Osteosarcoma

Key Points:

  • Osteosarcoma, otherwise known as osteogenic sarcoma, is a malignant tumor of bone that is primarily found in the extremities, but can also present in the axial skeleton.
  • Osteosarcoma is the most common primary bone tumor affecting children and young adults.
  • Osteosarcoma is recognized to have a bimodal age distribution. Approximately 75% of the patients are between 8 and 25 years of age.
  • These lesions are typically located in the metaphysis, and have involvement of the canal. They have a mixed radiodense (osteoblastic) and radiolucent (osteolytic) pattern with extension into the adjacent soft tissue.
  • Staging studies for the workup of a patient suspected to have a malignancy include radiographs of the bone involved, MRI of the extremity, whole-body bone scan to evaluate for skeletal metastasis, and CT scan of the chest to assess for metastatic disease.
  • Surgery and systemic chemotherapy are the mainstays of treatment for patients with osteosarcomas.

Description:

Osteosarcoma, also known as osteogenic sarcoma, is a malignant tumor of bone that is primarily found in the extremities, but may present in the axial skeleton. The histologic diagnosis is defined by the specific finding of osteoid or woven bone within a stroma or background of malignant spindle cells. Historically, the different types of osteosarcomas have been classified into “classical” or “juxtacortical”. This distinction not only highlighted the natural history of these tumors, but also their clinical presentations and the prognosis as well. Currently, the more common osteosarcoma is referred to as classic high-grade or conventional osteosarcoma. The other, less common variants are juxtacortical (parosteal or periosteal), intracortical, telangiectatic, extraskeletal, and secondary osteosarcoma. The latter is often related to post-radiation effects or malignant transformation associated with Paget disease.

Epidemiology:

Osteosarcomas account for approximately 1% of all cancers diagnosed annually in the US, and about 3% of all childhood cancers. They are the most common primary bone tumors affecting children and young adults. They are recognized to have a bimodal age distribution. Approximately 75% of the patients are between 8 and 25 years of age.

Clinical Findings:

Imaging Studies:

On imaging, the radiographs of a patient with an osteosarcoma are usually very telling. These lesions are typically located in the metaphysis, and have involvement of the canal. They have a mixed radiodense (osteoblastic) and radiolucent (osteolytic) pattern with extension into the adjacent soft tissue. Since these are high-grade malignant tumors, the destructive growth pattern of the tumor is typically bound or contained by a periosteal reaction. If the lesion is growing rapidly but steadily there may be enough time for Sharpey’s fibers to ossify and produce a “sunburst” pattern. However, if the lesion is growing rapidly, the periosteum will appear to be lifted off or tented at its margins, often referred to as a “Codman triangle”.
 
The appearance of the lesion on radiographs will correlate with the predominant tissue type within the sarcoma. This is primarily true for the high-grade telangiectatic osteosarcoma that has large vacuous blood-filled cysts and can sometimes be mistaken for an aneurysmal bone cyst (ABC) or a giant cell tumor (GCT).
 
In addition to radiographs, MRI is an essential study for evaluating the suspected osteosarcoma. The intraosseous extent and soft-tissue component of the lesion are more clearly defined by an MRI with and without intravenous contrast. MRI also identifies the presence or absence of a margin between the tumor and the neurovascular bundles and predicts the feasibility of a limb salvage resection.
 
Since approximately 20% of patients present with pulmonary metastasis, a CT scan of the chest should be performed, as part of the initial group of staging studies. A technetium-99 bone scan is another crucial staging study that is useful for screening the entire skeleton. While the lung is the most common site for metastatic involvement, the whole-body bone scan is excellent for identifying occult metastatic skeletal lesions or skip lesions within the same bone.

Etiology:

While hereditary predisposition accounts for a minority of cases of osteosarcoma, the majority are sporadic. However, several risk factors have been recognized.
  • Hereditary
    • Hereditary retinoblastoma, Li-Fraumeni syndrome, Rothmund-Thomson syndrome, and the related Bloom and Werner syndromes.
  • Post-Irradiation
    • Osteosarcoma is the most frequent cancer occurring during the first 20 years following radiation therapy for a solid malignant tumor in childhood. 
  • Paget disease
    • Transformation into osteosarcoma is most often seen in long-standing Paget disease and usually presents in adults in their 5th or 6th decades of life.

Treatment:

Initial treatment of a suspected osteosarcoma consists of an incisional biopsy with adherence to well-defined tumor principles, ideally by the surgeon that will be performing the definitive procedure.
 
The treatment protocol for high-grade osteosarcoma includes chemotherapy and surgical resection. This consists of neoadjuvent chemotherapy with three or four courses of a multidrug regimen to decrease tumor load and increase tumor necrosis prior to surgical treatment.  This is followed by surgical resection and additional chemotherapy. The course of treatment can take up to a year.
 
Limb salvage is possible due to advancements in imaging and chemotherapy, as surgical resection can almost always be done without an amputation of the extremity. The use of neoadjuvant chemotherapy reduces tumor size, making the resection easier, and gives the pediatric oncologist a prognostic predictor of the patient’s chance of survival based on the necrosis of the resected sarcoma. Unfortunately, this has not produced increased survival compared with postoperative adjuvant chemotherapy alone.
 
For lesions involving either the upper or lower extremity, a limb salvage surgical resection can improve functional outcome without sacrificing local disease control as long as complete tumor resection is anatomically possible. Allografts and metal endoprostheses are common means of reconstructing bone defects that result from sarcoma resections. Expandable prostheses have been developed for reconstruction in skeletally immature children and allow lengthening of the limb, thus making limb salvage surgery an option in the younger, skeletally immature patient.

Complications:

  • Oncologic complications can be due to the extent of disease and acute complications associated with the chemotherapy agents (Methotrexate, Doxorubicin, Cisplatin).
  • Growth disturbance and leg length discrepancy due to resection of an extremity growth plate.
  • Long term complications from chemotherapy such as congestive heart failure, myelodysplasia, and acute leukemia.

References:

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Top Contributors:

Henock T. Wolde-Semait, MD
Scott B. Rosenfeld, MD