Intraductal Papillary Mucinous Neoplasms (IPMNs)
Frequently Asked Questions on Intraductal Papillary Mucinous Neoplasms (IPMNs)
A growing number of patients are being diagnosed with an intraductal papillary mucinous neoplasm (IPMN) of the pancreas. The management of these lesions can be complicated, and we thought it would be helpful if we provided general answers to the most common questions our patients have about intraductal papillary mucinous neoplasms. We hope you find this information helpful.
- What are intraductal papillary mucinous neoplasms?
Intraductal papillary mucinous neoplasms are tumors (neoplasms) that grow within the pancreatic ducts (intraductal) characterized by the production of thick fluid by the tumor cells (mucinous). Intraductal papillary mucinous neoplasms are important because some of them progress to invasive cancer (transform from a benign tumor to a malignant tumor) if they are left untreated. Just as colon polyps can develop into colon cancer if left untreated, so too do some intraductal papillary mucinous neoplasms progress into an invasive pancreatic cancer. Intraductal papillary mucinous neoplasms therefore represent an opportunity to treat a pancreatic tumor before it develops into an aggressive, hard-to-treat cancer. - How common are intraductal papillary mucinous neoplasms?
Intraductal papillary mucinous neoplasms form cysts (small cavities or spaces) in the pancreas and these lesions are surprisingly common. We just completed a study here at Johns Hopkins Hospital in which we carefully studied the pancreatic findings in a large series of patient who underwent computerized tomography (CT) scanning that included their pancreas (see reference 1). Only patients who did not have known pancreatic problems and who did not have symptoms from their pancreas were included. 2,832 consecutive CT scans were reviewed and a total of 73 patients were found to have a pancreatic cyst. In other words, 2.6 out of every 100 individuals examined had a pancreatic cyst, and remember these were patients without any symptoms. Most of these cysts were intraductal papillary mucinous neoplasms. There was a strong correlation between pancreatic cysts and age. No cysts were identified among patients less than 40 years of age, while 8.7 percent of the patients age 80 to 89 years had a pancreatic cyst. Thus, intraductal papillary mucinous neoplasms of the pancreas are actually fairly common, particularly in the elderly. - What do intraductal papillary mucinous neoplasms look like pathologically?
The main pancreatic duct is the long branching tube-like structure that runs down the center of the pancreas. It collects the digestive enzymes made by the pancreas from branch ducts that run into it like a stream into a river, and delivers them to the intestine (duodenum). Intraductal papillary mucinous neoplasms (IPMNs) arise within one of these ducts. Grossly (using the naked eye), intraductal papillary mucinous neoplasms (IPMNs) form long thin structures that project into the duct (click here to compare IPMNs with other cycts.). 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 (thick fluid).
Pathologists classify intraductal papillary mucinous neoplasms (IPMNs) into two broad groups - those that are associated with an invasive cancer and those that are not associated with an invasive cancer. This separation has critical prognostic significance. Patients with a surgically resected intraductal papillary mucinous neoplasm without an associated invasive cancer have an excellent prognosis (>95% will be cured), while patients with a surgically resected intraductal papillary mucinous neoplasm with an associated invasive cancer have a worse prognosis.
Intraductal papillary mucinous neoplasms without an associated invasive cancer can be further subcategorized into three groups. They are IPMN with low-grade dysplasia, IPMN with moderate dysplasia, and IPMN with high-grade dysplasia. This categorization is less important than the separation of IPMNs with an associated cancer from IPMNs without an associated invasive cancer, but this categorization is useful as IPMNs are believed to progress from low-grade dysplasia to moderate dysplasia to high-grade dysplasia to an IPMN with an associated invasive cancer. - What is the difference between a main duct and a branch duct intraductal papillary mucinous neoplasm?
Intraductal papillary mucinous neoplasms, as mentioned earlier, form in the main pancreatic duct or in one of the branches off of the main pancreatic duct. Intraductal papillary mucinous neoplasms that arise in the main pancreatic duct are called, as one might expect, “main duct type” IPMNs. Intraductal papillary mucinous neoplasms that arise in one of the branches of the main duct are called “branch duct type” IPMNs. The distinction between main duct type and branch duct type IPMNs is important because several studies have shown that, for each given size, branch duct IPMNs are less aggressive (less likely to have an invasive cancer) than are main duct IPMNs (see references 2,3). - What symptoms do intraductal papillary mucinous neoplasms cause?
Intraductal papillary mucinous neoplasms can come to clinical attention in a variety of different ways. The most common symptoms include abdominal pain, nausea and vomiting. The most common signs patients have when they come to medical attention include jaundice (a yellowing of the skin and eyes caused by obstruction of the bile duct), weight loss, and acute pancreatitis (see reference 4). These signs and symptoms are not specific for an intraductal papillary mucinous neoplasm, making it more difficult to establish a diagnosis. Doctors will therefore often order additional tests (see question 6 below).
A growing number of patients are now being diagnosed before they develop symptoms (asymptomatic patients). In these cases, the lesion in the pancreas is discovered accidentally (by chance) when the patient is being scanned (x-rayed) for another reason. For example, we have seen patients who had a CT scan because they were in a car accident and the CT scan happened to include the pancreas and it revealed an unsuspected IPMN. - How are intraductal papillary mucinous neoplasms diagnosed?
Once a doctor has reason to believe that a patient may have an intraductal papillary mucinous neoplasm, he or she can confirm that suspicion using one of a number of imaging techniques. These include computerized tomography (CT), endoscopic ultrasound (EUS), and magnetic resonance cholangiopancreatography (MRCP). These tests will reveal dilatation of the pancreatic duct or one of the branches of the pancreatic duct. (Click here to see an example of a CT scan showing an IPMN).
In some cases a fine needle aspiration (FNA) biopsy can be obtained to confirm the diagnosis. Fine needle aspiration biopsy can be performed through an endoscope at the time of endoscopic ultrasound, or it can be performed through the skin using a needle guided by ultrasound or CT scanning. - How are main duct type intraductal papillary mucinous neoplasms treated?
As many as 70% of main duct type intraductal papillary mucinous neoplasms harbor high-grade dysplasia (the step right before an invasive cancer develops) or an invasive cancer. Main duct type IPMNs are therefore significant lesions, and, in general, most main duct intraductal papillary mucinous neoplasms should be surgically resected if the patient can safely tolerate surgery (see reference 5). It is important that this surgery is carried out by surgeons with ample experience with pancreatic surgery (see reference 5).
Intraductal papillary mucinous neoplasms in the tail of the pancreas are usually resected using a procedure called a "distal pancreatectomy." Surgeons at Johns Hopkins, including Drs. Martin Makary, Matthew Weiss, Kenzo Hirose and Chris Wolfgang some distal pancreatectomies using minimally invasive procedures (laproscopic pancreatectomy). IPMNs in the head or uncinate process of the pancreas are usually resected using a Whipple procedure(pancreaticoduodenectomy). A total pancreatectomy (removal of the entire gland) may be indicated in the rare instances in which the intraductal papillary mucinous neoplasm involves the entire length of the pancreas. - How are branch duct type intraductal papillary mucinous neoplasms treated?
The management of branch duct IPMNs is more complicated than is the management of main duct type IPMNs. It is likely that many, if not most, branch duct IPMNs are harmless and the risks associated with surgery may outweigh the benefits of resecting small branch duct IPMNs. International consensus guidelines for the treatment of branch duct IPMNs were established in 2006. These guidelines try to balance the risks and benefits of treating patients with a branch duct type IPMN (see reference 5).
The guidelines suggest that asymptomatic patients with a branch duct IPMN that a) is less than 3 cm in size, b) not associated with dilatation (ballooning) of the main pancreatic duct, and c) does not contain a solid mass (mural nodule), can be followed safely without surgery. By contrast, the guidelines recommend the surgical resection of branch duct type IPMNs that cause symptoms, that are larger than 3 cm, that contain a mass (mural nodule), OR which are associated with dilatation of the main pancreatic duct. These guidelines have been supported by a number of recent papers (see reference 6-10). Unfortunately, some resected branch duct IPMNs that are less than 3 cm have been found to have cancer, so the guidelines do not perfectly distinguish patients with benign or malignant disease. Additionally, the size cutoff of 3 cm will either be further validated or changed based upon ongoing studies. Depending on the circumstances, sometimes branch duct IPMNs less than 3 cm are resected because of their rate of growth and or preferences of the patient and surgeon. As was true for main duct IPMNs, intraductal papillary mucinous neoplasms should be surgically resected only if the patient can safely tolerate surgery.
Branch duct IPMNs that are not surgically resected should be monitored radiographically to make sure that they do not grow. Growth of a branch duct IPMN or the development of a mass (mural nodule) may be an indication to surgically remove the IPMN.
Several imaging technologies can be used to monitor branch duct IPMNs for growth. These include computerized tomography (CT), endoscopic ultrasound (EUS), and magnetic resonance cholangiopancreatography (MRCP). In general, smaller branch duct IPMNs less than 1 cm in diameter can be followed with an annual exam. Patients with larger IPMNs should have an examination more frequently, some as frequently as every three months. If you have an IPMN, you should consult with a physician to determine the the most suitable methodology to follow your IPMN as well as the frequency of follow-up. - If I had an IPMN surgically removed, am I cured?
While patients who undergo resection of an IPMN not associated with an invasive cancer are “cured” of that lesion, IPMNs can be multiple and these patients remain at risk for developing a second lesion (see references 11,12). Your doctor may therefore recommend routine follow-up visits. Should you develop a second IPMN, management will depend on it’s characteristics. - If I have an IPMN, am I at increased risk of developing tumors outside of my pancreas?
Patients with an IPMN have been shown to have a slightly increased risk of developing tumors of the colon and rectum (see reference 12). Your doctor may therefore recommend periodic follow-up imaging of your colon." - How can I arrange to be evaluated and treated at the Johns Hopkins Hospital?
If you would like to consult with a physician at Johns Hopkins we recommend that you contact one of our expert surgeons. We encourage you to take advantage of our tremendous experience in caring for patients with intraductal papillary mucinous neoplasms. It is extremely important that you choose a team of specialists with the most up to date knowledge, broad experience, and compassion. We pledge to take great care of you.
References You Might Find Helpful
Pancreatic cysts are fluid-filled sacs or growths that develop in the pancreas.
The pancreas is a gland about 6 inches long that is shaped like a thin pear lying on its side between the stomach and the spine. The wider end of the pancreas is called the head, the middle section the body, and the narrow end the tail. The pancreas makes digestive enzymes — juices that help break down food for digestion while endocrine (islet) cells in the pancreas produce hormones, such as insulin, that control blood sugar levels in the body.
By BruceBlaus (Own work) [CC BY-SA 4.0], via Wikimedia Commons
Causes
Some pancreatic cysts occur as a consequence of having pancreatitis, an inflammation of the pancreas. Most, however, develop sporadically without a clear etiology, and are discovered as an incidental finding during a CT or MRI scan done for another purpose. Advances in the field of imaging technology such as 64 and 256-slice CT scanners have dramatically increased the number of pancreatic cysts found as incidental findings.
Most pancreatic cysts are benign (noncancerous) and do not cause symptoms. However, some are precancerous with the potential to develop into pancreatic cancer. It is therefore critically important to identify the type of cyst and whether it has malignant potential.
Types of Pancreatic Cysts
There are approximately twenty types of pancreatic cysts. Among the most common are:
Intraductal Papillary Mucinous Neoplasms (IPMNs)
Intraductal papillary mucinous neoplasms are the most common type of precancerous cyst. These start in the pancreatic ducts, those that connect the pancreas to the intestine. IPMNs produce proteins in large amounts that form mucus or mucin within the cyst lining and fluid. it is difficulty to predict when an IPMN will become malignant (cancerous). IPMNs that involve the main pancreatic duct seem to create a greater risk.
Serous Cystadenomas (SCAs)
Serous cystadenomas are characterized by thick, fibrous walls and are composed of clear fluid. Almost all SCAs are benign. However, they may cause pain, jaundice, and other discomfort as they increase in size.
Mucinous Cystic Neoplasms (MCNs)
Mucinous cystic neoplasms are precancerous growths which start in the body and tail of the pancreas, and develop predominantly in women. Larger cysts with septations, tiny walls that divide the cyst into compartments, may be more likely to become malignant.
Pseudocysts
Pseudocysts are noncancerous (benign) pockets of fluids lined with scar or inflammatory tissue. Because they do not contain the type of cells found in true cysts, they are called pseudocysts. They are a common complication of acute pancreatitis, inflammation of the pancreas. Pseudocysts are unlikely to develop in the absence of pancreatitis or pancreas injury.
Monitoring Pancreatic Cysts
The UCSF Pancreas Center is a high volume center of excellence. Each year, specialists in the program evaluate a wide spectrum of pancreatic cysts, from the most common to rare variants and subtypes, for their malignant potential. The Center also has state-of-the-art monitoring program and conducts research to better identify which cysts are the most dangerous and how best to monitor and treat them.
Diagnosis
Pancreatic pseudocysts may be difficult to diagnose because their symptoms may are similar to other other diseases and condition. Because the pancreas is located deep within the abdominal cavity, cross-sectional imaging is frequently used to locate and diagnose pancreatic cysts and pseudocysts.
One or more of the following tests may be performed to help characterize the type of cyst involved:
- Transabdominal Ultrasound - Sound waves are used to detect a pancreatic pseudocyst, or gallstones that could potentially cause them.
- Abdominal CT (Computed Tomography) scan, which provides more detailed information about the surrounding anatomy and pathology than ultrasound.
- MRI (Magnetic Resonance Imaging) and MRCP (Magnetic Resonance Cholangiopancreatography) which provide a more precise imaging of fluids and debris in pseudocysts than do CT scans.
- EUS (Endoscopic Ultrasound) and Biopsy - In this procedure, a thin needle is inserted into an endoscope.Then ultrasound images are used to guide the needle into the cyst so fluid and cells can be removed. The Carcinoembryonic Antigen (CEA) Blood Test can be done simultaneously to identify the presence of a pancreatic cyst. A pathologist will then analyze this tissue under a microscope to see determine which type of cyst or pseudocyst is present.
- ERCP (Endoscopic Retrograde Cholangiopancreatography) enables a full and detailed visualization of the structure of the common bile duct, other bile ducts, and the pancreatic duct.
UCSF pathologists are experts in analyzing the fluid in pancreatic cysts and determining whether it represents a likely benign course and has malignant potential.
Treatment Overview
Pancreatic cysts with any potential for malignancy must be monitored carefully over time. The decision whether to remove the cyst surgically versus maintaining active surveillance is dependent on the risk or likelihood that the cyst is cancerous or could progress to malignant state at any given time. Balanced against that risk is the fact that pancreatic surgery is a major physically demanding operation. Because of the location of the organ, cysts in the pancreas cannot simply be drained or suctioned out (aspirated).
Surgery remove a pancreatic cyst is indicated in the following circumstances.
- The cyst is larger than 3 cm
- The cyst has a solid component
- The main drainage system of the pancreas, the pancreatic duct, has widened or dilated.
- The cyst is growing and is causing pressure or pain on the bile duct of other structures or organs.
Although these characteristics of the cyst may not have existed at initial diagnosis, they might have developed over time during during the period of surveillance.
Surgery for Pancreatic Cysts
Our surgeons offer a number of options to remove pancreatic cysts dependent on their size and location. Patients may be offered open, laparoscopic, or robot-assisted surgery depending on a number of factors.
The goals of surgery include removal the malignant or pre-malignant lesion and preservation of digestive function.
Studies show that surgical outcomes for removal of pancreatic cysts are best at centers of excellence where cancer surgeons, also known as surgical oncologists, perform a high volume of pancreatic surgeries, and are complemented by a multidisciplinary team of specialists. UCSF pancreatic cancer surgeons are among the most experienced in the U.S. in diagnosing and treating pancreatic cysts.
Open Surgical Procedures
Whipple Procedure
The Whipple Procedure (also known as a pancreatoduodenectomy) is used to remove cysts in the head of the pancreas. Surgeons remove the head of the pancreas; the duodenum, part of the small intestine; the lower half of the bile duct; the surrounding lymph nodes; the gallbladder, and, in some cases, the pylorus, part of the stomach. (Where the pylorus is not removed, the procedure is called a pylorus-preserving Whipple procedure.) The stomach, bile duct, and remaining part of the pancreas are joined to the small intestine to enable the digestion of food.
Distal Pancreatectomy
When the cyst is located in the tail or left part of the pancreas, surgeons may perform a distal pancreatectomy, removing the tail of the pancreas, and in most cases the spleen (splenectomy).
Total Pancreatectomy
A total pancreatectomy, complete removal of the pancreas, is recommended when the cyst has involvement throughout the organ. Patients will then need to take insulin and pancreatic enzymes for the duration of their lives.
Minimally Invasive Surgery
UCSF pancreatic surgeons utilize state-of-the-art minimally invasive surgical approaches to treating pancreatic cysts, laparoscopy and the da Vinci® Surgical System. Each results in a smaller incision, shorter hospital stay, faster return to work and daily activities and reduced complications.
Laparoscopy
The surgeon inserts a thin, lighted tube with a video camera at its tip (a laparoscope) through a tiny incision in the abdominal wall, through which the surgeon operates with special instruments.
Robotic Surgery
The Da Vinci® Surgical System allows the surgeon to precisely remove the cyst with similar post-operative benefits, namely a shorter hospital stay, faster return to daily activities and reduced complications.