Author(s): Denesh Ratnasingam, MD, Kimberly C Hartman, MD, MHPE, Rachel Perera, MS
Originally published: September 15, 2015 Last updated: March 26, 2026
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Disease/Disorder

Definition

Primary bone tumors are defined as tumors originating in a bone. They can be benign or malignant and are classified according to the 2020 World Health Organization (WHO) Classification of Tumors of Bone and Soft Tissue.1 They are classified based on histological features (i.e., chondrogenic, osteogenic, fibrogenic, etc.). Most bone tumors are benign. Benign tumors are subdivided into nonaggressive (i.e., nonossifying fibroma) or aggressive (i.e., aneurysmal bone cyst). The most common malignant bone tumors in children are osteosarcoma and Ewing sarcoma.  Undifferentiated pleomorphic sarcoma of bone (formerly termed malignant fibrous histiocytoma) is now recognized as a distinct high-grade sarcoma in updated classifications.1

Etiology

The etiology of most primary malignant bone tumors remains incompletely understood. Advances in molecular genetics have identified several tumor-associated mutations and chromosomal translocations that contribute to pathogenesis. Some inherited syndromes, such as Li-Fraumeni syndrome, hereditary multiple exostoses, Ollier’s disease, Maffucci syndrome, familial retinoblastoma syndrome, Werner syndrome or Rothmund-Thomson syndrome, increase the risk of bone malignancy. Benign bone lesions may rarely transform into malignant lesions (osteochondroma into chondrosarcoma; bone infarct dedifferentiation into osteogenic sarcoma, fibrosarcoma or malignant fibrous histiocytoma). Osteosarcoma and undifferentiated pleomorphic sarcoma of bone have been associated with radiation exposure, chronic osteomyelitis, and Paget disease. Trauma does not cause malignant bone tumors but often prompts evaluation due to persistent pain.

Epidemiology including risk factors and primary prevention

Primary malignant bone tumors are rare. Recent Surveillance, Epidemiology, and End Results (SEER) data estimate an annual incidence of approximately 8–11 cases per million children and adolescents under age 20 in the United States.2,3 Of these, 56% are osteosarcomas and 34% are Ewing sarcomas.3 Osteosarcomas are slightly more common in African American than Caucasian populations. Ewing sarcoma affects predominantly Caucasian populations, and 80% of patients are under the age of 20 at the time of diagnosis. Bone tumor incidence peaks at the age of 15, which coincides with timing of the adolescent growth spurt.2

Patho-anatomy/physiology

In osteosarcoma, the malignant cell produces osteoid tissue. Osteosarcoma preferentially arises in the metaphyseal areas of the most rapidly growing long bones, which are the distal femur, proximal tibia, and proximal humerus. Over 50% of osteosarcomas occur around the knee. At diagnosis, approximately 15–20% of patients have radiographically detectable metastases6; however, micrometastatic disease is presumed present in majority of patients. Metastatic lesions are most common in lung and bone tissue.

Ewing sarcoma is a high-grade small round cell sarcoma characterized by EWSR1 gene rearrangements, most commonly the t(11;22)(q24;q12) translocation resulting in EWSR1-FLI1 fusion.7  Ewing sarcoma is no longer considered of neural crest origin; current evidence suggests a mesenchymal stem cell lineage.7 Ewing sarcoma arises in the lower extremity in 46% of cases, followed by the pelvic bone (20%). Roughly 20% have evidence of macroscopic metastatic disease at diagnosis with a larger portion presumed to have microscopic metastasis.7

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time):

Natural history of untreated osteosarcoma and Ewing sarcoma is disease progression ultimately resulting in death. As mentioned previously, the most common site of metastatic disease is the lungs and bone elsewhere, including the spine. As for non-metastatic disease, prognosis has improved significantly over the past few decades.

Patients with newly diagnosed malignant bone tumors typically undergo extensive work up and imaging. Treatment regimens typically consist of chemotherapy (systemic control) and surgery (local control – tumor resection, limb sparing procedure or amputation) and/or radiation therapy.  For localized osteosarcoma, 5-year overall survival is approximately 65–75%.6 Survival decreases below 30% for patients with metastatic disease at diagnosis.6 Histologic response to neoadjuvant chemotherapy (≥ 90–95% tumor necrosis) is a key positive prognostic factor in osteosarcoma.6 For localized Ewing sarcoma, 5-year survival now exceeds 70–80%, but falls below 40% in metastatic disease.7 For Ewing sarcoma, patients commonly undergo thoracotomies and/or whole lung irradiation (WLI) if there is a concern for or evidence of lung metastases.

Specific secondary or associated conditions and complications

Multi-regimen chemotherapy used for systemic control of disease may have negative physical, psychosocial, and socioeconomic sequelae. Physical complications include weakness, pain, neuropathy, impaired balance, and cardiac dysfunction. Surgery used for local control may result in impaired wound healing, infection, or pain. Depending on the type of limb-sparing surgery performed, patients might have weight bearing and activity restrictions. Radiation therapy may result in impaired skin integrity and fatigue in the treatment of primary tumors, while it can also result in pneumonitis or fibrosis in the treatment of lung metastases.8 Long-term survivors require risk-based surveillance according to Children’s Oncology Group (COG) Long-Term Follow-Up Guidelines.9

Essentials of Assessment

History

Most patients with malignant bone tumors typically present with several months of localized pain. About half of them will also report swelling and limited range of motion. A minority (10-15%) present with pathological fracture. History of trauma is not uncommon. While systemic symptoms are uncommon in osteosarcoma (unless disease is advanced), fever is present in 20% of patients with Ewing sarcoma at presentation. A comprehensive pain history should be obtained, including red flags of worsening/persistent pain, night and morning pain, pain with activity/weight bearing, and pain lasting longer or more severe than expected in those with a preceding trauma. Osteoid osteoma presents with progressively worsening night pain and is relieved by aspirin or nonsteroidal anti-inflammatory drugs.

Physical examination

Comprehensive physical examination should be performed. Vital signs should be obtained. In addition to cardiac, pulmonary, and abdominal exam, assessment for lymphadenopathy should be included along with a complete musculoskeletal (including evaluation of scoliosis and leg length discrepancy), vascular, neurological, and functional evaluation. Pain on palpation, visible deformity, restrictions, or asymmetry in range of motion, focal weakness, abnormal gait, or focal neurological findings warrant further investigation. Pain with weight bearing raises a concern for a pending pathological fracture and requires immediate work up.

Clinical functional assessment: mobility, self-care cognition/behavior/affective state

Prior functional status should be ascertained. Inquire about patient’s functional goals and environmental barriers. Impairments in mobility and self-care as well as need for assistive devices and bracing should be assessed. Home environment and availability of caregiver support should be taken into consideration. Children with bone tumors may be at risk for depression, anxiety, and kinesiophobia.13 Emotional state, adjustment to diagnosis and identity, and coping of the patient and the family should be assessed and appropriate referrals initiated.

Laboratory studies

Labs in a patient with suspected bone cancer should include inflammatory markers (ESR, CRP), blood count, chemistry including alkaline phosphatase and LDH. Patients undergoing treatment typically require frequent lab monitoring. Physiatrists should always review the most recent laboratory studies and imaging to prescribe appropriate rehabilitation interventions and guide/modify exercise program based on results (i.e., thrombocytopenia).

Imaging

Plain radiography is the initial modality and remains the first-line evaluation for suspected bone tumors. Benign tumors are generally discrete with sclerotic margins and usually do not require additional imaging. Malignant tumors are ill-defined and may have a periosteal reaction or soft-tissue calcification and may require additional imaging. On plain films, osteosarcoma has a classic “sunburst” appearance whereas Ewing is described as an “onion skin” or “hair-on-end” lesion. Computed tomography (CT) or magnetic resonance imaging (MRI) is the preferred modality for local staging and surgical planning. Positron emission tomography (PET)/CT and whole-body MRI are increasingly utilized for staging and assessing treatment response.

Supplemental assessment tools

Biopsy is often required to assess histology and biologic or immunologic markers and cytology. Urodynamic studies might be considered in patients with spine or pelvic tumors affecting the spinal cord or nerves. When etiology of pain or weakness is unclear, electrodiagnostic study might be of benefit.

Early prediction of outcomes

In osteosarcoma, more than 95% necrosis after chemotherapy is an important positive prognostic factor. Poor prognostic indicators include metastatic disease (for example, large pulmonary nodules in osteosarcoma), poor response to systemic chemotherapy, and location of disease in the spine or pelvis given its poor resectability. Other poor predictors include increased tumor size, increased serum alkaline phosphatase, and secondary osteosarcoma.6 Limb-sparing surgery is now feasible in more than 80% of patients treated at specialized centers, with functional outcomes comparable to amputation in appropriately selected patients.6

Environmental

Home environment might affect rehabilitation goals and home modifications to enhance patients’ independence may be recommended. Examples include a ramp to enter the house for children who utilize a wheelchair or a stair lift as needed. Bathroom accommodations such as an elevated toilet seat and grab bars may also be needed.

Social role and social support system

Meeting with the patient and their family/caregiver/support systems is critical to identify what are traditions and routines important to keep up and how to build in a schedule that helps them with not just activities of daily living but blocking time for things they enjoy. Children may receive homebound instruction during treatment, and some enjoy interaction with their classmates by attending classes virtually. Chronic overprotection by caregivers might limit the patient’s independence and sense of control. Some children need neuropsychological and rehabilitation evaluations to assess appropriateness for an individualized education plan (IEP) or 504 plan.

Professional issues

Discussion of prognosis should be deferred to the patient’s oncologist. Informing the child about his or her condition should be done at a developmentally-appropriate level by a trained professional and with parental permission. Quality of life and symptom management are of paramount importance. Safety of rehabilitation interventions should always be considered and discussed with the patient (if appropriate) and family.

Rehabilitation Management and Treatments

Available or current treatment guidelines

Treatments vary based on multiple factors, including type, grade, stage, and location of bone tumor. For instance, localized resectable high-grade osteosarcoma is treated with neoadjuvant chemotherapy for about 10 weeks, followed by surgery to remove the tumor (sometimes with adjuvant radiation therapy), followed by additional chemotherapy up to one year. The MAP regimen (high-dose Methotrexate, Doxorubicin, and Cisplatin) remains the backbone of therapy for osteosarcoma.

The goal of surgical resection is to achieve a wide margin while sparing the distal limb if able. Over two thirds of surgical treatments for osteosarcoma and Ewing sarcoma are limb-sparing. If the functional outcome would be unacceptable, amputation or rotationplasty may be recommended. Expandable endoprostheses allow for limb preservation in skeletally immature patients, and newer devices permit non-invasive lengthening.

At different disease stages

Patients benefit from rehabilitation interventions during the continuum of treatment. Symptomatic control (i.e., pain) and quality of life should always be among top considerations. Goals of rehabilitation interventions are to maximize function, minimize disability and increase independence.

Children undergoing oncological treatment may have physical and psychosocial ailments. Side effects of treatment can include wound infections/dehiscence, hardware failure in those with limb-sparing surgery, edema/lymphedema, cardiac dysfunction, neuropathy, weakness, impaired balance, and limited activity tolerance, as well as depression and anxiety.

Patients following limb-sparing surgery or amputation require rehabilitation interventions to assist with early mobility, prevention of contractures, proximal and core muscle strengthening, residual limb shaping, provision of prosthesis and other assistive devices, gait training, pain management, and strengthening.  Rehabilitation protocols exist for commonly performed limb-sparing procedures but should be individualized to each patient.

Patients with metastatic or recurrent disease commonly undergo additional chemotherapy and surgical/radiation treatments including thoracotomies, orthopedic surgeries, and/or radiation therapy. They will continue to benefit from rehabilitation interventions focusing on managing pain, energy conservation, optimizing independence in self-care and mobility and caregiver education and training.

Coordination of care

Patients benefit from interdisciplinary rehabilitation team consisting of physicians, nursing staff, physical therapists, occupational therapists, psychologists, case managers, child-life specialists, and social workers. Rehabilitation physicians should communicate closely with the therapists regarding rehabilitation goals and precautions based on clinical developments and lab and imaging findings.

Patient & family education

Family education should include recommended home exercise program, weight-bearing or activity restrictions and appropriate use of and care for prostheses and assistive devices. Fall and safety precautions should be reviewed. Rationale for continued rehabilitation interventions should be shared with the family. The American Cancer Society website contains helpful patient and family education information related to tumor type and treatments.

Measurement of treatment outcomes, including those that are impairment-based, activity participation-based and environmentally-based

Measurement of treatment outcomes should span impairment, activity, and participation domains to capture overall function and quality of life. The Musculoskeletal Tumor Society (MSTS) score is a clinician-reported measure of pain and functional ability following surgical treatment.10 The Pediatric Toronto Extremity Salvage Scale (pTESS) and Toronto Extremity Salvage Scale (TESS) are validated patient-reported tools assessing physical function after extremity sarcoma treatment.10 The Pediatric Outcomes Data Collection Instrument (PODCI) evaluates functional health across pediatric musculoskeletal conditions.10 Broader health-related quality of life is commonly assessed with the Short Form-36 version 2 (SF-36v2).10

Translation into practice: Practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

Weight-bearing and activity/range of motion precautions should always be explicitly communicated by the orthopedic surgeon to the rehabilitation team. Patients with lower extremity osteosarcoma might need to use crutches following biopsy until definitive surgery is performed as they are at increased risk for pathological fracture. Exercise program should be adjusted based on laboratory values (i.e., hemoglobin, platelets). Neutropenic patients may be treated in protective isolation.

A substantial percentage of survivors of osteosarcoma and Ewing sarcoma have self-reported physical performance limitations (40.8% and 30.9%, respectively).11 The Children’s Oncology Group has published Long-Term Follow-up Guidelines for survivors, including risk-based, exposure-related recommendations for screening and managing late effects of cancer treatments.9 Additionally, the American College of SportsMedicine has “Moving Through Cancer” resources for caregivers, survivors, clinicians, and exercise professionals that emphasize the benefits of exercise during and after cancer treatment.14

Cutting Edge/Emerging and Unique Concepts and Practice

Molecular profiling and gene expression analysis are being studied to better predict chemotherapy response and guide risk-adapted therapy.12 Immunotherapeutic approaches, including GD2-targeted therapies and CAR-T cell strategies, are under investigation in osteosarcoma and Ewing sarcoma.12 Various types of internal prostheses used for limb sparing surgeries can be expanded without the need for additional surgeries. Intensity modulated radiation therapy (IMRT) limits the dose to normal tissues while delivering high doses to the tumor, resulting in more effective control of tumor growth. Proton therapy allows delivery of higher doses of radiation to the tumor with little damage to normal tissues. Despite advances, outcomes for metastatic and relapsed osteosarcoma have improved minimally over the past two decades, highlighting an urgent need for novel therapies.6

Gaps in the Evidence-Based Knowledge

The Children’s Oncology Group is a clinical trials group supported by a National Cancer Institute and their research has led to significant improvement in treatment outcomes of pediatric tumors. It has nearly 100 clinical trials open at any time.9 Significant gaps remain though, including limited improvement in survival for metastatic osteosarcoma, the need for reliable predictive biomarkers, and insufficient evidence guiding the optimal timing and intensity of rehabilitation during chemotherapy. Additionally, long-term functional outcomes beyond 20 years are not well characterized, particularly as survivors transition into adulthood.

References

  1. WHO Classification of Tumours Editorial Board. WHO Classification of Tumours: Soft Tissue and Bone Tumours. 5th ed. IARC; 2020.
  2. National Cancer Institute. Surveillance, Epidemiology, and End Results (SEER) Program. Cancer Stat Facts: Bone and Joint Cancer. Updated 2024.
  3. American Cancer Society. Cancer Facts & Figures 2024.
  4. National Comprehensive Cancer Network. Bone Cancer (Version 2024). http://www.nccn.org/professionals/physician_gls/pdf/bone.pdf
  5. Luetke A, Meyers PA, Lewis I, and Juergens H. Osteosarcoma treatment: where do we stand? A state of the art review. Cancer Treatment Reviews. 2014;40(4), 523-532. 
  6. Isakoff MS, Bielack SS, Meltzer P, Gorlick R. Osteosarcoma: Current Treatment and a Collaborative Pathway to Success. J Clin Oncol. 2015;33(27):3029–3035.
  7. Grunewald TGP, Cidre-Aranaz F, Surdez D, et al. Ewing sarcoma. Nat Rev Dis Primers. 2018;4:5.
  8. Krasin MJ, Constine LS, Friedman DL, Marks LB. Radiation-related treatment effects across the age spectrum: differences and similarities or what the old and young can learn from each other. Semin Radiat Oncol. 2010;20(1):21-29. doi:10.1016/j.semradonc.2009.09.001
  9. Children’s Oncology Group. Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers. Version 6.0, 2023.
  10. Nagarajan R., Clohisy DR, Neglia JP, Yasui Y, Mitby PA, Sklar C, et al. Function and quality-of-life of survivors of pelvic and lower extremity osteosarcoma and Ewings sarcoma: The Childhood Cancer Survivor Study. British Journal of Cancer. 2004;91(11): 1858-1865.
  11. Ness KK, Hudson MM, Ginsberg JP, et al. Physical performance limitations in the Childhood Cancer Survivor Study cohort. J Pediatr Oncology Nursing. 2009;27(14):2382-2389.
  12. Roberts RD, Lizardo MM, Reed DR, et al. Provocative questions in osteosarcoma basic and translational biology. Cancer. 2019;125(20):3511-3524.
  13. Yılmaz GG, Tanrıverdi M, Önal G, Yiğit AB, Şahin S, Çakır FB. Understanding kinesiophobia in pediatric bone tumors: investigating its presence and predictive factors. Eur J Pediatr. 2025;184(3):195.
  14. American College of Sports Medicine. Moving Through Cancer. 2021.  Accessed: March 10, 2026.  https://www.exerciseismedicine.org/eim-in-action/moving-through-cancer-2/

Original Version of the Topic

Katarzyna Ibanez, MD. Primary bone tumors in children and teens. 9/15/2015

Previous Revision(s) of the Topic

Kimberly Hartman, MD, Elizabeth George, MSIV. Primary bone tumors in children and teens. 12/19/2019

Kimberly Hartman, MD, Abigail Bowser. Primary Bone Tumors in Children and Teens. 4/20/2023

Author Disclosure

Denesh Ratnasingam, MD
Nothing to Disclose

Kimberly Hartman, MD, MHPE
Nothing to Disclose

Rachel Perera, MS
Nothing to Disclose