Intraductal Papillary Mucinous Neoplasm

An intraductal papillary mucinous neoplasm (IPMN) is a cyst that grows in the ducts of your pancreas and has the potential to become cancer. While not all of these tumors turn into cancer, researchers believe they are responsible for 20% to 30% of pancreatic cancer cases.

Table of contents

• What is IPMN?
• Associated anatomy
• Who is affected?
• Symptoms
• Causes and risk factors
• Types of IPMN
• Diagnosis
• Treatment
• Outlook

What is IPMN?

An intraductal papillary mucinous neoplasm is a benign (noncancerous) cystic tumor that develops in the ducts of your pancreas^[1]. Healthcare providers consider these tumors precancerous, which means they are not cancer but have the ability to become cancer later in life^[1].

The cysts contain a jelly-like substance called mucin, a thick fluid produced by the tumor cells^[1]. When benign cystic tumors become cancerous, they secrete more mucin, which can block your pancreatic ducts^[1].

IPMNs are important because some of them progress to invasive cancer if left untreated. Just as colon polyps can develop into colon cancer if left untreated, some IPMNs can progress into invasive pancreatic cancer^[4]. This represents an opportunity to treat a pancreatic tumor before it develops into an aggressive cancer. On the other hand, most IPMNs will never progress to cancer, and it can be safe to observe those IPMNs that don’t progress^[4].

When IPMNs do lead to cancer, they can become pancreatic ductal adenocarcinoma (PDAC), which is the most common type of pancreatic cancer, accounting for about 95% of pancreatic cancers^[6]. Researchers believe IPMNs are responsible for 20% to 30% of pancreatic cancer cases, meaning 2 or 3 out of 10 people with pancreatic cancer may have developed it from an IPMN^[1].

Associated anatomy

• Pancreas
• Pancreatic ducts
• Main pancreatic duct
• Branch ducts

The pancreatic ducts are small tubes that carry digestive juices from the pancreas to the main duct, which connects to the bile duct^[6]. The main pancreatic duct runs down the center of the pancreas and collects digestive enzymes made by the pancreas from branch ducts that run into it, then delivers these enzymes to the intestine^[4].

Who is affected?

Healthcare providers aren’t sure exactly how many people may have these tumors^[1]. The true incidence of IPMNs is unknown because most of them are small and cause no symptoms^[2]. Studies show IPMNs are most often found in men who are between ages 50 to 70 years old^[1]. The age of presentation is typically between the 5th and 7th decades^[2].

Studies that evaluated imaging scans of patients without a history of pancreatic problems have shown that approximately 2.6 to 13.5% of adults have pancreatic cysts, and the incidence increases with age^[2]. At Johns Hopkins Hospital, researchers found that 2.6 out of every 100 healthy individuals examined had a pancreatic cyst. There was a strong connection between pancreatic cysts and age. No cysts were identified among people less than 40 years of age, while 8.7 percent of patients age 80 to 89 years had a pancreatic cyst^[4].

Symptoms

Many people have this condition without feeling sick or having specific symptoms^[1]. Many times, people learn they have these tumors while being tested for other conditions^[1]. You can have this kind of tumor for several years before noticing symptoms^[1].

When symptoms are present, they can include^[1]:

• Stomach pain that comes and goes (some people have stomach pain after eating, which can affect their appetite)
• Unintended weight loss
• Nausea and vomiting
• Back pain
• Oily poop (stool)

These tumors can also cause signs and symptoms similar to specific conditions. Blocked ducts can cause pancreatitis (inflammation of the pancreas), a painful condition that may be a symptom of an intraductal papillary mucinous neoplasm^[1]. Other symptoms may include^[1]:

• Jaundice (yellowing of skin and whites of the eyes) because of blocked bile ducts
• New-onset diabetes (high blood sugars) because of the effect on the pancreas itself

Causes and risk factors

Researchers believe IPMN happens when genes that manage cell growth or prevent tumors begin to change, or mutate^[1]. IPMNs are thought to progress from benign tumors to invasive cancers through DNA damage and mutation. The damaged DNA loses protective factors and undergoes malignant change leading to uncontrolled growth. KRAS and GNAS mutations have been identified in IPMNs^[2].

The risk factors of IPMNs are not completely clear^[2]. A few conditions have been identified as possible risk factors and include^[2]:

• Diabetes (especially patients on insulin)
• Chronic pancreatitis
• A family history of pancreatic ductal adenocarcinoma
• Smoking

People with family members who have or have had pancreatic ductal adenocarcinoma have an increased risk of developing an IPMN^[1].

Types of IPMN

Healthcare providers identify specific IPMNs by category based on their location in the pancreas^[1]. IPMNs can involve the main pancreatic duct, a branch duct, or sometimes both^[2]. Based on location and extent, three subtypes can be identified^[12]:

Main duct type (MD-IPMN): These are tumors blocking your main pancreatic duct, making it get bigger. In all cases of main branch duct type involvement, surgical removal is recommended^[2]. Main-duct IPMNs have approximately a 50% chance of being cancerous^[5], with some studies showing a 57% to 92% risk of becoming cancerous^[6].

Branch duct type (BD-IPMN): These develop in the smaller tubes that deliver digestive enzymes to the main pancreatic duct. Branch duct-type cases may be observed rather than surgically removed. Branch duct type IPMNs are generally believed to carry less risk of becoming cancerous compared to main duct IPMNs^[2]. According to research, branch-duct IPMNs have a 6% to 46% risk of becoming cancerous tumors^[6].

Mixed type (MT-IPMN): When both the main duct and side branch ducts are involved, the tumor is called mixed type IPMN. Mixed type IPMNs are treated like main duct IPMNs^[5].

Diagnosis

Healthcare providers diagnose IPMN with imaging devices^[1]. In most cases, IPMNs are diagnosed based on clinical and imaging criteria^[5]. The main imaging test used is magnetic resonance cholangiopancreatography (MRCP), a special imaging exam that uses an MRI machine. It creates detailed pictures of your liver, bile ducts, gallbladder, pancreas and pancreatic duct^[1].

Other diagnostic procedures may include^[1]:

Endoscopic ultrasounds (EUS) may also be used by doctors to produce detailed images of your pancreas and the tumor. During this procedure, a thin tube with an ultrasound probe is inserted into the digestive tract to get a close-up view of the pancreas^[2]. Fine-needle aspiration (FNA), a type of biopsy, can be used during this procedure to obtain a sample from the tumor. The sample is then examined under a microscope for signs of abnormal cell growth, and genetic testing may be run to estimate the risk that it will develop into cancer^[1].

When examined using a microscope, intraductal papillary mucinous neoplasms can be seen to be composed of tall (columnar) tumor cells that make lots of mucin^[4]. Confirmation of the diagnosis with tissue is rarely necessary^[5].

Treatment

IPMNs are either treated with surgery or carefully monitored over time^[1]. The challenge for clinicians is to determine which IPMNs need to be removed surgically and which IPMNs can be safely observed^[4].

Surgical treatment: Malignant IPMNs are treated with surgery^[1]. The treatment of choice for main-duct IPMNs is surgical removal due to approximately 50% chance of being cancerous^[5]. Surgery can include^[1]:

• Removal of the head of the pancreas (a pancreaticoduodenectomy, also known as the Whipple procedure)
• Removal of the body and tail of the pancreas (a distal pancreatectomy)
• Rarely, removal of the entire pancreas (a total pancreatectomy)

In selected cases the surgery can be performed using minimally invasive techniques such as laparoscopy or robotic surgery^[5].

Observation: If an IPMN is thought to be low risk, doctors may consider closely monitoring the tumor^[1]. Many benign IPMNs don’t progress to cancer. Side-branch IPMNs are occasionally monitored with regular CT or MRIs, but many are eventually removed^[5].

When the decision is made to observe rather than remove a branch duct type IPMN, it should be evaluated periodically, typically with either MRI/MRCP or endoscopic ultrasound examination. The timing of interval surveillance (for example, 3 months, 6 months, 1 year, 2 years, or 3 years) depends on several factors such as the cyst growing larger over time and cyst size. The goal of surveillance is to identify high-risk changes in the cyst over time, should they develop, so that surgical removal can prevent the development of pancreatic cancer^[20].

Indications for surgical removal include jaundice, an enhancing nodule larger than 5 mm, and pancreatic duct widening (greater than 10 mm)^[5].

Outlook

Patients with a surgically removed intraductal papillary mucinous neoplasm without an associated invasive cancer have an excellent outlook (more than 95% will be cured), while patients with a surgically removed intraductal papillary mucinous neoplasm with an associated invasive cancer have a worse outlook^[4].

Pancreatic cancer cases are relatively rare. They account for 3% of all cancer cases in the United States, but also account for 7% of all deaths caused by cancer. Too often, pancreatic cancer isn’t found early enough when treatment can make a difference^[1].