**5. Clinical presentation**

#### **5.1. Risk factors**

**3.1. Pancreatic malignancies**

74 Challenges in Pancreatic Pathology

*3.1.1.1. MD-IPMN*

*3.1.1.2. BD-IPMN*

*3.1.1. Pancreatic cancer arising from IPMN*

gression from "low-risk" BD-IPMN to invasive tumors.

incidence of only 2 cases per 1000 per year and an annual risk of 0.2%.

*3.1.2. Pancreatic cancer distinct from IPMN*

**3.2. Extrapancreatic malignancies**

ated with IPMNs [15–17].

**4. Pathogenesis**

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).

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 pro-

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

Colorectal, gastric, bile duct, renal cell, and thyroid cancers are relatively frequently associ-

IPMNs are mucinous cystic lesions of the pancreas that are characterized by neoplastic, mucin-secreting, and papillary cells projecting from the pancreatic ductal surface. They arise from the epithelial lining of the main pancreatic duct or its side branches. Intraductal proliferation of mucin-producing columnar cells is the main histologic characteristic of IPMNs, and It has been described that previous history of diabetes, especially with insulin dependency, chronic pancreatitis, or a familial history of pancreatic ductal adenocarcinoma (PDAC), may have a higher risk for IPMN [25]. Also, several studies have noticed that the presence of autoimmune disease in general population is around 5%; however, in patients diagnosed with IPMN, the number rises up to 22%. IPMNs can be associated with systemic diseases such as: systemic lupus erythematous and rheumatoid arthritis an inflammatory bowel disease, leading to think that IMPNs may be one manifestation of a more systemic disease [26].

#### **5.2. Symptoms**

Most IPMNs are diagnosed between 60 and 70 years of age. There is a slightly higher prevalence in men than women [7]. Some patients present symptoms at the time of diagnosis (7–43%), being more frequent the presence of abdominal pain, jaundice, and previous history of pancreatitis. Other symptoms are as follows: weight loss, nausea or vomiting, and diabetes [5, 6, 27].
