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

• Clear Cell Endocrine Tumor of Pancreas
• Lipid-Rich Clear Cell Neuroendocrine Tumor of Pancreas
• Lipid-Rich Clear Cell Pancreatic Neuroendocrine Tumor

What is Clear Cell Pancreatic Endocrine Tumor? (Definition/Background Information)

• Clear Cell Pancreatic Endocrine Tumor is a rare, malignant endocrinal tumor of the pancreas. It typically occurs in adults, commonly in association with genetic disorders von Hippel-Lindau (vHL) syndrome or multiple endocrine neoplasia type 1 (MEN 1)
• There can be multiple tumors affecting any part of the pancreas. Clear Cell Pancreatic Endocrine Tumor can cause abdominal pain, indigestion, and loss of appetite
• Complications that arise from Clear Cell Pancreatic Endocrine Tumor may include gastrointestinal and biliary tract obstruction (causing jaundice) and liver metastasis
• In majority of cases, a complete surgical excision is the preferred mode of treating this malignant tumor. Although, the treatment of Clear Cell Pancreatic Endocrine Tumor would also involve treating the underlying vHL syndrome or MEN 1
• The prognosis of Clear Cell Pancreatic Endocrine Tumor depends upon many factors including the stage of the tumor and overall health of the individual. It also depends upon the severity of vHL syndrome or MEN 1 disorder

The pancreas is an important organ of the digestive system.

• Based on function of the pancreas, it can be functionally divided into 2 parts, namely:
  • Exocrine pancreas, which produces digestive enzymes, and
  • Endocrine pancreas that produces hormones such as insulin, glucagon, and somatostatin. Insulin and glucagon helps with controlling sugar levels in blood
• 95% of the pancreas is exocrine portion and 5% is endocrine portion. Pancreatic tumors (both benign and malignant) can arise from both the exocrine and the endocrine part
• Based upon 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 area of the pancreas more than the other areas.

Hence, localizing the tumor site can guide the healthcare provider to arrive at a probable diagnosis.

Who gets Clear Cell Pancreatic Endocrine Tumor? (Age and Sex Distribution)

• Clear Cell Pancreatic Endocrine Tumor are very infrequent and occurs in adults
• It can affect both males and females
• The condition can occur worldwide; individuals of all racial and ethnic background may be affected

What are the Risk Factors for Clear Cell Pancreatic Endocrine Tumor? (Predisposing Factors)

The risk factors for Clear Cell Pancreatic Endocrine Tumor include:

• von Hippel-Lindau syndrome (an autosomal dominant genetic disorder causing the formation of cysts and tumors in the body)
• Multiple endocrine neoplasia type 1 (autosomal dominant genetic disorder affecting the endocrine system)
• Individuals with a family history of vHL syndrome or MEN 1 are also highly susceptible to this type of pancreatic tumor

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 Clear Cell Pancreatic Endocrine Tumor? (Etiology)

The exact cause of Clear Cell Pancreatic Endocrine Tumor development is unknown.

• Nevertheless, it is seen to occur in the background of von Hippel-Lindau syndrome or multiple endocrine neoplasia type 1, in most of the cases
  • vHL syndrome is a genetic disorder inherited in an autosomal dominant pattern. The condition occurs due to mutations in the VHL gene
  • MEN type 1 is also a genetic disorder inherited in an autosomal dominant pattern. The condition occurs due to mutations in the MEN1 gene

What are the Signs and Symptoms of Clear Cell Pancreatic Endocrine Tumor?

The signs and symptoms of Clear Cell Pancreatic Endocrine Tumor depend upon the size and location of the tumor. During the initial stages, small tumors may not cause any signs and symptoms that are readily recognized. Hence, these tumors are only detected incidentally, when being worked-up for other conditions (i.e., diagnostic tests and exams undertaken for other health conditions).

Later on, the following signs and symptoms may be manifested that include:

• Abdominal pain, back pain
• Loss of appetite
• Weight loss
• Indigestion
• Yellowing of skin (jaundice)
• Nausea and vomiting
• Dark-colored urine
• Fatigue (getting tired easily)
• Signs and symptoms of the underlying vHL syndrome or MEN type 1 (if present)

General features of Clear Cell Pancreatic Endocrine Tumor include:

• There may be multiple tumors present anywhere in the pancreas
• The tumor size may range from a few centimeters to 10 cm

How is Clear Cell Pancreatic Endocrine Tumor Diagnosed?

Frequently, pancreatic tumors are difficult to detect/diagnose in the early stages. The signs and symptoms can be very similar to other conditions. Since the pancreas is located in the peritoneum, behind many organs, there is a lot of space for the tumor to grow (often unnoticed).

The following are the diagnostic methods that may be used to detect Clear Cell Pancreatic Endocrine Tumor:

• A thorough physical examination and a complete medical history is very important
• Blood test to check for serum amylase levels
• Complete blood count with differential
• Blood tests that may involve tumors markers, such as:
  • Carcinoembryonic antigen (CEA)
  • CA 19.9
  • CA 15.3
  • Alpha fetoprotein
• Radiological studies that may include:
  • Abdominal ultrasound: A procedure where high-frequency sound waves are used to produce real-time images
  • Endoscopic ultrasound: It is a minimally-invasive procedure that uses high-frequency sound waves to obtain detailed images of the pancreas
  • CT scan of abdomen: It may be helpful in detecting recurrences, or if metastasis to other organs has occurred
  • MRI scan of abdomen: It helps produce high-quality pictures of certain body parts including the tissues, muscles, nerves, and bones
• Additionally, the following magnetic resonance imaging procedures may be used particularly in individuals suspected of having pancreatic tumor/cancer:
  • MR cholangio-pancreatography (MRCP)
  • MR angiography (MRA)
• Positron emission tomography (PET) scan: It is particularly helpful in visualizing the spread of the cancer to other body parts (metastasis) and/or recurrence
• Percutaneous transhepatic cholangiography (PTC): A contrast material is injected into the bile ducts to visualize the structure
• Endoscopic retrograde cholangio-pancreatography (ERCP): This technique is used when symptoms of pancreatic cancer are present in the individual. A special equipment and dye injections are used to obtain a series of images. If required, a biopsy sample may also be collected during the procedure
• Invasive diagnostic procedures such as:
  • Laparoscopy: A special device is inserted through a small hole into the abdomen, to visually examine it. If necessary, a tissue sample is obtained for further analysis. Exploration of the abdomen using a laparoscope is called ‘exploratory laparoscopy’
  • Laparotomy: The abdomen is opened through an incision for examination, and if required, a biopsy sample obtained. Exploration of the abdomen using laparotomy procedure is called ‘exploratory laparotomy’
• Tissue biopsy: A tissue biopsy is performed and sent to a laboratory for a pathological examination to the pathologist, who 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

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
  • A fine needle aspiration of the cyst has limited diagnostic value; however, the aspirated fluid can be analyzed for a variety of proteins such as CEA, CA 19.9, CA 15.3, alpha fetoprotein, and others. Such an evaluation will help in arriving at a diagnosis and classifying the type of cyst
• Core biopsy of the pancreatic tumor
• Open biopsy of the pancreatic tumor

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.

What are the possible Complications of Clear Cell Pancreatic Endocrine Tumor?

The complications due to Clear Cell Pancreatic Endocrine Tumor may include the following:

• Gastrointestinal obstruction
• Biliary tract obstruction causing jaundice
• Compress adjoining organs if the tumor size is large, affecting their function
• Injury to local region
• If the tumor destroys enough islet cells of the pancreas, it can result in diabetes
• The tumor can metastasize to the liver

There may be complications from the associated vHL syndrome or MEN type 1 disorder.

How is Clear Cell Pancreatic Endocrine Tumor Treated?

The treatment is linked to treating the underlying von Hippel-Lindau syndrome or multiple endocrine neoplasia type 1, if any present. The treatment of Clear Cell Pancreatic Endocrine Tumor may be undertaken as:

• In most cases, a surgical excision and removal of the entire tumor is the preferred treatment option. This may be followed by radiation therapy and/or chemotherapy
• If the tumor has metastasized, then a combination of chemotherapy, radiation therapy, and invasive procedures may be used to treat the tumor
• Due to the presence of multiple tumors, a pancreatectomy (partial or total removal of the pancreas) may be performed
• Other treatment options may include:
  • Chemotherapy-radiotherapy: Where a combination therapy is used to treat the cancer
  • Targeted therapy: It used to target abnormal cancer cells and reduce the chance of cancer spreading to other parts of the body
  • Biological therapy: Also, known as immunotherapy, where certain bacteria or vaccines are used to indirectly treat the cancer
• Post-operative care is important: One must maintain minimum activity levels, until the surgical wound heals
• Follow-up care with regular screening and check-ups are important and encouraged

How can Clear Cell Pancreatic Endocrine Tumor be Prevented?

Currently, there are no specific methods or guidelines to prevent Clear Cell Pancreatic Endocrine Tumor. But, if there is a family history of vHL syndrome or MEN type 1, then:

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders
• Regular medical screening at periodic intervals with tests, scans, and physical examinations are mandatory

What is the Prognosis of Clear Cell Pancreatic Endocrine Tumor? (Outcomes/Resolutions)

• Clear Cell Pancreatic Endocrine Tumor is a malignant tumor and its prognosis depends upon a set of several factors, which include:
  • 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 respectability 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 to 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 a poorer prognosis compared to tumors that do not recur
  • Response to treatment: Tumors that respond to treatment have better prognosis compared to tumors that do not respond so well to treatment
• The prognosis also depends upon the severity and management of the underlying von Hippel-Lindau syndrome or multiple endocrine neoplasia type 1, if it is associated with the pancreatic tumor
• An early diagnosis and prompt treatment of the tumor generally yields better outcomes than a late diagnosis and delayed treatment
• However, regular follow up visits with the healthcare provider are important

Additional and Relevant Useful Information for Clear Cell Pancreatic Endocrine Tumor:

It is estimated that the average lifetime risk of developing pancreatic cancer is about 1.5%.