**8. Cystic pancreatic endocrine neoplasms (CPENs)**

CPENs encompass 8% of all pancreatic cystic tumors and about 15% of pancreatic neuroen‐ docrine tumors [45, 46]. The majority of CPENs are non‐functioning and asymptomatic. These neoplasms usually are diagnosed in elderly patients (sixth–seventh decades) without sex prevalence. They can be associated with multiple endocrine neoplasia types. The diagnosis, generally incidental, is based on imaging examinations (US, MRI, and CT). Cystic mass is usually with hypervascular rim, and in several cases, there is septation or a solid component [45]. The lesions are generally well circumscribed with regular wall around areas of cystic degeneration.

EUS‐guided FNA can reveal low levels of CEA. Immunohistochemical staining for chromog‐ ranine and synaptophysin is present. Malignant potential of CPENs is not clearly defined because it is difficult to detect malignancy on biopsy. The lesions are considered premalignant, and surgical treatment is indicated especially for lesions plus than 2 cm in size. The resective surgery presents excellent results with very long survival (plus than 85% of patient treated) [46]. Observational strategy has been proposed [47] for CPENs based on the similar experience with non‐functioning pancreatic endocrine neoplasms (PENs) [48]. The results of non‐ operative choice are not defined.

### **9. Acute postnecrotic pseudocysts**

the pancreatic ductal system are characteristic of chronic pancreatitis. On the contrary, segmental and marked dilatations of the branch ducts with little calcifications are character‐

SPPNs represent 9% of all cystic pancreatic tumors and have the major incidence in young female patients (second–third decade). SPPNs are a neoplasm of unknown, not well‐defined origin: in fact, in the past, various descriptive names were employed. The macroscopic appearances of SPPNs are large solid masses (8–10 cm in size) and well encapsulated, and often the cut section shows areas of hemorrhage, cystic degeneration, and solid areas. The micro‐ scopic features are polygonal epithelioid cells that form solid pseudopapillary structures alternated hemorrhagic necrotic pseudocyst. There is also evident extensive vascular network, often with infiltrative growth pattern. Alterations in the antigen‐presenting cell/beta‐catenin pathway [42] and vimentine positive can be present. The histologic picture may resemble closely to pancreatic endocrine neoplasms (PEN) but chromogranin is negative. In some cases, histologic criteria of malignancy such as high nuclear grade, venous invasion, and atypical cells may be observed; the metastatic spread is possible (10–15% of cases). SPPNs can be located in all side of the pancreas. Clinical appearances are abdominal pain, palpable mass, nausea/ vomiting, jaundice, and weight loss. The imaging examinations (CT, MRI, and EUS) show a solid and cystic masses with a well‐defined and thick capsule with sometimes peripheral calcifications without septations. EUS‐FNA provides little information. SPPNs can be consid‐ ered lesions with low malignity and rare occurrence of metastasis, usually hepatic (10–15%). The recommended treatment is surgery and the complete resection is often possible (94%); the cure rate reaches 85–95% of patients [6, 44]. The pancreatic resection is based on the location

CPENs encompass 8% of all pancreatic cystic tumors and about 15% of pancreatic neuroen‐ docrine tumors [45, 46]. The majority of CPENs are non‐functioning and asymptomatic. These neoplasms usually are diagnosed in elderly patients (sixth–seventh decades) without sex prevalence. They can be associated with multiple endocrine neoplasia types. The diagnosis, generally incidental, is based on imaging examinations (US, MRI, and CT). Cystic mass is usually with hypervascular rim, and in several cases, there is septation or a solid component [45]. The lesions are generally well circumscribed with regular wall around areas of cystic

EUS‐guided FNA can reveal low levels of CEA. Immunohistochemical staining for chromog‐ ranine and synaptophysin is present. Malignant potential of CPENs is not clearly defined because it is difficult to detect malignancy on biopsy. The lesions are considered premalignant,

**7. Solid pseudopapillary neoplasms (SPPNs)**

istics of IPMNs.

104 Challenges in Pancreatic Pathology

of neoplasm in the gland [43, 44].

degeneration.

**8. Cystic pancreatic endocrine neoplasms (CPENs)**

Pancreatic pseudocysts are inflammatory lesions. They are evolutions and complications of chronic and acute pancreatitis. The etiologies of pancreatitis are various: alcoholic, biliary, or traumatic. The pseudocysts represent about 80% of all cystic lesions of the pancreas. The pseudocyst wall has no epithelial lining unlike the true cysts [49]. Histologically, the pseudo‐ cyst wall consists of fibrosis and inflammatory tissue. Moderate and severe acute pancreatitis are characterized by fluid necrotic collections in or near the pancreas at the beginning without wall. With the flogistic evolution, the fluid necrotic collections are surrounded by granulation and fibrous tissue [50]. Acute postnecrotic pseudocysts are the final evolution of necrotizing pancreatic gatherings, characterized by complete separation of the tissues, with liquid content and a fibrous wall [51]. The incidence of acute pseudocysts is low, at 5–16%. Several clinical imaging and chemistries features can be useful for differential diagnosis between pseudocysts and cystic pancreatic tumors. In the history, there is usually previous pancreatitis; the cystic walls are regular and thin, without calcification: in the 65–70% of cases, there is the commu‐ nication with Wirsung's duct; in the intracystic fluid, CEA, CA19‐9, and mucous cells, on the contrary increased amylase and lipase, are absent. The evolution of a lesion with a fibrous wall and the formation of a pseudocyst can be completed in several weeks and in some cases in a longer period (12–16 weeks). Small cysts (<5–6 cm) can develop for many months without clinical appearance. In some cases, spontaneous improvement until the resolution of the pseudocysts can occur [52].

Diagnosis of acute postnecrotic pseudocysts is greatly facilitated by the history of previous episodes of acute pancreatitis. The imaging examinations (transabdominal US, CT, MRI, and MRCP) are crucial for positive diagnosis (sensitivity of CT is very high 90–100%) [49]. Char‐ acteristic picture on CT is roundish cyst, fluid filled, without septations, and surrounded by a thick wall around the pancreas. EUS can be used for further evaluation but usually do not add other information on CT. EUS‐guided FNA and cyst fluid analysis can demonstrate high amylase concentration.

The size of pseudocysts (plus than 6–7 cm) and the clinical presentation and evolution (lesions symptomatic and/or persistent over many months) can direct the treatment [53].

The choice of therapeutic procedure should be based on the very frequent connection of the acute pseudocysts with pancreatic ducts [53]. The percutaneous US/CT‐guided drainage is usually complicated by pancreatic fistula with persistent leakage from the drain, infection, and repeated changes of the drain [53, 54]. Therefore, the intervention of choice must provide persistent drainage of pancreatic secretion by a cystodigestive anastomosis or fistulas [53].

Another pathological characteristic of acute pseudocysts is the close connections with various adjacent intestinal organs (stomach, duodenum, and small intestine) according to the ana‐ tomical site where the pseudocyst develops [53].

Drainage of the pseudocysts by endoscopic technique has been proposed [55, 56]: this is performed by creating a small opening between the cyst and the stomach. The disadvantage of this techniques is incomplete drainage with recurrence of pseudocysts and infections because the communication can be small and in site not declive [53, 57]. The surgical cystodi‐ gestive anastomosis can employ the more adjacent intestinal organ (stomach or duodenum or small intestine) and can perform cystogastrostomy or cystojejunostomy or cystoduodenosto‐ my [52, 53].

For cysts located in the body or tail of pancreas, the cystojejunostomy or cystogastrostomy is performed depending on the development of the cyst above or under the mesocolon. For pseudocysts located on the head of the pancreas, cystoduodenostomy is usually performed. The same surgical procedures can be performed with a laparoscopic approach with the advantage of the minimal invasiveness [53].
