The pancreas is a glandular organ located deep in the abdomen. It produces insulin and other hormones for blood sugar regulation, and creates digestive enzymes that flow into the small intestine. A pancreatic cyst is a fluid-filled sac that forms within or on the surface of this organ. These findings are increasingly common due to the widespread use of high-resolution abdominal imaging. Pancreatic cysts are diverse, with causes ranging from simple inflammation to complex genetic changes. Understanding their origin is the first step in determining potential risk and guiding medical management.
Classification of Pancreatic Cysts
Pancreatic cysts are classified into two major categories based on their origin: inflammatory collections and true cystic neoplasms. Inflammatory collections, often called pseudocysts, are not true cysts. Their wall is composed of fibrous tissue resulting from physical damage or chemical irritation, not a lining of epithelial cells.
Neoplastic cysts are considered “true cysts” because they arise from the abnormal growth of epithelial cells lining the pancreatic ducts or glands. These true cysts are sub-divided into distinct types, many of which carry a risk of becoming cancerous. The most frequently encountered types are the Serous Cyst Neoplasm (SCN), the Mucinous Cystic Neoplasm (MCN), and the Intraductal Papillary Mucinous Neoplasm (IPMN). This cellular distinction is important, as the causes, behavior, and required follow-up for each type differ significantly.
Etiology of Inflammatory Cysts
The formation of inflammatory cysts, or pseudocysts, is a direct consequence of pancreatic damage, with acute or chronic pancreatitis being the primary trigger. Pancreatitis occurs when digestive enzymes become active prematurely inside the organ, causing the pancreas to digest itself. This process leads to significant inflammation and tissue necrosis.
A pseudocyst forms when the pancreatic duct system is disrupted, allowing enzyme-rich fluid to leak into the surrounding tissue. The body responds by attempting to contain the fluid, forming a non-epithelialized wall of fibrous tissue around the collection. This encapsulation process typically takes four to six weeks, classifying the collection as a pseudocyst. Risk factors for the pancreatitis that leads to pseudocysts include long-term heavy alcohol use and the presence of gallstones. Severe abdominal trauma or injury to the pancreas can also cause ductal disruption, leading to enzyme leakage and pseudocyst formation.
Etiology of Neoplastic Cysts
Neoplastic cysts originate from the abnormal proliferation of epithelial cells that line the pancreas. The causes of these true cysts are rooted in cellular and genetic mutations that drive uncontrolled cell growth. The underlying etiology varies significantly among the three main types: SCN, MCN, and IPMN.
Genetic Drivers of Cystic Growth
The development of Intraductal Papillary Mucinous Neoplasms (IPMNs) and Mucinous Cystic Neoplasms (MCNs) is linked to specific genetic mutations that alter cell signaling. The KRAS gene, a common oncogene, is mutated in a significant proportion of both IPMNs and MCNs, promoting abnormal cell growth and mucin production. The GNAS gene mutation is highly characteristic of IPMNs, found in approximately 66% of these lesions, and is rarely detected in MCN or SCN.
These genetic changes allow ductal lining cells to secrete large amounts of thick mucin, which fills and expands the pancreatic duct system. Serous Cyst Neoplasms (SCNs) are genetically distinct, showing no association with KRAS or GNAS mutations. Instead, SCN development is strongly linked to the Von Hippel-Lindau (VHL) tumor suppressor gene. Inactivation of the VHL gene leads to the formation of the glycogen-rich clear cells that characterize SCNs.
Demographic and Syndromic Associations
Specific patient demographics and inherited conditions are associated with particular cystic types. MCNs are overwhelmingly found in middle-aged women, with a female-to-male ratio as high as 20:1. MCNs are unique in that they contain a dense, hormone-responsive “ovarian-type” stroma beneath the epithelial lining.
SCNs are also more common in women, typically affecting middle-aged to elderly individuals. A small number of SCNs are associated with the inherited Von Hippel-Lindau syndrome, which involves a germline mutation of the VHL gene. In contrast, IPMNs are found more often in men, usually between 50 and 70 years old. Their risk is increased in people with a history of cigarette smoking or diabetes. The IPMN risk is also elevated in rare inherited conditions like Peutz-Jeghers syndrome, which involves mutations in the STK11 tumor suppressor gene.