Anatomic and Histologic Variants

Osteosarcoma is the most common primary tumor of bone, yet its absolute incidence among malignant tumors is low. Within its strict histologic definition, osteosarcoma comprises a family of lesions with considerable diversity in histologic features and grade. Its prognosis is dependent not only on these parameters but also on its anatomic site. It may occur inside the bones (in the intramedullary or intracortical compartment), on the surfaces of bones, and in extraosseous sites. Information of diagnostic or prognostic significance has not been elucidated from studies of its cytogenetics. This review summarizes the anatomic and histologic variations of osteosarcoma and offers a schema for its subclassification. At an estimated incidence of 2 cases per million persons per year, osteosarcoma is the most common malignant primary bone tumor excluding hematopoietic intraosseous tumors. Although it occurs at any age, its peak incidence is in the second and third decades. Its statistical distribution roughly parallels skeletal growth; it is more frequent in tall people than in short people and in larger animals than in smaller animals.1 Bones having the fastest rates of growth have the highest frequency of occurrence. When osteosarcoma appears earlier than the second decade or after the cessation of skeletal growth, there is often an association with another osseous abnormality. This may be a genetic predisposition such as the Li-Fraumeni or Beckman-Wiederman syndrome,2,3 an underlying abnormality such as Paget disease4 or fibrous dysplasia that has a predilection for the development of osteosarcoma,5 or previous radiation of the bone involved. The definition of osteosarcoma is deceptively straightforward. It is a malignant tumor of connective tissue (mesodermal) origin within which the tumor cells produce bone or osteoid (often referred to as “tumor bone” or “tumor osteoid” in the vernacular). Although this makes it seem as though the cells giving rise to osteosarcoma must be of osteoblastic derivation, there is no evidence that osteoblasts, once they differentiate from osteoprogenitor cells, can actually revert to more primitive cells, let alone malignant ones. This implication is inherent in the more arcane term osteogenic sarcoma, which has fallen into disuse. An additional feature often encountered in osteosarcomas is their propensity to produce variable amounts of cartilage matrix and fibrous tissue. In some cases, the cartilage matrix or fibrous tissue may so strikingly dominate the tumor tissue that the actual production of bone must be carefully sought to