|Epidemiology|| The age of presentation of osteosarcoma occurs chiefly in two groups : 10 25 years of age, and more than 60 years of age. Osteosarcoma may arise as a de novo lesion or develop secondarily to a known premalignant lesion such as Paget disease, osteogenesis imperfecta, bone lesion, chronic osteomyelitis, fibrous dysplasia, giant cell tumor, osteoblastoma, or to a process such as radiation therapy. Several chemical agents such as beryllium oxyde were shown to be inducers of osteosarcoma.|
Some cases of osteosarcoma appear to be familial : in particular children with familial bilateral retinoblastoma have a incidence of osteosarcoma several hundred times that of an age-matched general population. This appears to represent both a genetic predisposition to de novo neoplasia and an increased susceptibility to radiation-induced sarcoma.
Patients with hereditary diseases such as Rothmund-Thomson syndrome, Bloom syndrome, and Li-Fraumeni syndrome were found to have increased risk of having osteosarcoma develop.
|Clinics|| Approximately 85 % of patients with de novo osteosarcoma present before 20 years of age. More than 60 % are in their second decade of life. Males are affected more often than females. Conventional osteosarcoma shows a marked predilection for the metaphyseal regions of the long bones. The distal femur accounts for one third of all cases, followed by proximal tibia, and the proximal humerus. |
The most common presenting complaint is pain, usually from 1 to 8 months duration. Pathologic fractures are uncommon occuring in less than 5 % of patients.
The classic radiographic finding is a large infiltrating metaphyseal lesion that arises in medullar bone and erodes through the cortex to from a large soft tissue mass. Osteosarcomas appear most often with a mixed lytic and sclerotic appearance.
| Microscopic features : osteoblastic osteosarcoma with atypical cells elaborating immature osteoid.|
|Pathology|| Osteosarcoma is composed of proliferating spindle-shaped cells that directly produce osteoid or immature bone (fig 1). |
Approximately 75 % of osteosarcomas arise in the intramedullary cavity and are referred to as "classical" or "conventional" osteosarcoma (fig 2). "Conventional" osteosarcomas can be divided into histological subtypes according to their predominant stromal differentiation : fibroblastic, telangiectatic and giant-cell rich.
Others types of osteosarcomas are :
Cortex-associated osteosarcomas Low grade (central) osteosarcomas Osteoblastoma-like osteosarcomas Disease-associated osteosarcomas Multicentric osteosarcomas Post-irradiation osteosarcomas Osteosarcoma of the gnathic bones.
Most osteosarcomas are easily recognized based on their hight-grade obviously anaplastic cells and uniquivocal osteoid production. The neoplastic cells in high grade conventional osteosarcomas have marked nuclear pleiomorphism, conspicious chromatin abnormalities, prominent nucleoli and many mitotic figures some of which are atypical. In the fibrosarcomatous pattern of osteosarcoma, the stroma is composed of spindle cells. Osteosarcomas may contain large areas that resemble malignant fibrous histiocytoma.
| Macroscopy aspect of an osteosarcoma : hemorragic and destructive tumor of the metaphysis of the right tibia. Bilateral rupture of cortical and invasion of epiphyseal plate.|
|Treatment|| Osteosarcoma is a chemosensitive tumor specially to high-dose methotrexate. The usual therapy is 8 to 12 weeks pre-operative chemotherapy, followed by conservative surgery or amputation, then by post-operative chemotherapy adapted to the histological response to pre-operative chemotherapy. But, 30 to 40 % of patients have a bad histological response to pre-operative treatment and a worse long term prognosis.|
|Prognosis|| Molecular events associated with disease aggressiveness and chemotherapy response may serve as prognostic factors.|
Age, localisation, tumoral mass, initial metastatic disease are prognostic factors. The most important predictor of outcome at diagnosis is the presence or absence of metastases. The most reliable prognostic factor is the histological response to pre-operative chemotherapy. Elevated expression of P-glycoprotein in immunochemistry was associated with a decreased probability of event-free survival. The expression of HER2/neu may be a predictor of chemotherapy response and prognosis in osteosarcoma. For some authors, it is correlated with a poor survival rate.
At present, RB gene LOH (loss of heterozygosity) appears as an early predictive feature for primary osteosarcomas, indicating a possible unfavourable outcome whereas its absence is correlated with a favourable prognostic.
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