New biomarkers may improve pancreatic cyst management

In the last decade, the number of diagnosed pancreatic cystic neoplasms (PCNs) has increased dramatically, mainly due to a corresponding increase in imaging studies. Most pancreatic cysts are found incidentally in older adults undergoing radiologic imaging for symptoms unrelated to the pancreas. PCNs correlate with age, occurring in 7 to 9 percent of people over age 70.

Many PCNs are not malignant. Nonmucinous cysts (serous cystadenomas) are always benign, and small, asymptomatic branch duct cysts have very little malignant potential. But mucinous cystic neoplasms (MCNs) and some intraductal papillary mucinous neoplasms (IPMNs) can display a range of neoplastic transformations, from low- to high-grade dysplasia and invasive carcinoma.

Still, the overall incidence of cyst-related pancreatic malignancies is relatively low. In a recent retrospective study published in The American Journal of Gastroenterology, Kaiser Permanente researchers reported that 53 (2.9 percent) of 1,815 patients with confirmed PCN were diagnosed with cyst-related malignancy during the study period from 2005 to 2010.

"The challenge is finding that select subgroup with larger cysts that are likely to progress to cancer," says Rahul Pannala, M.D., a gastroenterologist at Mayo Clinic's campus in Arizona.

That challenge is complicated by a lack of diagnostic tools that adequately distinguish between mucinous and nonmucinous cysts. By some estimates, diagnosis is accurate in 50 to 70 percent of cases. Branch duct IPMNs are also problematic. Less aggressive than main duct neoplasms, they are usually managed differently, but guidelines for their management may not discriminate well between patients with benign and malignant disease.

Thus, determining which cysts should undergo surveillance — and for how long — and which should be resected poses real challenges for clinicians.

Consensus guidelines

In 2012, an international group issued recommendations to help guide management of MCNs and IPMNs. Among the recommendations included in the Sendai guidelines:

  • MRI imaging of all cysts larger than 1 cm to help identify solid components, dilation of the main pancreatic duct more than 10 mm, obstructive jaundice and mural nodules
  • Endoscopic ultrasound (EUS) with fine-needle aspiration for all cysts with certain features (thickened cyst wall, main pancreatic duct dilation between 5 and 9 mm, mural nodules) and for cysts 3 cm or larger without these features
  • Surgical resection of main duct IPMNs for patients safely able to tolerate surgery
  • MRI or EUS monitoring of large (3 mm or greater) branch duct IPMNs every three to six months, and monitoring of small branch duct cysts every two to three years

Multidisciplinary Pancreas Clinic and biobanking

At Mayo Clinic's multidisciplinary Pancreas Clinic, cyst surveillance is a matter of clinical judgment, based on cyst type, size, and features such as pancreatic duct dilation and mural nodules. High-quality MRI is used at baseline for cysts larger than 3 cm to identify solid nodules within the cyst. EUS with cytology is used for 2- to 3-cm cysts.

"To monitor low-risk cysts, we repeat MRI in two or three years," Dr. Pannala says. "Cysts that are 2 to 3 cm need careful attention, so we typically have patients return in six months and then gradually lengthen the time between checkups. If patients have 2 to 3 cm cysts and are young and healthy, we tend to think about surgery because the surveillance burden is so long."

Conversely, older adults may have comorbidities that make surgery a higher risk than observation. Patient age, health and preferences play a clear role in the difficult choices involved in treating pancreatic neoplasms.

"Patient anxiety is a very big component in decision-making," Dr. Pannala notes. "We tell patients that cysts are different from pancreatic cancer, but we have to watch for cancer and make decisions based on imperfect data. I address this upfront, inform patients of the clinical guidelines and the relatively low risk of cancer, and I find that many are helped by this information."

In Arizona, the Pancreas Clinic recently initiated a pancreatic cyst fluid biobank. Specimens will be used to test new and evolving biomarkers, such as microRNAs (miRNAs) — small, noncoding RNAs that regulate post-transcription gene expression. In a 2014 study published in Clinical and Translational Gastroenterology, miRNA expression profiling accurately diagnosed serous cystadenoma, MCN and IPMN and distinguished MCN from branch duct-IPMN.

"MiRNA profiling is one of the most exciting new developments in pancreatic cyst research because it may help differentiate between benign and malignant lesions," Dr. Pannala says. "We're eagerly waiting to learn more."

For more information

Wu BU, et al. Prediction of malignancy in cystic neoplasms of the pancreas: A population-based cohort study. The American Journal of Gastroenterology. 2014;109:121.

Tanaka M, et al. International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas. Pancreatology. 2012;12:183.

Lee LS, et al. Investigating microRNA expression profiles in pancreatic cystic neoplasms. Clinical and Translational Gastroenterology. 2014;5:e47.