I have had a strong interest in the epidemiology and natural history of the benign precursor lesions that are associated with the various epithelial solid tumors—cervical intraepithelial neoplasia whose association with cervical cancer has been studied and recognized by Papanicolaou since 1945; the adenoma-carcinoma sequence in the large bowel that was established in the 1970s; and ductal carcinoma-in-situ and breast cancer. Their early discovery/diagnosis and management has had profound effects on prognosis for their associated tumors.
And now we have a newcomer to this category of precursor tumors. IPMN is not yet as well studied as the others. Nonetheless, at present, it is estimated that about 30% of invasive pancreatic adenocarcinomas, the most common and deadly form of pancreatic cancer, occur as the result of progression from IPMNs.
Intraductal papillary mucinous neoplasm—boy, that is a real mouthful. Let us refer to it by its acronym, IPMN. IPMN is a benign cyst in the pancreas that has the potential to develop into the real thing—a malignant pancreatic cancer. To the degree that its risk factors are known, they appear to parallel those of invasive pancreatic cancer—tobacco, diabetes and pancreatitis. They occur more or less equally in both genders and begin to appear in individuals starting at age 50.
A large meta-analysis of 17 studies published in 2019 that included over 48,000 patients demonstrated that about 8% of asymptomatic adults over age 50 harbor pancreatic cysts. In the early 1980s, small reports from Japan indicated that most pancreatic cysts had the characteristics indicated by the name of IPMN—they were in the ducts of the pancreas (rather than the glandular tissue), had papillary histology when studied under the microscope by the pathologist (finger-like projections of tissue), and produced mucin (high molecular weight glycoproteins that are produced and secreted by various epithelial tumors and tissues). The ducts are the tubes within the pancreas that carry its secretions, primarily the digestive juices its glands produce, to the small bowel.
Suspected lesions generally require endoscopy, usually with ERCP (endoscopic retrograde cholangiopancreatography) in order to obtain histologic or cytologic confirmation as to the diagnosis of IPMN. This is a procedure in which the endoscope is passed by the gastroenterologist through the small bowel to the ampulla of Vater (the opening of the bile duct), passed through into the biliary ductal system, and through there into the ductal system of the biliary tree and pancreas. At that point, a decision must be made as to whether to recommend surgical resection or to simply monitor and observe the lesion. This decision depends on the malignant potential of the lesion. The factors that go into this decision include the patient’s age, health, and the presence of high-grade dysplasia or invasive cancer.
What is also of great relevance is the location of the IPMN within either the branched side ducts of the pancreas or the main duct of the pancreas. A recent cohort study from the Mayo Clinic included 2,114 patients who underwent CT scans from about 2000 to 2015. Of these, 231 were found to have IPMNs (10.9%). Of these, 210 (90.9%) were in the branch ducts while 21 were in the main duct (9.9%), the large central duct of the pancreas. After a median follow-up of 12 years, four of the patients with IPMN developed pancreatic cancer—this was similar to the rate in the non-IPMN group. Thus, the actual rate of progression of IPMNs is really rather limited and not dramatically increased over the incidence rate of pancreatic cancer in the general population.
A meta-analysis of studies of branched duct IPMNs (as the name implies, smaller ducts that branch off the main duct) that underwent long-term surveillance found that the risk of progression to invasive pancreatic cancer was very low in the absence of high-risk features. This progression was certainly less than 1% per year and thus surveillance, rather than surgery, was certainly warranted for these lesions.
The much less common IPMNs which arise in the main pancreatic duct progress at a much higher rate to invasive pancreatic cancer. These lesions need to be treated with much more respect and care, and if any high-risk features—size, age of the patient, dysplasia—present themselves, surgery and resection should be considered as a preventive measure.
Again, not all of pancreatic cancer arises from IPMNs, but clearly a substantial fraction does. As always, the individual should discuss this problem with his/her healthcare provider and seek consultation with a specialist.
Alfred I. Neugut, MD, PhD, is a medical oncologist and cancer epidemiologist at Columbia University Irving Medical Center/New York Presbyterian and Mailman School of Public Health in New York. Email: [email protected].
This article is for educational purposes only and is not intended to be a substitute for professional medical advice, diagnosis, or treatment, and does not constitute medical or other professional advice. Always seek the advice of your qualified health provider with any questions you may have regarding a medical condition or treatment.
