Osteosarcoma (osteogenic sarcoma) is a malignant tumor of the bone.
Osteosarcoma is the most common primary bone tumor comprising about 45% of all bone tumors. 75-85% of osteosarcomas locate intramedullary, the other 15% are found on the surface of the bone or extraskeletally. Commonly osteosarcomas originate from the thighbone/femur (42%), shinbone/tibia (19%) or humerus (10%).
Osteosarcoma usually occurs during growth spurts in adolescents due to high proliferation rates.
In general primary bone tumors are rare, whereas bones are often involved in a metastatic process. Osteosarcoma is the most common primarybone tumor. It accounts for 3-5% of all childhood cancers and 1% of adult cancers.
Young males are more likely to develop osteosarcoma than young females (with a ratio 1,43-1.28:1). Interestingly the diagnosis of osteosarcoma is usually made in adolescents and six decade patients.
It is supposed that tall children and Africans are more likely to be affected.
Causes and risk factors
This kind of tumors tends to originate from the areas of bone growth, probably due to a larger amount of gene mutations in the sites of proliferation. Probably the mutations of the chromosomes 3q, 13q, 17p and 18q may be the cause.
Risk factors for osteosarcoma include retinoblastoma, Li–Fraumeni (TP53 mutation), Rothmund–Thomson (autosomal recessive disease characterized by congenital bone defects, hair and skin dysplasias, hypogonadism, and cataracts) syndrome, multiple hereditary exostosis (hereditary factors), radiation exposure, Paget disease and polyostotic fibrous dysplasia (non-hereditary factors).
- Intramedullary (conventional) osteosarcoma is the usual type of tumor and comprises about 80% of all osteosarcoma. In the conventional sarcoma bone tissue may be dominant (osteoblastic tumor), cartilage (chondroblastic tumor) or fibrous tissue (fibroblastic tumor).
- Surface or juxtacortical osteosarcomas include intracortical, parosteal (parallel bone trabecules with bone spicules) and periosteal osteosarcoma (mostly cartilaginous), comprising 10-15% of these neoplasms.
- Extraskeletal osteosarcoma comprise 5% of the tumors.
The tumor appears as a firm, painful mass, adjacent to the underlying bone. However, if the tumor is relatively small it may be not detected. Usually the person experience pain in the affected area, which worsens at night, its intensity may vary. The range of motions or function of the limb may also be deteriorated. Often the pathological fracture of the bone is the first symptom of the tumor.
Later the metastases may be found in the lungs (causing pulmonary metastatic disease, which may be deadly) and other bones. They appear approximately within two years of initial diagnosis. Metastases via lymphatic systems are relatively rare for this type of tumor.
To verify the diagnosis, assess the tumor dissemination and prognosis the following examination should be performed:
- X-ray examination of the area and the whole skeleton – Codman triangle, the triangular area of new subperiosteal bone caused by the raised periosteum, is characteristic for osteosarcoma;
- CT/MRI of the lesion;
- PET scan;
- Biopsy of the neoplasm and nearby lymph nodes – the tumor appear as solid hard neoplasm, microscopically it is composed of osteoid with irregular trabecules and calcification;
- Lactate dehydrogenase (LDH), alkaline phosphatase;
The treatment commonly includes the combination of surgery and chemotherapy. Radiotherapy is performed usually for metastatic disease.
When the tumor is local (low-grade tumor) wide excision may be the only treatment needed. If the tumor develops fast and the cells appear non-differentiated (high-grade osteosarcoma) chemotherapy should be performed following the surgery.
After the surgery allograft or endoprotesis may be needed. In some cases amputation of the limb is required.
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Chemotherapy may be used prior to surgery or after it (adjuvant chemotherapy). In total six cycles of chemotherapy are administered.
- Cisplatin 100–120 mg/m2 intravenous + doxorubicin 60–75 mg/m2 intravenous over 48‐hour continuous infusion every 3 weeks. It should be accompanied by the granulocyte‐colony stimulating factor (G‐CSF).
- Cisplatin 50–60 mg/m2/day intravenous × 2 days + doxorubicin 30–37.5 mg/m 2/day intravenous for 2 days + methotrexate 8–12 g/m2× one dose intravenous on Days 22 and 29) of a 35‐day cycle.
For metastatic disease the following chemotherapy regimens are used:
- Ifosafamide 3.5 g/m2/day + etoposide 100 mg/m 2/day for 5 days every 3 weeks + G‐CSF on Day 6;
- Ifosfamide 1.8 g/m2/day + etoposide 100 mg/m2/day + carboplatin 400 mg/m2/day on Days 1–5 every 3 weeks + G‐CSF on Day 6;