Osteosarcoma is the most commonly diagnosed primary malignancy of bone, particularly among children and adolescents. Osteosarcoma arising in a background of paget's disease of bone and post-radiation osteosarcoma are examples of secondary osteosarcoma. The former affects elderly patients, and has a poor prognosis and response to treatment1. The later affects a wide age group, and has a prognosis and response to treatment comparable with primary osteosarcoma. Unlike primary osteosarcoma in young patients, which arises most often in the metaphyses of long bones, such as the distal femur, proximal tibia, and proximal humerus, secondary osteosarcoma tends to occur more commonly in axial locations and in areas that have been previously exposure to radiation therapy2, alkylating agents2 or that have underlying diseases such as paget's disease3, Rothmund-Thompson4, retinoblastoma5, Ewing's sarcoma6 and Li-Fraumeni syndrome7.
Paget disease, originally described by Sir James Paget in 1877, is a focal disorder of bone remodelling, involving increased bone resorption and formation. The etiology is uncertain but both environmental and genetic factors are thought to be involved in pathogenesis. Recent study suggested that sporadic Paget disease of bone may due to somatic mutations in SQSTM18. It is generally considered when there is radiographic evidence of cortical destruction, expansion of bone, coarsened trabeculae, and/or bone sclerosis. Paget disease usually affects bones of the skull, spine, pelvis, and lower extremities, but it also reported in hand9. Paget disease is associated with significant disability, impaired quality of life and a variety of complications such as pathological fracture, arthritis in adjacent joints, hearing loss, other neurological and cardiac complications, and lastly, secondary osteosarcoma10.
Secondary osteosarocma is a rare but serious complication of paget's disease and paget's osteosarcoma mainly affect elderly population. Most recent study by Mirabello et al11 shows that age-adjusted incidence rates in 0-24 years age group is 4.4 per million, which represents approximately 53% of all reported osteosarcoma cases with only 1 case of Paget's osteosarcoma in this age group. Individuals ages 25 to 59 years had the lowest incidence rates of osteosarcoma (1.7 per million) that included 4 cases of osteosarcoma in Paget's disease. Osteosarcoma in elderly (>60 years old) represented approximately 19% of all reported osteosarcoma cases (4.2 per million) with 62 cases of osteosarcoma occurring in Pagets disease11.
Although the overall survival rate for secondary osteosarcomas is arguable similar to primary osteosarcomas 12-14, paget's osteosarcoma remains an incurable disease with a poor prognosis. Shaylor et al15 reported in their study of 26 patient with osteosarcoma in Paget' s disease .The survival rate was 53% at 1 year, 25% at 2 years and no patient survived for 5 years despite modern methods of management of bone tumors. All patients died of metastatic disease. The median survival was 21 months for those treated with curative intent and 7 months for those treated palliatively. Four of the five patients treated with limb sparing surgery developed local recurrence between 5 and 12 months, the fifth died at 14 months. There was no difference in survival between amputation and limb salvage.
Contributed by Faye F Gao, MD., PHD and Uma N.M. Rao, MD