Symptoms & Causes
Introduction
Secondary osteosarcoma is a type of osteosarcoma that develops in previously abnormal bone, often associated with conditions like Paget disease or prior radiation therapy.
Reference
WHO Classification of Tumours Editorial Board. Soft tissue and bone tumours [Internet]. Lyon (France): International Agency for Research on Cancer; 2020 [cited 2024 09 11]. (WHO classification of tumours series, 5th ed.; vol. 3). Available from: https://tumourclassification.iarc.who.int/chapters/33.
Related Terminology
Acceptable: Paget sarcoma; osteosarcoma in Paget disease of bone (PDB); radiation-associated osteosarcoma.
Not recommended: postirradiation sarcoma; radiation-induced sarcoma
Subtype(s)
Osteosarcoma in Paget disease of bone; radiation-associated sarcoma; infarct-related osteosarcoma; osteosarcoma due to chronic osteomyelitis; implant-related osteosarcoma; osteosarcoma secondary to early postzygotic disorders such as fibrous dysplasia
Symptoms
New pain and an enlarging mass in a patient with a history of predisposing bone condition suggest the diagnosis of secondary osteosarcoma; occasionally, the underlying condition is unknown. Paget sarcoma typically develops in a background of polyostotic symptomatic PDB. Tumors are frequently lytic, occasionally mineralized, and may be multifocal. Pathological fracture is common.
Localization
Paget sarcoma most commonly affects the femur (34%), pelvis (24%), and humerus (24%), reflecting the distribution of uncomplicated PDB, except for a disproportionately high and low incidence in the humerus (24%) and the spine (2%), respectively. Multifocal synchronous tumors may occur (2–17%). Long bone lesions tend to be metaphyseal, and tumors have been noted to occur at the site of a previous fracture. Radiation-associated osteosarcoma occurs at the site of radiotherapy, most frequently in the flat bones of the chest wall and pelvis.
Osteosarcoma related to premalignant bone syndromes generally affects the same locations as non-syndromic osteosarcoma. However, tumors may be multifocal in Rothmund–Thomson syndrome and occur at unusual sites in Werner syndrome (foot and ankle, patella). Bone sarcomas outside the radiation field in hereditary retinoblastoma develop predominantly in the lower limbs.
Epidemiology
Osteosarcoma is the most common sarcoma associated with PDB. PDB develops predominantly in populations of English descent: 50% of bone sarcomas in patients aged > 50 years are secondary to PDB in endemic areas. In areas where PDB is not found, there is no second, older peak in the bimodal incidence of osteosarcoma. The incidence of Paget sarcoma in PDB is 0.7–6.3%, but as the incidence of PDB is declining, Paget sarcoma also appears to be less frequent and is occurring at older ages. Most patients are in the sixth to seventh decades of life (range: 32–86 years).
Radiation-associated osteosarcoma most commonly arises in bone after treatment of tumors with long survival (breast and cervical carcinomas, Hodgkin lymphoma, retinoblastoma). Radiation-associated osteosarcoma is estimated to occur in 0.03% of patients receiving radiotherapy, with osteosarcoma accounting for 21–77%. The median latency period after radiotherapy is 10 years (range: 3–55 years). Most patients are in the fifth decade of life, with an earlier peak in the second decade (children treated for hereditary retinoblastoma and other malignancies). Osteosarcoma in older populations is most frequently due to Paget disease or irradiation.
Etiology
Ionizing irradiation is the strongest risk factor for developing secondary osteosarcoma. Development of a radiation-associated osteosarcoma appears to be dose-dependent, with lower, potentially mutagenic doses at the edge of the radiation field. Most patients who develop radiation-associated osteosarcoma have received a median of 50 Gy. Bone infarction is an acknowledged cause of undifferentiated sarcoma, and an association between caisson disease, sickle cell disease, other biological insults, and osteosarcoma is now recognized. Sarcomas, including osteosarcoma, infrequently develop adjacent to orthopedic implants. A causal link to the constituents of implanted material, which may be carcinogenic in vitro, has been suggested but not proven.
