What are the other Names for this Condition? (Also known as/Synonyms)

• Extraosseous Ewing’s Sarcoma of Pancreas
• Pancreatic Ewing Sarcoma
• Primitive Neuroectodermal Tumor (PNET) of Pancreas

What is Ewing Sarcoma of Pancreas? (Definition/Background Information)

• Ewing Sarcoma (ES) of Pancreas is a malignant tumor of the pancreas, which arises from a primitive cell (either the neural crest or mesenchymal stem cell). It is extremely rare, with less than 25 cases being reported worldwide (as of 2016). Such tumors constitute about 1% of pancreatic sarcomas
• Individuals of Caucasian origin are more prone to Ewing Sarcoma of Pancreas. This type of tumor may affect children and adults. Most affected individuals present with symptoms of abdominal pain, a lump in the abdomen, nausea, vomiting and jaundice
• It is believed that Ewing sarcoma tumors are caused by cytogenetic alterations on chromosomes 11 and 22, which result in aberrant fusion proteins. The risk factors for the tumor may include maternal exposure to certain chemicals and smoking
• A combination of surgery and chemotherapy is an effective treatment method for Ewing Sarcoma of Pancreas. The type, location and extent of cancer, as well as the overall health of the affected individual, and his/her response to treatment may determine the prognosis of this pancreatic tumor

The pancreas is an important organ of the digestive system.

• Functionally, the pancreas can be divided into 2 parts, namely:
  • Exocrine pancreas, which produces digestive enzymes, and constitute about 95% of this important organ
  • Endocrine pancreas, which secretes hormones such as insulin, glucagon, gastrin, and somatostatin. Insulin and glucagon regulate sugar levels in blood

Pancreatic tumors (benign and malignant) can arise from both the exocrine and the endocrine components of the organ. Most endocrine tumors are benign and develop at a slower rate than exocrine tumors.

• Based on the anatomy of the pancreas, it can be divided into 3 main parts, namely the:
  • Head,
  • Body, and
  • Tail

Pancreatic tumors can affect the head, body, and tail region of the pancreas. Some tumors can affect one region of the pancreas more than the other.

Who gets Ewing Sarcoma of Pancreas? (Age and Sex Distribution)

• Ewing Sarcoma of Pancreas is extremely rare, contributing to about 1% of all types of pancreatic sarcomas. This type of cancer occurs more commonly among the Caucasians
• Although the sarcoma can arise at any age, it is more common in younger individuals, who are in their teens and twenties
• Both males and females may be affected

What are the Risk Factors for Ewing Sarcoma of Pancreas? (Predisposing Factors)

The following are some known risk factors for Ewing Sarcoma of Pancreas:

• Age: Childhood, adolescence, and young adulthood
• Race: Caucasians are the most vulnerable racial group for Pancreatic Ewing Sarcoma

In general, the following risk factors are attributed to Ewing sarcoma:

• Parental smoking
• Mother’s occupation (such as farming), leading to a possible exposure to toxic chemicals
• The presence of hernias and surgery for treatment of the same

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Ewing Sarcoma of Pancreas? (Etiology)

Ewing’s sarcoma, in general, including ES of Pancreas, are caused by re-arrangement of genetic material on chromosomes 8, 11, 12, and 22.

• This type of cytogenetic alteration, known as translocation, changes the position of segments of DNA (and genes) between involved chromosomes
• New fusion genes form due to the translocation process
  • Fusion genes form when the process of translocation joins genes that would otherwise be separated on different chromosomes
  • These fusion genes code for aberrant proteins
• Therefore, these mutations have a potentially cancerous outcome
• The trigger(s) for chromosomal translocations is not known at the present time

What are the Signs and Symptoms of Ewing Sarcoma of Pancreas?

The signs and symptoms of Ewing Sarcoma of Pancreas depend on a number of factors such as the following:

• Size of the tumor
• Histological type of the tumor
• Whether the tumor is a cyst or a solid mass
• Whether the tumor produces hormones
• Local spread of the tumor
• Extent of bleeding within the tumor

Typically, the signs and symptoms of Pancreatic Ewing Sarcoma may not occur until later stages of the cancer development. The type and severity of symptoms may vary among affected individuals, and it may include: 

• Anorexia (loss of appetite)
• Jaundice, manifested as yellowing of the skin and white part of the eyes
• Dark urine, also a sign of jaundice
• Pain in the upper part of the abdomen or middle of the back
• Fluid accumulation in the abdomen (ascites), abdominal swelling
• Persistent feeling of abdominal bloating with nausea or vomiting
• Feeling full soon after eating less (having a feeling of satiety after eating less)
• Changes in bowel movements, such as constipation
• Fatigue, feeling tired easily
• Unintended weight loss
• Depression
• Enlarged uterus
• Premature puberty in girls

Some of the other features of Ewing Sarcoma of Pancreas include:

• The tumor may present as a single mass or multiple nodules within the organ
• If there is cyst formation, it may occasionally rupture, spilling its contents into the belly
• These tumors can be locally aggressive, meaning that the tumor may spread to local areas

How is Ewing Sarcoma of Pancreas Diagnosed?

Currently, there is no standard diagnostic method to accurately detect Ewing Sarcoma of Pancreas during the early stages. However, healthcare professionals and specialists may sometimes incidentally discover a pancreatic tumor when testing for other conditions.

There are a variety of tests that a healthcare provider may use, to detect, locate, and diagnose Ewing Sarcoma of Pancreas on appearance of the signs and symptoms. These tests and exams include:

• Physical examination and medical history evaluation: Diagnosing pancreatic cancer usually begins with a thorough physical examination and evaluation of complete medical history. During a physical exam, the overall health status and symptoms (such as pain, loss of appetite, and weight loss) of the affected individual are checked
• Computerized tomography (CT) scan of the pancreas: With this radiological procedure, detailed three-dimensional images of structures inside the body are created. CT scans may be also helpful in detecting recurrences, or if Ewing Sarcoma of Pancreas has metastasized to other organs
• Magnetic resonance imaging (MRI) scan of the pancreas: An MRI scan uses magnetic fields that create high-quality pictures of certain body parts, such as tissues, muscles, nerves, and bones. These high-quality images may indicate to a physician if any cancer is present
• In addition, there are certain specific types of MRI scans that can be used in an individual who may have pancreatic cancer. Such radiological procedures include:
  • MR cholangiopancreatography (MRCP): It is a noninvasive test that uses a powerful magnetic field to produce images of soft tissues, bones, organs, and all other internal body structures
  • MR angiography (MRA): It is a noninvasive test that uses a powerful magnetic field to evaluate the blood vessels
• Endoscopic ultrasound (EUS): This is a minimally invasive procedure recommended for individuals who are suspected to have Ewing Sarcoma of Pancreas. An ultrasound device is inserted through a thin tube (called endoscope) down the stomach and into a part of the small intestine. It uses high-frequency sound waves to generate detailed images of the pancreas
• Endoscopic retrograde cholangiopancreatography (ERCP): A procedure used when an individual has developed symptoms of Ewing Sarcoma of Pancreas. An ultrasound device is inserted through a thin tube (called endoscope) down the stomach and into the first part of the small intestine. A dye is injected into the pancreas and bile ducts. The movement of the dye is followed through a series of images. A small tissue sample (biopsy) can be collected during this procedure
• Tissue biopsy: A tissue biopsy of the cyst (including the fluid inside the cyst) or mass is performed and sent to a laboratory for a pathological examination. A pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis. Examination of the biopsy under a microscope by a pathologist is considered to be gold standard in arriving at a conclusive diagnosis
  • Biopsy specimens are studied initially using Hematoxylin and Eosin staining. The pathologist then decides on additional studies depending on the clinical situation
  • Sometimes, the pathologist may perform special studies, which may include immunohistochemical stains, molecular testing, and very rarely, electron microscopic studies, to assist in the diagnosis
• The tissue for diagnosis can be procured in multiple different ways, and they include:
  • Fine needle aspiration (FNA) biopsy of the pancreatic tumor: A FNA biopsy may not be helpful, because one may not be able to visualize the different morphological areas of the tumor. Hence, a FNA biopsy as a diagnostic tool has certain limitations, and an open surgical biopsy is preferred
  • Core biopsy of the pancreatic tumor
  • Open biopsy of the pancreatic tumor
  • Endoscopic retrograde cholangiopancreatography
• Positron emission tomography (PET): A PET scan is a nuclear medicine imaging technique that generates three-dimensional images to show how tissue and organs are functioning. A small amount of radioactive material may be injected into a vein, inhaled or swallowed. A PET scan is also helpful in detecting recurrences, or if any metastasis (to the surrounding lymph nodes of the pancreas) has occurred
• Blood tests to check for liver functions, excess hormones, and detect tumor markers (such as carcinoembryonic antigen or CA 19.9)

The diagnostic tests aid in determining the extent of cancer, based on a system of classification, such as the “AJCC system for staging of pancreatic cancer”.

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

Determination of type and extent of cancer:

Once a diagnosis of Ewing Sarcoma of Pancreas has been made, the extent to which the tumor has spread is assessed, known as staging. The system used most often to stage pancreatic cancer is the American Joint Committee on Cancer (AJCC) TNM system, which is based on 3 key pieces of information.

The TNM classification for different types of pancreatic cancer is given below:

Tumor extent (T):

• TX: The main tumor cannot be assessed
• T0: No evidence of a primary tumor
• Tis: Carcinoma in situ (the tumor is confined to the top layers of pancreatic duct cells). (Very few pancreatic tumors are found at this stage.)
• T1: The cancer has not grown outside the pancreas and is 2 centimeters (cm) (about ¾ inch) or less across.
• T2: The cancer has not grown outside the pancreas but is larger than 2 cm across
• T3: The cancer has grown outside the pancreas into nearby surrounding structures but not into major blood vessels or nerves
• T4: The cancer has grown beyond the pancreas into nearby large blood vessels or nerves

Lymph node spread of cancer (N):

• NX: Nearby (regional) lymph nodes cannot be assessed
• N0: The cancer has not spread to nearby lymph nodes
• N1: The cancer has spread to nearby lymph nodes

Distant spread of cancer (M):

• M0: The cancer has not spread to distant lymph nodes (other than those near the pancreas) or to distant organs such as the liver, lungs, brain, etc.
• M1: The cancer has spread to distant lymph nodes or to distant organs

Stage grouping: Once the T, N, and M categories have been assigned, this information is combined to assign an overall stage in a process called stage grouping. The stages identify tumors that have a similar outlook and are treated in a similar way.

Stage 0 (Tis, N0, M0):

• The tumor is confined to the top layers of pancreatic duct cells and has not invaded deeper tissues. It has not spread outside of the pancreas
• These tumors are sometimes referred to as pancreatic carcinoma in situ or pancreatic intraepithelial neoplasia III (PanIN III)

Stage IA (T1, N0, M0):

• The tumor is confined to the pancreas and is 2 cm across or smaller (T1)
• The cancer has not spread to nearby lymph nodes (N0) or distant sites (M0)

Stage IB (T2, N0, M0):

• The tumor is confined to the pancreas and is larger than 2 cm across (T2)
• The cancer has not spread to nearby lymph nodes (N0) or distant sites (M0)

Stage IIA (T3, N0, M0):

• The tumor is growing outside the pancreas but not into major blood vessels or nerves (T3)
• The cancer has not spread to nearby lymph nodes (N0) or distant sites (M0)

Stage IIB (T1-T3, N1, M0):

• The tumor is either confined to the pancreas or growing outside the pancreas but not into major blood vessels or nerves (T1-T3)
• The cancer has spread to nearby lymph nodes (N1) but not to distant sites (M0)

Stage III (T4, Any, N, M0):

• The tumor is growing outside the pancreas and into nearby major blood vessels or nerves (T4)
• The cancer may or may not have spread to nearby lymph nodes (Any N). It has not spread to distant sites (M0)

Stage IV (Any T, Any N, M1): The cancer has spread to distant sites (M1).

(Source: “The AJCC system for staging pancreatic cancer”; information provided by the American Cancer Society, May 2016)

What are the possible Complications of Ewing Sarcoma of Pancreas?

Complications of Ewing’s Sarcoma of Pancreas may occur as the condition progresses, and may include:

• Jaundice owing to biliary tract obstruction
• Abdominal pain due to tumor growth pressing on the nerves in the abdomen
• Gastrointestinal obstruction
• Diabetes, if the tumor destroys enough islet cells of the pancreas
• Weight loss
• Metastases to the liver and lymph nodes
• Recurrence of pancreatic cancer following treatment
• Side effects from the chemotherapy (such as toxicity) and radiation therapy

How is Ewing Sarcoma of Pancreas Treated?

The treatment methods for Ewing Sarcoma of Pancreas are determined by several factors, such as, how advanced the cancer is, the overall health of the affected individual, as well as his/her personal preference(s). The healthcare provider determines and plans the best course of treatment on a case-by-case basis.

Once the extent of cancer has been determined, the following treatment methods may be employed:

• A debulking surgery to reduce the tumor mass (followed by a combination of chemotherapy and radiation therapy may be employed in some instances)
• The debulking procedure helps the chemotherapy treatment in being more effective, since there is lesser tumor mass left for the drugs to act on

Surgery for tumors located in the pancreatic head: Pancreatoduodenectomy

• A surgical procedure that involves the removal of part of the pancreas, part of the small intestine, and the gallbladder
• This procedure is typically used when the tumor is confined to the head of the pancreas
• The technique is also known as a Whipple procedure

Surgery for tumors in the pancreatic tail and body of the pancreas: Distal pancreatectomy

• A surgical procedure that involves the removal of the lower half or tail end of the pancreas
• Post-operative care is important: A minimal physical activity is advised, until the surgical wound heals

After surgical treatment and post-operative care, the attending healthcare professional/specialist may discuss the details of the cancer with the individual. Based on this, further treatment measures may be required that include:

Chemotherapy: It may be administered before or after the debulking procedure, depending on the individual’s specific circumstances.

• Chemotherapy is a treatment that uses drugs to kill cancer cells. In this treatment, a combination of two or more chemotherapy drugs is generally used
• These drugs may be administered orally (by mouth), or intravenously (through a vein in the arm)
• Chemotherapy may be used in addition to radiation therapy (chemoradiation). Chemoradiation is usually used to treat pancreatic cancers that have spread to surrounding organs, but not to distant body regions
• This combination may also be used after surgery to decrease the risk of cancer recurrence

Radiation therapy:

• Radiation therapy attempts to destroy cancer cells by aiming high-energy beams at the cancer cells
• Radiation therapy can be administered either by a machine placed outside the body (external beam radiation), or internally, by a device positioned directly at, or close to the malignant tumor
• This technique may be used before surgery, to decrease the size of a tumor, thus allowing for its easy removal; or after surgery, to kill the remaining cancer cells
• Radiation therapy and chemotherapy are sometimes used as a combination tool

How can Ewing Sarcoma of Pancreas be Prevented?

The US Preventive Services Task Force (USPSTF) currently does not have any recommendation for screening Ewing Sarcoma of Pancreas for the general population. However, taking steps to modify certain behavioral/lifestyle choices may help decrease its risk. These measures include:

• Smoking cessation: Smoking is the most significant risk factor associated with all types of pancreatic cancer. 20% to 30% of all pancreatic cancers develop due to smoking
• Physical activity: Obesity increases the risk for pancreatic cancers due to increased levels of inflammation in the body, which negatively impacts the overall immunity. Individuals, who participate in a modest amount of physical activity, may decrease their risk
• Adequate consumption of fruits and vegetables: A healthy diet, low in saturated fats and rich in many fruits and vegetables, may help decrease one’s risk for pancreatic cancer

Due to the metastasizing potential and chances of recurrence of Ewing Sarcoma of Pancreas, regular medical screening at periodic intervals with blood tests, radiological scans, and physical examinations are often needed, once an individual is diagnosed with the cancer.

What is the Prognosis of Ewing Sarcoma of Pancreas? (Outcomes/Resolutions)

The prognosis of Ewing Sarcoma of Pancreas depends upon a set of several factors, which includes:

• Stage of tumor: With lower-stage tumors, when the tumor is confined to site of origin, the prognosis is usually excellent with appropriate therapy. In higher-stage tumors, such as tumors with metastasis, the prognosis is poor
• The surgical resectability of the tumor (meaning, if the tumor can be removed completely)
• Overall health of the individual: Individuals with overall excellent health have better prognosis compared with those with poor health
• Whether the tumor is occurring for the first time, or is a recurrent tumor. Recurring tumors have worse prognosis 
• Response to treatment: Tumors that respond to treatment have better prognosis compared to tumors that do not respond to treatment

Following surgery and chemotherapy, the overall 5-year survival rate for Ewing’s Sarcoma of Pancreas is around 80%.

Additional and Relevant Useful Information for Ewing Sarcoma of Pancreas:

• It is estimated that the average lifetime risk of developing Pancreatic Cancer is about 1 in 67 (1.5%)
• Individuals can reduce their risk of developing Pancreatic Cancer through lifestyle or behavioral changes