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

• Mucinous Cystadenocarcinoma of Pancreas
• Pancreatic MCN with Associated Invasive Carcinoma
• Pancreatic Mucinous Cystic Neoplasm with Associated Invasive Carcinoma

What is Mucinous Cystic Neoplasm of Pancreas with Associated Invasive Carcinoma? (Definition/Background Information)

• Mucinous Cystic Neoplasm (MCN) of Pancreas is an exocrine, benign or precancerous lesion, typically in the body and tail regions of the pancreas, and is characterized by the presence of mucin inside the cells (cytoplasm). Mucin is a glycoprotein and a component of the mucus
• Approximately, 20% of pancreatic MCN lesions can transition into a malignant state, when it is known as Mucinous Cystic Neoplasm of Pancreas with Associated Invasive Carcinoma. This type of cancer predominantly affects women in their 40s or older
• The exact cause of Mucinous Cystic Neoplasm of Pancreas with Associated Invasive Carcinoma is not known. Molecular analysis of invasive lesions has indicated KRAS, SMAD4, and p53 gene mutations, indicating a molecular basis for this type of cancer
• The affected individuals may be asymptomatic, or present with symptoms, such as abdominal pain, back pain, jaundice, diabetes and weight loss, among others
• Several imaging techniques, such as endoscopic ultrasound, magnetic resonance imaging (MRI) and computed tomography (CT) scans may be employed to diagnose Pancreatic MCN with Associated Invasive Carcinoma, in combination with tissue biopsy and analysis of fluids in the cyst
• The treatment may involve a combination of surgery, chemotherapy, and radiation therapy, based on the healthcare provider’s assessment. The 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 Mucinous Cystic Neoplasm of Pancreas with Associated Invasive Carcinoma

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 Mucinous Cystic Neoplasm of Pancreas with Associated Invasive Carcinoma? (Age and Sex Distribution)

• Mucinous Cystic Neoplasm of Pancreas with Associated Invasive Carcinoma is a rare type of pancreatic cancer, reported worldwide
• The cancer predominantly affects perimenopausal women (aged 40 years or older), with the average age of diagnosis at 45 years
• Rarely, men can develop this form of pancreatic cancer as well

What are the Risk Factors for Mucinous Cystic Neoplasm of Pancreas with Associated Invasive Carcinoma? (Predisposing Factors)

The risk factors for developing Mucinous Cystic Neoplasm of Pancreas with Associated Invasive Carcinoma may include: 

• Female gender, possibly in pre-menopausal state; age over 40 years
• Smoking habit
• Exposure to toxic chemicals
• Having been diagnosed with MCN of pancreas
• Family history: Individuals, with one or more (immediate) family members or relatives with a history of pancreatic ductal adenocarcinoma, may have an increased risk

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 Mucinous Cystic Neoplasm of Pancreas with Associated Invasive Carcinoma? (Etiology)

The exact cause of Mucinous Cystic Neoplasm of Pancreas with Associated Invasive Carcinoma is not known. The following may contribute to the development of the cancer:

• Some individuals may be born with a preexisting abnormality in their DNA that predisposes them to certain types of cancer, when compared to other individuals in the general population. Some gene mutations that are associated with MCN of Pancreas with Associated Invasive Carcinoma include:
  • Mutation(s) in the KRAS family of oncogenes, which code for proteins that play a role in regulating cell division
  • SMAD4 gene mutations - codes for a protein, which functions as a transcription factor that transmits cellular signals (from outside of cells to the nucleus), as well as a tumor suppressor
  • p53 gene mutations - this gene plays a role in tumor suppression
• Genetic changes brought about by certain infections, or exposure to toxic chemicals via smoking and/or one’s occupation

What are the Signs and Symptoms of Mucinous Cystic Neoplasm of Pancreas with Associated Invasive Carcinoma?

The signs and symptoms of Mucinous Cystic Neoplasm of Pancreas with an Associated Invasive Carcinoma may depend on the site and size of the malignant lesions. Many individuals with early stages of lesion formation may be asymptomatic. If symptoms do develop, they 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

How is Mucinous Cystic Neoplasm of Pancreas with Associated Invasive Carcinoma Diagnosed?

When an individual present with symptoms of Mucinous Cystic Neoplasm of Pancreas with Associated Invasive Carcinoma, the following methods may be employed to diagnose the cancer:

• Physical examination and medical history evaluation: Diagnosing Mucinous Cystic Neoplasm of Pancreas with Associated Invasive Carcinoma usually starts 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 the cancer 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
• 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 pancreatic cancer. 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 pancreatic cancer. 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 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
  • In case of MCN, the fluid inside the cysts is generally analyzed as well
• 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

A number of blood tests can also be helpful in the diagnosis pancreatic cancer or to help determine the treatment options. The tests may include:

• Liver function blood tests
• Blood tests that may involve tumor markers, such as carcinoembryonic antigen (CEA) and CA 19.9
• Insulin levels in blood

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 Mucinous Cystic Neoplasm of Pancreas with Associated Invasive Carcinoma?

The following potential complications may develop during the progression of Mucinous Cystic Neoplasm of Pancreas with Associated Invasive Carcinoma:

• 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 other organs and tissue in the abdominal cavity
• Abnormal fistula formation between pancreas and other abdominal organs
• Recurrence of pancreatic cancer following treatment
• Side effects from the chemotherapy (such as toxicity) and radiation therapy

How is Mucinous Cystic Neoplasm of Pancreas with Associated Invasive Carcinoma Treated?

The treatment options for Mucinous Cystic Neoplasm of Pancreas with Associated Invasive Carcinoma may vary, depending on the size and location of the cystic lesion. 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

Biological or targeted drug therapy:

• Targeting tumor cells while leaving healthy cells relatively unharmed is the goal of many cancer treatments
• Ongoing scientific research has yielded targeted drug therapy, wherein the unique traits of cancer cells are taken advantage of to destroy those cells

Targeted drug therapy can be effective in many ways, such as:

• Deliver toxic drugs to abnormal cells
• Block pathways that cancer cells use to proliferate without control
• Stop blood supply to actively dividing cancer cells
• Activate the immune system to fight and destroy cancer cells: Living organisms or products from living organisms may be suitably modified and used to initiate an immune response to specifically attack and destroy cancer cells
• Alter the cancer cells to trigger their cell death mechanism

The advantages of targeted therapy over conventional chemotherapy are:

• Increased concentration of medication delivered to specific target cells
• Prolonged interaction of medication with abnormal cells for effective destruction of such cells
• Decreased effect on healthy cells
• Possibly fewer side effects

One type of targeted drug therapy approved for treatment of pancreatic cancer is Erlotinib. Erlotinib is designed to disrupt the epidermal growth factor receptor (EGFR) protein on cancerous cells (located on the exterior of a cell), to arrest cell division. The drug is orally (in pill-form) administered to individuals and usually taken in combination with chemotherapy.

Follow-up care with regular screening and check-ups are important, to monitor the status of the tumor.

How can Mucinous Cystic Neoplasm of Pancreas with Associated Invasive Carcinoma be Prevented?

Presently, no specific methods or guidelines exist for the prevention of Mucinous Cystic Neoplasm of Pancreas with Associated Invasive Carcinoma.

• If an individual is diagnosed with MCN, a thorough investigation of the cystic lesion and regular monitoring may be helpful in early detection of MCN transition to malignancy
• If there is a family history of pancreatic cancer, genetic testing to check for pertinent gene mutations may help detect the tumor early
• Regular medical screening at periodic intervals with blood tests, scans, and physical examinations, particularly for those who have a family history of pancreatic cancer, may be helpful in diagnosing MCN of Pancreas with Associated Invasive Carcinoma in the early stages

What is the Prognosis of Mucinous Cystic Neoplasm of Pancreas with Associated Invasive Carcinoma? (Outcomes/Resolutions)

The prognosis of Mucinous Cystic Neoplasm of Pancreas with Associated Invasive Carcinoma depends upon a set of factors, including:

• 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

In many cases, this type of cancer is not detected in the early stages. Owing to its metastasizing potential, the overall 5-year survival rate of individuals with Mucinous Cystic Neoplasm of Pancreas with Associated Invasive Carcinoma is guarded.

Additional and Relevant Useful Information for Mucinous Cystic Neoplasm of Pancreas with Associated Invasive Carcinoma:

• 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 
• Several clinical trials are ongoing or scheduled for targeted drug therapy. Information may be found on www.clinicaltrials.gov