**6. Cystic focal pancreatic lesions**

#### **6.1. Pseudocysts**

Neuroendocrine tumors are hypervascular lesions [30]. On standard US, they have a similar aspect to ductal adenocarcinoma, as hypoechoic masses (**Figure 7**). The differential diagnosis among the two entities is extremely important, for prognosis, as well as for therapeutic strategy,

**Figure 7.** Neuroendocrine tumor in the pancreatic head, standard US: hypoechoic mass (TU). Dilated main biliary duct

On CEUS, there are different enhancing patterns according to the size and tumor vascularity [23]. Thus, large tumors show an intense enhancement in the early phase, excepting the necrotic areas that are unenhancing, while medium‐sized lesions will also by enhancing in the arterial phase (**Figure 8**) [31]. Both types of lesions are hypoenhancing in the late phase (**Figure 9**). On the other hand, nonfunctioning neuroendocrine tumors can be hypovascular due to their dense

**Figure 8.** Neuroendocrine tumor in the pancreatic head, CEUS—arterial phase: hyperenhancing mass (arrows). Dilated

hyaline stroma (they also appear as hypointense on CE‐CT) [31, 32].

and this is where CEUS can make a difference.

(MBD). GB—gallbladder.

148 Challenges in Pancreatic Pathology

main biliary duct (MBD). GB—gallbladder.

Pseudocysts are the most frequent cystic pancreatic lesions and are characterized by a fibrous wall with no epithelium [33]. On standard US, they usually appear as anechoic lesions in the pancreatic area. Sometimes echoic material can be seen inside the lesions, usually in the lower areas (**Figure 10**). Association with an episode of acute pancreatitis in the recent history of the patient can be useful for a positive diagnosis.

**Figure 10.** Pancreatic cystic lesion, standard US. Anechoic well‐defined lesion, with thick, irregular walls that also have echoic protrusions.

In CEUS, pseudocysts appear as completely unenhancing due to the fact that they are avascular structures, even if in standard US they may have an echoic content (**Figure 11**). This feature is very important for the differential diagnosis with cystic pancreatic tumors [2, 23, 34]. The method has up to 100% sensitivity and specificity in characterizing these lesions [34].

**Figure 11.** Pancreatic cystic lesion the same as in **Figure 10**, CEUS—arterial phase. Anechoic content with unenhancing walls and protrusions. Definitive diagnosis: pancreatic pseudocyst.

#### **6.2. Mucinous cystadenomas and cystadenocarcinomas**

Mucinous cystadenomas of the pancreas are rather rare and considered to be premalignant lesions. If found they should be resected to avoid malignant transformation. Differentiation between pancreatic serous cystadenoma and mucinous cystadenoma is difficult and is based on fine needle aspiration (FNA) that will reveal in the later high levels of carcinoembryonic antigen (CEA) in the aspirated fluid as well as a low level of pancreatic enzymes [35, 36]. They are cystic pancreatic masses, usually multilocular, rarely unilocular when they must be differentiated from pancreatic pseudocysts and from serous cystadenomas [37–41].

On standard US, mucinous cystic tumors appear as cystic masses with thick wall and septa, with echoic protrusions from the wall and with the content (mucin) not always anechoic, sometimes with peripheric calcifications (**Figure 12**). On CEUS, the cystic wall as well as the septa will enhance following the contrast bolus, being easy to differentiate from the unen‐ hancing content (**Figure 13**). The presence of enhancing walls, protrusions, and septa is the differential element from pancreatic pseudocysts [23, 41–43].

**Figure 12.** Large lesion in the body of the pancreas, standard US: lesion with thick walls and mixed content: anechoic component as well as echoic protrusion.

**Figure 13.** Large lesion in the pancreatic body: CEUS—arterial phase: the walls and the protrusion are enhancing. Con‐ clusive for cystic tumor of the pancreatic body.

The diagnosis of intra‐ductal papillary mucinous neoplasms (IPMN), main‐duct or side branch‐duct types, is based on MRI and endoscopic ultrasound. CEUS can be also helpful for differentiating between perfused (tumoral) and nonperfused (clot) regions [44].

#### **6.3. Serous cystadenomas**

In CEUS, pseudocysts appear as completely unenhancing due to the fact that they are avascular structures, even if in standard US they may have an echoic content (**Figure 11**). This feature is very important for the differential diagnosis with cystic pancreatic tumors [2, 23, 34]. The

**Figure 11.** Pancreatic cystic lesion the same as in **Figure 10**, CEUS—arterial phase. Anechoic content with unenhancing

Mucinous cystadenomas of the pancreas are rather rare and considered to be premalignant lesions. If found they should be resected to avoid malignant transformation. Differentiation between pancreatic serous cystadenoma and mucinous cystadenoma is difficult and is based on fine needle aspiration (FNA) that will reveal in the later high levels of carcinoembryonic antigen (CEA) in the aspirated fluid as well as a low level of pancreatic enzymes [35, 36]. They are cystic pancreatic masses, usually multilocular, rarely unilocular when they must be

On standard US, mucinous cystic tumors appear as cystic masses with thick wall and septa, with echoic protrusions from the wall and with the content (mucin) not always anechoic, sometimes with peripheric calcifications (**Figure 12**). On CEUS, the cystic wall as well as the septa will enhance following the contrast bolus, being easy to differentiate from the unen‐ hancing content (**Figure 13**). The presence of enhancing walls, protrusions, and septa is the

differentiated from pancreatic pseudocysts and from serous cystadenomas [37–41].

walls and protrusions. Definitive diagnosis: pancreatic pseudocyst.

150 Challenges in Pancreatic Pathology

**6.2. Mucinous cystadenomas and cystadenocarcinomas**

differential element from pancreatic pseudocysts [23, 41–43].

method has up to 100% sensitivity and specificity in characterizing these lesions [34].

Serous cystadenomas are benign cystic lesions, with a lobulated microcystic structure with thin and centrally oriented septa, which are vascularized on CEUS [43]. It may mimic a solid lesion, both on conventional US and on CEUS, but they are hyperenhanced on CEUS [44].

The criteria used for the differential diagnosis of pancreatic masses (standard US, Doppler US and CEUS) are presented in **Table 1**.


**Table 1.** Differential diagnosis of pancreatic masses [1, 9, 45, 46].

Several studies proved the utility of CEUS for the characterization of pancreatic tumors [2, 9, 17, 47–49]. The accuracy for the diagnosis of solid pancreatic lesions varies from 91.7% [2] to 92.9% [17] or 93.8% in other series [48].

In a recent meta‐analysis that included 23 CEUS studies, the pooled estimate of CEUS sensitivity for the diagnosis of ductal adenocarcinoma was 0.89 (95% CI, 0.85–0.92), while the average specificity was 0.84 (95% CI, 0.77–0.89). For the differentiation of neoplastic and nonneoplastic lesions, the reported pooled sensitivity and specificity were 0.95 (95% CI, 0.93– 0.96) and 0.72 (95% CI, 0.58–0.83) [50].
