**3. Malignancy risk**

There has been an increased prevalence of pancreatic cystic neoplasms, frequently being found in elderly asymptomatic patients. This is partially caused by the greater number of cross-sectional studies being performed. Though images obtained through the use of computed tomography (CT-scan) and magnetic resonance imaging (MRI), we are able to estimate the prevalence of pancreatic cysts in 2.5% of the population. This figure increases over time; around the age of 70 years or older, 10% of the population has pancreatic cysts and 20–50% of them are IPMN [8].

The real risk of malignancy may be very low, but the diagnosis is associated with anxiety and usually leads to further medical testing in order to confirm malignancy. The most frequently used tests are likely to include: consultations con gastroenterologists and/or oncologists, endoscopic ultrasound with or without percutaneous biopsy, and occasionally surgery [6, 8, 9]. This is one of the reasons why more and more studies are focusing on evaluating the malignancy rate for pancreatic cancer distinct from IPMN and also for pancreatic cancer arising from IPMN. Figures are rather variable, but over the course of several years, we have been able to see how the rates for malignancy, especially in SB-IPMN, are found to be lower.

Not only IMPNs are associated with pancreatic malignancies but also it is known that extrapancreatic malignancies are more frequently found in these patients.

#### **3.1. Pancreatic malignancies**

#### *3.1.1. Pancreatic cancer arising from IPMN*

#### *3.1.1.1. MD-IPMN*

The malignancy risk in this type of situation is very clear which makes the decision to perform surgery also much easier. Many studies have estimated the overall risk ranges between 36 and 92% [10–13]. Overall, the prognosis after resection is generally favorable as long as its invasion remains within minimally invasive or in T1a status (depth of stromal invasion <5 mm).

#### *3.1.1.2. BD-IPMN*

In this case, there are more controversial figures. Estimated rates here can range from 6 to 47% [8, 11–13]. In 2013, Gardner et al. [8] lower the current 25% lifetime risk of malignant transformation and presented the prevalence of mucin-producing adenocarcinoma in patients diagnosed with pancreatic cysts to be 33.2 per 100,000 patients. A linear increment was detected when studying male patients between the ages of 80–84. In that group, the prevalence was 38.6 per 100,000 patients. Only one systematic review by Crippa et al. [14] is considered to be the first meta-analyses focused in the risk of developing pancreatic malignancies, including malignant BD-IPMNs and PDAC, as well as the risk of death due to pancreatic malignancy in patients undergoing nonoperative management for BD-IPMNs. The estimated overall pancreatic malignancy rate is 3.7%, an incidence of malignancy in 7 cases per 1000 per years and an annual risk on only 0.7%. This is the rate that is entirely comparable with the 90-day postoperative mortality rate following pancreatic resections found at many high-volume centers. Thus, choosing surgery in these cases does not justify for avoiding the unlikely progression from "low-risk" BD-IPMN to invasive tumors.

#### *3.1.2. Pancreatic cancer distinct from IPMN*

There appears to be a "field defect," which may give rise to both IPMN and pancreatic duct adenocarcinoma (frequently related to gastric subtype) occurring in 2–5% of patients diagnosed with IPMN [6, 10]. Also, Crippa et al. [14] lower the previous rates with an estimate of incidence of only 2 cases per 1000 per year and an annual risk of 0.2%.

#### **3.2. Extrapancreatic malignancies**

Colorectal, gastric, bile duct, renal cell, and thyroid cancers are relatively frequently associated with IPMNs [15–17].
