Generality
Ewing's sarcoma is a particular malignant tumor of the bones, to which a precise cause of onset has not yet been attributed. It usually affects the femur, tibia or humerus and can cause lung metastases if it is not diagnosed early.
Only with an accurate diagnosis can the most appropriate treatment be established; treatment consisting of chemotherapy, radiotherapy and surgery.
Brief reminder of what sarcomas are
Sarcomas are uncommon malignant tumors that can affect different areas and tissues of the body: bones, cartilage, fatty tissue, muscles, tendons, blood and lymphatic vessels, hematopoietic cells and nerves.
From a histological point of view, sarcomas are divided into bone sarcomas and soft-tissue sarcomas . The first, as one can guess from the name, are malignant tumors that originate in the bones; the latter, instead, are those charged to all the fabrics mentioned above, excluding bones.
Given the numerous districts of the body involved, there is a huge variety of sarcomas, even around 100 kinds.
In Italy, around 3, 000 people develop sarcomas each year.
What is Ewing's sarcoma?
Ewing's sarcoma is a primary (or primary) malignant tumor of the bones. The primitive term means that the neoplasm begins in the bone tissue and is not the result of a metastasis (secondary tumor).
All bones can develop Ewing's sarcoma, but usually the most affected are long ones of legs and arms ( femur, tibia and humerus ), those of the pelvic area, ribs and clavicles .
Ewing's sarcoma is named after Dr. James Ewing, who described it for the first time in 1920.
Bones, by far, most affected by Ewing's sarcoma:
- Bones of the pelvis
- Femur
- Tibia
NB: in oncology, all primitive bone tumors are bone sarcomas. This clarification is a must, as there are secondary bone tumors, or the result of metastases, which are not at all sarcomas. In light of this, saying primitive bone tumor or bone sarcoma is the same thing.
VARIOUS TYPES OF BONE SARCOMAS
Ewing's sarcoma is not the only existing primitive bone tumor ; in fact, based on the bone cells from which the neoplasia originates, there are also:
- Osteosarcoma . It is the most widespread bone cancer. It affects, preferably, adolescents and young people; however, it is not excluded that it may also occur in adulthood. The most affected bones are the femur and tibia.
- Chondrosarcoma . Less common than osteosarcoma and Ewing's sarcoma, it initially develops in the bone cartilage and only subsequently affects the actual bone tissue. Although the starting point is not really a bone, it is still considered a bone sarcoma. The most affected bones are: femur, pelvis, scapula, humerus and ribs.
- Post-cell sarcoma . From a symptomatological point of view, it is very similar to osteosarcoma, but, instead of arising at a young age, it usually appears around the age of 40.
- The chordoma . It is a tumor of the bones that make up the spine. The most affected vertebrae are the sacral vertebrae. The age of onset is between 40 and 50 years.
Epidemiology
Ewing's sarcoma, which represents 16% of all primitive bone tumors, is quite rare: according to an Italian study, in fact, less than 100 people a year get sick.
These individuals are, in most cases, adolescents and young adults, therefore in the age range between 10 and 20 years.
Ewing's sarcoma is uncommon among children (about two cases per million) and is considered an almost exceptional event among adults.
According to epidemiological data, males seem to be more at risk than females.
Causes
At the origin of tumors there are one or more genetic mutations of DNA. These alterations, at the site where they occur, cause the rapid and uncontrolled growth of a cell mass (called tumor or neoplastic mass ).
In about 85% of Ewing's sarcomas, the tumor mass derives from a translocation, or from a reciprocal exchange of pieces of DNA, between chromosome 11 and 22. The genes involved are EWS, located on chromosome 22, and FLI1, placed on chromosome 11.
But what causes this deleterious exchange between chromosomes suddenly?
Apart from identifying a series of circumstances favoring bone sarcomas, this question is still without a precise and satisfactory answer.
Other translocations observed:
- Between chromosomes 21 and 22
- Between chromosomes 7 and 22
RISK FACTORS OF BONE SARCOMAS
Thanks to the analysis of the clinical histories of those who suffered from bone sarcoma, it was possible to identify some favoring factors.
Here's what it's about:
- Paget's bone disease . It is a very rare condition that weakens the bones of the body. On average, one person in 100 affected by the disease develops a bone sarcoma in the course of life.
- Li-Fraumeni syndrome . It is another very rare disease that affects one person every 140, 000.
- Predisposition to retinoblastoma . Retinoblastoma is an eye cancer that typically occurs in children. Those who fall ill, are at great risk of developing bone sarcomas.
- Exposure to radiation . Like all cancers, bone sarcomas are also favored by radiation exposure and radiation therapy.
- Umbilical hernia . It seems that children with umbilical hernia, compared to healthy children, are three times more exposed to Ewing's sarcoma. Nevertheless, the danger is still quite low.
- Fast bone growth in puberty. In some young individuals, a remarkable and sudden growth of the bones is observed. This would seem to favor the onset of genetic mutations in bone cells.
DEGREE AND STAGE OF A BONE SARCOMA
The severity of bone sarcomas depends on the medical analysis of two interconnected parameters: the degree and the stage (or staging).
The degree indicates the growth rate of the tumor : if it is high, it means that the growth is very rapid; vice versa, if it is low, it means that growth is slow. A slow-growing tumor is less severe than a fast-growing one, because it is less likely to expand and spread; however, there are exceptions to this statement, as some tumors may have a slow growth rate but cause the same metastasis; or they can suddenly increase their growth rate.
The stage, or staging, is an index of the size of the tumor mass and how widespread it is in the body. The distinction of 4 different evolutionary stages allows us to describe the characteristics possessed by a bone sarcoma (see the following table).
Stages of evolution of a bone sarcoma
Stage 1 :
- The tumor has a low rate of growth and measures less than 8 cm.
- The tumor has a low rate of growth and is larger than 8 cm (or the bone in which it is formed is affected by the tumor at several points).
Stage 2 :
- Bone sarcoma has a high rate of growth and measures less than 8 cm.
- Bone sarcoma has a high rate of growth and is larger than 8 cm.
Stage 3 :
- Bone sarcoma has a high rate of growth and has affected more parts of the same bone, in which it is formed.
Stage 4 :
- The tumor spread from the bone, where it formed, and reached the lungs (pulmonary metastases). The degree of growth can be both slow and fast.
- In addition to the lungs, the tumor has also affected the lymph nodes and other organs of the body. As in the previous case, the growth rate can be both slow and fast.
Symptoms and Complications
The main symptom of Ewing's sarcoma is pain affecting the bone affected by the tumor. This pain is persistent and has a peculiarity: it worsens during the night.
The intensity of the pain sensation depends on how large the tumor mass is and on the area of its onset.
OTHER SYMPTOMS AND SIGNS
Sometimes, the painful area can swell and transmit a burning sensation. As in the case of pain, the extent of swelling and burning depends on the size and location of the tumor mass.
Furthermore, the affected bone becomes more fragile and undergoes easy rupture, even after minor trauma.
Finally, although they are very rare pathological manifestations, Ewing's sarcoma can cause:
- Temperature
- Inexplicable drop in body weight
- Excessive sweating
- Motor difficulties (if the tumor is located near the joints)
COMPLICATIONS
Complications arise when Ewing's sarcoma spreads to the rest of the body, in other words when it gives rise to metastases .
This process, if it occurs, initially affects the lungs ( lung metastases ) causing respiratory problems, such as shortness of breath, hemoptysis, cough and chest pain. After that, it can also affect other organs.
WHEN TO REFER TO THE DOCTOR?
A medical consultation is a must when the pain of a given bone arises suddenly and without apparent explanation, is persistent and worsens during the night.
In addition to pain, other signs not to be overlooked are: an unexplained high fever and an unjustified drop in body weight.
Diagnosis
To diagnose Ewing's sarcoma, different types of controls are needed.
As often happens, it begins with an objective examination, in which the patient's symptoms and clinical history are evaluated. After that, the investigation continues with several radiological and nuclear medicine tests, and with a bone tissue biopsy . All these tests, definitively clarifying the origin and characteristics of the disorder, allow us to plan the most appropriate treatment.
EXAMINATION OBJECTIVE
The doctor's investigations on symptomatology and clinical history are necessary to understand if the patient's complaints are actually due to Ewing's sarcoma.
Figure: two Ewing's sarcomas seen with a nuclear magnetic resonance. On the left, the affected bone is the femur; on the right, however, the affected bone is the humerus.
Very often, a thorough physical examination provides valuable information and gives a precise address to the diagnosis.
RADIOLOGICAL TESTS
Radiological examinations, to which a patient may be subjected with Ewing's suspected sarcoma, are two:
- Nuclear magnetic resonance ( RMN ): provides clear images of the painful bone. If there is a tumor mass, this is easily recognizable. The limit is represented by the fact that it is not possible to establish the type of bone cancer. The exam is not invasive.
- Computerized axial tomography ( TAC ): provides a detailed image of multiple areas of the body. It is practiced to see if the tumor has spread elsewhere (metastasis). TAC uses harmful ionizing radiation, even in small doses.
NUCLEAR MEDICINE
Nuclear medicine uses radioactive substances (or radiopharmaceuticals ), using them both in diagnostics and in therapy.
The following exams provide useful information:
- Bone scintigraphy . Through the injection of a radiopharmaceutical intravenously, it allows to obtain images related to the anatomy and metabolic activity of the bones. This is a very sensitive diagnostic test, because it clearly shows if there are pathological changes; however, at the same time, a non-specific examination appears, as it does not clarify the nature of the disturbances highlighted.
- Positron emission tomography ( PET ). Visualize the activity of the cells that make up the various tissues and organs of the body. A tumor mass or metastases are very active cellular entities, therefore visible to PET. As with bone scintigraphy, a radiopharmaceutical is injected intravenously.
BIOPSY
It involves the taking of some cells, which make up the tumor mass, and their observation under a microscope.
Usually, it is done through a needle and under local anesthesia; however, in certain situations open air surgery and general anesthesia are required ( open biopsy ).
WHY A DIAGNOSTIC ROUTE SO LONG?
The symptoms of Ewing's sarcoma are very similar to those of other diseases, such as infections ( osteomyelitis ) and accidental traumas to the bones. This means that numerous tests and checks are required to establish a correct diagnosis.
Treatment
To treat Ewing's sarcoma, one uses the combined use of chemotherapy, surgery and radiotherapy . The stages of the therapeutic path are established based on the characteristics of the tumor (size, position, grade and stage).
Generally, one begins with the taking of chemotherapy drugs, continues with surgical removal and radiotherapy, and ends, again, with chemotherapy. Any changes are at the discretion of the treating oncologist and depend on the evolution of the tumor.
CHEMOTHERAPY
Chemotherapy consists of the administration of drugs capable of killing all rapidly growing cells, including cancer ones.
In the case of Ewing's sarcoma, this therapy, which opens and closes the course of treatment, is practiced in order to slow down the growth of the tumor mass and to prevent the spread of metastases.
The duration of the initial treatment is about 8-12 weeks; the duration of the post-surgical operation is variable.
Main side effects of chemotherapy:
- Nausea
- He retched
- Hair loss
SURGERY
In the past, when the medicine was still very backward, the surgery was the only treatment available and consisted in the drastic amputation of the limb affected by the tumor (clearly, if the affected bones were different from those of the arms and legs, not even the amputation was feasible).
Today, however, amputation has become a secondary choice, because, thanks to the progress of surgery, intervention procedures have been developed through which the tumor is removed and the part of the affected bone is replaced with a prosthesis or a bone transplant .
The success of today's surgery depends on the severity and location of the tumor.
RADIOTHERAPY
Radiation therapy involves subjecting the patient to various cycles of ionizing radiation (high energy X-rays), in order to destroy the tumor cells.
In the case of Ewing's sarcoma, radiotherapy treatments are usually performed at the end of the surgery, to permanently eliminate the last cancer cells. However, it is not excluded that they can be implemented even earlier, in association with chemotherapy.
The intensity of radiotherapy, as well as its success, depends on the severity of the tumor.
The side effects consist of: fatigue, headache, skin irritation and increased risk of developing other cancers.
CONTINUOUS MONITORING
Throughout the therapeutic course, the patient undergoes periodic checks and diagnostic tests.
This continuous monitoring allows the doctor to evaluate how the tumor responds to treatment. The data that emerge are fundamental, because they allow us to establish whether or not we need to change the therapies in progress.
Prognosis
For those suffering from Ewing's sarcoma, the prognosis depends on the following factors:
- Early or late diagnosis . Early diagnosis allows treatment to start when the tumor is still small and not widespread. This ensures that there is a good chance of recovery.
- Tumor stage . Advanced cancers have a poor prognosis, although the diagnosis is not so late.
- Quality and side effects of therapy . If Ewing's sarcoma is located in an uncomfortable position and / or is particularly severe, surgery, radiotherapy and chemotherapy can also be very invasive. In fact, amputation and the appearance of other tumors are possible circumstances that make the prognosis negative.
- Metastasis . They are the natural consequence of a late diagnosis or a very serious tumor. Their appearance almost always has a fatal outcome, so the prognosis of Ewing's sarcoma is ominous.
It has been calculated that, if all the aforementioned conditions are favorable (ie early diagnosis, absence of metastases, non-severe cancer and efficient treatment), the survival rate of Ewing's sarcoma, 5 years after its appearance, is 70-80 %.
