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 and Barish Edil, perform 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
- Laffan, T. A., Horton, K. M., Klein, A. P., Fishman, E. K., Johnson, P. T., and Hruban, R. H. Prevelance of unsuspected pancreatic cysts on MDCT. AJR.American Journal of Roentgenology . 2008. In Press.
- Terris, B., Ponsot, P., Paye, F., Hammel, P. R., Sauvanet, A., Molas, G., Bernades, P., Belghiti, J., Ruszniewski, P., and Flejou, J. F. Intraductal papillary mucinous tumors of the pancreas confined to secondary ducts show less aggressive pathologic features as compared with those involving the main pancreatic duct. Am J Surg Pathol, 24: 1372-1377, 2000.
- Bernard, P., Scoazec, J. Y., Joubert, M., Kahn, X., Le Borgne, J., Berger, F., and Partensky, C. Intraductal papillary-mucinous tumors of the pancreas: predictive criteria of malignancy according to pathological examination of 53 cases. Arch Surg, 137: 1274-1278, 2002.
- Tanaka, M., Chari, S., Adsay, N. V., Fernandez-del Castillo, C., Falconi, M., Shimizu, M., Yamaguchi, K., Yamao, K., and Matsuno, S. International consensus guidelines for management of intraductal papillary mucinous neoplasms and mucinous cystic neoplasms of the pancreas. Pancreatology, 6: 32, 2006.
- Tanno, S., Nakano, Y., Nishikawa, T., Nakamura, K., Sasajima, J., Minoguchi, M., Mizukami, Y., Yanagawa, N., Fujii, T., Obara, T., Okumura, T., and Kohgo, Y. Natural History of Branch Duct Intraductal Papillary-Mucinous Neoplasms of the Pancreas without Mural Nodules: Long-term Follow-up Results. Gut, 2007.
- Lee, C. J., Scheiman, J., Anderson, M. A., Hines, O. J., Reber, H. A., Farrell, J., Kochman, M. L., Foley, P. J., Drebin, J., Oh, Y. S., Ginsberg, G., Ahmad, N., Merchant, N. B., Isbell, J., Parikh, A. A., Stokes, J. B., Bauer, T., Adams, R. B., and Simeone, D. M. Risk of Malignancy in Resected Cystic Tumors of the Pancreas </=3 cm in Size: Is it Safe to Observe Asymptomatic Patients? A Multi-institutional Report. J Gastrointest.Surg., 2007.
- Rodriguez, J. R., Salvia, R., Crippa, S., Warshaw, A. L., Bassi, C., Falconi, M., Thayer, S. P., Lauwers, G. Y., Capelli, P., Mino-Kenudson, M., Razo, O., McGrath, D., Pederzoli, P., and Fernandez-del Castillo, C. Branch-duct intraductal papillary mucinous neoplasms: observations in 145 patients who underwent resection. Gastroenterology, 133: 72-79, 2007.
- Tada, M., Kawabe, T., Arizumi, M., Togawa, O., Matsubara, S., Yamamoto, N., Nakai, Y., Sasahira, N., Hirano, K., Tsujino, T., Tateishi, K., Isayama, H., Toda, N., Yoshida, H., and Omata, M. Pancreatic Cancer in Patients With Pancreatic Cystic Lesions: A Prospective Study in 197 Patients. Clin.Gastroenterol.Hepatol., 2006.
- Allen, P. J., D'Angelica, M., Gonen, M., Jaques, D. P., Coit, D. G., Jarnagin, W. R., Dematteo, R., Fong, Y., Blumgart, L. H., and Brennan, M. F. A Selective Approach to the Resection of Cystic Lesions of the Pancreas: Results From 539 Consecutive Patients. Ann.Surg., 244: 572-582, 2006.
- Chari, S. T., Yadav, D., Smyrk, T. C., DiMagno, E. P., Miller, L. J., Raimondo, M., Clain, J. E., Norton, I. A., Pearson, R. K., Petersen, B. T., Wiersema, M. J., Farnell, M. B., and Sarr, M. G. Study of recurrence after surgical resection of intraductal papillary mucinous neoplasm of the pancreas. Gastroenterology, 123: 1500-1507, 2002.
- Zamora, C., Sahel, J., Cantu, D. G., Heyries, L., Bernard, J. P., Bastid, C., Payan, M. J., Sielezneff, I., Familiari, L., Sastre, B., and Barthet, M. Intraductal papillary or mucinous tumors (IPMT) of the pancreas: report of a case series and review of the literature. Am J Gastroenterol, 96: 1441-1447, 2001.
- Sugiyama, M. and Atomi, Y. Extrapancreatic neoplasms occur with unusual frequency in patients with intraductal papillary mucinous tumors of the pancreas. Am J Gastroenterol, 94: 470-473, 1999.