Osteosarcoma is the most common, non hematopoietic, primary malignant bone tumor, in which the neoplastic cells produce osteoid, even if only in small amounts. It occurs most frequently in young adults (with slight male preponderance). The peak incidence is in the second decade of life.  The metaphysis of the long bones of the appendicular skeleton, in particular, distal femur,  proximal tibia and proximal humerus are mostly affected.  The diaphysis may also be affected, but the involvement of the epiphysis is rare.  The radiographic appearance of conventional osteosarcoma is extremely variable. However, in most cases, it is a mixed lytic/blastic lesion accompanied by cortical destruction and tumor extension into the soft tissue. Tumor and periosteal interaction may lead to a variety of manifestations secondary to periosteal elevation (e.g. Codman’s triangle). 

Histologically, the neoplastic cells tend to be highly anaplastic and pleomorphic with epithelioid, plasmacytoid, fusiform, ovoid, small round cells, clear cells, spindle cells, mono or multinucleated giant cells. Most cases, however, have a complex mixtures of two or more of these cell types. The tumoral osteoid must be identified in order to make a diagnosis of osteosarcoma (Tumoral osteoid appears as a fine lacelike network, sheets, interlacing trabeculae). Osteosarcoma can also produce varying amounts of cartilage and/or fibrous tissue. Some investigators further subdivide osteosarcoma based on the matrix (chondroblastic, fibroblastic and osteoblastic). 

There are complex cytogenetic aberations. Amplifications at 1q21-23 and at 17p are frequent findings in conventional osteosarcoma. In aggressive osteosarcomas CDK4 is most consistently amplified. Overexpression of MET and FOS has been reported in more than 50% of osteosarcoma cases, while MYC is expressed in less than 15% of cases. There is no specific immunohistochemical or electron microscopic findings. 

Aggressive local growth and rapid hematogenous spread mark its course. Osteosarcoma most frequently metastasizes to the lungs. Currently, response to pre-operative therapy is the most sensitive indicator of survival. It must be recognized, however, that a single system does not apply to all cases. 

Typical osteosarcoma will not be confused with other bone lesions as long as one

1)       Finds areas of tumoral bone formation even when the matrix is chondroblastic or fibroblastic.

2)       One differentiates between osteoid/tumoral bone from reactive bone formation. Reactive bone usually has the regular structure of bone with osteoblastic rimming with loose/vascular stroma.

Once again, Never make the diagnosis of a bone tumor in a vacuum, always get the radiographic film / report. Be very cautious if there is a lack of correlation between radiology and histology.

References:

Fletcher, CBM, Unni, KK, Mertens, F (Eds.): World Health Organization Classification of Tumors. Pathology and Genetics of Tumors, Soft Tissue and Bone. IARC Press: Lyon 2002.