pain suggests a dedifferentiated area or marrow invasion. The mass is fixed to bone.

Examine the mass size, tenderness, mobility, knee range of motion, neurovascular state (popliteal vessels and tibial nerve), and regional lymph nodes.

• Radiographs: a dense, lobulated, heavily ossified mass attached by a broad base to the posterior distal femoral cortex, with a "stuck on" appearance. A thin lucent cleft between the mass and the cortex may be visible early, and later the tumour wraps around the shaft.
• MRI: shows the surface mass with low signal (ossified), medullary involvement (T1 marrow replacement), soft tissue extension and neurovascular relationship. A high signal non-ossified area suggests dedifferentiation.
• CT: shows the ossification pattern, cortical continuity, and canal invasion; CT chest for staging.
• Biopsy (core or open, in the line of the planned incision), taken from a non-ossified area, since a sample from the ossified part may look benign. MDM2 amplification confirms the diagnosis.
• Blood tests: full blood count, alkaline phosphatase and lactate dehydrogenase (usually normal), renal and liver function.

Differential diagnosis.

• Osteochondroma and myositis ossificans.
• Periosteal and high grade surface osteosarcoma.
• Conventional osteosarcoma and juxtacortical chondrosarcoma.
• Heterotopic ossification and bizarre parosteal osteochondromatous proliferation.

Surgery is the treatment. The aim is a wide margin with limb salvage.

Surgery.

• Wide en bloc resection with a cuff of normal tissue, including the biopsy tract and the posterior knee capsule when involved, with reconstruction (endoprosthesis, osteoarticular allograft or intercalary allograft). Recurrence is under 5% after wide resection, and up to 60% or more after marginal or intralesional excision.
• Limited resections of the posterior cortex with the tumour (surface resection) preserve the knee in selected small tumours without canal invasion, but have higher recurrence.
• Recurrence: re-resection with wide margins, sometimes amputation.

Chemotherapy. Not used for conventional low grade disease. It is given for a dedifferentiated (high grade) tumour, with the regimen used for osteosarcoma.

Doxorubicin 25 mg/m2 intravenously daily on days 1 to 3 (total 75 mg/m2 in a cycle) and cisplatin 100 mg/m2 intravenously on day 1, every 3 weeks, for 3 cycles before and 3 cycles after surgery.

Monitor blood count, creatinine clearance (cisplatin needs at least 60 mL/min), magnesium, potassium, audiometry and echocardiography. The lifetime ceiling of doxorubicin is 450 mg/m2. Avoid with an ejection fraction under 50%, hearing loss and significant neuropathy.

Give hydration (at least 1 L of 0.9% sodium chloride before and after cisplatin) and antiemetics (ondansetron 8 mg orally or intravenously before chemotherapy and every 12 hours for 2 days; dexamethasone 8 mg once on day 1 of each cycle).

Radiotherapy. Reserved for unresectable tumours or positive margins that cannot be re-excised.

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, with levels and creatinine checked in prolonged cases.

Thromboprophylaxis. Enoxaparin 40 mg subcutaneously once daily, started 6 to 12 hours after surgery and continued for 28 to 35 days after major joint reconstruction. 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 bone healing or osteointegration is awaited.

Monitoring. Clinical review, local imaging (radiograph, MRI) and chest CT every 6 months for 3 years, then yearly for at least 10 years, since late recurrence and dedifferentiation occur. Function of the reconstruction, and complications (infection, loosening, fracture).

Referral and escalation. Refer every suspected parosteal osteosarcoma to a sarcoma centre before biopsy. Urgent referral for a rapidly growing mass, new pain, a non-ossified component, or suspected recurrence.

Special groups.

• Dedifferentiated tumours: managed with the high grade osteosarcoma regimen of chemotherapy and wide resection.
• Women of reproductive age: fertility preservation before chemotherapy; avoid pregnancy during treatment.
• Recurrent disease: wider resection; imaging for dedifferentiation.
• Kidney impairment: avoid cisplatin and NSAIDs, reduce morphine doses, and adjust enoxaparin.