Ewing’s sarcoma – Diagnostics – Overview of Information and Clinical Research

Finding out if someone has Ewing’s sarcoma involves several careful steps, from first noticing worrying symptoms to performing specialized tests that confirm the diagnosis. Understanding what to expect during the diagnostic process can help patients and families feel more prepared and less anxious about the journey ahead.

Introduction: Who Should Seek Diagnostic Testing

Anyone experiencing persistent bone pain that doesn’t come from a known injury should consider seeing a healthcare professional. This is especially important for children, teenagers, and young adults, as Ewing’s sarcoma most commonly affects people between the ages of 10 and 20 years old. The pain often starts gradually and may come and go at first, but it typically gets worse over time and becomes more noticeable at night.^[1]

If you or your child notices a lump or swelling near a bone that feels warm or soft to the touch, this warrants medical attention. Sometimes people discover these lumps on their arms, legs, or chest without any obvious cause. Fever that persists without explanation, bone fractures that happen without any injury, or unexplained weight loss and tiredness are also warning signs that should prompt a visit to a doctor.^[2]

Parents should trust their instincts when something doesn’t seem right with their child’s health. Young people who are very active in sports may initially dismiss bone pain as a normal part of physical activity, but pain that doesn’t improve with rest or that interferes with daily activities deserves professional evaluation. The tumor may be present for many months before it becomes large enough to cause noticeable symptoms, which is why seeking help early when symptoms first appear is so important.^[5]

⚠️ Important

Making an appointment with a healthcare professional is crucial if you or your child has ongoing signs and symptoms that cause worry. While many of these symptoms can be caused by other more common health problems, only a healthcare provider can determine if cancer is present. Early recognition and treatment are essential to reduce the risks of complications and improve outcomes.

Classic Diagnostic Methods

Physical Examination

The diagnostic journey typically begins with a thorough physical examination. Healthcare providers will ask detailed questions about symptoms, including when they started, how they’ve changed over time, and what makes them better or worse. They will also ask about medical history and family health history. During the physical exam, the doctor may feel for any lumps or bumps on the bones and surrounding tissues, checking for areas that are swollen, warm, or tender to the touch.^[2]

Imaging Tests

Imaging tests are essential tools that allow healthcare providers to see inside the body and examine bones and soft tissues in detail. These tests create pictures that can reveal the presence of tumors, their size, and their exact location. Different types of imaging provide different kinds of information, so doctors often use several tests together to get a complete picture.^[8]

X-rays are usually the first imaging test performed when bone problems are suspected. An X-ray uses a small amount of radiation to create images of the bones. This simple test can show abnormal areas in the bone that might indicate a tumor. However, X-rays alone cannot confirm a diagnosis of Ewing’s sarcoma, so additional tests are needed.^[2]

Magnetic resonance imaging (MRI) scans use powerful magnets and radio waves instead of radiation to create very detailed images of soft tissues and bones. An MRI can show the size of the tumor, whether it has grown into nearby soft tissues like muscles or tendons, and how it relates to important structures like blood vessels and nerves. This test is particularly helpful for planning surgery because it shows exactly where the tumor begins and ends.^[2]

Computed tomography (CT) scans take many X-ray images from different angles and use a computer to combine them into detailed cross-sectional pictures of the body. CT scans are especially useful for checking the chest to see if cancer has spread to the lungs, which is one of the most common places Ewing’s sarcoma can spread.^[8]

Bone scans involve injecting a small amount of radioactive material into a vein. This material travels through the bloodstream and collects in areas of bone where there is active growth or damage. A special camera then detects the radioactivity and creates images showing these areas. Bone scans can help determine if cancer has spread to other bones in the body.^[2]

Positron emission tomography (PET) scans also use a small amount of radioactive material, but they work differently from bone scans. The material used in PET scans is a form of sugar that cancer cells absorb more readily than normal cells. A PET scan can show areas of cancer throughout the body and is sometimes combined with a CT scan to provide both structural and functional information about tumors.^[8]

Biopsy: The Definitive Test

While imaging tests can suggest the presence of Ewing’s sarcoma, a biopsy is the only way to confirm the diagnosis with certainty. A biopsy involves removing a small sample of tissue from the suspected tumor so it can be examined under a microscope by a specialist called a pathologist. The biopsy is a critical step because the treatment plan depends entirely on knowing exactly what type of cancer is present.^[8]

There are two main ways to perform a biopsy. In a needle biopsy, a doctor uses a special needle inserted through the skin to reach the tumor and remove a small piece of tissue. This procedure is less invasive than surgery and can often be done with local anesthesia to numb the area. Sometimes imaging tests like ultrasound or CT scans are used to guide the needle to exactly the right spot.^[8]

In some cases, a surgical biopsy may be needed. This involves making a small cut in the skin to remove a larger sample of tissue or even the entire tumor if it’s small enough. Surgical biopsies are usually done under general anesthesia, which means the patient is asleep during the procedure. The choice between needle and surgical biopsy depends on the tumor’s location, size, and other factors.^[8]

Laboratory Testing of Tumor Cells

Once a tissue sample is obtained through biopsy, it undergoes detailed laboratory testing. Under the microscope, Ewing’s sarcoma cells have a distinctive appearance—they are small, round, and blue when stained with certain dyes. However, looking at the cells’ shape alone isn’t enough to distinguish Ewing’s sarcoma from other similar cancers.^[3]

Special tests are performed to look for specific changes in the tumor cells’ DNA, which is the genetic material inside cells that contains instructions for how they work. Ewing’s sarcoma is characterized by a particular genetic change where two genes that are normally separate become joined together. In about 85% of cases, a gene called EWSR1 on chromosome 22 becomes fused with a gene called FLI1 on chromosome 11. This creates a new abnormal gene called EWS-FLI1 that causes cells to multiply uncontrollably and form tumors.^[3]

In about 10 to 15% of Ewing’s sarcoma cases, the EWSR1 gene fuses with a different gene called ERG instead of FLI1, or with other less common genes. Testing the tumor cells to identify these specific genetic fusions is crucial for confirming the diagnosis. Finding one of these characteristic gene fusions is like finding a fingerprint that identifies the cancer as Ewing’s sarcoma rather than another type of tumor.^[8]

Tests to Check if Cancer Has Spread

Once Ewing’s sarcoma is diagnosed, additional tests are needed to determine if the cancer has spread beyond its original location. This process is called staging. About 25% of people with Ewing’s sarcoma have cancer that has already spread to other parts of the body at the time of diagnosis. The lungs are the most common site where Ewing’s sarcoma spreads, followed by other bones and bone marrow.^[4]

To check for spread to the lungs, doctors typically order a chest CT scan, which can detect even small tumors. A bone scan or PET scan can reveal if cancer has spread to other bones. If there’s concern that cancer may have spread to the bone marrow (the soft, spongy tissue inside bones where blood cells are made), a bone marrow biopsy may be performed. This involves using a needle to remove a small sample of bone marrow, usually from the hip bone, for examination under a microscope.^[2]

⚠️ Important

Biopsies should always be performed by experienced surgeons who specialize in treating bone and soft tissue tumors. The way a biopsy is done can affect future treatment options, especially surgery. The biopsy site and approach must be carefully planned so that any tissue that might have been contaminated with cancer cells can be completely removed during later surgery if needed.

Distinguishing Ewing’s Sarcoma from Other Conditions

One of the challenges in diagnosing Ewing’s sarcoma is that its symptoms can resemble those of many other, more common conditions. Bone pain and swelling might initially be mistaken for a sports injury, growing pains, or bone infection (osteomyelitis). Fever can make doctors suspect an infection rather than cancer at first.^[4]

Other types of bone cancer, particularly osteosarcoma (the most common type of bone cancer in young people) and neuroblastoma (another cancer that can affect children), may look similar to Ewing’s sarcoma on imaging tests. This is why the biopsy and genetic testing are so essential—they allow doctors to distinguish Ewing’s sarcoma from these other conditions with certainty. Each type of cancer requires different treatment, so getting the diagnosis exactly right is critical.^[4]

Diagnostics for Clinical Trial Qualification

Clinical trials are research studies that test new treatments or new combinations of treatments to find better ways to help patients. For patients with Ewing’s sarcoma, participating in a clinical trial may provide access to promising new therapies that aren’t yet widely available. However, clinical trials have specific requirements that patients must meet in order to participate, and diagnostic tests play a crucial role in determining eligibility.^[7]

Standard Diagnostic Criteria

To be enrolled in a clinical trial for Ewing’s sarcoma, patients typically must have a confirmed diagnosis based on both the microscopic appearance of tumor cells and the presence of characteristic genetic changes. Most trials require documentation showing that the tumor cells contain one of the typical gene fusions, such as EWSR1-FLI1 or EWSR1-ERG. This confirmation ensures that all patients in the study have the same type of cancer, which makes the research results more reliable and meaningful.^[7]

Imaging Requirements

Clinical trials generally require complete staging information before enrollment. This means patients must undergo a full set of imaging tests to determine whether the cancer is localized (confined to one area) or metastatic (spread to other parts of the body). Typical imaging requirements include MRI of the primary tumor site, chest CT scan, bone scan, and often PET scan. These baseline images serve as a reference point to measure how well the treatment works during the trial.^[7]

Blood Tests and Other Laboratory Work

Before joining a clinical trial, patients usually need blood tests to check their overall health status. These tests measure how well major organs like the kidneys, liver, and bone marrow are functioning. Clinical trials often exclude patients whose organs aren’t working well enough because some treatments can put additional stress on these organs. Blood tests typically include a complete blood count (to measure different types of blood cells), kidney function tests, liver function tests, and sometimes tests of heart function.^[7]

Performance Status Assessment

Clinical trials also evaluate patients’ general physical condition and ability to carry out daily activities. This is called performance status and is usually measured using standardized scales. Doctors assess whether patients can walk, work, and care for themselves. Performance status helps researchers understand the patient’s overall health and predict how well they might tolerate intensive treatments being tested in the trial.

Age and Disease Stage Criteria

Different clinical trials are designed for different patient populations. Some trials focus specifically on newly diagnosed patients with localized disease, while others study treatments for cancer that has spread or come back after previous treatment. Age requirements also vary—some trials are open only to children and adolescents, others include young adults, and some accept patients of all ages. The diagnostic tests help determine whether a patient’s disease characteristics match what the trial is designed to study.^[7]

Prognosis and Survival Rate

Prognosis

The outlook for patients with Ewing’s sarcoma depends on several important factors. People with cancer that hasn’t spread beyond its original location generally have a much better chance of long-term survival than those whose cancer has already spread at the time of diagnosis. The location of the tumor also matters—tumors in the arms or legs tend to respond better to treatment than tumors in the pelvis, spine, or chest. The age of the patient can influence outcomes as well, with younger patients sometimes having better results than older adolescents or adults.^[7]

How well the tumor responds to chemotherapy given before surgery is another crucial factor affecting prognosis. When chemotherapy successfully kills most of the cancer cells before surgery, the chances of cure are higher. The size of the tumor at diagnosis also plays a role—smaller tumors are generally associated with better outcomes than very large tumors. Whether the tumor can be completely removed by surgery is another important consideration. When surgeons can remove all visible cancer with good margins (meaning they also remove some healthy tissue around the tumor), the prognosis is better.^[3]

Unfortunately, cancer that comes back after treatment (recurrent disease) is very difficult to cure. The risk of recurrence remains a significant concern even for patients who respond well to initial treatment. However, continuous advances in treatment approaches have dramatically improved outcomes over the past several decades. Long-term monitoring after treatment completion is essential because complications from the cancer or its treatment can develop months or years later. These late effects may include problems with growth and development in children, organ damage, difficulties with learning and memory, emotional and mental health challenges, and fertility issues.^[2]

Survival Rate

Over the past 40 years, significant progress in both chemotherapy and local treatment (surgery and radiation) has led to remarkable improvements in survival rates for Ewing’s sarcoma. Before modern combination chemotherapy was developed, the five-year survival rate was less than 20%. Today, for patients with localized disease (cancer that hasn’t spread), the five-year survival rate has improved to greater than 70%. This means that more than 7 out of 10 people diagnosed with localized Ewing’s sarcoma are still alive five years after diagnosis.^[3]

However, survival rates are considerably lower for patients whose cancer has already spread to other parts of the body at the time of diagnosis. About 25% of patients have metastatic disease at diagnosis, and their outcomes remain challenging despite intensive treatment. The five-year survival rate is approximately 70% overall when considering all stages together, but this number varies significantly depending on whether the disease is localized or metastatic.^[4]

It’s important to understand that survival statistics are based on large groups of patients and represent averages. They cannot predict what will happen to any individual person. Many factors influence an individual’s outcome, and every patient’s situation is unique. Additionally, survival statistics are usually based on data from patients diagnosed several years ago, so they may not reflect the benefits of the newest treatments that are currently available or being studied in clinical trials.^[10]