Pancreatic Cysts: A New Way to Detect Their Malignant Potential

Kurt J. Isselbacher


AccessMedicine from McGraw-Hill 

As a result of more frequent use of abdominal imaging, more pancreatic cysts are being identified. Once a cyst is identified, however, it poses a challenge since some are benign, some are of low-grade malignancy, and others show evidence of being precursors of invasive pancreatic ductal adenocarcinomas (PDAs). The distinction among cyst types is therefore critical in the effective management of patients. Unfortunately it is often difficult to determine the type of cyst from conventional clinical, radiologic, or cytologic findings.

It turns out that 60% of cysts are malignant or have malignant potential. There are predominantly four types: (1) intraductal papillary mucinous neoplasms (IPMNs), (2) mucinous cystic neoplasms (MCNs), (3) serous cystadenomas (SCAs), and (4) solid pseudopapillary neoplasms (SPNs). Of these categories, IPMNs and MCNs have the greatest potential of progressing to PDAs and becoming invasive if not surgically excised. In the case of  IPMNs, there are reports suggesting that there is about a 5-year lag from the time of initial diagnosis to evidence of invasion. Thus, there is a broad window for curative resection if the malignant or premalignant cysts are accurately identified. 

Cyst fluids can easily and safely be obtained from patients with pancreatic cysts by endoscopic aspiration. These fluids are often acellular and therefore typically not useful for cytologic diagnosis. However, they can be analyzed for their DNA. Recently Dr. Bert Vogelstein and his group at Johns Hopkins (Wu et al., 2011) determined the exomic sequences of DNA from the neoplastic epithelium of eight surgically resected cysts representing the four types described above. They identified numerous mutations, especially in genes involved in protein degradation. Without going into the scientific details of their studies, it is evident that sequencing the DNA isolated from these cysts will be an important advance for both the diagnosis and treatment of patients with pancreatic cystic tumors.