Ewing sarcoma is a rare condition characterized by cancer cells in the bone, with or without affecting the surrounding soft tissues. The condition is highly aggressive and requires prompt diagnosis and management.
It is a cancer of the bone and may or may not involve the surrounding soft tissues, such as nerves or cartilage. The common sites for this condition are the feet, arms, legs, pelvis, chest, hands, skull, and spine. Although Ewing sarcoma may occur at any age, it is relatively more common in children and adolescents. Ewing tumors should be diagnosed and treated early for better health outcomes.
Ewing sarcoma is a rare condition. It is the second most common cancer of the bone in children and adolescents. A study reported its prevalence as 2.9 cases per million in individuals between the ages of one and 19 years. Almost 80% of cases of Ewing tumor are reported in individuals below 18 years of age. The cases of Ewing tumors in adults over 40 years old are < 1%. There is a higher incidence of Ewing tumor in Caucasians than in Africans and Asians. In India, Ewing sarcoma accounts for almost 15% of all bone cancers. Males and females between the ages of 10 and 14 have incidence rates of 4.4 and 2.9 per million, respectively.
Some of the types of Ewing sarcoma are:
It is the most common form of Ewing sarcoma and constitutes about 87% of the total wing sarcoma cases. This tumor was initially described by Dr. James Ewing, who reported that the cells of these tumors are different from osteosarcoma (another common bone tumor). Ewing's sarcoma of the bone is sensitive to radiation therapy.
These are also known as extraskeletal Ewing sarcoma. It initiates in the soft tissues that surround the bones. The properties of malignant cells are similar to those of the Ewing sarcoma of the bones. However, the outcomes and patient characteristics of the EOE may differ from those of the Ewing sarcoma of the bones. The most common symptoms include pain and a growing mass.
The methods for diagnosing EOE include immunohistochemical tissue examination, histopathological examination, ultrasound, computed tomography, and magnetic resonance imaging. There are no specific imaging characteristics of the EOE. The condition may be confused with benign lesions. Although EOE is radiosensitive, radiation therapy-related side effects and advancements in surgical techniques limit the use of radiation therapy.
These are aggressive malignancies commonly developed in the abdomen, pelvis, and thoracopulmonary region and less commonly in the neck and head. The tumors may originate in the bone or soft tissues at the affected site and have features similar to those of bone and EOE sarcoma. In the pelvic region, PNET generally occurs in the cervix, ovaries, uterine corpus, and vulva. Genetic studies and immunohistochemical profiles of the tumor assist pathologists in differentiating it from other small round-cell tumors.
A peripheral primitive neuroectodermal tumor (PNET) in the thoracopulmonary region is known as Askin’s tumor. It usually occurs in the chest wall, especially in the paravertebral region. Diagnosis is challenging as it mimics various other pulmonary conditions, such as neuroblastoma, tuberculosis, lymphoma, and rhabdomyosarcoma. The patients are presented with pain, loss of weight, and dyspnea. The disease is highly aggressive, with a poor prognosis and a short survival period. As the condition is rare, there are no standard treatment guidelines. Usually, the oncologists follow a multimodal treatment approach that comprises surgery, radiation therapy, and chemotherapy.
Depending on the extent of the disease's spread, the following are the Ewing sarcoma stages:
The American Joint Committee classifies Ewing sarcoma based on two classification systems. One classification is for bone cancer (Ewing sarcoma of the bone), and the other is for soft tissue sarcoma (EOE). The staging of Ewing tumors is done according to the TNMG system. It is based on tumor size and location, lymph node invasion, metastatic status, and tumor grade.
Stage 1 is generally not assigned to Ewing tumors, as they are considered to be of high grade. However, other bone cancers, assigned as grade 1, can be assigned stage 1.
Stage 2 is subdivided into stages 2A and 2B. In Stage 2A, the tumor is less than 8 cm, of high grade, and does not spread to lymph nodes and other organs. In stage 2B, the tumor is more than 8 cm, of high grade, and does not spread to lymph nodes and other organs.
In stage 3 Ewing sarcoma, the tumors are present at multiple sites on a single bone and are of high grade. The tumors do not spread to the lymph nodes or other organs.
Stage 4 Ewing sarcoma is subdivided into stages 4A and 4B. In stage 4A, the tumor is of any size and grade and spreads to the lungs and nearby lymph nodes. However, it does not spread to other organs. In stage 4B, the tumor is of any size and grade and does not spread to the lungs but to other organs. It may or may not have invaded the lymph nodes.
Ewing sarcoma does not cause any symptoms in most patients during the early stages of the disease. Also, the commonly observed Ewing tumor symptoms, such as fatigue, bone pain, and loss of appetite, overlap with other conditions. The exact cause of Ewing sarcoma is not known.
Ewing sarcoma may occur to any person. However, specific populations are more likely to develop this condition than others. Ewing sarcoma commonly occurs in individuals during puberty, as there is rapid bone growth during this period. Children between the ages of 10 and 20 are more likely to be affected by Ewing sarcoma. Males are at higher risk of developing this condition than females.
Some of the Ewing sarcoma symptoms include:
Bone pain is one of the most common Ewing sarcoma symptoms. During the early stage of the disease, the patients do not experience persistent pain; instead, the pain occurs during the night, exercise, or other activities. However, as the disease progresses, the size of the tumor grows, resulting in persistent pain. In some cases, the patients may experience intense pain due to a fracture of the bone, which is weakened by the cancer. The common sites for developing Ewing sarcoma include the chest wall, pelvis, and legs.
Patients may also experience a lump on the skin surface as an Ewing sarcoma symptom. The tumor that was small during the early stage of the disease progressively gets bigger, and the patients may start noticing a lump or growth on the skin's surface. In most cases, the tumor is noticed in the Ewing sarcoma of the hands and legs. However, tumors of the chest wall can also be noticed in patients with advanced diseases.
Patients may also experience swelling at the site of the tumor. The swelling is more pronounced when the surrounding soft tissues are involved. It is to be considered that the tumor is present for a long time before it causes pain and swelling. In some patients, the swelling is progressive.
Fatigue is an Ewing sarcoma symptom that occurs during the progression of the disease and treatment. There are several reasons for experiencing fatigue. Ewing sarcoma may result in a loss of appetite, resulting in less food consumption. It results in weakness and fatigue. Further, tumor-induced hypermetabolic states are another cause of fatigue. During this state, the malignant cells compete with the healthy cells for nutrition, resulting in fatigue. Chronic pain also results in fatigue. Apart from this, cancer therapy, such as radiation therapy and chemotherapy, also causes significant fatigue.
Patients with Ewing sarcoma also experience fever as a malignancy manifestation, particularly known as neoplastic fever. The fever as an Ewing sarcoma symptom may occur due to the production of cytokines, such as interleukin-1, interleukin-6, and tumor necrosis factor, by host macrophages. In some cases, the cytokines may also be released by the tumor. The cytokines induce the synthesis of prostaglandins that act on the temperature regulation site of the hypothalamus, resulting in fever.
Like other malignant conditions, patients with Ewing sarcoma also experience weight loss. It may be due to multiple reasons. First, there is a loss of appetite in these patients, resulting in reduced nutritional uptake. Further, a tumor-induced hypermetabolic state also results in weight loss. The patients also lose weight during the treatment, as conventional treatment approaches, such as chemotherapy and radiation therapy, also result in diarrhea, loss of appetite, and vomiting.
Patients with Ewing sarcoma also have an increased risk of fracture. It is due to reduced bone strength because of the development and progression of the tumor. It has been reported that approximately one-third of the children with Ewing sarcoma of the femur had fractures during disease progression. Some studies reported no negative prognosis with pathological fractures in patients with Ewing sarcoma.
The Ewing sarcoma causes are not known. However, it is believed that, like other cancers, Ewing sarcoma also occurs due to gene mutations. There are two types of genes present in the cell. One is the tumor suppressor gene that controls cell division and repairs any defect in DNA, while the other is the oncogene, which is responsible for cell division and growth. Due to certain factors, the tumor suppressor gene is turned off, or the oncogene is turned on, resulting in malignant conditions. It is believed that genetic changes in the genes are not inherited; rather, they occur during the child's life.
An alteration in the EWSR1 gene causes Ewing sarcoma. This gene is present on chromosome 22. The mutation is done through translocation. During translocation, a piece of chromosome 11, chromosome 21, or another chromosome is translocated on chromosome 22, resulting in turning on the EWSR1 gene.
Ewing sarcoma diagnosis is done through several techniques. Ewing sarcoma therapy options include radiation therapy and chemotherapy. The Ewing sarcoma cancer survival rate depends upon the stage of the disease, organs affected, and response to treatment.
The procedure or tests for an Ewing sarcoma diagnosis are:
The patients should consult the doctors if they experience persistent pain, swelling, and joint stiffness, especially when the pain worsens at night. The doctor may perform a comprehensive medical evaluation to determine the cause of the symptoms. The patients may be asked about any recent falls or trauma that may have caused the symptoms. The patients may also be asked about the unexplained weight loss and recent fever, as these are also symptoms of Ewing sarcoma, particularly in advanced stages. The doctor may also evaluate the patient's respiratory health to detect pleural signs or asymmetric breath sounds. Purpura or petechiae due to thrombocytopenia, if present, are evaluated.
Clinicians face challenges in Ewing sarcoma diagnosis due to the presence of similar symptoms in benign bone lesions and pseudotumoral lesions. The initial staging of the disease, the biopsy, the choice of therapy, and follow-up care depend upon the results of the imaging techniques. Clinicians take extra care while choosing the suitable imaging technique for an accurate diagnosis and optimal treatment.
X-rays are usually the first imaging method clinicians recommend in cases of bone-related conditions. X-ray images assist clinicians in diagnosing Ewing sarcoma. The characteristics of the affected bone seen during the Ewing sarcoma radiology examination include diffuse bone destruction, periosteal reactions, and soft tissue involvement. A study reported that the mean time from the onset of symptoms to the first Ewing sarcoma X-ray examination was several months. Due to the vascular characteristics of Ewing sarcoma, the spread is greater than that indicated in the X-ray images.
The visualization of Ewing sarcoma on the MRI depends upon the location, size, and stage of the tumor. MRI assists clinicians in detecting and localizing the primary tumor occurring in the bone and soft tissues. It also provides important information related to soft tissue and bone marrow involvement that affects treatment strategies. During diagnosis, MRI also helps determine the stage of diagnosis. It also helps plan the surgery and monitor the response to treatment and recurrence.
A CT scan has a role in the diagnosis and management of Ewing sarcoma. Ewing sarcoma CT scans assist clinicians in detecting and staging the disease. Sometimes, the doctors may advise the patients to undergo complete body imaging for appropriate staging. Besides providing detailed information about the size and extent of tumors and soft tissue involvement, CT scans also assist in lung evaluation to detect pulmonary metastasis. Like an MRI, a CT scan also monitors the treatment response and recurrence.
PET scans use radioactive sugar analogs that are injected into the body and predominantly taken up by tumor cells. A special device is used to detect the presence of radioactive material. A PET scan plays an important role in diagnosing and staging the disease by scanning the body. It also assists in differentiating the residual disease from the scar tissue. It helps the oncologists plan the treatment and provides additional prognostic information. The technique is usually combined with a CT scan (PET/CT) for a comprehensive evaluation.
Ewing sarcoma typically involves the bones, and a bone scan is an effective method to detect the sites of increased bone activity. This technique involves injecting a low dose of radioactive material into the blood. The radioactive material travels to the bones and is detected by a special camera. The sites with active bone changes have an accumulation of radioactive substances that appear as "hot spots" on the imaging. Although these may suggest the presence of a tumor, other skeletal conditions also give similar results to bone scans. Bone scans should accompany other tests, such as MRIs or X-rays. As there is a complete scan of the skeleton, the bone scan provides information about the spread of the tumor to other sites. As a PET scan gives similar information, the doctor may not advise a bone scan if the patient has already undergone a PET scan.
Although blood tests do not diagnose Ewing sarcoma, they provide valuable information about the patient's health. In some cases, blood tests also inform about the spread of Ewing sarcoma to other organs, such as the liver or kidneys, by detecting the levels of various substances in the blood.
Patients with Ewing sarcoma may have anemia (low red blood cells), leucopenia (low white blood cells), and thrombocytopenia (low platelets). A complete blood count detects these conditions, suggesting the involvement of bone marrow. However, these conditions are not exclusive to Ewing sarcoma and may occur due to other diseases.
A comprehensive metabolic panel involves testing several markers in the blood to detect the spread of Ewing sarcoma. A liver function test is performed to determine the level of various liver enzymes. Kidney function tests are conducted to determine the health status of the kidneys. Kidney function tests are also important during treatment, as chemotherapy may affect kidney function in many patients. Erythrocyte sedimentation rate and C-reactive protein evaluation are important for determining the inflammatory process.
Serum levels of lactate dehydrogenase may assist in cancer cells' diagnosis, prognosis, and treatment response. However, abnormal lactate dehydrogenase levels are not specific to Ewing sarcoma and may occur with other diseases. Elevated levels of LDH, which are generally due to tissue breakdown or damage, suggest a higher tumor burden. Patients diagnosed with Ewing sarcoma and having elevated TDH levels have a relatively unfavorable prognosis.
A biopsy is a technique that involves obtaining the samples suspected of Ewing sarcoma and analyzing the samples in the laboratory to confirm the presence of malignant cells. There are two methods for obtaining the samples.
This procedure involves obtaining the fluid portion from the abnormal tissues with the help of a thin, hollow needle. The doctor cleans and numbs the needle insertion site with local anesthesia before this procedure
Bone marrow aspiration is generally followed by a bone marrow biopsy. It involves obtaining the solid portion, such as bone or marrow. The needle used in the bone marrow biopsy is relatively thicker.
Once the diagnosis of Ewing sarcoma is confirmed and the disease is staged, specialists chart a personalized care plan that comprises various treatment approaches. The following are the different Ewing sarcoma treatments recommended:
The type of surgical intervention for Ewing sarcoma treatment depends upon several factors, such as the location and size of the tumor, health and age, and the effect on the function of the affected part after surgery. During surgery, the oncological surgeon removes the tumor and surrounding healthy tissues to reduce the risk of recurrence. This procedure is known as a wide excision. The goal of Ewing sarcoma surgery as a part of Ewing sarcoma treatment is to perform limb salvage surgery for Ewing sarcoma of the legs and arms. In rare cases, amputation is required. The surgery may also be performed for tumors of the chest, spine, and hipbone.
Chemotherapy is another option for Ewing sarcoma treatment. Medical oncologists use a combination of various chemotherapy drugs to treat Ewing sarcoma. Chemo for Ewing sarcoma is delivered in cycles, with a resting period between the two cycles. The drug is administered orally or directly into the tissues through injection.
Radiation therapy is also an option for Ewing sarcoma treatment. This technique is effective as the Ewing tumors are sensitive to high-energy radiation. Radiation therapy is generally used with chemotherapy or surgery. The radiotherapy techniques recommended for Ewing sarcoma treatment include conformal proton beam radiation therapy, intensity-modulated radiation therapy, and three-dimensional conformal radiation therapy.
Diagnosis and management of Ewing sarcoma are challenging and require modern techniques and state-of-the-art treatment facilities for a favorable prognosis. HCG Center has excellent diagnostic and treatment facilities that provide a one-stop solution for patients with Ewing sarcoma. The hospital is equipped with imaging facilities, including bone scans. Medical and surgical oncologists are experts in performing complex surgeries related to Ewing sarcoma with a high success rate.
Several factors increase the risk of Ewing sarcoma. It is important to detect these risk factors and implement measures to mitigate the risk of Ewing sarcoma.
Some of the most common Ewing sarcoma risk factors include:
Age is one of the most important Ewing sarcoma risk factors. Ewing sarcoma is predominantly diagnosed in children and adolescents, with young children and young adults less commonly diagnosed. Ewing sarcoma is rare in adults, and an older age at diagnosis may result in a less favorable prognosis.
Ewing sarcoma is rare; however, race and ethnicity may serve as Ewing sarcoma risk factors. Studies have reported that Hispanics and non-Hispanics, are at increased risk for developing Ewing sarcoma compared to Asian Americans and African Americans. The exact reason for this racial disparity remains unknown; however, the difference in the genetic makeup of people of different races and ethnicities could be the probable cause.
Ewing sarcoma may affect men and women; however, males have a higher risk of developing this condition than females. A study reported that the ratio of the likelihood of Ewing sarcoma in males and females is 1.5:1.
Genetic mutations or changes may also serve as an Ewing sarcoma risk factor. People with specific genetic mutations have a higher risk of developing this condition. The gene for Ewing sarcoma is present on chromosome 22. Genetic changes that increase the risk of Ewing sarcoma occur through translocation, which is a process where specific sections of a gene translocate to another gene.
There is no known method as to how to prevent Ewing sarcoma. However, certain measures may help reduce its risk. The following are a few measures that can be considered to reduce the risk of Ewing Sarcoma:
Smoking may increase the risk of Ewing Sarcoma due to the presence of several chemicals that may cause genetic mutation. Quitting smoking may help reduce the risk of Ewing sarcoma.
Excessive weight, or obesity, is a risk factor for various cancers. It is because patients with excessive weight or a higher BMI have chronic inflammation that has the potential to cause genetic changes. These alterations in the genes may result in cancer. Maintaining a healthy weight reduces the overall cancer risk.
A regular medical checkup is another way to detect and treat cancer in its early stages. The patients should not ignore any of the symptoms of Ewing sarcoma, such as bone pain, unexplained weight loss, or persistent fatigue.
Ewing sarcoma is a rare cancer that begins in the bone and the soft tissues around the bones. The types of Ewing sarcoma include Ewing sarcoma of the bone, soft tissue (extraosseous Ewing) tumor, peripheral primitive neuroectodermal tumor, and Askin's tumor. The stages of Ewing tumors are defined based on both the bone cancer staging system and the soft tissue sarcoma system.
