Ewing's sarcoma: what is it, symptoms, causes, treatment, prognosis

What is Ewing's sarcoma?

Ewing's sarcoma Is a rare bone tumor that occurs most commonly in adolescents. It can also occur outside the bone in soft tissue. Ewing's sarcoma is also associated with another type of tumor known as primitive neuroectodermal tumor (PNET). The researchers found that these tumors are associated with the same chromosomal abnormality (balanced reciprocal translocation) and have many physiological characteristics. Consequently, these tumors are sometimes collectively classified as tumors of the Ewing family (OCU). This general term encompasses Ewing's sarcoma of bone, extraosseous Ewing's sarcoma, primitive neuroectodermal tumor, and Askin's tumor (chest wall tumor).

Ewing's sarcoma of bone accounts for about 70% of tumors in this family. Generally, the term Ewing's sarcoma is preferred because, despite the different names, molecularly it is one tumor. Ewing's sarcoma most commonly affects the long bone of the legs (femur) and flat bones such as the bones of the pelvis and chest.

Ewing's sarcoma is an aggressive cancer that can spread (metastasize) to the lungs, other bones, and bone marrow, potentially causing life-threatening complications. The exact cause of these tumors is unknown.

Ewing's sarcoma was first described in the medical literature in 1921 by Dr. James Ewing. Ewing's sarcoma is the second most common primary bone tumor in children and accounts for approximately 2% of all childhood cancer diagnoses.

Signs and symptoms

People with a tumor in the Ewing family may have pain and swelling near the affected part of the body. The pain often comes and goes (interspersed) at first, gradually progressing, becoming more consistent. Weakness and numbness in the affected area can also occur. In some cases, patients may also experience fever, lack of energy, weight loss, low circulating red blood cells (anemia) and an increased level of circulating leukocytes (leukocytosis). A palpable mass is often present.

Ewing's sarcoma most commonly affects the midsection (diaphyseal region) of the long bones of the arms and legs, especially the long shin bone (femur). These tumors also commonly affect flat bones such as the bones of the pelvis, chest wall, and spine (vertebrae). Ewing's sarcoma can occur in any bone in the body, such as the bones of the foot, hand, mandible, skull, and / or elsewhere. Soft tissue tumors develop most often in the trunk and chest. However, the most common site is the pelvis, accounting for about 25% of cases. Ewing's sarcoma can weaken bones, sometimes leading to fractures.

These tumors are often aggressive and can spread (metastasize) to additional areas of the body, especially other bones and lungs. In rare cases, it can affect the bone marrow.

The symptoms associated with these tumors are secondary to their location. For example, swelling in the leg can lead to lameness, swelling in the lungs can lead to breathing problems and fluid buildup in tissue layers, that line the lungs and chest cavity (pleural effusion), or a swelling in the spine can cause weakness or paralysis of the affected muscles (paraplegia).

Causes

The exact cause of Ewing's sarcoma is unknown and the underlying cell type has not been identified. Most cases are believed to happen by chance, without any specific reason (sporadically).

Chromosomal (cytogenetic) studies have shown that Ewing's sarcoma cells are often characterized by an abnormal change in their genetic makeup, known as reciprocal translocation. Mutual translocation means that pieces of two separate chromosomes break apart and "swap places." Chromosomes, which are present in the nucleus of human cells, carry the genetic information of each person. Pairs of human chromosomes are numbered 1 through 22, and an additional 23rd pair of sex chromosomes includes one X and one Y chromosome in males and two X chromosomes in females. Each chromosome has a short arm, labeled "p", and a long arm, labeled "q". Chromosomes are further subdivided into many numbered bands.

In Ewing's sarcoma, the chromosome regions are the long arms (q) of chromosomes 11 and 22 (11q24-22q12). These pieces are torn apart and swapped. In most cases, this results in an abnormal fusion of two genes, usually genes EWS and FLI. Genes usually produce (code) proteins that have multiple functions in the body. Abnormal fusion of the EWS and FLI genes results in a "fusion" gene that produces an abnormal protein product. Researchers believe that this abnormal protein may contribute to or influence the development of Ewing's sarcoma, although the exact function or effect of this protein is not fully understood at this time.

The reason why a chromosomal translocation occurs between chromosomes 11 and 22 is also unknown. However, by some estimates, more than 85 percent of tumors in the Ewing family of tumors have this translocation. Less commonly, the EWS gene can be fused with another gene other than the FLI gene; these are often genes from the same family as FLI1, most often involving a gene ERG.

In very rare cases, Ewing's sarcoma can develop as a second malignant neoplasm, which means that the disorder develops as a late complication of an earlier treatment of another form cancer.

Affected populations

Ewing's sarcoma affects men more often than women. The disease can affect people of any age, but it is most common in people 10-20 years old. The annual incidence is 2.93 children per 1,000,000 people. Approximately 200-250 children and adolescents are diagnosed with a tumor of the Ewing family each year. Two thirds survive for a long time (more than five years). The tumor is more common in Caucasians and extremely rare in African Americans and Asians.

Studies have shown that there are clear differences between extraosseous (extraosseous) Ewing's sarcoma (ECS) and bone Ewing's sarcoma. ECS is more common in people over 35 or under 5 years of age, whose average age is higher than in people with Ewing's sarcoma of the bone.

Related disorders

Symptoms of the following disorders may be similar to those of Ewing's sarcoma. Comparisons can be useful for differential diagnosis:

• Osteosarcoma - a tumor that affects the bones. This is the most common form of bone cancer. Approximately 60 percent of cases occur in children and adolescents during the second decade of life. Osteosarcomas affect men twice as often as women. Bones are most commonly affected - the long bones of the arms and legs. Symptoms can vary depending on the location and extent of the disease. Pain, swelling, tenderness, and eventually lump formation can occur in the affected area. Common symptoms can include fever, weight loss, anemia, and lack of energy. Osteosarcomas can weaken the surrounding bone, resulting in fractures. Osteosarcomas can spread (metastasize) to other areas of the body. The exact cause of osteosarcoma is unknown.
• Additional tumors should also be differentiated from Ewing's sarcoma, including:
  • chondrosarcomas;
  • osteochondromas;
  • medulloblastomas;
  • neuroblastoma;
  • rhabdomyosarcoma;
  • bone lymphomas.
• Osteomyelitis - a bone infection, usually caused by bacteria. Osteomyelitis can be acute or chronic. The disorder usually results from an infection in one part of the body that is transported through the bloodstream to a bone in a distant location. Among children and adolescents, the long bones of the legs and arms are most commonly affected. In adults, osteomyelitis most commonly affects the vertebrae of the spine and / or hip. Initially, there may be several days of fever and a general feeling of ill health (malaise). Osteomyelitis can be accompanied by fever, deep localized bone pain, chills, sweating, swelling, and painful or limited movement of nearby joints. The skin near the affected bone may be red (erythema), and there may be pus, destruction of surrounding tissue (necrosis), and damage or deformation of the bone.
• Eosinophilic granuloma is a subset of a rare spectrum of disorders known as Langerhans cell histiocytosis (LCC). GCR is characterized by overproduction (proliferation) and accumulation of a certain type of leukocytes (histiocytes) in various tissues and organs of the body. These can include certain distinctive granulocytes (Langerhans cells) involved in certain immune responses, as well as other white blood cells (eg, monocytes, eosinophils). Most people with HCL develop single or multiple bone lesions (eosinophilic granulomas) caused by an abnormal accumulation of Langerhans cells and eosinophils. In some cases, these lesions may not be accompanied by any symptoms. However, in most cases, the lesions are associated with bone pain and swelling of adjacent tissues. In many cases, bone calcium loss (osteolysis) can also occur. The skull, spine, and long bones of the arms and legs are most commonly affected. Secondary complications may also occur, including spontaneous long bone fractures or vertebral collapse and spinal cord compression.

Diagnostics

The diagnosis of a tumor of the Ewing family is based on careful clinical evaluation, identification of characteristic symptoms and physical findings, a detailed history of the patient, and various specialized tests. Such testing includes microscopic evaluation of tumor cells and diseased tissue (histopathology) and molecular analysis in search of an EWS-FLI1 translocation.

- Clinical testing and examination.

An x-ray may be taken initially, especially if there is a palpable mass. X-rays are used to take images of a tumor or lesion. More specialized imaging techniques can be used to assess the size, location and spread of the tumor (for example, into soft tissue or bone marrow), to determine if the tumor has spread (metastasized) to other areas of the body (for example, the lungs and other bones), and to serve as an aid for future surgical procedures. Such imaging techniques can include computed tomography (CT), magnetic resonance imaging (MRI), and bone scans. A bone marrow biopsy can show if the tumor has spread to the bone marrow.

The diagnosis of Ewing's sarcoma can be made by surgical removal (biopsy) and microscopic examination of a portion of the affected tissue. A specialized surface protein known as CD99, is found in most tumors of the Ewing tumor family. Detecting the presence of this protein can aid in the diagnosis of Ewing's sarcoma.

Another test used to diagnose Ewing's sarcoma is polymerase chain reaction (PCR). PCR is a laboratory technique that has been described as “photocopying”. It allows researchers to enlarge and repeatedly copy DNA sequences. As a result, they can thoroughly analyze DNA and more easily identify genes and genetic changes, such as reciprocal translocation that characterizes Ewing's sarcoma. This test is available on a research basis.

Standard treatments

Therapeutic management of patients with Ewing's sarcoma may require a coordinated effort by a team of healthcare professionals such as doctors who specialize in the diagnosis and treatment of cancer in children (pediatric oncologists), adult oncologists, radiation specialists for the treatment of cancer (radiation oncologists), surgeons (orthopedists), oncology nurses and other specialists (depending on the place of primary tumors).

Specific therapeutic procedures and interventions may vary depending on the many factors such as the location of the primary tumor, the grade of the primary tumor (stage) and the degree malignancy; Whether the tumor has spread to lymph nodes or distant sites the person's age and general health; and / or other elements. Decisions regarding the use of certain interventions must be made by doctors and others. members of the healthcare team in careful consultation with the patient, based on the characteristics of his case; careful discussion of potential benefits and risks; patient preferences; and other relevant factors.

Individuals with Ewing's sarcoma and their families are advised to seek advice after staging diagnosis and before starting treatment, as the diagnosis can cause anxiety, stress and extreme psychological disorders. Psychological support and counseling, both at the professional level and in support groups, is recommended for victims of sarcoma and their families.

Individuals with a tumor in the Ewing tumor family are treated with several anticancer drugs (chemotherapy) in combination with surgical procedures and / or radiation. Surgical removal of the malignant tumor and diseased tissue or radiation is used to treat the primary tumor. Chemotherapy kills cancer cells at the primary site, as well as hidden cancer cells that may have spread to other areas of the body. Typically, systemic chemotherapy is given first, followed by surgery or radiation. Surgery or radiation therapy without adjuvant chemotherapy was much less effective than combination therapy. Radiation is often used to treat inoperable tumors and sometimes in metastatic disease.

Doctors use several chemotherapy drugs because different drugs work differently in destroying tumor cells and / or preventing them from multiplying. Chemotherapy drugs commonly used to treat patients with Ewing's sarcoma include doxorubicin, vincristine, cyclophosphamide, dactinomycin, ifosfamide, and etoposide.

Forecast

According to the American Cancer Society, the overall five-year survival rate for localized Ewing's sarcoma is 70%. Patients with metastatic disease have a five-year survival rate of 15-30%.