Cystic Neoplasms of the Pancreas

Mucinous cystic neoplasms (MCNs) encompass a spectrum ranging from benign but potentially malignant to carcinoma with a very aggressive behavior. There is often heterogeneity within the lesions with benign and malignant appearing regions making it impossible to exclude malignancy with preoperative biopsy. Mucinous cystic neoplasms are commonly seen in perimenopausal women and about two thirds are located in the body or tail of the pancreas. Like cystadenomas, most MCNs are now incidental findings identified during imaging performed for other reasons.

When symptoms are present, they are usually nonspecific and include upper abdominal discomfort or pain, early satiety, and weight loss. On imaging studies, the cysts have thick walls and do not communicate with the main pancreatic duct. There may be nodules or calcifications within the wall of the cyst. The cysts are lined by tall columnar epithelium that fills the cyst with viscous mucin. The submucosal layer consists of a highly cellular stroma of spindle cells with elongated nuclei similar to the “ovarian stroma” which is a key pathologic feature distinguishing these lesions. Elevated CEA levels in the fluid (>200 ng/mL) may suggest malignant transformation. Solid areas may contain atypical cells or invasive cancer and extensive sampling of the specimen once it is removed surgically is necessary to accurately predict prognosis.

Intraductal papillary mucinous neoplasms (IPMNs) usually occur within the head of the pancreas and arise within the pancreatic ducts. The ductal epithelium forms a papillary projection into the duct and mucin production causes intraluminal cystic dilation of the pancreatic ducts. Imaging studies demonstrate diffuse dilation of the pancreatic duct and the pancreatic parenchyma is often atrophic due to chronic duct obstruction. However, classic features of chronic pancreatitis such as calcification and a beaded appearance of the duct are not present. At ERCP, mucin can be seen extruding from the ampulla of Vater, a so called “fish-eye” lesion that is virtually diagnostic of IPMN.

Initial reports suggested a male predominance, but more recent series indicate an equal distribution. Patients are usually in their seventh to eighth decade of life and present with abdominal pain, or recurrent pancreatitis, thought to be caused by obstruction of the pancreatic duct by thick mucin. Five to ten percent of the patients have steatorrhea (fat in stool), diabetes, and weight loss secondary to pancreatic insufficiency.

Some IPMNs primarily involve the main pancreatic duct, while others involve the branch ducts. Branch-duct type IPMNs are often found in the uncinate process, are sometimes asymptomatic, and are less frequently associated with malignant transformation. The surgical management of IPMNs is complicated by the fact that the lesion itself is small and preoperative imaging studies show a dilated pancreatic duct but not necessarily the mass. Mucus can dilate the duct proximal and distal to the lesion. Furthermore, these lesions can spread microscopically along the duct and there can be skip areas of normal duct between the diseased portions. Therefore, thorough preoperative imaging including EUS, MRCP or ERCP, and sometimes pancreatic ductoscopy, which can also be repeated intraoperatively, is useful. The surgeon needs to be prepared to extend the resection if necessary based on intraoperative findings and frozen section of the margin. Extending the resection to the point of total pancreatectomy is controversial due to the morbidity of this operation.

Like MCNs, the IPMNs require careful histologic examination of the entire specimen for an invasive component which is present in about 35-40% of cases. Survival of patients with IPMN, even when malignant and invasive, can be quite good. As with MCN, patients with borderline tumors or carcinoma in situ are usually cured. With invasive carcinoma, the 5 and 10-year survival is 60% and 50% which is much better than typical pancreatic adenocarcinoma. For this reason, if there is recurrence in the remaining pancreas, further resection is warranted because several series have shown that some of these cases are salvageable. Patients with IPMN are also at risk for other malignancies and should undergo colonoscopy and close cancer surveillance.

Serous cystadenomas are essentially considered benign tumors without malignant potential. Serous cystadenocarcinoma has been reported very rarely (<1%). Therefore, malignant potential should not be used as an argument for surgical resection and the majority of these lesions can be safely observed in the absence of symptoms due to mass effect or rapid growth. The average rate of growth is about 0.45 cm/year. About 50% of cystadenomas are asymptomatic and are detected as an incidental finding. Most symptomatic patients have mild upper abdominal pain, epigastric fullness, or moderate weight loss. Occasionally, cystadenomas can grow to a size capable of producing jaundice or gastrointestinal obstruction due to mass effect. For symptomatic patients with serous cystadenoma, surgical resection is indicated. For lesions in the tail, splenectomy is not necessary given the benign nature of the tumor. In appropriate candidates, a laparoscopic approach to distal pancreatectomy can be considered. These cysts are frequently found in older patients in which pancreatic resection for a benign neoplasm should be avoided in the absence of significant symptoms. All regions of the pancreas are affected with half in the head/uncinate process, and half in the neck, body, or tail of the pancreas. They have a spongy appearance, and multiple small cysts (microcystic) are more common than larger cysts (macrocystic or oligocystic). These lesions contain thin serous fluid which does not stain positive for mucin and is low in CEA (<200 ng/mL). Typical imaging characteristics include a well circumscribed cystic mass, small septations, fluid close to water density, and sometimes a central scar with calcification. If a conservative management is adopted, it is important to be sure of the diagnosis. EUS-FNA should yield nonviscous fluid with low CEA and amylase levels, and if cells are obtained, which is rare, they are cuboidal and have a clear cytoplasm.

Mucinous cystic neoplasms (MCNs) encompass a spectrum ranging from benign but potentially malignant to carcinoma with a very aggressive behavior. There is often heterogeneity within the lesions with benign and malignant appearing regions making it impossible to exclude malignancy with preoperative biopsy. Mucinous cystic neoplasms are commonly seen in perimenopausal women and about two thirds are located in the body or tail of the pancreas. Like cystadenomas, most MCNs are now incidental findings identified during imaging performed for other reasons.

When symptoms are present, they are usually nonspecific and include upper abdominal discomfort or pain, early satiety, and weight loss. On imaging studies, the cysts have thick walls and do not communicate with the main pancreatic duct. There may be nodules or calcifications within the wall of the cyst. The cysts are lined by tall columnar epithelium that fills the cyst with viscous mucin. The submucosal layer consists of a highly cellular stroma of spindle cells with elongated nuclei similar to the “ovarian stroma” which is a key pathologic feature distinguishing these lesions. Elevated CEA levels in the fluid (>200 ng/mL) may suggest malignant transformation. Solid areas may contain atypical cells or invasive cancer and extensive sampling of the specimen once it is removed surgically is necessary to accurately predict prognosis.

Resection is the treatment of choice for most mucin-producing cystic tumors. Malignancy cannot be ruled out without removal and extensive sampling of the tumor. Current thinking is that all of these tumors will eventually evolve into cancer if left untreated. Malignant transformation is more common with larger tumors, and older patients, and there appears to be a stepwise accumulation of mutations (K-ras, p53). The length of time it takes for a benign MCN to transform into a malignant mucinous cystadenocarcinoma is unknown.

Since most MCNs are located in the body and tail of the pancreas, distal pancreatectomy is the most common treatment. For small lesions, it may be appropriate to preserve the spleen but splenectomy ensures removal of the lymph node basin that can potentially be involved. It is very important not to rupture the cyst during resection and the tumor should be removed intact, not morselized. Therefore, a laparoscopic approach may not be appropriate for larger lesions.

Completely resected MCNs without atypia are usually cured especially if small (< 3 cm). Even patients with moderate dysplasia or carcinoma in situ are usually cured by complete resection. In the presence of invasive carcinoma, mucinous cystadenocarcinoma, the prognosis is similar to typical ductal adenocarcinoma of the pancreas which underscores the need to remove MCNs at the time of diagnosis.

The most common cystic lesion of the pancreas is the pseudocyst which of course has no epithelial lining and is a nonneoplastic complication of pancreatitis or pancreatic duct injury. The diagnosis is usually straight forward from the clinical history of an episode of acute pancreatitis. Although not usually necessary, analysis of pseudocyst fluid would reveal a high amylase content. Pseudocysts can often be observed until resolution. Sometimes pseudocysts require surgical drainage into the gastrointestinal track, usually the stomach. The danger comes in mistaking a cystic pancreatic neoplasm for a pseudocyst and incorrectly draining a cystic neoplasm into the gastrointestinal tract rather than resecting the neoplasm. For this reason, biopsy of the pseudocyst wall is a recommended step in the surgical management of pancreatic pseudocysts.

Rarely, typical ductal adenocarcinoma of the pancreas may undergo cystic degeneration due to central necrosis. Occasionally, this will create difficulty in the proper preoperative diagnosis and should be kept in mind when deciding to conservatively follow a cystic pancreatic neoplasm. It is more common, 5-10 percent, for neuroendocrine tumors of the pancreas to contain cysts. These cysts are filled with serosanguineous fluid rather than necrotic debris. Lymphoepithelial cysts of the pancreas usually occur in men in their fifth to sixth decade. These benign lesions may be unilocular or multilocular and vary widely in size. The contents of the cyst are also variable and may be thin serous fluid or cheesy/caseous material if there is increased keratin formation. A substantial number of patients with von Hippel-Lindau syndrome develop pancreatic cysts that resemble serous cystadenomas. There may be multiple lesions scattered throughout the pancreas. Patients with polycystic kidney and hepatic disease may also develop benign pancreatic cysts (cystadenomas). With all of these rare cystic neoplasms careful clinical history, high-quality pancreatic imaging, and sampling of the cyst fluid for analysis will guide proper treatment.

Lymphoma can affect the pancreas. Primary involvement of the pancreas with no disease outside the pancreas also occurs. The clinical presentation often is similar to pancreatic adenocarcinoma, with vague abdominal pain and weight loss. Identification of a large mass often involving the head and body of the pancreas should raise suspicion. Percutaneous or EUS-guided biopsy will confirm the diagnosis in most cases. If the diagnosis cannot be confirmed preoperatively, laparoscopic exploration and biopsy is indicated. There is no role for resection in the management of pancreatic lymphoma. Endoscopic stenting can be done to relieve jaundice. Chemotherapy is often quite effective in the treatment of lymphoma.