Differences Between Ewing Sarcoma and Osteosarcoma

In this article, we will review Ewing Sarcoma and Osteosarcoma, two types of bone cancer. We will explore their differences in terms of occurrence, affected areas, common symptoms, diagnostic methods, treatment options, and prognosis.
Jakub Hantabal

Jakub Hantabal

Postgraduate student of Precision Cancer Medicine at the University of Oxford, and a data scientist.

A blue image with text saying "Ewing Sarcoma vs Osteosarcoma"

Differences Between Ewing Sarcoma and Osteosarcoma

Ewing sarcoma and osteosarcoma are both types of bone cancer, but they differ in several ways. Ewing sarcoma often occurs in the pelvis, femur, and humerus, while osteosarcoma typically affects the knee and upper arm. Additionally, Ewing sarcoma is more common in children and young adults, whereas osteosarcoma can occur at any age. The treatment and prognosis for these cancers also vary.

What is Ewing Sarcoma?

Ewing sarcoma is a subtype of sarcoma, a cancer of the connective tissues, that primarily occurs in children and adolescents. Ewing sarcoma most commonly affects bone, with the prevalence of 1 to 3 in a million people every year [1]. This tumour is slightly more common in males, and rarely affects black populations [2, 1].

Signs and symptoms of Ewing Sarcoma

The main symptoms of Ewing sarcoma is pain and swelling in the area of the tumour (located most commonly in the pelvis, ribs or upper arms or thighs), as well as presence of a lump or mass. Unexplained fractures (bone breaking) are also a symptom.

Other symptoms are non-specific, including unexplained fever, weight loss, fatigue, and in some cases, functional disability and visual disorders [2, 3].

Diagnosis of Ewing Sarcoma

Ewing sarcoma is diagnosed through imaging and biopsy. Imaging such as a CT scan or magnetic resonance imaging (MRI) is used to confirm the location of the tumour and measure its mass, as well as involvement in surrounding anatomy, which is very important in planning of surgery.

Definitive diagnosis is achieved by histological examination of a biopsy, where a sample of the affected bone is obtained (either under local or general anaesthesia) and examined under the microscope, often stained with dyes that allow for visualisation of certain molecules and cells.

Common findings include clusters of small, round cells (which is abnormal in a healthy bone), which take up an eosin stain to the cytoplasm. The nuclei of Ewing sarcoma cells appear oval and vesicular (meaning they contain unpacked chromatin, which is important for rapid proliferation of cancer cells) [2].

Treatment for Ewing Sarcoma

Ewing sarcoma is a very aggressive disease, therefore, the treatment is also very aggressive, involving a combination of chemotherapy, radiotherapy and surgery. Surgery is often used to remove the primary tumour, and radiotherapy to the tumour site is used to either pre-operatively to shrink the tumour or if surgery is not possible due to surrounding anatomy, or post-operatively to ensure that all cancer cells are removed or killed [4].

Systemic cytotoxic chemotherapy is also administered, with a regimen of vincristine, doxorubicin, and cyclophosphamide (VDC) and etoposide and ifosfamide (IE) being the preferred options - this combination is often abbreviated to VDC-IE [4].

Despite the aggressive treatment, the prognosis remains poor. Therefore, there is an urgent need to identify novel, experimental therapies for Ewing sarcoma. These include small molecules targeting the biological drivers of the disease, usually one or a combination of proteins. One promising target is the EWS-FLI1 transcription factor, which is found in more than 90% of Ewing sarcoma cases [5].

Prognosis for Ewing Sarcoma

The prognosis of Ewing sarcoma is generally poor, as the disease is very aggressive and can spread very quickly. Despite the aggressive chemotherapy being the standard of care, 20-40% of patients with localised disease and almost 80% of patients with metastatic disease at presentation do not survive [6].

However, with the VDC-IE combination therapy, the 2-year overall survival rate and progression-free survival rate can be as high as 80.0% [4].

What is an Osteosarcoma?

Osteosarcoma is another type of sarcoma of the bone, which is prevalent in people reaching early adolescence. This age group is more susceptible to osteosarcoma due to the rapid bone growth they are experiencing. Osteosarcomas most commonly occur in the femur (thighbone) near the knees, or on the upper humerus near the shoulder [7, 8].

Signs and Symptoms of Osteosarcoma

The common symptoms of osteosarcoma include bone pain, either at rest, in motion, or while lifting objects.

Other symptoms can include unexplained fractures, swelling and redness in the affected area, and limitation of motion and limping. The pain ranges from dull to so severe that the patients cannot sleep because of it. However this varies from patient to patient.

In some cases, the muscles on the affected extremity may appear smaller than those in the healthy limb [7, 8].

Diagnosis of Osteosarcoma

Osteosarcoma is diagnosed through a combination of imaging and biopsy. CT and PET scans are used to visualise the tumour, and are essential to the staging, which is done according to the Musculoskeletal Tumor Society staging system.

A biopsy is required for a definitive diagnosis, with common histological findings including osteoid and woven bone matrix. A woven bone matrix is characterised by a random arrangement of collagen fibrils (fibre-like structures). Osteoid is unmineralised bone that is not mature (i.e. is still growing and has not hardened) [8].

Treatment for Osteosarcoma

Interestingly, osteosarcomas are highly radioresistant, meaning that radiotherapy is not effective at killing the cancer cells. Consequently, surgery and chemotherapy constitute the primary treatment.

Firstly, neoadjuvant chemoterapy is administered to kill the tumour, and minimise the chance of metastasis. Drugs of choice are aggressive, including cisplatin, doxorubicin, high-dose methotrexate, and ifosfamide.

This is followed by surgery, aiming to remove the tumour with very wide margins (portions of the healthy-appearing bone to ensure that all cancerous cells were taken out in the surgery). The surgery aims to be as conservative as possible, with more than 90% of patients not requiring an amputation.

However, with more advanced cases, an amputation of the limb may be necessary. Following surgery, the chemotherapy may be resumed to kill all remaining cancer cells [8, 9].

Prognosis for Osteosarcoma

The advancements in combined chemotherapy regimens improved the prognosis significantly. With the standard of care treatment, 5-year survival rates reach 60% or more [6, 5].

Several experimental approaches, including gene therapies (where a gene is introduced to the tumour to improve susceptibility to a certain agent) or biophysical approaches utilising highly-concentrated energy (such as heat, ultrasound or various forms of electromagnetic radiation) are being developed and investigated, however, these are still in early development and the surgery-chemotherapy approach produces the best results.

Summary: What are the differences?

Ewing sarcoma and osteosarcoma are both types of bone cancers that primarily affect children, teens, and young adults. However, they differ in several key aspects:

Location and Appearance

Osteosarcoma tumors typically grow along the edge of long bones, most commonly found around the knee and upper arm. On the other hand, Ewing sarcoma can develop in any bone, and is most common in the pelvis, ribs, upper arms and thighs.

Epidemiology and risk factors

Both osteosarcoma and Ewing sarcoma share risk factors such as age and gender, with both tumours being slightly more common in boys. However, the two tumours occur at different rates in different ethnicities: Black and Hispanic children have a higher risk of osteosarcoma, while white children have a higher risk of Ewing sarcoma. Osteosarcoma has additional risk factors including height and rapid growth.


The two tumours look differently on a magnetic resonance imaging (MRI) scan, with Ewing sarcoma showing a lower apparent diffusion coefficient, which is a measure of movement of water molecules between tissues.

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Jakub Hantabal

Jakub Hantabal

Jakub is a postgraduate student of Precision Cancer Medicine at the University of Oxford, and a data scientist. His research focuses on the impact of hypoxia on genetic and proteomic changes in cancer. Jakub also consults and collaborates with multiple institutions in the United Kingdom and Slovakia supporting research groups with advanced data analysis, and he also co-founded an NGO organising educational events in data science.