Case of the Week

Background:

• The role of radiation therapy is well established in adjuvant/neoadjuvant, radical, as well as palliative treatment of various malignancies with increasing implementation owing to availability and feasibility. Radiation-induced osteosarcoma is a well-recognized, rare, long-term complication of radiation therapy.
• In all irradiated individuals, incidence varies from 0.01% to 0.03%, and represents 5.5% of all osteosarcomas. While cancer treatments have improved survival, the prevalence of radiation-induced malignancies is rising in the oncology community.
• The pathogenesis of postirradiation sarcoma is unknown. Various predisposing factors have been suggested: radiation dose, age of the patient at radiation exposure, association with chemotherapy, and genetic predisposition.

Clinical Presentation:

• Any patient who presents with a painful lump or swelling in a previously irradiated region should be suspected of having radiation-associated sarcoma. Radiation-induced bone sarcoma is thought to have a long latent period of at least 4 years and a mean of between 8.3 and 21.3 years.
• Compared with their naturally occurring analog, these are apparently far more aggressive with poor survival rates. Patients older than 40 years, metastases at presentation, and central tumor sites are all indicators of a poor prognosis.
• Asymmetry in the head and neck region, pain, trismus, epistaxis, diplopia, jaw numbness, and dysphagia are symptoms that are related to the location of the tumor itself.

Key Diagnostic Features:

• The imaging features are typically not pathognomonic and can be similar to those of sporadic osteosarcoma of the greater sphenoid wing (OGS), which include a bony destructive lesion with soft tissue component, osteoid matrix, aggressive periosteal reaction seen on radiography, CT, and MR imaging. While MR is better for defining the extent of lesions, marrow involvement, skip lesions, and lesion characterization, CT is better for detection of matrix and periosteal reaction; hence, both can be used in conjunction. On MRI, osteoid is seen as T1/T2 hypointense areas with corresponding blooming on T2* imaging.
• Distinctive features from that of conventional OGS may include large size, rapid growth, extensive invasion, and highly heterogeneous appearance.
• FDG-PET shows increased uptake and maybe helpful in differentiating from benign/inflammatory conditions.

Differential Diagnoses:

• Other radiation-induced conditions: radiation osteitis, osteoradionecrosis,  radiation-induced meningioma, and other radiation-induced sarcomas such as fibrosarcoma and angiosarcoma.
• Osteoradionecrosis: This is the main differential diagnosis. Clinically, early presentation (usually 4 months to 2 years), association with dental procedures/infections, and pain as a common symptom favor osteoradionecrosis. The osteoradionecrosis-related changes to the bone are localized to the radiation field and appear as patches of mottled bone, osteopenia, coarse trabeculations, and focally increased bone density. Most of the time, there is no associated soft-tissue mass and periosteal reaction, unlike osteosarcoma.
• Other radiation-induced sarcomas: Other sarcomas like fibrosarcoma and angiosarcoma may be considered in the absence of bone expansion, typical periosteal response, and osteoid matrix.
• Primary osteosarcoma: This may be radiologically indistinct from the radiation-induced osteosarcoma, however, the latter has a tendency to exhibit higher tumor matrix mineralization and bone growth than primary osteosarcoma. Location of tumor outside the radiation field also favors primary osteosarcoma.

Treatment:

• Radiation-induced sarcoma has a poor prognosis compared with primary sarcoma. Surgery is the most important and preferred treatment that might improve patient survival.
• A multidisciplinary approach is adopted in unresectable cases; chemotherapy alone or re-radiation with or without chemotherapy may be of help.