Secondary osteosarcoma

Last revised by Joachim Feger on 19 Dec 2022

Secondary osteosarcomas are osteosarcomas growing on abnormal bone in the setting of various underlying osseous disorders.

Other acceptable terms include Paget sarcoma, osteosarcoma in Paget disease of bone or radiation-associated osteosarcoma, if applicable. The terms postirradiation sarcoma and radiation-induced sarcoma are discouraged 1.  

Osteosarcoma is the most common sarcoma in Paget disease of bone and it accounts for >50% of osteosarcomas in patients over the age of 50 years in patients where Paget disease of bone is prevalent and occurs with an estimated frequency of up approximately 1% in patients with the disease 1-3. It occurs predominantly in Caucasians and people of English descent most often seen in older ages in the 6th and 7th decade 1,2.

Radiation-associated osteosarcoma occurs in bone after radiotherapy in tumors with long survival times such as Hodgkin lymphoma, retinoblastoma, breast and cervical carcinoma with a median latency of 10 years after irradiation and an estimated frequency of 0.03% 1,3.

The diagnosis is based on a combination of pathological and typical imaging features as well as the presence of an underlying bony abnormality or history of radiotherapy 1.

Diagnostic criteria according to the WHO classification of soft tissue and bone tumors (5th edition) 1:

  • imaging features of a bone tumor

  • osteoid matrix with neoplastic bone formation

  • osteosarcoma histology

  • history of known underlying bony abnormality or previous irradiation

The histological confirmation of the underlying bony abnormality is a further desired criterion.

Clinical signs and symptoms include new pain and swelling in patients with a known predisposing osseous condition such as Paget disease of bone or irradiation. Sometimes the underlying predisposing condition might not be known 1.

Complications of secondary osteosarcomas include pathological fractures, skip metastases and distant metastases.

Secondary osteosarcoma is pathologically not different from primary osteosarcoma except that it occurs in sites of abnormal bone with possible pathological correlate of the underlying disease 1.

Causes of secondary osteosarcomas include 1,3:

  • ionizing radiation

  • dose-dependency most patients received a median of 50 Gy

  • potentially mutagenic doses at the edge of the radiation field

  • bone infarction (sickle cell disease, caisson disease)

  • orthopedic implants (very infrequent)

Secondary osteosarcomas occur at the sites of the abnormal or diseased bone 1,2:

  • Paget sarcoma often affects the femur, pelvis and the humerus and more rarely in the vertebral bodies, skull or mandible with possible multifocal synchronous lesions

  • radiation-associated osteosarcomas usually occur at the site of radiotherapy and often affects the pelvis and the chest wall, and might develop in the lower limbs outside the radiation field (retinoblastoma)

  • secondary osteosarcomas related to premalignant osseous syndromes show a similar distribution as conventional osteosarcoma

  • infarct-related osteosarcomas often occur in the knee

Secondary osteosarcomas can be classified into the following subtypes 1:

Additional histological features of secondary osteosarcoma include:

  • Paget osteosarcoma

    • the overall appearance of exaggerated chaotic bony remodeling

    • osteoclast-rich giant cells

    • atypical pleomorphic spindle cells

Imaging features are not very different from primary osteosarcomas and include expansile lytic osseous lesion and cortical destruction, soft tissue extension, and an extraosseous tumor mass in addition to the features of the underlying bone condition 1,2.

Secondary osteosarcomas often show a lytic destruction of the pagetic bone.

CT imaging features include cortical destruction and soft tissue extension. Additionally, CT can aid in the demonstration of the mineralization of the mass 2.

MRI imaging features are similar to those of primary osteosarcoma with the addition that MRI might show changes related to the underlying disease. Individual features which help in the differentiation of the underlying bone condition include the following 1:

  • replacement of the heterogeneous fatty pagetic bone marrow

  • aggressive trabecular and cortical bone destruction

  • soft tissue extension and extraosseous mass formation

Bone scintigraphy can depict underlying disease as Paget disease 2.

PET-CT is characterized by avid uptake of FDG in malignancy 2.

The radiological report should include a description of the following:

  • form and location

  • tumor margins and transition zone

  • cortical destruction

  • soft tissue extension

  • signs of underlying bone condition

  • skip metastases

  • distant metastases

Management is complicated. Paget sarcoma and radiation associated osteosarcoma are typically high-grade tumors poorly responding to chemotherapy with a worse prognosis than conventional osteosarcoma. Almost 30% of patients with Paget sarcoma present with pulmonary metastases and the 2-year survival rate is grim with approximately 25%. The five-year survival or radiation associated osteosarcoma is also poor 4,5 ranging between 10% and 30%. The prognosis in the setting of predisposition syndromes is similar to non-syndromic osteosarcomas 1.

Paget disease-related bone sarcomas were already described by the English surgeon Sir James Paget in 1877 2,6. Radiation associated osteosarcoma has been first described by the German physician A Beck in 1922 3,7.

Secondary osteosarcoma mimic the appearance of primary osteosarcoma  beyond that it can look like other bone tumors including 1,2:

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