Osteosarcoma of the Distal Femur

24-year-old male with leg pain. Diagnosis? • Xray of the Week

Figure 1. Preoperative radiographs of the left distal femur. (A) Frontal radiograph demonstrates an aggressive mineralized lesion centered in the distal left femur with a large mineralized extraosseous soft-tissue component (yellow arrow). (B) Lateral radiograph further demonstrates the densely mineralized lesion and associated soft- tissue mass arising from the distal femur (yellow arrow).

Figure 2. Postoperative imaging of the left femur. (A) Frontal postoperative CT Scout image demonstrates postoperative changes with metallic endoprosthetic reconstruction of the distal femur extending across the knee (yellow arrow). (B) Coronal CT image demonstrates the postoperative femoral reconstruction and prosthetic components (yellow arrow).

Figure 3. Pulmonary metastatic disease in osteosarcoma. Axial CT image of the chest demonstrates a peripheral pulmonary nodules (red arrows), consistent with the pulmonary metastatic disease documented in the primary case.

Figure 4. Recurrent osteosarcoma with calcified pulmonary metastases in a separate illustrative patient. (A) Coronal CT image demonstrates densely calcified pulmonary metastatic nodules (yellow arrows). (B) Postoperative radiograph demonstrates mineralized recurrent soft-tissue disease adjacent to the distal femoral endoprosthesis (red arrow). (C) Magnified radiograph further demonstrates the mineralized recurrent tumor adjacent to the prosthesis (black arrow).

Epidemiology

Osteosarcoma is the most common primary malignant bone tumor in children and adolescents, with an incidence of approximately 3–5 cases per million persons per year in younger populations [1]. Incidence peaks during adolescence and is slightly higher in males. Osteosarcoma most commonly arises in the metaphyses of long bones, particularly around the knee [2]. The distal femur is the most frequent site, followed by the proximal tibia and proximal humerus.

Clinical Findings

Pain is the most common presenting symptom of osteosarcoma and may initially be intermittent before becoming persistent. Local swelling, a palpable mass, restricted joint movement, and limp may occur as the tumor enlarges [3]. Pathological fracture is an uncommon presentation, while systemic symptoms are generally unusual. In the primary case, the 24-year-old male presented with left leg pain.

Pathology

Osteosarcoma is a malignant mesenchymal neoplasm characterized by production of osteoid or immature bone directly by malignant tumor cells. Conventional osteosarcoma is typically a high-grade intramedullary tumor composed of malignant pleomorphic cells with variable production of osteoid and other extracellular matrix. Tumor osteoid is often irregular and disorganized and may undergo mineralization. Histological response following neoadjuvant chemotherapy, particularly the degree of tumor necrosis, has important prognostic significance.

Classification

Osteosarcoma comprises seven recognized primary subtypes: conventional, telangiectatic, low-grade central, small cell, parosteal, periosteal, and high-grade surface osteosarcoma [4]. Conventional osteosarcoma is the most common subtype, accounting for approximately 75–80% of cases, and may demonstrate osteoblastic, chondroblastic, or fibroblastic differentiation according to the predominant matrix. Surface osteosarcomas include parosteal, periosteal, and high-grade surface variants, which differ in histologic grade, imaging appearance, treatment, and prognosis.

Radiographic Features

Plain radiography is usually the initial imaging modality. Conventional osteosarcoma typically appears as an aggressive metaphyseal lesion with mixed lytic and sclerotic components, cortical destruction, an ill-defined zone of transition, mineralized osteoid matrix, and an associated soft-tissue mass [4,5]. Aggressive periosteal reactions, including sunburst-type spiculation and a Codman triangle, may occur.

CT better depicts cortical destruction and mineralized tumor matrix and is important for assessment of pulmonary metastatic disease. MRI is the preferred modality for local staging, defining intramedullary and soft-tissue extent, relationship to neurovascular structures and joints, and the presence of skip lesions.

Pulmonary metastases usually appear as solid pulmonary nodules on chest CT and may be multiple and bilateral. Calcification or ossification can occur and represents a recognized atypical appearance of osteosarcoma lung metastases [6].

Postoperative imaging provides a baseline for assessment of the reconstruction and subsequent surveillance. Comparison with prior examinations is important when evaluating for suspected local recurrence, with MRI particularly useful for assessing recurrent soft-tissue disease. Treatment and Prognosis

Treatment of high-grade osteosarcoma generally combines systemic chemotherapy with complete surgical resection of the primary tumor. Limb-salvage surgery is feasible in many patients when adequate oncologic margins and a functional extremity can be achieved; amputation remains necessary in selected cases [7-9]. Histologic response to chemotherapy and the presence of metastatic disease are important prognostic factors.

Contemporary series report 5-year survival of approximately 70–75% for patients with localized extremity osteosarcoma, whereas outcomes are substantially poorer in patients with metastatic or recurrent disease. The lungs are the predominant site of distant metastasis. In patients with resectable pulmonary metastatic disease, complete surgical removal of metastases is an important component of management and is associated with better outcomes in selected patients [10].

Conclusion

Osteosarcoma is an aggressive primary bone malignancy that predominantly affects adolescents and young adults. Imaging plays a central role in diagnosis, local staging, treatment planning, and surveillance. Recognition of characteristic aggressive osseous features and careful assessment for pulmonary metastatic and recurrent disease are essential because disease stage and treatment response strongly influence prognosis.

References

1. Ottaviani G, Jaffe N. The epidemiology of osteosarcoma. Cancer Treat Res. 2009;152:313. https://doi.org/10.1007/978-1-4419-0284-9_1

2. Durfee RA, Mohammed M, Luu HH. Review of osteosarcoma and current management. Rheumatol Ther. 2016;3(2):221-243. https://doi.org/10.1007/s40744-016-0046-y

3. Fox MG, Trotta BM. Osteosarcoma: review of the various types with emphasis on recent advancements in imaging. Semin Musculoskelet Radiol. 2013;17(2):123-136. https://doi.org/10.1055/s-0033-1342969

4. Yarmish G, Klein MJ, Landa J, Lefkowitz RA, Hwang S. Imaging characteristics of primary osteosarcoma: nonconventional subtypes. Radiographics. 2010;30(6):1653- 1672. https://doi.org/10.1148/rg.306105524

5. Crombé A, et al. Imaging of osteosarcoma: presenting findings, metastatic patterns, and features related to prognosis. J Clin Med. 2024;13(19):5710. https://doi.org/10.3390/jcm13195710

6. Silva JAM, Marchiori E, Amorim VB, Barreto MM, et al. CT features of osteosarcoma lung metastasis: a retrospective study of 127 patients. J Bras Pneumol. 2023;49(2):e20220433. https://doi.org/10.36416/1806-3756/e20220433

7. Bielack SS, Kempf-Bielack B, Delling G, et al. Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols. J Clin Oncol. 2002;20(3):776-790. https://doi.org/10.1200/JCO.2002.20.3.776

8. Luetke A, Meyers PA, Lewis I, Juergens H. Osteosarcoma treatment—where do we stand? A state of the art review. Cancer Treat Rev. 2014;40(4):523-532. https://doi.org/10.1016/j.ctrv.2013.11.006

9. Briccoli A, Rocca M, Salone M, Guzzardella GA, Balladelli A, Bacci G. High grade osteosarcoma of the extremities metastatic to the lung: long-term results in 323 patients treated combining surgery and chemotherapy, 1985-2005. Surg Oncol. 2010;19(4):193-199. https://doi.org/10.1016/j.suronc.2009.05.002

10. Garner HW, Kransdorf MJ, Peterson JJ. Posttherapy imaging of musculoskeletal neoplasms. Radiol Clin North Am. 2011;49(6):1307-1323. https://doi.org/10.1016/j.rcl.2011.07.011

Umaiza Ihsan, MD, is a medical graduate of King Edward Medical University,

Pakistan. She completed her internship at Mayo Hospital, Lahore, including a three-

month rotation in Radiology, which further strengthened her interest in diagnostic

imaging. She has gained additional clinical exposure in Radiology through observerships at Mon Health Morgantown and the University of Maryland, Baltimore. She has a strong interest in Radiology, particularly diagnostic imaging and its role in clinical decision-making, and is actively interested in clinical research, with experience in systematic reviews and medical research.

Kevin M. Rice, MD is the president of Global Radiology CME and is a radiologist with Cape Radiology Group. He has held several leadership positions including Board Member and Chief of Staff at Valley Presbyterian Hospital in Los Angeles, California. Dr. Rice has made several media appearances as part of his ongoing commitment to public education. Dr. Rice's passion for state of the art radiology and teaching includes acting as a guest lecturer at UCLA. In 2015, Dr. Rice and Natalie Rice founded Global Radiology CME to provide innovative radiology education at exciting international destinations, with the world's foremost authorities in their field. In 2016, Dr. Rice was nominated and became a semifinalist for a "Minnie" Award for the Most Effective Radiology Educator. He was once again a semifinalist for a "Minnie" for 2021's Most Effective Radiology Educator by AuntMinnie.com. He has continued to teach by mentoring medical students interested in radiology. Everyone who he has mentored has been accepted into top programs across the country including Harvard, UC San Diego, Northwestern, Vanderbilt, and Thomas Jefferson.

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