Practice Essentials
Pancreatic cysts represent a small yet increasingly detected entity of pancreatic abnormalities. Approximately 70% of pancreatic cystic lesions are discovered incidentally. The most frequently encountered neoplastic pancreatic cysts include intraductal papillary mucinous neoplasm (IPMN), serous cystadenoma (SCA), mucinous cystic neoplasm with ovarian stroma (MCN), and solid pseudopapillary epithelial neoplasm. IPMN is further subdivided into branch duct (BD), main duct, and combined forms. Together, these constitute 90% of premalignant pancreatic, primarily cystic, tumors.
In contrast, pseudocyst, true epithelial cyst, lymphoepithelial cyst, and mucinous non-neoplastic cyst have no malignant potential.
Malignancy occurs only in mucinous cysts. SCA is considered a nonmalignant lesion, and malignant serous tumors reported in the literature have not been found to meet the WHO criteria for SCN.
IPMN can progress from lower to higher grades of dysplasia and, ultimately, pancreatic ductal adenocarcinoma (PDAC). IPMNs involving the main duct have a higher malignancy rate than those in the branches, with the risk of malignancy estimated to be 62%; the risk for malignancy of MCNs is less than 15%.
Other, rarer cystic lesions, such as solid pseudopapillary epithelial neoplasm and cystic pancreatic neuroendocrine tumor (cPNET), tend to harbor features that suggest a specific diagnosis, usually leading to surgical removal.
To study the frequency of incidental pancreatic cysts in asymptomatic individuals, Kromrey performed a magnetic resonance cholangiopancreatography (MRCP) examination in 1077 participants enrolled in a population-based cohort study. Of the original group, 676 people underwent a repeat examination 5 years later. At the time of the initial exam, 49% had at least one cyst ≥2 mm in diameter. The incidence of new cysts during the follow-up period was 2.6% per year. Cyst presence was strongly related to age; by 75 years of age, 75% of participants had one or more cysts. The discrimination between benign and premalignant or malignant pancreatic cysts is of high importance so as to avoid unnecessary procedures, such as radiologic follow-up examinations or surgical resection.
Mucinous cystic neoplasm with ovarian stroma (MCN)
MCNs are common in middle-aged women, are usually well defined, and are predominantly in the tail of the pancreas (>90%). Compared with serous cystic tumors, MCNs are larger (>20 mm in diameter) and less numerous (usually < 6). The biologic behavior of MCNs is variable, and different histologic patterns frequently coexist in the same tumor. The tumors may be entirely benign, as are mucinous cystadenomas or intraductal papillary mucinous adenomas. Some tumors are borderline, showing cellular dysplasia, whereas others are frankly malignant. Malignant cystadenocarcinoma and intramedullary mucinous carcinomas may be further subdivided into noninvasive and invasive types.
(The radiologic characteristics of MCNs are demonstrated in the images below.)
Sonogram through the left hypochondrium shows a large septate mass anterior to the kidney (K).
Nonenhanced axial CT scans. Image 1 shows a large septate mass in the left hypochondrium. Note the smooth external contour typical of a mucinous cystic neoplasm.
Intraductal papillary mucinous neoplasm (IPMN)
On the basis of involvement of the pancreatic duct, IPMNs are classified as either main duct IPMN, side-branch IPMN, or mixed variant IPMN involving both the main pancreatic duct and the side branches. Main duct IPMNs often have intestinal-type epithelium, and side-branch IPMNs usually have gastric-type epithelium. Although all morphologic variants of IPMN can progress to cancer, invasive adenocarcinoma originating in gastric-type IPMNs is associated with a significantly worse survival rate than that originating from other types of IPMNs. However, the imaging features are not specific for differentiating the various histologic variants of IPMNs.
Side-branch IPMNs are commonly detected in older men and are more frequently located in the proximal pancreas (head and uncinate process). An important differentiating feature between MCN and IPMN is visualization of pancreatic ductal communication. If a clear channel of communication with the pancreatic duct is visualized, the diagnosis of side-branch IPMN is almost certain because SCAs and MCNs do not communicate with the pancreatic ductal system.
Despite the low incidence of aggressiveness of mucinous cystic lesions 3 cm and smaller, the incidence is not low enough to dismiss the lesions entirely, and careful review of the imaging features is mandated. In addition, patients whose condition is found not to be suitable for surgical management often need frequent assessments for growth and change in imaging features.
(IPMNs are seen in the images below.)
Pancreatic intraductal papillary mucinous tumor (IPMT). Contrast-enhanced axial CT scans through the pancreas show a 5.5-cm cystic tumor in the pancreatic head. Note the upstream, gross dilatation of the pancreatic duct. The accessory pancreatic duct is also dilated.
Pancreatic intraductal papillary mucinous tumor (IPMT). (Top) Superior mesenteric angiogram shows capillary vascularity in the mass in the pancreatic head during the arterial phase. (Bottom) The portal venous phase image shows displacement of the portal venous branches and encasement of the junction of the superior mesenteric vein and the portal vein. M denotes the pancreatic mass.
Pancreatic intraductal papillary mucinous tumor (IPMT). Contrast-enhanced axial CT scans through the pancreas show a multiseptate tumor in the head of the pancreas.
Pancreatic intraductal papillary mucinous tumor (IPMT). Contrast-enhanced CT scans through the pancreas show gross dilatation of the pancreatic duct. At surgery, IPMT was confirmed.
Serous cystadenomas
Serous cystadenomas (microcystic adenomas) (see the images below) are the second most common cystic tumors of the pancreas. The clinical presentation of serous cystadenomas is similar to that of mucinous cystic pancreatic tumors.
Pancreatic microcystic adenoma. Plain radiograph shows tumor calcification in a microcystic adenoma (left upper quadrant). Calcification in the microcystic adenoma presents as a central cluster arranged in a sunburst or stellate arrangement. Central calcification is better evaluated with CT than with radiography.
Pancreatic microcystic adenoma. Sonogram shows a cystic mass in the region of the tail of the pancreas.
Pancreatic microcystic adenoma. Contrast-enhanced axial CT scans show a hypervascular tumor in the pancreatic tail with sunburst calcification. Note the Swiss-cheese enhancement.
Because of increasing use of cross-sectional imaging, many of these tumors are detected as an incidental, asymptomatic finding.
On cross-sectional images, serous cystadenomas appear as numerous tiny cysts separated by delicate fibrous septa, which give them a honeycomb appearance. The cysts are filled with clear, watery fluid and are often arranged around a central stellate scar, which may be calcified. On CT scans, sunburst central calcification in a spongy mass is pathognomonic of this tumor, but this finding occurs in only 10% of patients.
Endoscopic ultrasonography (EUS) allows better resolution of the honeycomb structure than does CT. At times, the cysts may be large, a feature that makes it difficult to differentiate these cysts from MCNs.
Hypervascularity may be demonstrated on angiograms, and some tumors occur with intra-abdominal hemorrhage.
Differential diagnoses
Pancreatic pseudocyst or pancreatic fluid collections
Fluid collections occur in as many as 50% of cases of acute pancreatitis. Pseudocysts are usually seen as anechoic fluid spaces on sonograms, but they may show internal echoes if they contain necrotic tissue or clot.
Imaging findings that suggest a diagnosis of pseudocyst rather than of cystic neoplasm include the following: lack of septae, loculations, solid components, or cyst-wall calcifications on computed tomography (CT) scans; hypovascularity on angiograms; and communication between the cyst and pancreatic ducts on endoscopic retrograde cholangiopancreatography (ERCP). Most pseudocysts are extrapancreatic, whereas pancreatic cystic neoplasms are intrapancreatic.
Pancreatic abscess
Pancreatic abscess is usually secondary to infection of a pseudocyst, but in rare cases, it can occur as a result of direct spread from renal or colonic infection. Typically, a pancreatic abscess occurs 2-4 weeks after an episode of acute pancreatitis.
On images, these abscesses may appear similar to pseudocysts. Generally, the appearance depends on their age. In the acute phase, the changes may be subtle, with only loss of normal pancreatic contour associated with obliteration of the pancreatic outline and the peripancreatic vascular and other soft tissue spaces. These changes may be indistinguishable from those found in severe acute pancreatitis. In the subacute and chronic stages, when central necrosis occurs, an anechoic or complex cystic mass is usually seen. A debris level may be observed in the dependent portion of the abscess. In the subacute or chronic phase, through transmission is usually good except when gas is present within the abscess. In the presence of gas, the abscess may become echogenic and may shadow.
The walls of subacute and chronic pancreatic abscess have variable features. The walls may be thick, irregular, and well defined, or the abscess may have no definable wall at all. The sonographic findings are nonspecific, but in the appropriate clinical setting, a diagnosis of an abscess may be suggested and confirmed by means of percutaneous aspiration or CT.
Parasitic cysts
Echinococcus granulosis cysts and multilocularis cysts of the pancreas have been described, although pancreatic involvement is exceptionally rare. E. granulosis cysts may be unilocular, multilocular, or complex cystic.
On imaging alone, differentiation of these and other cystic masses is difficult. Serologic tests may be useful in the appropriate clinical setting. E. multilocularis cysts show an echogenic infiltrative pattern. This diagnosis should be entertained in endemic regions when such a pattern is seen.
Solid and papillary epithelial pancreatic tumors
Solid and papillary epithelial neoplasm of the pancreas may be solid or cystic. These are rare tumors that are often mistaken for mucin-secreting tumors or nonfunctioning adenomas.
Solid and papillary epithelial pancreatic tumors are most often located in the pancreatic tail. They are large, well-encapsulated masses with areas of hemorrhage and necrosis. On sonograms, they appear as heterogeneous, round, solid masses with a cystic necrotic center and dystrophic calcification, which may shadow.
Dysontogenic cysts
Dysontogenic cysts are hamartomatous cysts that are often associated with renal cysts, cerebellar angiomas, and encephaloceles. Imaging reveals a large, thin-walled cyst with a mulberry configuration.
Pseudoaneurysms
Pseudoaneurysms are usually not truly intrapancreatic, and they may be confused with a pancreatic cyst. These aneurysms are a complication of pancreatitis in 3.5-10% of patients. Doppler sonography may show turbulent arterial flow within a pseudoaneurysm, whereas color flow Doppler sonography shows bidirectional flow and swirling within the anechoic mass. Doppler imaging may permit tentative identification of the artery feeding the pseudoaneurysm.
Retroperitoneal neurofibroma or schwannoma
These tumors may be hyperechoic or hypoechoic/cystic lesions with sporadic internal echoes. This is a common feature in larger tumors in which cystic degeneration and hemorrhage have occurred. The tumors are retroperitoneal but may mimic pancreatic masses.
Pancreatic sarcoma
Pancreatic sarcoma is a rare tumor of the mesenchymal supporting structures of the pancreas. It is a relatively sonolucent mass and may be mistaken for a fluid collection or pseudocyst. Sonographic results may be normal, or sonograms may demonstrate a retroperitoneal mass, which is relatively sonolucent compared with the surrounding tissues. Therefore, this lesion may be confused with a cystic pancreatic mass.
Pancreatic lymphoma
Primary pancreatic lymphoma is rare. The clinical presentation is not unlike that of pancreatic carcinoma. Sonography may reveal a homogeneous, sonolucent, or complex mass. These masses are usually echo-poor and may mimic cystic lesions. As the prognosis of a pancreatic lymphoma is favorable, its differentiation from a carcinoma is crucial. The correlation of sonographic, CT, and angiographic findings may result in a correct diagnosis. However, if doubt exists, sonography-guided biopsy may reveal the true nature of the mass.
Pancreatic acinar cell carcinoma
Pancreatic cell carcinomas (PACCs) constitute approximately 1% of exocrine pancreatic tumors. PACC is an epithelial neoplasm with evidence of acinar differentiation. Patients with acinar cell carcinoma have a better prognosis than do patients with ductal-type adenocarcinomas but a worse prognosis than do patients with pancreatic endocrine tumors. On CT, PACC has been described in a variety of ways, including as a poorly defined dense mass; as a well-defined mass with central necrosis; and as a cystic mass surrounded by a thick hypervascular wall.
Preferred examination
MRI is the preferred technique for the diagnosis of cystic pancreatic tumors. MRIs are usually helpful in differentiating between pseudocysts and cystic neoplasms.
Magnetic resonance cholangiopancreatography (MRCP) can depict biliary and pancreatic duct anatomy noninvasively, and it helps in the diagnosis of intraductal tumors.
Ultrasonography is generally the first technique in a patient with epigastric symptoms. This is an excellent modality for the diagnosis of cystic pancreatic masses. Sonography also provides an opportunity for guided intervention, such as aspiration and biopsy. Doppler sonography provides an added benefit in the evaluation of hypervascular tumors and vascular thrombosis/occlusion associated with pancreatic tumors. Echo-enhanced power Doppler sonography has high sensitivity and specificity in the differential diagnosis of pancreatic tumors.
In equivocal cases or in cases in which malignancy is highly suspected, EUS-FNA gives the best diagnostic yield, as it permits the acquisition of cytologic samples and cystic fluid for the analysis of various tumor markers.
Occasionally, despite complete evaluation of a cystic mass, the type of cyst may remain indeterminate. Although expensive and invasive, laparoscopic sonography, biopsy of the cyst wall, and analysis of the cystic aspirate significantly contribute to the differential diagnosis of pancreatic cystic lesions.
CT shows tumor calcification and is an excellent modality for the detection of local and distant metastases. Although CT and MRI cannot be used to differentiate mucin content from pancreatic juice, communication between the cystic lesion and the dilated MPD and a bulging papilla with a patulous orifice are characteristics of IPMT. The internal architecture of mucinous tumors is displayed at least as well on MRI scans as it is on CT scans, with the exception of calcification within the lesion (which MRI has only a limited ability to reveal).
Spiral and/or multisection CT are excellent techniques for imaging the pancreas, providing superb spatial resolution and anatomic detail. With thin collimation and arterial and venous phases and multiplanar and/or 3-dimensional (3D) reconstructions, excellent detail of the vascular anatomy is depicted; most centers now seldom use angiography to assess pancreatic tumors.
Plain radiographs are often obtained to look for pancreatic calcification. Upper GI barium studies may be performed in the context of epigastric pain. With pancreatic tumors, barium studies may depict extrinsic displacement of the stomach and duodenum.
Limitations of techniques
MRI is not universally available, is expensive, and poses a problem for patients with claustrophobia. The ACG guidelines recommend caution when using imaging to diagnose cyst type or concomitant malignancy; the accuracy of MRI or MRCP in diagnosing cyst type is 40-50% and is 55–76%in determining benign vs. malignant tumors.
Visceral gas, patient habitus, and operator dependency limit the value of sonography. Laparoscopic ultrasonography is invasive. EUS imaging cannot reliably distinguish benign from malignant IPMNs, and it is unclear whether imaging features of mucinous lesions with increased malignant potential are sufficiently predictive to influence clinical management. When surgical histology is used as a reference standard, the diagnostic accuracy of EUS imaging ranges from 40 to 96%. A single prospective study demonstrated that the sensitivity (56%) and specificity (45%) of EUS morphology alone for differentiating mucinous cysts (mucinous cystic neoplasms and IPMNs) from nonmucinous cysts were low, resulting in poor overall accuracy (51%).
Plain radiographs and upper GI barium studies are nonspecific, and similar findings may be encountered in a variety of pathologies. CT carries a significant ionizing radiation burden and uses iodinated contrast material with a risk of anaphylaxis and nephrotoxicity.
Cross-sectional studies, including ultrasonography, CT, and MRI, cannot be used to distinguish between mucinous cystadenoma and cystadenocarcinoma unless the tumor has metastasized or invaded neighboring organs. Angiography is nonspecific and invasive. It also requires iodinated contrast medium, with the risk of anaphylaxis and nephrotoxicity.
Follow-up imaging
ACG guidelines recommend cyst surveillance be offered to surgically fit candidates with asymptomatic cysts that are presumed to be IPMNs or MCNs. All surgically resected IPMNs require postoperative surveillance, but resected MCNs without pancreatic cancer do not. MRCP is the preferred modality for surveillance; EUS may also be the primary surveillance tool when MRI scans are contraindicated. In the absence of concerning features that warrant increased surveillance or referral for further evaluation, cyst size guides surveillance intervals for presumed IPMNs and MCNs.
Guidelines
Guidelines for the diagnosis and management of pancreatic cysts have been published by the following organizations:
American College of Gastroenterology (ACG)
European Study Group on Cystic Tumours of the Pancreas
American College of Radiology (ACR)
The 2018 ACG guidelines recommend magnetic resonance imaging (MRI) or magnetic resonance cholangiopancreatography (MRCP) as the preferred diagnostic modality because of their noninvasiveness, lack of radiation, and greater accuracy in assessing communication between the main pancreatic duct and the cyst (which is a characteristic of side-branch IPMNs). Pancreatic protocol computed tomography (CT) or endoscopic ultrasound (EUS) were deemed “excellent alternatives” if MRI is contraindicated. EUS fine-needle aspiration (FNA) and cyst fluid analysis should be considered in cysts in which the diagnosis is unclear and where the results are likely to alter management.
Analysis of cyst fluid CEA may be considered to differentiate IPMNs and MCNs from other cyst types, but it cannot be used to identify IPMNs and MCNs with high-grade dysplasia or pancreatic cancer. IPMNs or MCNs with any of the following features should undergo EUS with or without FNA and/or be referred to a multidisciplinary group for further evaluation
:
Any of the following symptoms or signs: jaundice secondary to the cyst, acute pancreatitis secondary to the cyst, significantly elevated serum CA 19-9
Any of the following imaging findings: the presence of a mural nodule or solid component either within the cyst or in the pancreatic parenchyma, dilation of the main pancreatic duct of >5 mm, a focal dilation of the pancreatic duct that is concerning for main duct IPMN or an obstructing lesion, or mucin-producing cysts measuring ≥3 cm in diameter
The presence of high-grade dysplasia or pancreatic cancer on cytology
The 2018 European guidelines also recommend MRI as the preferred method for the diagnosis of pancreatic cystic neoplasms (PCN). Multimodality imaging should be considered in cases where the identification of calcification is important, for tumor staging, or for diagnosing postoperative recurrent disease. However, the accuracy remains relatively low for identifying the specific type of PCN, for differentiating small PCN from nonneoplastic or nonepithelial cysts, or for connection to the ductal system.
CT should be considered in the following clinical situations
:
For the detection of parenchymal, mural or central calcification, and especially when differentiating pseudocysts associated with chronic pancreatitis from pancreatic cystic neoplasms
When there is suspicion of malignacy or concomitant pancreatic cancer and when assessment of vascular involvement, peritoneal disease, or metastatic disease is required.
When there is suspicion of postoperative recurrence of pancreatic cancer.
The European guidelines find EUS helpful for identifying PCN with features that should be considered for surgical resection. Similar to MRI and CT, EUS has low accuracy for identifying the exact type of PCN. EUS-FNA improves diagnostic accuracy for differentiating mucinous versus nonmucinous PCN, as well as malignant versus benign PCN, in cases where CT or MRI findings are unclear. Additional recommendations for the use of EUS-FNA include the following:
EUS-FNA should only be performed when the results are expected to change clinical management
EUS-FNA should not be performed if the diagnosis is already established by cross-sectional imaging or where there is a clear indication for surgery
Relative contraindications for EUS-FNA in PCN is a distance of >10 mm between the cyst and the transducer, the presence of a high-risk of bleeding due to bleeding disorder, or the use of dual antiplatelet drugs