eMedicine Specialties > Pediatrics: General Medicine > Oncology

Osteosarcoma

Author: Timothy P Cripe, MD, PhD, Associate Professor of Pediatric Hematology/Oncology, University of Cincinnati; Director, Translational Research Trials Office, Department of Pediatrics, Cincinnati Children's Hospital Medical Center
Contributor Information and Disclosures

Updated: Aug 7, 2008

Introduction

Background

Osteosarcoma is the third most common cancer in adolescence, occurring less frequently than only lymphomas and brain tumors. It is thought to arise from a primitive mesenchymal bone-forming cell and is characterized by production of osteoid. The mainstay of therapy is removal of the lesion. Limb-sparing procedures can often be used to preserve function. Chemotherapy is also required to treat micrometastatic disease, which is present but not detectable in most patients at diagnosis.

Pathophysiology

Osteosarcoma is a bone tumor that can occur in any bone. It most commonly occurs in the long bones of the extremities near metaphyseal growth plates. The most common sites include the femur (42%), with 75% of tumors in the distal femur; tibia (19%), with 80% of tumors in the proximal tibia; and humerus (10%), with 90% of tumors in the proximal humerus.1 Other locations of note include the skull or jaw (8%) and pelvis (8%).

Any sarcoma that arises from bone is technically called an osteogenic sarcoma. Therefore, this term includes fibrosarcoma, chondrosarcoma, and osteosarcoma, all named for their morphologic characteristics. The focus of this article is osteosarcoma. Numerous variants of osteosarcoma are known and include conventional types (ie, osteoblastic, chondroblastic, fibroblastic types) and telangiectatic, multifocal, parosteal, and periosteal types.

Frequency

United States

The incidence is 400 cases per year (4.8 cases per million persons <20 y).

Mortality/Morbidity

The overall 5-year survival rate for patients whose condition was diagnosed between 1974 and 1994 was 63% (59% for male patients, 70% for female patients).

Race

The incidence is slightly higher in African Americans than in Caucasians (data from the National Cancer Institute [NCI] Surveillance, Epidemiology, and End Results [SEER] Study Pediatric Monograph, 1975-1995).1

  • In African Americans, the annual incidence is 5.2 cases per million population younger than 20 years.
  • In Caucasians, the annual incidence is 4.6 cases per million population younger than 20 years.

Sex

The incidence is slightly higher in male individuals than in female individuals.

  • In male individuals, the incidence is 5.2 cases per million population per year.
  • In female individuals, the incidence is 4.5 cases per million population per year.

Age

Osteosarcoma is rare in children younger than 5 years, in whom the annual incidence is approximately 0.5 cases per million population. The incidence increases steadily with age; a relatively dramatic increase in adolescence corresponds with the growth spurt.

  • In children aged 5-9 years, the annual incidence is 2.6 cases for African Americans and 2.1 cases for Caucasians per million population.
  • In children aged 10-14 years, the annual incidence is 8.3 cases for African Americans and 7 cases for Caucasians per million population.
  • In adolescents aged 15-19 years, the annual incidence is 8.9 cases for African Americans and 8.2 cases for Caucasians per million population.
  • Patients whose disease is diagnose during their growth spurt are taller than average, although patients identified in adulthood have average height.

Clinical

History

Symptoms may be present for weeks, months, or occasionally longer before osteosarcoma is diagnosed. The most common presenting symptom of osteosarcoma is pain, particularly with activity. Patients may complain of a sprain, arthritis, or so-called growing pains. The patient often has a history of trauma, although pathologic fractures are not particularly common. The exception is the telangiectatic type of osteosarcoma, which is commonly associated with pathologic fractures. If pain affects a lower extremity, it may result in a limp.

The patient may have a history of swelling, depending on the size of the lesion and its location. Systemic symptoms, such as fever and night sweats, are rare. Tumoral spread to the lungs rarely results in respiratory symptoms, and such symptoms usually indicate extensive lung involvement. Metastases to other sites are extremely rare; therefore, other symptoms are unusual. Only 15-20% of patients present with metastases, which primarily affect the lungs but can also affect other bones. Manifestations at several bone sites at diagnosis may indicate multifocal sclerosing osteosarcoma.

Osteosarcoma most commonly involves the distal femur and proximal tibia, followed by the proximal humerus and mid and proximal femur. As many as 20% of patients present with tumors of the flat bones of the body including the skull and pelvis. Tumors of the jaw are relatively uncommon.

Physical

Physical findings are usually limited to those of the primary tumor site.

  • Mass: A palpable mass may be present. The mass may be tender and warm, although these signs are indistinguishable from those of osteomyelitis. Increased skin vascularity over the mass may be discernible. Pulsations or a bruit may be detectable.
  • Decreased range of motion: Joint involvement should be obvious on physical examination.
  • Lymphadenopathy: Involvement of local or regional lymph nodes is unusual.
  • Respiratory findings: Auscultation is usually uninformative unless extensive pulmonary disease is present.

Causes

The exact cause of osteosarcoma is unknown. However, numerous risk factors are known.

  • Rapid bone growth appears to predispose patients to osteosarcoma, as suggested by the increased incidence during the adolescent growth spurt,2 the high incidence among large dogs (eg, Great Danes, St Bernards, German shepherds), and the typical location of osteosarcomas near the metaphyseal growth plate of long bones.
  • Exposure to radiation is the only known environmental risk factor.
  • A genetic predisposition may be present.
    • Retinoblastoma, especially the combination of a constitutional mutation of the RB gene (germline retinoblastoma) with radiation therapy, is associated with a particularly high risk of osteosarcoma development. Of note, the genetic locus retinoblastoma at band 13q14 has also been implicated in the pathogenesis of sporadic osteosarcoma.
    • Bone dysplasias, including Paget disease, fibrous dysplasia, enchondromatosis, and hereditary multiple exostoses, increase the risk for osteosarcoma.
    • Li-Fraumeni syndrome (germline TP53 mutation) is a predisposing factor for osteosarcoma.
    • Rothmund-Thomson syndrome (ie, autosomal recessive association of congenital bone defects, hair and skin dysplasias, hypogonadism, cataracts) is associated with an increased risk of osteosarcoma.

More on Osteosarcoma

Overview: Osteosarcoma
Differential Diagnoses & Workup: Osteosarcoma
Treatment & Medication: Osteosarcoma
Follow-up: Osteosarcoma
Multimedia: Osteosarcoma
References
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References

  1. Ries LAG, Smith MA, Gurney JG, et al. Cancer incidence and survival among children and adolescents: United States SEER Program 1975-1995. NIH publication No. 99-4649. Bethesda, Md. National Institutes of Health;. 1999;[Full Text].

  2. Longhi A, Pasini A, Cicognani A, et al. Height as a risk factor for osteosarcoma. J Pediatr Hematol Oncol. Jun 2005;27(6):314-8. [Medline].

  3. Bacci G, Longhi A, Ferrari S, et al. Prognostic significance of serum lactate dehydrogenase in osteosarcoma of the extremity: experience at Rizzoli on 1421 patients treated over the last 30 years. Tumori. Sep-Oct 2004;90(5):478-84. [Medline].

  4. Mialou V, Philip T, Kalifa C, et al. Metastatic osteosarcoma at diagnosis: prognostic factors and long-term outcome--the French pediatric experience. Cancer. Sep 1 2005;104(5):1100-9. [Medline].

  5. Ilhan IE, Vural G, Berberoglu S, Kapucuoglu N, Cila A, Eke S. Quantitative thallium-201 scintigraphy in childhood osteosarcoma: Comparison with technetuim-99m MDP and magnetic resonance imaging in the evaluation of chemotherapeutic response. Pediatr Hematol Oncol. Mar 2005;22(2):153-62. [Medline].

  6. McCarville MB, Christie R, Daw NC, Spunt SL, Kaste SC. PET/CT in the evaluation of childhood sarcomas. AJR Am J Roentgenol. Apr 2005;184(4):1293-304. [Medline].

  7. Volker T, Denecke T, Steffen I, et al. Positron emission tomorgraphy for staging of pediatric sarcoma patients: results of a prospective multicenter trial. J Clin Oncol. Dec 1 2007;25(34):5435-41.

  8. Pignatti G, Bacci G, Picci P, et al. Telangiectatic osteogenic sarcoma of the extremities. Results in 17 patients treated with neoadjuvant chemotherapy. Clin Orthop Relat Res. Sep 1991;99-106. [Medline].

  9. Saab R, Rao BN, Rodriguez-Galindo C, Billups CA, Fortenberry TN, Daw NC. Osteosarcoma of the pelvis in children and young adults: the St. Jude Children's Research Hospital experience. Cancer. Apr 1 2005;103(7):1468-74. [Medline].

  10. Briccoli A, Rocca M, Salone M, et al. Resection of recurrent pulmonary metastases in patients with osteosarcoma. Cancer. Oct 15 2005;104(8):1721-5. [Medline].

  11. Man TK, Chintagumpala M, Visvanathan J, et al. Expression profiles of osteosarcoma that can predict response to chemotherapy. Cancer Res. Sep 15 2005;65(18):8142-50. [Medline].

  12. Mikulic D, Ilic I, Cepulic M, et al. Tumor angiogenesis and outcome in osteosarcoma. Pediatr Hematol Oncol. Oct-Nov 2004;21(7):611-9. [Medline].

  13. Kreuter M, Bieker R, Bielack SS, et al. Prognostic relevance of increased angiogenesis in osteosarcoma. Clin Cancer Res. Dec 15 2004;10(24):8531-7. [Medline].

  14. Chan HS, Grogan TM, Haddad G, DeBoer G, Ling V. P-glycoprotein expression: critical determinant in the response to osteosarcoma chemotherapy. J Natl Cancer Inst. Nov 19 1997;89(22):1706-15. [Medline].

  15. Link MP, Goorin AM, Miser AW, et al. The effect of adjuvant chemotherapy on relapse-free survival in patients with osteosarcoma of the extremity. N Engl J Med. Jun 19 1986;314(25):1600-6. [Medline].

  16. Link MP, Goorin AM, Horowitz M, et al. Adjuvant chemotherapy of high-grade osteosarcoma of the extremity. Updated results of the Multi-Institutional Osteosarcoma Study. Clin Orthop Relat Res. Sep 1991;8-14. [Medline].

  17. DeLaney TF, Park L, Goldberg SI, et al. Radiotherapy for local control of osteosarcoma. Int J Radiat Oncol Biol Phys. Feb 1 2005;61(2):492-8. [Medline].

  18. Anderson PM, Wiseman GA, Dispenzieri A, et al. High-dose samarium-153 ethylene diamine tetramethylene phosphonate: low toxicity of skeletal irradiation in patients with osteosarcoma and bone metastases. J Clin Oncol. Jan 1 2002;20(1):189-96. [Medline].

  19. Lewis IJ, Nooij MA, Whelan J, et al. Improvement in histologic response but not survival in osteosarcoma patients treated with intensified chemotherapy: a randomized phase III trial of the European Osteosarcoma Intergroup. J Natl Cancer Inst. Jan 17 2007;99(2):112-28. [Medline].

  20. Nagarajan R, Clohisy D, Weigel B. New paradigms for therapy for osteosarcoma. Curr Oncol Rep. Nov 2005;7(6):410-4. [Medline].

  21. Paiva MG, Petrilli AS, Moises VA, Macedo CR, Tanaka C, Campos O. Cardioprotective effect of dexrazoxane during treatment with doxorubicin: a study using low-dose dobutamine stress echocardiography. Pediatr Blood Cancer. Dec 2005;45(7):902-8. [Medline].

  22. Meyers PA, Schwartz CL, Krailo MD, et al. Osteosarcoma: the addition of muramyl tripeptide to chemotherapy improves overall survival--a report from the Children's Oncology Group. J Clin Oncol. Feb 1 2008;26(4):633-8. [Medline].

  23. Gralla RJ, Osoba D, Kris MG, et al. Recommendations for the use of antiemetics: evidence-based, clinical practice guidelines. American Society of Clinical Oncology. J Clin Oncol. Sep 1999;17(9):2971-94. [Medline].

  24. Stohr W, Langer T, Kremers A, et al. Cisplatin-induced ototoxicity in osteosarcoma patients: a report from the late effects surveillance system. Cancer Invest. 2005;23(3):201-7. [Medline].

  25. Nagarajan R, Clohisy DR, Neglia JP, et al. Function and quality-of-life of survivors of pelvic and lower extremity osteosarcoma and Ewing's sarcoma: the Childhood Cancer Survivor Study. Br J Cancer. Nov 29 2004;91(11):1858-65. [Medline].

  26. Grimer RJ, Bielack S, Flege S, et al. Periosteal osteosarcoma--a European review of outcome. Eur J Cancer. Dec 2005;41(18):2806-11. [Medline].

  27. Bacci G, Briccoli A, Longhi A, Ferrari S, Mercuri M, Faggioli F, et al. Treatment and outcome of recurrent osteosarcoma: experience at Rizzoli in 235 patients initially treated with neoadjuvant chemotherapy. Acta Oncol. 2005;44(7):748-55. [Medline].

  28. Bacci G, Mercuri M, Longhi A, et al. Grade of chemotherapy-induced necrosis as a predictor of local and systemic control in 881 patients with non-metastatic osteosarcoma of the extremities treated with neoadjuvant chemotherapy in a single institution. Eur J Cancer. Sep 2005;41(14):2079-85. [Medline].

  29. Deutsch M, Tersak JM. Radiotherapy for symptomatic metastases to bone in children. Am J Clin Oncol. Apr 2004;27(2):128-31. [Medline].

  30. Laverdiere C, Hoang BH, Yang R, et al. Messenger RNA expression levels of CXCR4 correlate with metastatic behavior and outcome in patients with osteosarcoma. Clin Cancer Res. Apr 1 2005;11(7):2561-7. [Medline].

  31. Minegishi Y, Saito M, Morio T, et al. Human tyrosine kinase 2 deficiency reveals its requisite roles in multiple cytokine signals involved in innate and acquired immunity. Immunity. Nov 2006;25(5):745-55. [Medline].

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Further Reading

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Keywords

osteosarcoma, osteogenic sarcoma, osteoblastic osteosarcoma, chondroblastic osteosarcoma, fibroblastic osteosarcoma, telangiectatic osteosarcoma, multifocal osteosarcoma, parosteal osteosarcoma, periosteal osteosarcoma, bone cancer, bone tumor, fibrosarcoma, chondrosarcoma, limp, arthritis, lymphadenopathy, retinoblastoma, Paget disease, fibrous dysplasia, enchondromatosis, hereditary multiple exostoses, Li-Fraumeni syndrome, Rothmund-Thomson syndrome, hearing loss

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Contributor Information and Disclosures

Author

Timothy P Cripe, MD, PhD, Associate Professor of Pediatric Hematology/Oncology, University of Cincinnati; Director, Translational Research Trials Office, Department of Pediatrics, Cincinnati Children's Hospital Medical Center
Timothy P Cripe, MD, PhD is a member of the following medical societies: American Association for the Advancement of Science, American Society of Hematology, and American Society of Pediatric Hematology/Oncology
Disclosure: Nothing to disclose.

Medical Editor

Samuel Gross, MD, Professor Emeritus, Department of Pediatrics, University of Florida, Clinical Professor, Department of Pediatrics, UNC, Adjunct Professor, Department of Pediatrics, Duke University
Samuel Gross, MD is a member of the following medical societies: American Association for Cancer Research, American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology, American Society of Hematology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

Managing Editor

Steven K Bergstrom, MD, Assistant to the Chairman, Department of Pediatrics, Division of Hematology-Oncology, Kaiser Permanente Medical Center of Oakland
Steven K Bergstrom, MD is a member of the following medical societies: Alpha Omega Alpha, American Society of Clinical Oncology, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Children's Oncology Group, and International Society for Experimental Hematology
Disclosure: Nothing to disclose.

CME Editor

Helen SL Chan, MBBS, FRCP(C), FAAP, Senior Scientist, Research Institute; Professor, Division of Hematology/Oncology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Canada
Helen SL Chan, MBBS, FRCP(C), FAAP is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Society of Hematology, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

Chief Editor

Max J Coppes, MD, PhD, MBA, Executive Director, Center for Cancer and Blood Disorders, Children's National Medical Center, Washington, DC; Professor of Medicine, Oncology, and Pediatrics, Georgetown University
Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American Association for Cancer Research, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

 
 
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