Osteosarcoma

Robert E. Turcotte, M.D., FRCSC
Division of Orthopaedic Surgery and Department of Oncology
McGill University Health Centre
Montreal, QC

Osteosarcoma is defined by the production of osteoid by malignant cells and represents the most common primary malignant bone tumour. Its incidence is estimated at only 1.6 per million per year representing 50 new cases yearly across Canada. It affects mainly teenagers and young adults but can occur at any age. The cause of osteosarcoma remains unknown. Studies have shown multiple chromosomes and gene anomalies to occur in this tumour but have failed to pinpoint any specific pattern. Most osteosarcoma arise de novo from normal bone but in rare instances, it may develop following a benign condition such as fibrous dysplasia or Paget's disease.

Medical attention is usually sought for progressing pain, a bump or swelling affecting the limb. A recent traumatic event is sometimes reported and may initially confuse the clinical picture. Pathologic fracture is, at times, the reason for consultation. Half of the cases arise near the knee joint (distal femur or proximal tibia or fibula). Involvement of pelvis, scapula, ribs or spine is infrequent compared to Ewing's sarcoma. Physical findings are usually subtle in the form of poorly defined enlargement, swelling or firmness over the affected bone. Moderate joint effusion can be noted as well as muscle atrophy or minimal restriction in range of motion. Significant limitation of joint amplitude or massive joint effusion could be related to violation of joint integrity by tumour. Lymph node enlargement is unusual in osteosarcoma.

Osteosarcoma classically manifests as a destructive lesion of long bone involving the metaphysis. Malignant bone production is usually easy to recognize but most often the lesion is mixed with areas of lysis that sometimes can constitute most of the lesion. A soft tissue extension is most often visible with prominent periosteal reaction including classical sunburst appearance and Codman's triangle. (Figure 1)

turcottefigure_1.jpg
Figure 1: Radiograph of proximal humerus osteosarcoma. Following neoadjuvant chemotherapy, reconstruction was performed with a modular endoprosthesis.

Following plain radiographs, local imaging studies to be performed include CT scan and MRI. These studies allow for precise delineation of bone and soft tissue involvement as well as matrix production and location of major nerves and vessels in relation to the tumour. When malignancy is suspected, a coronal or saggital section of the whole bone should be performed to exclude skip lesions (Figure 2). Systemic staging will include a total body bone scan to confirm the bone lesion as unique and CT of the chest to exclude lung metastases. The usefulness of PET scan is still under investigation. Blood tests are usually within normal values except for a slight elevation of the erythrocytes sedimentation rate. Increased level of alkaline phosphatase, seen in nearly half of the cases, carries a worse prognosis.

A biopsy is always required to confirm the diagnosis. This critical procedure should be performed following the well-known principles of oncologic surgery such that the biopsy site be included within the resection at time of definitive surgery6. Osteosarcoma has many subtypes that are important with regard to prognosis and treatment (Figure 3).

Most osteosarcoma require a multimodality approach consisting of neoadjuvant chemotherapy followed by ablation of the affected segment of bone. Localized low-grade tumours such as parosteal osteosarcoma or low-grade central osteosarcoma are usually treated with surgery alone. Limb salvage can most often be achieved, even in context of pathologic fracture, providing good a chemotherapy response and wide surgical margins are obtained. Amputation has not resulted into better survival figures but should still be considered in some instances as local recurrence impacts badly on survival. Reconstruction of the limb is usually achieved using modular endoprostheses (Figure 1). These have shown interesting medium-term results3,5,7. Allograft reconstruction, especially at the knee, have lost popularity as they show more complications and poorer functional outcomes in the context of chemotherapy7. Composite reconstruction (allograft and prosthesis) may represent a viable alternative when functional soft tissue reattachment is needed such as extensor mechanism for the proximal tibia or rotator cuff for the proximal humerus. In children, amputation also has become less frequent. Rotationplasty, and sometimes allograft, can be indicated for some patients. Growing endoprostheses are becoming more popular as progressive lengthening can now be achieved non-invasively with newer designs. Longevity of such implants remains a concern in immature skeletons but work is underway to improve outcomes.

 

In osteosarcoma, cure correlates with tumour response to neo-adjuvant chemotherapy. Tumour viability, as assessed by in-depth histopathologic examination, remains the most important prognostic factor. Five-year survival rates of 70% are reported when tumour necrosis is more than 90% as opposed to 48% when tumour necrosis is found to be less1. Researchers and clinicians are still in search of effective second line drugs for poor responders to the initial chemotherapy regimen.

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Local recurrence represents a major threat to survival2 (up to 85% ultimately dying) and correlates to surgical margins and chemotherapy response. Metastases most often involve the lungs. Additional chemotherapy and pulmonary wedge resections, sometimes multiple, can lead to cure in some. Bone or solid organs metastases are much more difficult to manage.

In osteosarcoma, known prognostic factors include: tumour volume (> 200 ml), location (pelvis and spine), surgical stage, elevated alkaline phosphatase, presence of skip or distant metastases at time of diagnosis, inadequate surgical margins, poor response to neoadjuvant chemotherapy and local recurrence.

References

  1. Bacci G., Longhi A., Versari M., Mercuri M., Briccoli A., Picci P. Prognostic factors for osteosarcoma of the extremity treated with neoadjuvant chemotherapy: 15-year experience in 789 patients treated at a single institution. Cancer. 2006 Mar 1;106(5):1154-61 amputation, survie alk phosph 5 yrs 67 vs 48%
  2. Bacci G., Longhi A., Cesari M., Versari M., Bertoni F. Influence of local recurrence on survival in patients with extremity osteosarcoma treated with neoadjuvant chemotherapy: the experience of a single institution with 44 patients. Cancer. 2006 Jun 15;106(12):2701-6
  3. Griffin A.M., Parsons J.A., Davis A.M., Bell R.S., Wunder J.S. Uncemented tumor endoprostheses at the knee: root causes of failure. Clin Orthop Relat Res. 2005 Sep;438:71-9
  4. Papagelopoulos P.J., Turcotte R.E., Galanis E.C., Wold L.E., Sim F.H. Primary cystic and neoplastic disease of bone, in Disorders of Bone and Mineral Metabolism, 2nd Edition, Eds Coe F.L. and Favus M.J., Lippincott Williams and Wilkins, Philadelphia, 2002, 1021-50
  5. Sharma S., Turcotte R.E., Isler M.H., Wong C., Limb salvage with a cemented rotating hinge endoprosthesis for tumours of distal femur Clin Orthop Relat Res. 2006 Sep;450:28-32.
  6. Turcotte R.E, Biopsy of Musculoskeletal Tumors. COA Bulletin, p. 16-17, May/June 1999.
  7. Wunder J.S., Leitch K., Griffin A.M., Davis A.M., Bell R.S. Comparison of two methods of reconstruction for primary malignant tumors at the knee: a sequential cohort study. J Surg Oncol. 2001 Jun;77(2):89-99

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