Ewing’s sarcoma

Definition

Ewing’s sarcoma is a malignant neoplasm that develops from bone tissue. It most often occurs in adolescence or young adulthood. It affects flat and long tubular bones. It is one of the most aggressive tumors, prone to early metastasis. It is manifested by pain, followed by swelling, local hyperemia, and hyperthermia, as well as local dilatation of the venous network. At later stages, the tumor itself is also determined; there is often a pathological fracture of the affected bone. Treatment is combined, including surgery (if possible – radical removal of the neoplasm) in combination with radiation therapy, as well as pre- and postoperative chemotherapy.

General information

Ewing’s sarcoma is a malignant bone tumor characterized by rapid growth and the early appearance of metastases. It usually develops in children, adolescents, and young adults. It is accompanied by pain and local soft tissue changes. At later stages, the tumor becomes visible on examination and palpation. An oncologist treats it and includes surgical removal of the tumor, chemotherapy, and radiation therapy.

Ewing’s sarcoma, the second most common malignant bone tumor occurring in childhood, accounts for 10 to 15% of all malignant bone neoplasms. It is rare in adults over 30 and children under five. The greatest number of cases occurs between the ages of 10 and 15. Boys get the disease more often than girls, Caucasians – more often than representatives of the Negroid and Mongoloid races.

In some cases, the primary neoplasm in this disease occurs in soft tissue rather than bone. This form of the disease is called extraosseous Ewing’s sarcoma. In addition, they are similar in character and structure, aggressive malignant tumors belonging to the group of so-called tumors of the Ewing sarcoma family. In this group, in addition to extraosseous and bone sarcomas, peripheral primitive neuroectodermal tumors (PNET) are included. Extraosseous forms and PNETs together account for about 15% of all cases of Ewing’s sarcoma.

Causes

The causes for developing Ewing’s sarcoma currently need to be precisely established. However, several researchers in the field of modern oncology believe that hereditary predisposition plays a role in the occurrence of this disease. In about 40% of cases, an association with previous trauma is detected. Data indicate an increased likelihood of disease development in patients with certain types of skeletal anomalies, as well as disorders of intrauterine development of the genitourinary system (renal system reduplication, hypospadias). No association with exposure to ionizing radiation has been established.

Symptoms of Ewing’s sarcoma.

Pain in the affected area is the first and earliest sign of the disease. At first, it is mild to moderate, spontaneously subsides or disappears, and then reappears. Unlike pain in inflammatory processes, such pain does not subside at rest, at night, or when fixing the limb. In contrast, Ewing’s sarcoma is characterized by increased pain at night.

As the pain progresses, it becomes more intense, sleep deprivation and limitation of daily activity. Painful contracture develops in the nearby joint. Palpation of the affected area is painful. The temperature of the skin above it is elevated. There is an edema of soft tissues, local hyperemia, and dilation of subcutaneous veins. The tumor rapidly enlarges and (usually a few months after the first symptoms) becomes so large that it can be felt. In later stages, a pathologic fracture often occurs in the area of the neoplasm.

Local clinical signs are combined with increasing symptoms of general tumor intoxication. Patients complain of weakness and loss of appetite. Weight loss up to emaciation is noted. Body temperature is elevated to subfebrile or even febrile figures. Regional lymphadenitis is detected. Blood tests reveal anemia. Some symptoms depend on the localization of the neoplasm. For example, if Ewing’s sarcoma occurs on the bones of the lower extremities, lameness may appear. If the vertebrae are affected, compression-ischemic myelopathy with pelvic organ dysfunction and paraplegia may develop. Respiratory failure, pleural effusion, and hemoptysis may occur with neoplasms in the thoracic bones.

Diagnosis

As a rule, patients are referred to traumatologists at the initial stage. Radiography of the affected bone is the first study that allows one to suspect Ewing’s sarcoma. This pathological process is characterized by a combination of reactive and destructive bone formation processes. The contours of the cortical layer are indistinct, and delamination and disintegration of the cortical lamina are determined.

If the periosteum is involved, radiographs show small lamellar or needle-like masses. In addition, the images show an area of soft tissue changes larger than the primary bone tumor. The soft tissue tumor component is homogeneous, with no cartilaginous inclusions, foci of calcification, or pathological bone formation.

If typical radiologic signs of Ewing’s sarcoma are detected, the patient is referred to the oncology department, where an extended examination is performed to assess the condition of the primary focus and detect metastases. During such an examination, computed tomography or magnetic resonance imaging of the bones and soft tissues affected by the malignant process is performed. These studies allow us to accurately determine the size of the neoplasm, the degree of its spread along the medullary canal, and the connection with the neurovascular bundle and surrounding tissues.

Computed tomography and lung radiography are used to detect pulmonary metastases. Positron emission tomography, ultrasound, and osteoscintigraphy are used to detect metastases in bones, bone marrow, and internal organs. In addition, several tests are performed to assess the nature of the neoplasm accurately.

A biopsy is performed, and the material is taken from the area of bone tissue near the medullary canal or, if this is not possible, from the soft tissue component of the tumor. Since Ewing’s sarcoma is characterized by local and distant bone marrow involvement, a bilateral trepanobiopsy is performed, during which bone marrow is taken from the wings of the iliac bone. Immunohistochemical examination and molecular genetic studies may also be performed to assess the nature of the process.

Ewing’s sarcoma treatment

Since this tumor belongs to the category of highly aggressive neoplasms that metastasize early, its treatment should include treatment of the entire body, not just the primary focus, even in cases where no metastases have been detected. There is a very high probability of early appearance of micrometastases, which cannot be detected with existing methods at the time of diagnosis. Treatment of Ewing’s sarcoma is combined, includes both conservative therapy and surgical interventions, and consists of the following components:

• Pre- and postoperative chemotherapy, usually with several drugs in various combinations, are used. After treatment, the tumor’s response to therapy is evaluated. A good result is no more than 5% of living tumor cells.
• Radiation therapy using high doses. It is performed on the primary focus and, in the presence of metastases to the lung tissue, on the lungs.
• Surgery. If possible, the tumor and soft tissue components are removed radically. In this case, the removed area of bone is replaced with an endoprosthesis. However, even if it is not possible to remove the tumor completely due to its location and size, surgical treatment (partial resection) can improve tumor control and increase the chances of a favorable outcome.

In the past, Ewing’s sarcoma was usually treated with mutilation – amputation and disarticulation. Modern techniques make it possible to perform organ-preserving surgery not only on small bones (fibula, radius, elbow, scapula, clavicle, and ribs) but also on large bones (humerus, femur, and even pelvic bones). 

All these treatment options are available in more than 780 hospitals worldwide (https://doctor.global/results/diseases/ewings-sarcoma). For example, Surgery for bone cancer can be done in 23 clinics across Turkey for an approximate price of  $5.4 K (https://doctor.global/results/asia/turkey/all-cities/all-specializations/procedures/surgery-for-bone-cancer). 

Prognosis and prevention

Timely combined treatment provides a 70% overall survival rate for patients with localized Ewing’s sarcoma. In the presence of metastases to bone and bone marrow, the prognosis is significantly worse, but the combination of high-dose chemotherapy, total radiation therapy, and bone marrow transplantation makes it possible to increase the survival rate of patients with metastatic forms of the disease from 10% to 30% and more.

All patients should undergo regular check-ups after cure for early detection of relapses and control of side effects. It should be remembered that several side effects may occur not only during treatment but also long after treatment. These include male and female infertility, cardiomyopathy, impaired bone growth, and increased likelihood of secondary malignancies. However, many patients treated for Ewing’s sarcoma can live a whole life.