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

• Clear Cell Myomelanocytic Tumor of Pancreas
• Pancreatic Perivascular Epithelioid Cell Neoplasm
• Perivascular Epithelioid-Cell Differentiation Tumor of Pancreas

What is Perivascular Epithelioid Cell Neoplasm of Pancreas? (Definition/Background Information)

• Perivascular Epithelioid Cell Neoplasm (PEComa) of Pancreas is a soft tissue tumor in the pancreas that shows perivascular epithelioid-cell (PEC) differentiation. Such tumors can be benign or malignant
• The PEComa is a large family of tumors and Perivascular Epithelioid Cell Neoplasm of Pancreas is extremely rare, with only about 20 cases being reported worldwide. This tumor type is known to develop in adults
• The risk for development of this tumor type increases, if an individual has a personal or family history of tuberous sclerosis complex. Additionally, a genetic predisposition to certain syndromes, such as neurofibromatosis type II and von Hippel-Lindau disease, may also increase one’s risk for Pancreatic PEComa
• The exact cause of Perivascular Epithelioid Cell Neoplasm of Pancreas formation is not clear. However, inherited and sporadic gene mutations may lead to formation of these tumors in the pancreas
• Since the number of reported cases of PEComa of Pancreas is very low, there are no standardized treatment methods available. In many cases, depending on the tumor type (whether benign or malignant), surgery and/or a combination of chemotherapy and radiation therapy may be employed
• 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 for Perivascular Epithelioid Cell Neoplasm of Pancreas

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 Perivascular Epithelioid Cell Neoplasm of Pancreas? (Age and Sex Distribution)

• Perivascular Epithelioid Cell Neoplasm of Pancreas is extremely rare, with only about 20 cases reported worldwide
• The condition is reported to affect adults 30 years and older, although individuals of all ages may be susceptible
• PEComa of Pancreas can occur in both genders; however, females are more affected than males
• It may occur in individuals of all races and ethnicities

What are the Risk Factors for Perivascular Epithelioid Cell Neoplasm of Pancreas? (Predisposing Factors)

The following factors may increase the risk of an individual developing Perivascular Epithelioid Cell Neoplasm of Pancreas:

• Advancing age
• Exposure to toxic chemicals
• A history (personal or family) of the following genetic disorders:
  • Von Hippel-Lindau syndrome, which occurs owing to genetic mutations in the VHL gene. This syndrome may lead to an increased risk of Pancreatic cancer and ampullary carcinoma
  • Neurofibromatosis type II
  • Tuberous sclerosis complex (TSC): It occurs as a result of mutations in the TSC1 and TSC2 genes. This inherited condition predisposes an affected individual to three different types of lesions in the brain, as well as other organs of the body

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s 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 Perivascular Epithelioid Cell Neoplasm of Pancreas? (Etiology)

The exact cause of Perivascular Epithelioid Cell Neoplasm of Pancreas development is unknown. It is researched that certain genetic mutations may lead to the formation of such tumors.

• The genetic material ‘DNA’ gives instructions to the cell and directs it to proliferate and/or mature into the type of cell that the body needs at each specific location
• Some individuals may be born with a preexisting abnormality in their DNA that predisposes them to certain types of cancer compared to other individuals in the general population. Some gene mutations that are associated with many types of PEComa include:
  • TSC1 and TSC2 gene - code for hamartin and tuberin, respectively. They interact and control cellular growth and size, and are tumor suppressors
  • VHL gene - the protein coded for by this gene, regulates the removal of proteins no longer required by the cell
  • NF2 gene - codes for a protein merlin, which regulates proper cellular growth and division
• However, DNA can be altered or damaged sporadically as well, which causes cells to become malignant (cancerous). DNA damage may trigger the transformation of normal cells into cancerous cells
• Conditions that can cause spontaneous damage to the DNA, resulting in the development of tumors and cancers include:
  • Exposure to certain toxins and poisons, such as some dyes used in tanning hides, industrial chemicals, and cigarette smoke
  • Certain types of bacterial and viral infection

What are the Signs and Symptoms of Perivascular Epithelioid Cell Neoplasm of Pancreas?

The signs and symptoms of Perivascular Epithelioid Cell Neoplasm of Pancreas depend on a number of factors such as the following:

• Size of the tumor
• Whether the tumor is a cyst or a solid mass
• Whether the tumor produces hormones
• Local spread of the tumor
• Rupture of the cystic mass
• Extent of bleeding within the tumor
• Whether the tumor is present as part of a syndrome, in which case, the signs and symptoms associated with the accompanying syndrome may be noted

Typically, the signs and symptoms of Perivascular Epithelioid Cell Neoplasm of Pancreas may not occur until later stages of tumor development. The type and severity of symptoms may vary among the affected individuals, and the symptoms 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
• Fatty stools
• The formation of blood clots in veins, swelling of legs
• Frequent urination (polyuria), excessive thirst, and blurred vision - all signs of elevated blood sugar levels in the body
• Fatigue, feeling tired easily
• Unintended weight loss
• Depression

Some other features of Perivascular Epithelioid Cell Neoplasm 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 Perivascular Epithelioid Cell Neoplasm of Pancreas Diagnosed?

Currently, there is no standard diagnostic method to accurately detect Perivascular Epithelioid Cell Neoplasm 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 PEComa of Pancreas on appearance of the signs and symptoms. These tests and exams include:

• Physical examination and medical history evaluation: Diagnosing Perivascular Epithelioid Cell Neoplasm of Pancreas 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 Perivascular Epithelioid Cell Neoplasm 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 Perivascular Epithelioid Cell Neoplasm of Pancreas 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 Perivascular Epithelioid Cell Neoplasm 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 Perivascular Epithelioid Cell Neoplasm 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
• Vascular angiographic studies of the tumor to check for the blood vessels feeding the tumor

A number of blood tests can also be helpful in the diagnosis PEComa of Pancreas or to help determine the treatment options. These include:

• Liver function blood tests
• Blood tests that may involve tumor markers, such as carcinoembryonic antigen (CEA) and 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 pancreatic cancer 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 Perivascular Epithelioid Cell Neoplasm of Pancreas?

Complications of Perivascular Epithelioid Cell Neoplasm of Pancreas may occur as the condition progresses, and these 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 tumor following treatment
• Side effects from the chemotherapy (such as toxicity) and radiation therapy

How is Perivascular Epithelioid Cell Neoplasm of Pancreas Treated?

The number of cases of Perivascular Epithelioid Cell Neoplasm of Pancreas is extremely low, and hence, the treatment options vary from one individual to another and are currently not well-standardized. The treatment measures for Pancreatic PEComa depend on whether it is benign or malignant. Most of the benign tumors, depending on its location, can be completely removed through surgery.

Malignant PEComa tumors may require a combination of surgery, chemotherapy, and radiation therapy, towards its treatment. The treatment measures may include:

• Surgical intervention with complete excision can result in a complete cure. It can also help reduce the chances of tumor recurrence
• In some cases, chemotherapy and/or radiation therapy may be administered to shrink the tumor size, prior to surgery (neoadjuvant therapy)
• Tumor embolization (performed on a case-by-case basis) is a possible treatment option. Here the blood supply to the tumor is blocked resulting in its shrinkage or death
• Targeted therapies have been attempted in some PEComa cases
• Treatment of the underlying or associated conditions, if any present
• Post-operative care is important: A minimum activity level is ensured, until the surgical wound heals
• Follow-up care with regular screening may be recommended by the healthcare provider

How can Perivascular Epithelioid Cell Neoplasm of Pancreas be Prevented?

• The US Preventive Services Task Force (USPSTF) currently does not have any recommendation for screening Perivascular Epithelioid Cell Neoplasm 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
• If there is a family history of inherited syndromes that are known to predispose an individual to Perivascular Epithelioid Cell Neoplasm of Pancreas, then regular monitoring to check for tumor development is important to help in their early detection
• Due to the metastasizing potential and chances of recurrence of malignant forms of Perivascular Epithelioid Cell Neoplasm 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 Perivascular Epithelioid Cell Neoplasm of Pancreas? (Outcomes/Resolutions)

• The prognosis of Perivascular Epithelioid Cell Neoplasm 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
  • Age of the individual: Older individuals generally have poorer prognosis than younger individuals
  • 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
• Those with non-syndromic (sporadic) tumors have a comparatively better prognosis than individuals with tumors that are seen in association with certain genetic disorders (termed syndromic PEComa of Pancreas)
• In most cases, the prognosis of small-sized, solitary, and benign tumors is excellent with surgical intervention or appropriate treatment
• Regular follow-up visits with the healthcare provider are important

Additional and Relevant Useful Information for Perivascular Epithelioid Cell Neoplasm 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