eMedicine - Pancreas, Mucinous Cystic Neoplasm : Article by Ali Nawaz Khan

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Pancreas, Mucinous Cystic Neoplasm

Article Last Updated: Feb 21, 2007

Background

Mucinous cystic neoplasms (MCNs) of the pancreas are uncommon, and their diagnosis, treatment and prognosis have yet to be fully uniformly determined. Differentiation of cystic lesions of the pancreas is difficult, as they can be benign (serous cystadenomas), inflammatory (pseudocyst of the pancreas), or malignant.

Mucinous pancreatic tumors can be subdivided into peripheral and ductal tumors according to the site of origin. The peripheral type of mucinous cystic tumors includes mucin-producing cystadenoma and cystadenocarcinoma. The ductal types originate from the main pancreatic duct (MPD) or its branches. Intraductal tumors have been referred to by different names; however, since 1997, the unified term intraductal papillary mucinous tumor (IPMT) has been adopted.

The biologic behavior of these tumors 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.

Other cystic neoplasms of the pancreas include papillary cystic tumors, cystic islet cell tumor, acinar cystadenocarcinoma, and lymphangioma. Accurate diagnosis for a cystic neoplasm of the pancreas is therefore important, as treatment depends on the tumor type because of variations in the biology and natural history of the lesions.

Pathophysiology

Serous cystadenomas are generally benign and well circumscribed, consisting of single or multiple cysts 1-25 cm in diameter.

Pseudocysts of the pancreas are inflammatory and commonly arise as a secondary event to acute pancreatitis. Pseudocysts can become infected and exhibit signs of necrosis and hemorrhage.

Mucinous cystic tumors of the pancreas, so-called macrocystic cystadenomas or cystadenocarcinomas, which predominate in the body and tail of the pancreas, have a strong female predilection. MCNs are the most common of cystic pancreatic tumors, accounting for 45-50% of tumors. They are multiloculated tumors with a characteristic smooth glistening surface. They arise from oversecretion of the mucus by the hyperplastic columnar lining of the ducts. The cysts contain thickened viscous material, which can also be hemorrhagic.

The individual cyst is 2-26 cm in diameter, with large tumors being more often malignant than smaller ones. The cyst walls are dense and fibrous with occasional calcification. These tumors display a wide range of clinicopathologic spectrum ranging from benign to frankly malignant. The tumors are classified by histology as benign, borderline, or malignant based on degree of dysplastic changes. This classification is well correlated with the prognosis and suggests that all these tumors be treated as potentially malignant. Accurate diagnosis requires examination of extensive samples of cyst epithelium followed by complete surgical resection.

Mucinous cysts are commonly precancerous and microscopically are recognized to have 3 distinct layers: (1) the innermost layer, which is the epithelial lining (hyperplastic, dysplastic); (2) the middle layer, which is the densely cellular mesenchymal stroma; and (3) the outermost layer, which is the hyalinized connective tissue.

These tumors may demonstrate histologic features of either malignant or benign mucinous epithelium; they are probably considered malignant or potentially malignant, partly because of the limited clinicopathologic experience with these tumors. The degree of atypia of the epithelial lining and the dilatation of the ducts can help determine the malignant nature of the cyst. In some cases, only foci of malignant change occur within a mucinous cyst. This, added to its indolent nature, makes accurate diagnosis and differentiation from the benign serous cystadenoma difficult. Mucinous cysts can invade the surrounding pancreatic parenchyma, which results in symptoms and signs of pancreatic cancer.

IPMT is a papillary neoplasm that arises within the MPD or its branches. The tumors hypersecrete mucin, which often leads to duct dilatation and/or chronic obstructive pancreatitis. IPMTs are premalignant and may histologically demonstrate areas ranging from hyperplasia to carcinoma within a single tumor. The tumors generally show intraluminal, longitudinal growth, but it is slow to invade periductal tissues radially and slow to metastasize. IPMTs are most commonly localized to the head of the pancreas, but they may occur at any site along the pancreatic ductal system. Ductal dilatation is often impressive and may mimic MCNs on CT scans.

Intraductal papillary mucinous neoplasm is recognized as predominantly a solid tumor with a central cyst. The cystic variety consists microscopically of cystlike spaces with papillary protrusions.

Nakamura and associates have proposed a new classification for IPMTs. In previous studies of the expression of MUC1 (for membrane-bound–type mucin) and MUC2 (for intestinal-type secretory mucin) in pancreatic tumors, invasive ductal carcinoma (IDC) usually showed MUC1+ and MUC2- expression, whereas IPMT showed MUC1- and MUC2+ expression.

However, other studies show that many IPMTs have MUC1- and MUC2- expression. In the study by Nakamura et al, the clinicopathologic features of 18 tumors with MUC2+ IPMTs and 32 MUC2- IPMTs and their potential for malignancy were compared. Most of the MUC2+ IPMTs were composed of dark, columnar cells, whereas most MUC2- were composed of clear columnar cells. The incidence of carcinomatous change and invasive proliferation of the carcinoma in MUC2+ tumors was significantly higher than in MUC2- tumors.

The clinical outcome for the patients with IPMT and the MUC2+ pattern tended to be worse than for those with IPMT and the MUC2- pattern, though the overall outcome for the 2 types of IPMT was significantly better than for those with IDC. Because of the differences in mucin-expression patterns and in the morphologic appearance and potential for malignancy between the 2 types of IPMT, the authors believe that they belong to different neoplastic lineages. Therefore, it may be reasonable to classify them as different entities, although the classification by the World Health Organization (WHO) includes a single clinicopathologic entity of IPMT forming an adenoma-carcinoma sequence. The authors concluded that classification of IPMTs by MUC2 expression pattern may be of value in the better assessment of the biologic behavior of IPMTs and their potential for malignancy.

Frequency

United States

Cystic tumors of the pancreas are relatively uncommon, accounting for 10% of cystic lesions of the pancreas and 1% of pancreatic neoplasms. MCNs, serous cystadenomas, and IPMT account for more than 90% of the primary cystic neoplasms of the pancreas, but other nonserous and nonmucous entities with cystic appearance are also known. Cystic neoplasms of the pancreas are an increasing entity.

International

No data suggest that the international incidence of mucinous pancreatic tumors is different from that in the United States.

Mortality/Morbidity

The long-term survival of patients with these tumors is generally better than that of patients with adenocarcinoma of the pancreas, and aggressive resection of the tumors is required in most patients. The prognosis is good after curative resection for serous cystadenomas and MCNs of the pancreas.

Race

Sex

Age

Anatomy

The pancreas is a lobulated retroperitoneal organ. It has a slender configuration and a length of 12-20 cm, depending on the patient's build. It weighs 60-100 g but often shows atrophy in the elderly. It does not have a true capsule and merges with the retroperitoneal fat; this feature accounts for its lobulated contour, which is more evident on CT than on sonography. This contour becomes more prominent with age.

As with other organs, the pancreas shows craniocaudal movement with respiration. However, being retroperitoneal and limited above by the celiac-axis origin from the aorta, the pancreas shows far less movement than the liver, spleen, and kidneys. Movement between inspiration and expiration is usually less than 1 cm, but movement up to 3.5 cm has been reported.

The pancreas lies on the posterior abdominal wall with its head in the C of the duodenal loop. The body and tail extend obliquely upward to the left, the pancreatic tail lying in the lienorenal ligament adjacent to the spleen and the upper pole of the left kidney. The head of the pancreas has an uncinate process that extends posteroinferiorly around the superior mesenteric vein at the portal vein origin. The uncinate process extends inferior to the main body of the pancreas; thus, it is important to scan the full extent of the pancreas, or carcinoma of the uncinate process may be missed.

The pancreas lies in the anterior pararenal space. The head lies within the curve of the duodenal loop with the inferior vena cava (IVC) and right renal vessels lying posteriorly. The common bile duct (CBD) receives the MPD as it passes through the pancreatic head and then drains into the second part of the duodenum at the ampulla of Vater. The gastroduodenal artery may be seen anteriorly at the pancreatic head and neck. The head of the pancreas is the most bulbous part of the gland, which then narrows at the neck.

The union of the superior mesenteric and splenic veins forming the portal vein posteriorly marks the anatomic position of the pancreatic neck. The pylorus and gastroduodenal artery lie anteriorly. The lesser sac lies anterior to the body of pancreas, while the splenic vein runs along its posterosuperior surface. The tail of the pancreas is related to the spleen, left adrenal glands, and upper pole of the left kidney.

Clinical Details

Clinical findings

In 50% of cases, MCNs occur as an incidental finding as a cystic mass in patients with no prior history of jaundice. Patients can also present with vague symptoms, such as nonspecific abdominal pain and possibly a mass effect. Patients with malignant changes may have a history of weight loss and jaundice. As mentioned, diagnostic methods are important because of the known indolent nature of MCNs. Furthermore, mucinous cystadenoma, cystadenocarcinoma, and IPMTs must be differentiated from serous cystadenoma, as all have differing biologic characteristics.

Levels of cystic carcinoembryonic antigen (CEA) can be increased in the mucin content of the cysts, which proportionally rises with the degree of malignancy of the tumor. Although mucinous pancreatic tumors are often hypervascular, GI bleeding is infrequent. In most cases, bleeding is from gastric varices, which develop from splenic vein obstruction as a result of compression or venous invasion from the tumor. Rarely, bleeding can be the result of direct stomach or duodenal invasion by the tumor. A frequent clinical finding is a palpable, firm, and nontender abdominal mass, which the patient often detects before he or she seeks medical help.

MCNs of the pancreas are low-grade malignant tumors with an insidious natural history. They can present with malignant symptoms of weight loss and jaundice. In severe cases, an acute illness occurs as a result of CBD obstruction. The main focus of investigation relies on diagnostic accuracy, as early and complete resection can offer a possibility of cure.

Pancreatitis and jaundice secondary to ductal obstruction are common in IPMTs of the pancreas. However, the incidence and severity of the complications of obstruction are not well documented. Pancreatic or CBD obstruction in IPMT may result in acute, life-threatening disease. Patients frequently present with abdominal pain or pancreatitis, and they may be found to have a past history of recurrent pancreatitis. Aggressive surgical therapy is warranted before development of complications of ductal obstruction or progression of tumor (Tibayan, 2000).

Rarely, IPMT manifests as new-onset diabetes. However, more frequently, IPMT is detected on cross-sectional imaging performed for the evaluation of nonspecific abdominal pain.

A variety of abnormalities have been reported in association with mucinous pancreatic cystic tumors. These include hypertension, diabetes mellitus, peptic ulcer, and biliary disease. The incidence of other neoplasms and deep venous thrombosis is also increased.

Differential diagnosis

The differential diagnosis includes the following: pancreatic pseudocyst or pancreatic fluid collections, serous cystadenomas, pancreatic abscess, benign pancreatic cysts, retention pancreatic cysts, parasitic cysts, lymphoepithelial cysts (LECs), pancreatic dermoid cysts, pancreatic hematoma and traumatic pancreatitis, von Hippel-Lindau (VHL) syndrome, papillary pancreatic tumors, dysontogenic cysts, pseudoaneurysms, retroperitoneal neurofibroma or schwannoma, obstructed roux loop, duodenal diverticula, gastric/duodenal leiomyosarcoma or leiomyoma, pancreatic sarcoma, pancreatic lymphoma, pancreatic metastases, and pancreatic tuberculosis.

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. Small fluid collections are often transient, and fluid collections smaller than 5 cm in diameter may be treated conservatively. They may dissect tissue planes; therefore, they can appear at a distance from the pancreas.

Patients with pseudocysts often report a history of acute or chronic pancreatitis. However, patients with cystic tumors lack this history.

Imaging findings that suggest a diagnosis of pseudocyst rather than cystic neoplasms include the following: lack of septae, loculations, solid components, or cyst-wall calcifications on CT; 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.

Fine-needle aspiration (FNA) of pseudocyst contents reveals high levels of amylase. When in doubt, it is better to resect a pseudocyst than to observe or drain a pancreatic cystic neoplasm, which allows tumor progression to unresectability, metastasis, and death.

Serous cystadenomas (microcystic adenomas) 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.

An association with VHL disease has been described. Most patients present with nonspecific symptoms of vague abdominal pain or discomfort, but many have a palpable mass. These tumors can be large, with a size of 1-25 cm. Because of increasing use of cross-sectional imaging, many of these tumors are detected as an incidental, asymptomatic finding.

On gross pathologic inspection, serous cystadenomas consist of well-circumscribed, externally lobulated pancreatic tumors. On cross-sectional images, these appear as numerous tiny cysts separated by delicate fibrous septae, 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 only in 10% of patients. Endoscopic ultrasonography (EUS) allows better resolution of the honeycomb structure than 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. Analysis of the cyst fluid characteristically reveals low viscosity and low levels of CEA, with negative cytologic results for malignant cells, as the vast majority of serous cystadenomas are benign.

Serous cystadenocarcinomas have been described, but they are exceedingly rare and account for fewer than 1% of known cases. It is safe to observe small, asymptomatic serous cystadenomas, as the risk of malignant degeneration is extremely small. Some serous cystadenomas show continued growth; therefore, surgery is indicated, because complications such as hemorrhage, obstructive jaundice, pancreatic insufficiency, or gastric outlet obstruction can result.

Surgical resection is the treatment of choice for symptomatic tumors and tumors that show continuous growth. Many of these tumors may require a Whipple procedure or distal pancreatectomy, depending on the anatomic location. Distal pancreatectomy may be performed and the spleen can be preserved, given the absence of malignant potential.

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.

Unlike cysts in the liver and kidneys, asymptomatic simple pancreatic cysts are uncommon. Most congenital pancreatic cysts are discovered in infants and children. Pancreatic cysts occur in a small percentage of patients with autosomal dominant polycystic kidney disease. Macroscopic pancreatic cysts are occasionally seen in patients with cystic fibrosis.

On sonograms, congenital cysts appear as well-defined, anechoic masses with good through transmission. The walls are smooth with no intramural excrescences or septations. Associated renal and hepatic cysts may be seen. Congenital cysts normally occur on the background of an otherwise normal-looking pancreas.

The differential diagnosis includes cystic neoplasms, pancreatic pseudocysts, and acquired cysts. Most congenital cysts occur in children, whereas cystic neoplasms occur in adults. Patients with pseudocysts often have a previous history of acute pancreatitis, and the lesions are often seen on a background of inflammatory pancreatic disease. Congenital pancreatic pseudocysts have been described in neonates; these lesions sometimes reach giant proportions.

Like pseudocysts, retention cysts are a complication of pancreatitis, usually a chronic, calcific type occurring in alcoholic patients. Alcohol causes precipitation of protein within the pancreatic duct, resulting in a protein plug that blocks the duct. Such blockage leads to proximal duct dilatation, forming a cyst.

These cysts are usually small (1-2 cm in diameter) and asymptomatic. However, in rare cases, these cysts may reach enormous proportions and no longer remain within the confines of the pancreas. Retention cysts have also been reported with ampullary stenosis and pancreatic carcinoma. Ultrasonography may reveal the underlying pancreatic abnormality (calcific pancreatitis) and small cysts in continuity with a dilated pancreatic duct. Stigmata of alcoholic liver disease may be present.

Both echinococcus granulosis and multilocularis cysts of the pancreas have been described, though pancreatic involvement is exceptionally rare. Echinococcus 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. Echinococcus multilocularis cysts show an echogenic infiltrative pattern. This diagnosis should be entertained in endemic regions when such a pattern is seen.

LECs of the pancreas are extremely rare. The pathologic features of LEC are well-defined, epithelia-lined cysts surrounded by a rim of lymphoid tissue. They present predominantly in middle-aged or elderly males with nonspecific symptoms such as abdominal pain and diarrhea. Ultrasonography, particularly EUS, is a sensitive means of diagnosing pancreatic cysts.

LECs are mainly cystic structures. However, they are not completely transonic, and they do contain some debris as a result of their keratin content. Cystic neoplasms and pseudocysts may have a similar appearance. As with some pseudocysts, an elevated CEA level is found in LEC aspirates; therefore, an elevated CEA level is not reliably predictive of malignancy.

Dermoid cysts within the pancreas are rare, but they do have some distinctive features. Besides the cystic component teeth, fat, bone and calcification may be found in these masses. However, it is not always possible to differentiate these masses from other neoplasms.

Although the pancreas moves with respiration, it is similar to other retroperitoneal organs in that it is relatively fixed compared to overlying bowel. Therefore, the pancreas is prone to injury due to blunt abdominal trauma when it is compressed against the spine. The pancreas is involved in 3-12% of abdominal injuries as a result of seat-belt or steering-column impact.

A mortality rate as high as 20% has been reported with pancreatic injuries, as these are often associated with trauma to other organs, such as the duodenum. Injury to the duodenum may give rise to an intramural hematoma obstructing the bowel lumen. Delayed retroperitoneal perforation of the duodenum may be present. Injury to the pancreas may also cause contusion or rupture. Rupture may be complete or incomplete, but both frequently cause pancreatitis and fluid collections or pseudocysts.

Pseudocysts usually form anteriorly, but they may be adjacent to any part of the gland and, occasionally, distant. Pancreatic lacerations are diagnosed when the loss of contiguity is present, but this finding may be masked by inflammation. Although sonography is excellent for showing fluid collections, patients are often immobile and often have gaseous distention, making CT a more suitable diagnostic study. Moreover, CT permits imaging of the retroperitoneum.

VHL syndrome is an autosomal dominant condition with variable penetrance and delayed expression. (For example, it is reported in identical twins.) Tumors and/or cysts occur in the central nervous system, genitourinary system, liver, spleen, pancreas, and adrenal glands. Cysts are found throughout the pancreas and vary from a few millimeters to 10 cm. These cysts are benign and usually give rise to symptoms when the CBD is obstructed.

Microcystic adenoma (serous cystadenoma) is associated with VHL syndrome and is an externally lobulated mass consisting of multiple small cysts separated by thick-walled stroma. The cysts are lined by cuboidal epithelium that is rich in glycogen but contains no mucin. These tumors are benign and not premalignant; they give rise to symptoms due to mass effect when they are large.

Mucinous cystadenoma is premalignant and is not associated with VHL. Microcystic adenoma may appear solid on sonograms because of the multiple interfaces caused by the cysts of varying sizes, mostly small ones. Other pancreatic tumors reported with VHL include adenoma, hemangioblastoma, and adenocarcinoma of the pancreas and ampulla of Vater. Islet cell tumors appear to be unrelated to pancreatic cystic disease in VHL. These lesions are frequently associated with pheochromocytoma.

A number of endocrinopathies have been reported with pancreatic islet cell tumors in VHL. These tumors are solid initially, but as they grow, central necrosis may occur. They may contain calcification. Because of their small size at presentation, they may not be visualized on sonograms. However, intraoperative sonography is extremely useful in identifying and staging these tumors.

Solid and papillary epithelial neoplasm of the pancreas may be solid or cystic. These are rare tumors often mistaken for mucin-secreting tumors or nonfunctioning adenomas. They represent a low-grade malignancy, which affects women 9 times more often than men; the average patient age is 27 years.

These 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 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 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% 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.

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 has occurred. The tumors are retroperitoneal but may mimic pancreatic masses.

Obstructed Roux loop after pancreatic cancer or bile duct surgery may appear as a cystic mass in the pancreatic bed. Sonography demonstrates an obstructed Roux loop as well as a patent biliary-enteric anastomosis. Echoes due to gas with or without comet-shaped artifacts are usually demonstrated.

Duodenal diverticula may mimic pancreatic neoplasms on sonograms, as they may have both complex and cystic appearances and may cause obstructive jaundice. Duodenal diverticula are a common finding and typically asymptomatic. When filled with gas or a combination of fluid and gas, duodenal diverticula are easily recognized on CT scans or MRIs. However, a duodenal diverticulum that is entirely filled with fluid may mimic a cystic neoplasm arising from the head of the pancreas.

Macari and associates described 7 patients with duodenal diverticula in whom initial CT or MRI findings were suggestive of a cystic neoplasm in the head of the pancreas. Recognizing the location in which duodenal diverticula characteristically arise and identifying small amounts of intradiverticular gas when present may aid diagnosis in patients with duodenal diverticula. With careful sonography, it is possible to demonstrate the presence of air in the diverticulum and its continuity with the duodenum. ERCP results may be diagnostic.

These tumors represent complex masses with a multicystic component. They may be confused with pancreatic masses, but careful scanning usually suggests their origin in bowel.

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.

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.

A variety of tumors may metastasize to the pancreas. Patients may present with acute pancreatitis due to pancreatic duct obstruction. The initial findings in this instance may be those of inflammatory disease of the pancreas complicated by pseudocysts and pancreatic ascites. Most metastases are solid, but cystic metastases may occur, particularly those from cystadenocarcinoma of the ovary and melanoma. A solitary pancreatic metastasis cannot normally be differentiated from a primary pancreatic tumor on CT scans or sonograms.

Pancreatic tuberculosis is extremely rare and is frequently misdiagnosed as a pancreatic neoplasm.

Liu et al described a 33-year-old man with a 6-month history of vague, intermittent right epigastric pain and weight loss. They found a solitary pancreatic cystic mass and diagnosed it as pancreatic cystadenocarcinoma. Abdominal sonograms showed an irregular, hypoechoic lesion of 6.6 X 4.4 cm in the head of the pancreas. The lesion was avascular on color Doppler flow images. Attempts to obtain pathologic evidence of the lesion by sonography-guided percutaneous FNA failed, and an exploratory laparotomy and incisional biopsy revealed a caseous abscess of the head of the pancreas without typical changes of tuberculous granuloma. However, results of acid-fast staining were positive.

Preferred Examination

Ultrasonography is generally the first imaging 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.

Occasionally, despite complete evaluation of a cystic mass, the type of cyst may remain indeterminate (Michael, 2002). 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. 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.

Spiral and/or multisection CT is an excellent modality in 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, and most centers now seldom use angiography to assess pancreatic tumors.

ERCP is the examination of choice for visualizing pancreatic and biliary duct anatomy, ductal displacement, ductal encasement, intraductal tumor, and filling of the tumor cavity with contrast material. ERCP results may establish a diagnosis of IPMT and permit its differentiation from a pseudocyst or cystic neoplasm of the pancreas. These techniques may also be used to assess the risk of malignancy and the extent of disease. They also allow tissue sampling and enable therapeutic intervention (Telford, 2002).

Angiography provides evidence of neovascularity, venous compression/invasion, and invasion of contiguous organs. 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 equally well, if not better, with MRI than with CT; the exception is the limited ability of MRI to reveal calcification within the lesion. MRI is an evolving modality and appears to be an excellent 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 with the diagnosis of intraductal tumors.

Limitations of Techniques

Visceral gas, patient habitus, and operator dependency limit the value of sonography. Laparoscopic ultrasonography is invasive. 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. MRI is not universally available and is expensive, and it also causes problems in patients with claustrophobia.

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 once again nonspecific and invasive. It also requires iodinated contrast medium, with the risk of anaphylaxis and nephrotoxicity.

Other Problems to be Considered

Pancreatic pseudocyst or pancreatic fluid collection
Serous (microcystic) cystadenoma
Pancreatic abscess
Benign pancreatic cyst
Retention pancreatic cyst
Parasitic cyst
Lymphoepithelial cyst
Pancreatic dermoid cyst
Pancreatic hematoma and traumatic pancreatitis
von Hippel-Lindau disease
Solid and papillary epithelial neoplasm
Dysontogenic cyst
Pseudoaneurysm
Retroperitoneal neurofibroma or schwannoma
Obstructed roux loop
Duodenal diverticula
Gastric, duodenal leiomyosarcoma, or leiomyoma
Pancreatic sarcoma
Pancreatic lymphoma
Pancreatic metastasis
Pancreatic tuberculosis

Findings

Plain radiographs may show tumor calcification in 10-15% of cases of microcystic adenomas. Calcification in microcystic adenoma presents as a central cluster arranged in a sunburst or stellate arrangement. In mucinous-type tumors, calcification tends to occur at the periphery of the tumor or in the walls of the cysts and appear curvilinear. CT is more sensitive for calcification.

Upper GI barium studies are nonspecific and usually show extrinsic displacement of the stomach or duodenum. As most symptomatic cystic neoplasms are large, these findings are not infrequent.

ERCP depicts ductal changes in cystic tumors of the pancreas in approximately 80% of patients. ERCP may show duct displacement, stretching, encasement, duct ectasia, cystic tumor filling, and tumor in the duct as a filling defect and duct obstruction. ERCP in MCN rarely shows cyst communication with pancreatic ducts, but it frequently shows duct displacement by mass effect or ductal obstruction.

ERCP results may establish the diagnosis of IPMT and permit its differentiation from a pseudocyst or cystic neoplasm of the pancreas. These techniques may also help in assessing the risk of malignancy, evaluating the extent of disease, allowing tissue sampling, and enabling therapeutic intervention (Telford, 2002). ERCP typically shows a patulous ampulla of Vater with discharging mucus, which is often diagnostic for IPMT. Other findings on ERCP include the following: main duct dilation, filling defects (viscid mucus), and communication between cystic areas and the MPD.

Degree of Confidence

ERCP can be used to attempt to differentiate mucinous cystadenoma from cystadenocarcinoma. ERCP typically shows a patulous ampulla of Vater with discharging mucus, which is often diagnostic for IPMT. Although no finding is an absolute indicator of benign and malignant disease, obstruction occurs in 60% of malignant lesions and in 2.5% of cases of benign disease. It can be assumed that these ductal changes can also be demonstrated by MRCP. ERCP remains the imaging modality of choice for diagnosis of IPMT.

False Positives/Negatives

There are several causes of calcification in the pancreatic bed; these include chronic pancreatitis, pancreatic hemorrhage, abscess, infarction, hyperparathyroidism, cystic fibrosis, and kwashiorkor. Many pancreatic tumors can become calcified, including adenocarcinoma (rare), islet cell tumor, microcystic adenoma–sunburst calcification, MCN (macrocystic cystadenoma), cavernous lymphangioma, hemangioma, and colonic carcinoma metastases.

Abnormalities on upper GI barium series are also nonspecific and can be caused by many neoplastic and nonneoplastic masses near the stomach and duodenum. Pancreatic duct calculi and chronic pancreatitis may mimic IPMT, and vice versa.

Reflux of contrast material due to mucin blobs or mural nodules may hinder filling of the ducts in IPMT on ERCP, causing diagnostic difficulties.

Findings

Nonenhanced CT scans show a well-defined, unilocular or multilocular, externally smooth, round-to-ovoid mass with fluid attenuation. The attenuation values of the multilocular cysts vary according to the degree of hemorrhage or protein in the mucoid cysts. Larger cysts may demonstrate small daughter cysts along its internal surface. Typically, they show a well-defined, multilocular cystic mass with thick internal septae separating the different cystic cavities of varying sizes. The cysts are 2-26 cm.

Visualization of nodular or papillary excrescences with irregular borders of the septae is possible. If present, calcification is curvilinear or punctate and confined to the cyst wall or septa. Contrast-enhanced CT scans show enhancement of the cyst wall, internal septations, mural nodules, and other intracavitary projections. CT may also allow the identification of solid components associated with cystic elements, which are features of borderline or malignant tumors but not benign variants. MCNs develop predominantly in the tail of the pancreas (>90%). CT more clearly demonstrates enhancement of cystic walls and septa than do other studies.

Compared with serous cystic tumors, the cysts in MCNs are larger (>20 mm in diameter) and less numerous (usually <6).CT-guided aspiration of the cyst can provide further diagnostic clues and enable their differentiation from other pancreatic cystic masses (eg, pseudocyst, serous cystadenoma, and solid and pseudopapillary neoplasm). MCN cyst fluid typically has a high viscosity, low amylase levels, and high CEA and carbohydrate antigen (CA) 72-4 levels, and they may show malignant cytology in patients with mucinous cystadenocarcinomas. Periodic acid-Schiff (PAS) and May-Grunwald/Giemsa (MGG) stains are usually positive for extracellular as well as intracellular mucin.

Main ductal IPMT may be focal or diffuse, the findings of which are reflected on imaging. However, main duct tumors may be difficult to differentiate from chronic pancreatitis, as the imaging features may be similar. In the early stages of focal or segmental involvement by IPMT, the features may be difficult to differentiate from focal chronic obstructive pancreatitis on cross-sectional imaging. In these cases, the findings on ERCP may be diagnostic. Rarely, segmental pancreatic duct dilatation may acquire a cystic appearance, whereas the MPD and the rest of the pancreas appear normal.

Cases with a cystic appearance may mimic a peripheral MCN. However, with a peripheral MCN, the pancreatic duct is almost always normal in appearance. When the tumor involves the head of the pancreas, imaging reveals upstream dilatation of the pancreatic duct. IPMT can be more confidently diagnosed when imaging reveals a filling defect in the main duct or a branch pancreatic duct.

The filling defects are hyperechoic on sonograms, high-attenuating on CT scans, and hypointense on T2-weighted MRIs relative to the surrounding fluid. When there is diffuse involvement of the MPD, dilatation is present along the whole length of the pancreatic duct. This dilatation is often associated with diffuse and generally uniform pancreatic atrophy. These features may be difficult to differentiate from those of chronic pancreatitis. However, dilatation of a branch duct is a frequent finding in IPMT, and the presence of mural nodules and mucin blobs is another finding that may be a clue to the diagnosis.

In late cases with advanced disease, mass effect from the tumor may cause CBD compression and dilatation of the biliary tree and compression or displacement of the stomach and duodenum. Pancreatobiliary fistula may be a late complication. Advanced stages of the disease may be complicated by pseudomyxoma peritonei as a result of dissemination of the disease to the peritoneum and retroperitoneum. Peritoneal seedlings can be identified as small foci that appear hyperechoic on sonography and hyperattenuating on CT.

Branch-duct IPMT may be easier to identify than main-duct IPMT, as the former generally appears as mass lesions on imaging. When these lesions are small, they are commonly an incidental finding in patients undergoing imaging for unrelated conditions. Branch IPMT is most frequently encountered in the region of the uncinate process. Branch IPMT may be microcystic or macrocystic. The microcystic variety may mimic serous cystadenomas/cystadenocarcinomas on imaging, but communication with the MPD (which is frequently dilated) may be a clue to the diagnosis. The macrocystic variety must be differentiated from other cystic masses. The thickness of the cyst wall and septa is variable with benign tumors; they tend to be thin and regular. In malignant tumors, the walls and septa appear irregular and thick, with solid nodules.

Degree of Confidence

CT findings can be highly specific and usually sufficient for a confident diagnosis. Bulging of the papilla into the duodenal lumen is virtually diagnostic of IPMT and is well demonstrated with CT and MRI.

False Positives/Negatives

CT is not useful for differentiating mucinous cystadenoma from cystadenocarcinomas except that papillary excrescences suggest malignancy and metastases prove malignancy. Mural nodules in IPMT can be difficult to differentiate from mucin blobs, as a clear attachment of the mural nodules to the pancreatic duct wall must be demonstrated; this may be difficult to define. However, mural nodules tend to enhance after the intravenous administration of contrast material, whereas mucin blobs do not. When IPMT involves the entire MPD, differentiation from chronic pancreatitis may not be possible on imaging.

Findings

The radiologic findings on cross-sectional imaging correlate well with the macroscopic features of mucinous cystadenoma and cystadenocarcinoma. Cystic lesions in MCN are hypointense or hyperintense on T1-weighted MRIs depending on protein content. Breathing-independent T2-weighted images, such as half-Fourier acquired single-shot turbo spin-echo (HASTE) images, show multiple hyperintense cysts separated by multiple hypointense septa. Intracystic excrescences and mural nodules also have low signal intensity, but they enhance significantly with gadolinium-based contrast agents.

Gadolinium-based contrast agents (gadopentetate dimeglumine [Magnevist], gadobenate dimeglumine [MultiHance], gadodiamide [Omniscan], gadoversetamide [OptiMARK], gadoteridol [ProHance]) have recently been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). For more information, see the eMedicine topic Nephrogenic Fibrosing Dermopathy. The disease has occurred in patients with moderate to end-stage renal disease after being given a gadolinium-based contrast agent to enhance MRI or MRA scans.

As of late December 2006, the FDA had received reports of 90 such cases. Worldwide, over 200 cases have been reported, according to the FDA. NSF/NFD is a debilitating and sometimes fatal disease. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of the eyes; joint stiffness with trouble moving or straightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs; and muscle weakness. For more information, see the FDA Public Health Advisory or Medscape.

MRCP allows depiction of pancreatic duct or CBD changes that may be associated with the tumors.

Hong and associates analyzed the CT and MRI features of IPMT of the pancreas in 8 patients with pathologically proven IPMT of the pancreas (1 papillary hyperplasia, 7 adenocarcinoma). The patients included 5 men and 3 women aged 42-82 years. Imaging studies included 6 thin-section dynamic CTs, 7 MRIs, 1 MRCP, and ERCP examinations.

The authors found only 1 benign IPMT, which appeared as a unilocular cyst in the pancreatic body with no mural nodules and no dilatation of the MPD. All 7 patients with malignant IPMT had multilocular cysts with papillary projections in the pancreatic head and/or uncinate process accompanied by dilated MPD (5 diffuse, 2 segmental). Communication between the cystic lesions and the MPD were evident in all 7 patients. One patient had small mural nodules in the branch ducts of the pancreatic body, and 5 had a bulging papilla with a patulous orifice. A mass effect resulting in biliary obstruction was shown in 1 patient. One patient had a ruptured cyst with mucin leakage into the right anterior pararenal space after sonography-guided aspiration.

The main imaging feature of IPMT in the 8 reported patients was a multilocular cyst with papillary projections in the pancreatic head and uncinate process. 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.

Differentiation between serous and mucinous neoplasms may be difficult on MRIs, as there is variability in the MRI appearance of serous cystadenomas and overlap with mucinous neoplasms. CT criteria can be applied to MRI except that calcification is often missed on MRI. Most serous tumors require histologic confirmation. MRCP is useful in differentiating between benign and malignant mucinous tumors, including IPMT of the pancreas. The presence of mural nodules is suggestive of malignancy; however, the absence of mural nodules does not indicate that the tumor is benign.

A maximum MPD diameter of greater than 15 mm and diffuse dilatation of the MPD are suggestive of malignancy in main duct–type tumors. Among branch duct–type tumors, malignant tumors tend to be larger than benign tumors; however, this finding is variable. The presence of MPD dilatation may be helpful in determining malignancy of branch duct-type tumors (Sahani, 2002).

Degree of Confidence

MRI is an excellent modality for the depiction of cystic pancreatic masses, showing their internal architecture to advantage. MRCP is a noninvasive technique.

False Positives/Negatives

As with other cross-sectional imaging techniques, several mimics of MCN can be depicted on MRIs. These include benign and malignant neoplastic cysts and cysts of inflammatory origin.

Findings

At presentation, mucinous cystic pancreatic neoplasms are usually larger than 5 cm. The walls of mucinous cysts are composed of thick, fibrous stroma that sometimes contain dystrophic calcification. Sonography reveals a large, cystic mass that sometimes contains numerous septa, tumor excrescences, and debris. The tumors may be 2-23 cm, and they usually have sharply marginated walls and smooth borders. The cystic portions show a good through transmission. Sonograms typically show a multilocular, fluid-containing mass with good transmission and strong acoustic enhancement.

Microcystic adenomas (serous cystadenoma) are mostly complex, with numerous internal echoes resulting in the appearance of an externally lobulated solid mass, sometimes with good through transmission. The central scar and calcification may be demonstrated on CT scans but are not well depicted on sonograms.

Rickes and associates selected 137 patients with a mean age of 60 years and clinically suspected pancreatic tumors. The patients were assessed with conventional sonography and nonenhanced and echo-enhanced power Doppler sonography. An experienced examiner blinded to the patients' clinical diagnoses performed the studies. The exact diagnosis was based on histologic evidence from surgical and fine needle biopsy or on a follow-up of at least 18 months.

Of the 137 patients, 47 had pancreatic cancer; 41 had masses associated with pancreatitis, 17 had neuroendocrine tumors, 12 had cystic lesions of the pancreas, and 10 had other pancreatic diseases. A normal pancreas was found in 10 patients. The sensitivity of echo-enhanced power Doppler sonography with respect to diagnosing pancreatic carcinoma was 87%, and its specificity was 94%. The corresponding values for chronic pancreatitis were 85% and 99%, respectively. The authors concluded that echo-enhanced power Doppler sonography has a high sensitivity and specificity in the differential diagnosis of pancreatic tumors. However, histologic study remains the criterion standard.

From the current data, EUS appears to be reliable in distinguishing between most benign lesions and neoplastic cystic lesions. In equivocal cases or in cases in which malignancy is highly suspected, EUS-guided FNA gives the best diagnostic yield, as it permits the acquisition of cytologic samples and cystic fluid for the analysis of various tumor markers. When the lesion is differentiated from other cystic masses and when the tumors are large and symptomatic, the best course of action is surgical resection. When small cystic lesions are encountered in asymptomatic patients, follow-up EUS may suffice.

Ikeda et al established EUS criteria for the follow-up of small cystic pancreatic lesions. Their guidelines can help in the decision-making process. The authors reported 31 patients with pancreatic cystic lesions of unknown etiology who were followed-up with semiannual EUS over 3 years. In 87.1%, the lesions were smaller than 2 cm. The cystic lesions remained stable in 30 patients, and only 1 lesion increased in size. This lesion was resected and found to be a retention cyst.

The criteria by Ikeda et al include the following: (1) a clear, thin wall; (2) a smooth contour; (3) a round or oval shape; (4) no septum or nodules; (5) an asymptomatic clinical presentation; and (6) no findings of chronic pancreatitis.

With the widespread use of advanced imaging techniques, cystic lesions of the pancreas are now diagnosed relatively frequently. The nature of these lesions varies from benign cysts (serous cystadenoma) or inflammatory processes (pseudocyst) to premalignant (mucinous cystadenoma) or frankly malignant (cystadenocarcinoma) lesions. The differentiation of various types of pancreatic cysts presents a diagnostic and therapeutic challenge, as the clinical presentation may be vague. Laparoscopic ultrasonography (LAPUS), biopsy of the cystic wall, and analysis of the cystic aspirate significantly contribute to the differential diagnosis of pancreatic cystic lesions (Schachter, 2002).

Degree of Confidence

Ultrasonography is an excellent modality in depicting cystic structures and particularly advantageous to show the internal septa, mural nodules, and solid excrescences of the cyst wall. IPMT of the pancreas encompasses a spectrum of pathologies ranging from benign conditions to malignant disease. IPMT must be differentiated from other cystic neoplasms of the pancreas, as well as inflammatory cystic lesions.

Because the pancreas is near the gastric and duodenal loop, EUS is ideally suited for imaging the pancreas. Additionally, EUS facilitates FNA of pancreatic cysts and/or a dilated pancreatic duct for cytologic and tumor marker analysis (Bounds, 2002). LAPUS is expensive and invasive.

False Positives/Negatives

There is a wide differential diagnosis of cystic lesions in the pancreas, and therefore, the potential for false-positive results is significant. For smaller cystic lesions, a false-negative finding is possible in obese patients or in patients with gaseous distention.

Findings

Sperti and associates assessed the reliability of fluorodeoxyglucose (FDG) positron emission tomography (PET) in distinguishing benign from malignant cystic lesions of the pancreas. During a 4-year period, 56 patients with a suspected cystic tumor of the pancreas underwent FDG PET in addition to CT, serum CA 19-9 assay, and (in some instances) MRI or ERCP. FDG PET images were visually and semiquantitatively analyzed by using the standard uptake value. The accuracy of FDG PET and CT was determined for preoperative diagnosis of a malignant cyst.

Seventeen patients had malignant tumors. Sixteen patients (94%) had FDG uptake with a standard uptake value of 2.6-12.0. Twelve patients (70%) were correctly identified as having malignancy by means of CT, CA 19-9 assay, or both. Thirty-nine patients had benign tumors. Only 1 mucinous cystadenoma showed increased FDG uptake (standard uptake value of 2.6). Five patients with benign cysts had CT findings of malignancy.

The authors concluded that FDG PET is more accurate than CT in identifying malignant pancreatic cystic lesions and should be used, in combination with CT and tumor marker assay, in the preoperative evaluation of patients with pancreatic cystic lesions. A positive result on FDG PET strongly suggests malignancy and, therefore, a need for resection. A negative result shows a benign tumor that may be treated with limited resection or, in select high-risk patients, with biopsy, follow-up, or both.

Degree of Confidence

The preoperative differential diagnosis of cystic lesions of the pancreas remains difficult. The most important determinant of the prognosis is the identification of malignant or premalignant cysts that require resection. FDG PET is a new imaging procedure based on the increased glucose metabolism by tumor cells and has been proposed for use in the diagnosis and staging of pancreatic cancer. Sperti and associates have reported sensitivity, specificity, and positive and negative predictive values in detecting malignant tumors. Values were, respectively, 94%, 97%, 94%, and 97%; and 65%, 87%, 69%, and 85%.

Sendler and associates performed FDG PET in 46 patients admitted to the hospital for pancreatic tumor surgery. The method yielded a sensitivity of 86% and a specificity of 67%. The authors concluded that PET does not allow the precise exclusion of malignant tumors and that, therefore, the use of invasive diagnostic procedures may not be reduced.

False Positives/Negatives

With FDG PET, there is a potential for false-positive scans as a result of physiologic activity. Kato and associates investigated pancreatic cancer with FDG PET. They reported 1 false-negative case (mucinous adenocarcinoma), in which the tumor contained a small number of malignant cells, and 1 false-positive case, in which lymphocytes densely accumulated in the mass in the pancreatic head.

Findings

Mucinous cystic pancreatic tumors are usually hypovascular on angiography. The only vascularity present is in the walls, septa, and mural nodules. In cystadenocarcinoma, there might be narrowing or obstruction of the splenic artery and vein due to direct tumor encasement or invasion. Angiography may also depict metastases and contiguous organ invasion.

Approximately 85% of microcystic adenomas are hypervascular or moderately vascular, and 84% are associated with parenchymal lucencies corresponding to cystic areas. The primary angiographic manifestations of microcystic adenomas are arterial displacement, arterial dilatation, and neovascularity; arterial encasement is unusual. Arteriovenous shunting is seen in 40% patients.

Degree of Confidence

The findings on angiograms alone are nonspecific, and a similar appearance may occur with other benign and malignant tumors.

False Positives/Negatives

Low-grade vascularization may occur in both benign and malignant pancreatic tumors. When MCNs have a low-grade vascularity or are avascular, differentiation from a pseudocyst may be difficult. Leiomyosarcoma and other retroperitoneal tumors may invade the pancreas and cause a similar angiographic appearance. Moreover, a variety of angiomatous lesions have been reported within the pancreas, with a potential for false-positive diagnosis of microcystic adenoma.

Despite advances in imaging, the diagnosis of pancreatic masses remains difficult. The differential diagnosis of a cystic pancreatic mass is large. Accurate diagnosis is imperative for appropriate patient management; therefore, occasionally obtaining tissue for histologic diagnosis may be essential.

Although the indications for percutaneous pancreatic biopsy are not standardized, in many circumstances, biopsy is clearly indicated. Such circumstances include cases of inoperable pancreatic tumor, suspected lymphoma, and metastasis or neuroendocrine tumors, as well as those in which cystic tumors must be differentiated.

Pancreatic biopsy is usually performed with fine needles used for cytology. The use of larger needles for core biopsy slightly improves sensitivity, especially in masses due to chronic pancreatitis or neuroendocrine tumors. Complications seldom occur; among them, acute pancreatitis and tumoral seeding are the most important. Percutaneous pancreatic biopsy is a safe, flexible, and reliable method for diagnosing pancreatic masses (Sparchez, 2002).

The roles of EUS and EUS FNA in the evaluation of cystic pancreatic lesions are evolving. The detailed images provided by EUS and, hence, the ability to target the biopsy at suspicious areas within the pancreatic cystic lesion may prove to be invaluable. Improvements in EUS equipment will further secure the role of this technology in evaluating patients for these lesions (Schwartz, 2002).

Anderson and Scheiman discuss the use of EUS in serous cystadenoma, which is the most common of the nonmucinous cystic pancreatic neoplasms. These microcystic tumors were previously termed glycogen-rich cystadenomas because of the presence of glycogen in the cyst epithelium. A small number of these lesions are macrocystic, and differentiating them from mucinous lesions may be difficult. However, EUS-guided FNA can provide diagnostic material from the cyst fluid. The second most common nonmucinous cyst is the islet cell tumor. These rare cystic tumors may or may not be accompanied by excess hormone production. EUS-guided aspiration may again be useful in establishing the diagnosis.

Analysis of cyst fluid obtained by image-guided aspiration is a useful adjunct in the evaluation of cystic pancreatic masses. Fluid amylase levels are characteristically increased in over 95% of pseudocysts; therefore, a normal amylase level can be used to exclude a pseudocyst. Fluid CEA levels can be elevated in a variety of cystic lesions, including mucinous cystic pancreatic tumors and some pseudocysts. However, this level is always low or normal in serous cystadenomas. If an accurate diagnosis is not achieved, resection rather than observation is the preferred option.

If diagnosed correctly, all mucinous cystic tumors of the pancreas should be resected, as a small risk of malignant potential exists. Complete resection has a favorable prognosis, with a low probability of recurrence. The prognosis is better than that for ductal adenocarcinoma of the pancreas, with intraductal papillary tumors having the best prognosis. Aspiration of the cyst is generally avoided due to the risk of a pancreatic fistula formation. The insidious nature of mucinous pancreatic cysts allows many patients to survive for many years symptom-free.

Pancreatic resection is the treatment of choice in IPMT, which successfully relieves symptoms and prevents progression to malignant degeneration. Conservative management techniques, such as sphincterotomy, stenting, and clearance of intraductal mucus are temporary measures that may relieve symptoms. However, they do not address the malignant potential of these tumors.

Pancreaticoduodenectomy is generally advocated, given the predominance of IPMT in the head of the pancreas, but distal pancreatectomy is usually performed for tumors in the pancreatic body or tail. When the tumor involves the entire ductal system, total pancreatectomy is the usual option. Intraoperative frozen sections are required to confirm disease-free margins after ductal resection. If the results are positive, extended resection is warranted.

Ikeda and associates clarified the patterns of recurrence and prognosis after resection of IPMTs in 14 patients with histologically proven intraductal papillary adenocarcinoma (12 patients) or intraductal papillary adenoma (2 patients). Six patients were alive with no evidence of disease. Two patients died from other causes. Six patients had recurrences. The median survival time was 46 months. In the 6 recurrent cases, the median postoperative disease-free interval was 38 months. Four patients died from recurrence, and the median survival time after recurrence was 6 months.

The major site of recurrence was the pancreatic remnant. The other sites were 2 liver metastases in 2 cases of peritoneal spread and 1 case of local spread. Because of the low frequency of lymph-node metastases, surgery to preserve pancreatic function may be recommended, especially for localized tumors such as the branch type of tumor. It is important to avoid incomplete resection by using intraoperative pancreatoscopy and ultrasonography. Long-term follow-up after surgery is necessary, even with curative resection. The authors recommended total pancreatectomy for recurrences without distant metastases.

If a pancreatic pseudocyst can be ruled out, evaluation should subsequently focus on identifying those tumors, which require surgical resection because of actual or potential malignancy. As opposed to ductal adenocarcinoma, cystic neoplasms with malignant potential are slow growing, and a relatively favorable prognosis has been reported, even in the setting of malignant degeneration. Tumors with malignant potential include MCNs, IPMTs, papillary cystic neoplasms, and cystic islet-cell tumors. In contrast, serous cystadenomas are almost universally benign. The diagnostic examination of choice is spiral CT with intravenous contrast enhancement, which allows tumor localization and, sometimes, discrimination of serous cystadenomas from other neoplasms.

Kitagawa and associates examined the case records of 63 patients with IPMT treated with resection to determine the predictors of prognosis. IPMT was diagnosed by using the surgical specimen and the WHO definition. Predictors were determined by using univariate and multivariate analyses.

Actuarial 3- and 5-year survival for patients with benign disease was 95% and 83%, and for those with malignant disease, rates were 52% and 44%, respectively (P = .0048). In the 33 patients with malignant disease (mean follow-up, 35 mo), gross mucus was a predictor of prolonged survival after univariate and multivariate analyses (odds ratios, 4.34 and 4.55, respectively), whereas alcohol abuse was a predictor of poor survival (odds ratios, 3.41 and 3.60, respectively). Gross mucus observed during endoscopy was a predictor of benign IPMT, and in the group with malignant IPMT, the presence of gross mucus was associated with better survival. Survival was also strongly associated with either benign IPMT or negative staining for p53 overexpression.

Recurrence in the duct of the pancreatic remnant after surgery in IPMT has not been reported after curative resection, and 5-year survival rates greater than 80% are common for noninvasive tumors.

Maire and associates examined case records of 73 patients with malignant IPMT to assess prognostic factors after surgical resection, and to compare long-term survival with that of patients surgically treated for ductal adenocarcinoma. Surgical treatments for IPMT were pancreaticoduodenectomy (n = 46) and distal (n = 14), total (n = 11), or segmentary (n = 2) pancreatectomy. The operative mortality rate was 4%. IPMT corresponded to in situ (n = 22) or invasive carcinoma (n = 51). In the latter group, 17 had lymph-node metastases.

Overall median survival was 47 months. In patients with in situ and invasive carcinoma, 5-year survival rates were 88% and 36%, respectively. On univariate analysis, the following were associated with a fatal outcome: abdominal pain, high serum CA 19-9 concentrations before surgery, caudal localization, invasive carcinoma, lymph-node metastases, peripancreatic extension, and malignant relapse. On multivariate analysis, lymph-node metastasis was the only prognostic factor (odds ratio, 7.5; 95% confidence interval, 3.4, 16.4).

The overall 5-year survival rate was higher in patients with malignant invasive IPMT than in those with pancreatic ductal carcinoma (36% vs 21%, P = .03). However, it was similar in the subset with stage II or stage III tumors. The authors concluded that the prognosis of patients with resected in situ or invasive stage I malignant IPMT is excellent. In contrast, the prognosis of those with locally advanced forms is as poor as that of patients with pancreatic ductal adenocarcinoma.

Nakagohri and associates published their long-term outcomes after surgical resection. They retrospectively reviewed the clinicopathologic features and outcomes in patients who underwent pancreatic resection for noninvasive and minimally invasive intraductal papillary mucinous adenocarcinoma. Minimally invasive structures were pathologically observed in 5. The mean age of patients with noninvasive (n = 16) or minimally invasive (n = 5) adenocarcinoma was 61 years. Of patients with minimally invasive adenocarcinoma, 4 had abdominal pain. Conversely, 7 patients with noninvasive adenocarcinoma had no complaint. The mean size of noninvasive and minimally invasive tumors was 2.5 cm (range, 0.8 -4.0 cm) and 3.3 cm (range, 2.5-4.5 cm), respectively.

The overall 5-year and 10-year survival rates for all 21 patients were 89% and 47%, respectively. Disease recurred in 3 patients; 2 patients with minimally invasive adenocarcinoma and 1 with noninvasive adenocarcinoma. Recurrence sites were the peritoneum (n= 2) and MPD of the remnant pancreas (n = 1). Five disease-free patients died from unrelated causes. The remaining 13 patients were alive and disease-free 3-12 years after surgery. Noninvasive and minimally invasive intraductal papillary mucinous adenocarcinoma had a favorable prognosis after surgical treatment.

Katoh et al treated 45 patients with cystadenoma and cystadenocarcinoma of the pancreas. Their patients were divided into 2 groups: group 1, which included 26 patients treated between 1963 and 1983, and group 2, which included 19 patients treated between 1984 and 1988. The rate of resection for cystadenoma was 67% for group 1 (n = 15) and 100% for group 2 (n = 11). The operative mortality rate was 0% for both groups. Pathologically, 17 patients (69%) had serous cystadenoma, and 9 (31%) had mucinous adenoma. Except for 5 of the 15 patients from group 1 who died from other causes, all patients were healthy.

The resection rate for cystadenocarcinoma was 36% for group 1 (n = 11) and 100% for group 2 (n = 8). In 2 patients from group 1 and in 1 patient from group 2, the tumors had previously been diagnosed as benign by means of operative biopsy of the cyst wall. No operative deaths occurred in either group. Cystic neoplasm was suspected from the sonographic and CT results in 70% patients in group 2. In 2 patients (25%), pseudocyst associated with chronic pancreatitis was preoperatively diagnosed. Adenocarcinoma was diagnosed in 3 patients by means of needle biopsy and cytologic examination of pancreatic juice. In group 1, 82% (9 patients) died from recurrent carcinoma; 2 patients were alive without disease at 5 and 8 years. In group 2, 38% (3 patients) died from recurrent carcinoma, 2 patients died from other causes, and 3 patients were still alive.

Horvath and Chabot reported results of an aggressive approach to cystic pancreatic neoplasms in a retrospective cohort analysis of 25 patients with cystic neoplasms of the pancreas. Data included patient demographics, presenting symptoms, operative procedure, pathologic diagnosis, perioperative morbidity and mortality rates, survival, and symptomatic follow-up data. Twenty-one patients were women, with a mean age of 60 years for the entire cohort. Mean follow-up was 24 months (range, 6 mo to 4.3 y). Complete follow-up was possible in 92%.

In 23 patients, resection was curative, and in 2, it was palliative. One patient with an uncinate mass underwent partial pancreatectomy; 4, distal pancreatectomy; and 9, distal pancreatectomy with splenectomy. Among 11 patients who required pancreatoduodenectomy, 4 had tumors involving the portal vein, which necessitated portal vein resection. Pathologic analysis revealed 12 serous cystadenomas, 4 mucinous cystadenomas, 3 mucinous cystadenocarcinomas, 5 intraductal papillary cystic neoplasms, and 1 serous cystadenocarcinoma.

The overall perioperative complication rate was 40%, with 5 major and 5 minor complications. The 11 patients who underwent pancreatoduodenectomy alone had 1 major and 4 minor complications. There were no pancreatic fistulas or portal vein thromboses and no operative mortalities. Two patients with mucinous cystadenocarcinomas died of their disease at 6 and 16 months postoperatively. All 11 pancreatoduodenectomy patients had only mild pancreatic insufficiency relieved by daily enzyme replacement.

The authors concluded that the good outcomes in this study supported an aggressive surgical approach in all patients with a cystic neoplasm of the pancreas, if they are medically fit to tolerate surgery. This approach was justified for the following reasons: (1) preoperative differentiation of a benign versus malignant tumor is unreliable, and routine testing for this purpose is of questionable utility; (2) potential adverse consequences of nonresectional therapy are significant; (3) perioperative morbidity and mortality rates are low with pancreatic surgery; and (4) the prognosis with curative resection is good.

Pancreas, Mucinous Cystic Neoplasm

AUTHOR AND EDITOR INFORMATION

INTRODUCTION

Background

Pathophysiology

Frequency

United States

International

Mortality/Morbidity

Race

Sex

Age

Anatomy

Clinical Details

Clinical findings

Differential diagnosis

Preferred Examination

Limitations of Techniques

DIFFERENTIALS

Other Problems to be Considered

RADIOGRAPH

Findings

Degree of Confidence

False Positives/Negatives

CT SCAN

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False Positives/Negatives

MRI

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Degree of Confidence

False Positives/Negatives

ULTRASOUND

Findings

Degree of Confidence

False Positives/Negatives

NUCLEAR MEDICINE

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Degree of Confidence

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ANGIOGRAPHY

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Degree of Confidence

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INTERVENTION

Medical/Legal Pitfalls

MULTIMEDIA