Radiation-induced sarcoma is an exceedingly rare entity associated with high morbidity and mortality even if radiation is received several years prior. Aggressive cancer surveillance following radiotherapy is essential for improving survival rates in patients with radiation-induced sarcoma. Surgical resection with negative margins is the most important factor affecting long-term survival. This case report describes secondary osteosarcoma of the distal third of the femur in a 32-year-old female following previous radiotherapy treatment for Ewing's sarcoma.
Keywords: Ewing's sarcoma, femur, magnetic resonance imaging, multidisciplinary approach, prognosis, radiation-induced sarcoma, secondary osteosarcoma
| Introduction|| |
Osteosarcoma is the most common primary malignant bone tumor originating from primitive bone-forming mesenchymal cells. Primary osteosarcoma has a bimodal age distribution, with the first peak occurring during adolescence at 10–14 years and the second peak occurring in adults older than 65 years of age. Osteosarcoma commonly arises from the metaphysis of long bones of the extremities with distal femur and proximal tibia being the most common sites followed by the proximal humerus. Size of the tumor, anatomic location, stage of the tumor at presentation, the presence of metastases, local recurrence, and prior administration of chemotherapy regimen are some of the factors having an effect on the outcome. Radiation-induced sarcoma is associated with a grave prognosis and increased morbidity when compared to primary osteosarcomas.
| Case Report|| |
A 32-year-old female was admitted to the department of orthopedics with complaints of pain and inability to bear weight on the right leg for 4 months. When the patient was 24 years of age, she was diagnosed with Ewing's sarcoma of the right femur. Subsequently, radiotherapy was initiated and adequate response was achieved. The current symptoms are attributed to the same site of previous Ewing's sarcoma in the right lower extremity. The patient was referred for magnetic resonance imaging (MRI) of the right thigh which demonstrated an ill defined T1 hypointense and T2 heterogeneously hyperintense mass lesion with cystic components located in the metadiaphysis of distal femur. The eccentric extraosseous soft-tissue component of the lesion measured 16 cm × 13 cm × 12 cm, the approximate volume of 1248 cc in orthogonal dimensions with wide zone of transition, periosteal elevation, and Codman's triangle at the site of the lesion with evidence of articular extension. A diagnosis of radiation-induced osteosarcoma was made at the site of previous Ewing's sarcoma in the lower third of the right femur [Figure 1]a and [Figure 1]b. Chest radiograph was performed to look for distant metastases. Computed tomography-guided biopsy of the lesion was undertaken, histopathology of which revealed hypercellularity with irregular spindle-shaped tumor cells with high nucleus-to-cytoplasm ratio, nuclear pleomorphism, and prominent nucleoli in the background of the osteoid matrix [Figure 2]. A final diagnosis of moderately differentiated, high-grade osteosarcoma was made based on findings of histopathology. Ten weeks of neoadjuvant chemotherapy was started initially to reduce the size of the tumor followed by limb-sparing radical resection of the distal femur. Surgery was tolerated well without complications. Follow-up contrast-enhanced MRI at 6 months revealed no features of recurrence.
|Figure 1: (a) Coronal T1-weighted image demonstrating a distal femoral metadiaphyseal exophytic lesion with a wide zone of transition and encasing the posterolateral circumference of the distal third of the femur. (b) Sagittal T2-weighted image demonstrating internal breakdown foci of fluid signal intensity. The lesion shows evidence of extraosseous soft-tissue component measuring 16 cm × 13 cm × 12 cm in orthogonal dimensions|
Click here to view
|Figure 2: Histopathology image demonstrating hypercellularity and irregular spindle-shaped tumor cells with high nucleus-to-cytoplasm ratio, nuclear pleomorphism, and prominent nucleoli in the background of osteoid matrix consistent with features of osteosarcoma (H and E, ×200)|
Click here to view
| Discussion|| |
Radiation-induced sarcoma is an exceedingly rare complication of radiotherapy regimens for the treatment of primary malignant bone tumors. Radiation-induced sarcoma was first described by Cahan et al. as a sarcoma diagnosed after a latency period of at least 5 years and confirmed on histopathology arising from the previous site of irradiation. The above definition was revised by Arlen et al. as malignant tumors arising from the previous site of irradiation with absent osteoblastic activity and also shortened the latency period to 3–4 years. Cases have been reported with a wide range of latency period between 6 months and 64 years following initial radiotherapy.
Factors affecting prognosis in the management of osteosarcoma include size and location of the tumor, Enneking staging and the tumor subtype on MRI, response to neoadjuvant chemotherapy, and clinical outcomes following limb-sparing surgery. Limb salvage procedures with a better survival rate are currently regarded as the standard treatment for malignant tumors affecting the extremities. Surgical intervention with negative margins is the most important factor affecting long-term survival in patients with radiation-induced sarcoma. Prosthesis reconstruction is necessary following segmental tumor resection for maintaining good limb function.
| Conclusion|| |
Radiation-induced sarcoma is a rare entity associated with a grave prognosis and increased morbidity. Timely management of the lesion using a multidisciplinary approach improves the prognosis of radiation-induced sarcoma. MRI assessment of the degree of extension of tumor with physeal and neurovascular bundle involvement, and articular extension is helpful in tumor restaging after neoadjuvant chemotherapy and for surgical planning.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Ottaviani G, Jaffe N. The epidemiology of osteosarcoma. Cancer Treat Res 2009;152:3-13.
Damron TA, Ward WG, Stewart A. Osteosarcoma, chondrosarcoma, and Ewing's sarcoma: National cancer data base report. Clin Orthop Relat Res 2007;459:40-7.
Kim MS, Lee SY, Cho WH, Song WS, Koh JS, Lee JA, et al.
Effect of increases in tumor volume after neoadjuvant chemotherapy on the outcome of stage II osteosarcoma regardless of histological response. J Orthop Sci 2009;14:292-7.
Kristenson S, Mann R, Leafblad K, Cook B, Chang J. Radiation-induced osteosarcoma following treatment of Ewing's sarcoma. Radiol Case Rep 2020;15:89-94.
Cahan WG, Woodard HQ, Higinbotham NL, Stewart FW, Coley BL. Sarcoma arising in irradiated bone; report of 11 cases. Cancer 1948;1:3-29.
Arlen M, Higinbotham NL, Huvos AG, Marcove RC, Miller T, Shah IC. Radiation-induced sarcoma of bone. Cancer 1971;28:1087-99.
Kalra S, Grimer RJ, Spooner D, Carter SR, Tillman RM, Abudu A. Radiation-induced sarcomas of bone: Factors that affect outcome. J Bone Joint Surg Br 2007;89:808-13.
Harrison DJ, Geller DS, Gill JD, Lewis VO, Gorlick R. Current and future therapeutic approaches for osteosarcoma. Expert Rev Anticancer Ther 2018;18:39-50.
Department of Radiology, St. John's Hospital, Kattappana - 685 515, Kerala
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2]