Mucinous cystic neoplasms of the pancreas.

Abstract: Mucinous cystic neoplasms of the pancreas (MCNP) are rare tumors with presentation and findings that differ in most cases from pancreatic pseudocysts. A simple pancreatic cystic lesion in a younger-aged patient with a history of pancreatitis and endoscopic retrograde cholangiopancreatography (ERCP) demonstration of ductal communication with the cyst strongly suggests the diagnosis of a benign pseudocyst. MCNP may have extensive areas without an epithelial lining, adding histologic sampling error to the potential for confusing these two entities. Pancreatic pseudocysts are benign lesions treated by enteric drainage procedures, while MCNP have significant malignant potential, and resection is advised. Even when clinical presentation and imaging are persuasive for a benign cyst, MCNP of the pancreas should be considered in planning, evaluation, and treatment.

Key Words: cystadenocarcinoma, cystic pancreatic tumors, mucinous cystadenoma

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Mucinous cystic neoplasms of the pancreas (MCNP) are rare tumors generally found in females over 50 years of age. Associated pancreatitis is very uncommon, and ductal communication with the cystic lesion has been reported in less than 30 cases. (1) MCNP have a spectrum of varied clinical presentations and imaging findings. Microscopically, the epithelium lining the cyst wall may be denuded, making intra-operative or even final pathologic diagnosis problematic. MCNP have significant malignant potential. Most authors feel these cystic neoplasms represent a dysplastic continuum from premalignant to malignant, and excision is advised even when carcinoma is not identified in the biopsy specimen. (2,3,4) If malignancy is not detected upon thorough histologic examination of the lesion, the long-term outcome is excellent. (5) Awareness of varied clinical presentations and potential histologic sampling problems is important in differentiating MCNP from benign pancreatic pseudocysts in unusual cases.

Case Report

A 28-year-old female with a four-month history of vague intraabdominal pain underwent laparotomy for possible endometriosis. No abnormality was detected, and a normal appendix was removed. She was later hospitalized with pancreatitis. Ultrasound demonstrated an 8 cm cystic lesion in the pancreatic tail, resulting in a general surgery consultation. A smooth, benign-appearing cystic lesion associated with pancreatitis and splenic vein thrombosis was seen on computed tomographic (CT) scan (Fig. 1). Biliary tract evaluation led to an endoscopic retrograde cholangiopancreatography (ERCP), demonstrating a normal pancreatic duct with the exception of a distal communication to the cystic lesion (Fig. 2). Follow-up studies found no resolution of the cyst, and elective drainage of the presumed pseudocyst was planned. Recurrent pancreatitis necessitated hospitalization with intravenous nutrition. At surgery, surrounding inflammatory changes typical of a pseudocyst were found. A single cavity was present with viscous fluid and debris. A portion of the cyst was sent for histology, and Roux-en-Y drainage of the presumed pseudocyst was established. A cholecystectomy demonstrated chronic cholecystitis. Final pathologic review of the cyst showed scattered areas of the internal surface to be lined by simple mucinous epithelium with underlying cellular stroma (Fig. 3). The patient was returned to surgery where a distal pancreatectomy was performed, and the previous Roux-en-Y segment was excised. A splenectomy was necessary due to inflammation and abutment of the cystic lesion into the hilum of the spleen. Surgical margins were free of tumor. She remains well two years later, as evidenced by normal examination and CT follow-up.

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Discussion

MCNP are believed to originate from ductal or stem cells within the pancreas. Columnar epithelium is usually present where the cyst lining has not been denuded. Goblet cells may be present. The epithelium may demonstrate clearly benign cuboidal cells or different phases of potential malignant progression, including atypia, dysplasia, carcinoma in situ, micropapillary projections, and/or invasive carcinoma. (6-8) As in our patient, dense, cellular stroma reminiscent of ovariantype stroma is characteristic. (7) Similar ovarian mucinous tumors with these features have suggested a common origin. (9) Compagno and Oertel (3) originally described the progressive spectrum of malignant potential within MCNP. Complete resection is generally recommended for these tumors, although routine resection of all pancreatic cysts has recently been challenged by Allen et al. (10) They safely followed small, asymptomatic cysts radiographically if no solid components were present.

The majority of MCNP occur in females older than 50 years of age. (2,7) When discovered, MCNP are generally symptomatic. Patients may have weight loss, abdominal or back pain, nausea, fever, a palpable mass, and/or jaundice. (7,11) Pancreatitis, however, is rare in patients with MCNP, ranging from 0 to 12%. (2,5,7,12) The most common defining test is a CT scan, with more than 80% of lesions demonstrating a finding other than a large simple cyst. Septations, macrocysts, calcifications, papillary projections, or discreet invasive tumors are frequently reported. (3,7,12)

Various reports have emphasized the risk of mistaking cystic tumors for pancreatic pseudocysts. (2,12) Grieshop et al (4) found a correct preoperative diagnosis made in only 9% of patients with cystic neoplasms. In retrospective evaluations, many individual cases had findings to suggest a cystic neoplasm. Percutaneous needle biopsy has been infrequently reported, and was misleading in more than 50% of cases. (13) ERCP demonstrates ductal communication with a pancreatic pseudocyst in 50 to 90% of patients. (2,3,12,14,15) Most reports of MCNP find no ductal communication by ERCP. (7,8,16-19) Rare cases demonstrating a ductal connection with MCNP have been reported and, when present, may suggest malignancy. (11,20,21) A recent literature review demonstrated only 27 reported cases of communication with a MCNP. (1) However, a deformed or occluded pancreatic duct may be seen in 50% of MCNP cases evaluated by ERCP. (16) Complete pathologic examination of the surgical specimen is necessary, as up to 50% of the epithelial lining of MCNPs may be absent in scattered or extensive areas. (6,16) This poses obvious problems for the use and interpretation of frozen section evaluation at surgery.

The largest published experience with MCNP is by the French Surgical Association (Multi-Center Study). Three hundred ninety-eight cases of cystadenoma and cystadenocarcinomas of the pancreas were reviewed. (11) Of these, 150 were classified as mucinous cystadenoma, and 78 were cystadenocarcinomas. Included in their study were 26 asymptomatic patients who had a nonoperative diagnosis of serous cystadenoma, and were successfully followed without complication or malignancy for up to 38 months. Typical serous cystadenomas will have a microcystic appearance by CT scan, each cyst generally smaller than 2 cm with calcifications and smooth walls. Contrast enhancement is common. Other articles have supported the potential for differentiation of benign serous cystadenomas from MCNP by nonoperative sampling of cyst contents. Carcinoembryonic antigen, cancer antigen 125, carbohydrate antigen 19-9, amylase, isoenzymes, and cytology have been used to define these two entities. (3,22)

[FIGURE 3 OMITTED]

MCNP is a separate entity from pancreatic mucinous duct ectasia or intraductal papillary mucinous neoplasms (IPMN). IPMN are characterized by dilation of the main pancreatic duct, intraluminal filling defects, and associated clusters of smaller cyst-like structures. (4,23,24) Mucin will be seen extruding from the ampulla during ERCP. IPMN are premalignant lesions and occur more often in men and in an older age than in MCNP. (2)

Conclusion

MCNP may occur in young patients and have a clinical presentation indistinguishable from a benign pseudocyst. ERCP may rarely demonstrate ductal communication with a cystic tumor. Resection is advised. Disease-specific survival of 100% has been reported for patients with MCNP when invasion is not found after complete resection and pathologic examination of the entire specimen. (3,5) When invasive adenocarcinoma is present, long-term survival is 40 to 50%. (3,6)

All truth passes through three stages. First, it is ridiculed. Second,
it is violently opposed. Third, it is accepted as being self-evident.
--Arthur Schopenhauer

Acknowledgments

The authors wish to acknowledge Kimberly G. Andes, Lin F. Peabody, LPN, CCRC, and Heather M. Vice, RN, BSN for their contributions to this study.

Accepted March 11, 2004.

References

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RELATED ARTICLE: Key Points

* Mucinous cystic neoplasms of the pancreas have a broad spectrum of clinical presentations and may occur in young patients.

* They may demonstrate ductal communication by ERCP ductography with a presentation typical of a benign pseudocyst.

* These neoplasms have significant malignant potential, and resection is advised.

Eugene O. Dickens, MD, A. K. Woodroof, MD, and William C. Jennings, MD, FACS 

From the Department of Surgery, University of Oklahoma College of Medicine, Tulsa, OK.

Reprint requests to William C. Jennings, MD, FACS, 1802 East 19th Street, St. John Medical Center, Kravis Building, Room 211, Tulsa, OK 74104-5425. E-mail: [e-mail]