Cystic lesion of the pancreas

Abstract

A 50-year-old healthy woman with no family history of cancer recently underwent a screening virtual colonoscopy (computed tomography [CT] colonography). No colonic polyps were identified but a 4.5-cm cyst was seen in the pancreas (at the junction of the body and tail) without calcification in the cyst or the pancreas. The patient denies a history of abdominal pain, alcohol abuse, pancreatitis, or biliary disease. She is now referred to you for recommendations regarding management of the pancreatic cystic lesion. Cystic lesions in the pancreas are being recognized with increasing frequency, likely related to the increased use of cross-sectional imaging for the evaluation of unrelated abdominal complaints or for the purpose of screening for another condition such as colon polyps with CT colonography. They are an increasing source of referral to specialists active in pancreatic diagnostics and treatment such as endosonographers and pancreatic surgeons. The approach to the patient with a pancreatic cyst begins with a detailed history to determine if the patient is experiencing symptoms related to the lesion itself or a related condition such as pancreatitis. Most asymptomatic patients have lesions that do not cause symptoms owing to their small size. Although large lesions may cause vague symptoms of pain, obstructive jaundice is uncommon, even for lesions located in the head. Typical symptoms of malignancy, such as weight loss, epigastric/back pain, nausea, vomiting, and severe malaise, usually are absent. Clinical decision making is driven by an understanding of the differential diagnosis of the cyst and, in the case of the asymptomatic patient, its likelihood of causing harm with and without testing and/or treatment. The fundamental issue to be addressed is whether the cyst is neoplastic or not and, if so, what is its risk for malignant degeneration. Although the spectrum of possible lesions is well established in the literature, the nature of the existing data, largely retrospective case-series analyses, precludes definitive evidence-based recommendations for many clinical situations. Inflammatory pancreatic cysts, pseudocysts, are by far the most common cystic lesion of the pancreas. These nonneoplastic cysts may represent up to 90% of all pancreatic cysts, but this estimate includes autopsy and radiology series whose data may not be relevant to clinical decision making for this patient presentation. 1Fernandez-del Castillo C. Targarona J. Thayer S.P. Rattner D.W. Brugge W.R. Warshaw A.L. Incidental pancreatic cysts clinicopathologic characteristics and comparison with symptomatic patients.Arch Surg. 2003; 138: 427-434Google Scholar The critical patient management issue is differentiating these inflammatory lesions from neoplastic ones. When a cyst arises in a patient with known chronic pancreatitis, the clinical concern of a neoplasm is minimal. When patients present with unexplained pancreatitis for the first time with a cyst, or have only subtle changes of chronic pancreatitis by a sensitive imaging modality such as endoscopic ultrasound (EUS), the clinician should consider whether the cyst may be a neoplasm and the lesion is the cause of the pancreatitis instead of assuming the cyst is the consequence of the pancreatitis. Cystic neoplasms of the pancreas represent a diverse collection of tumors with varied malignant potential and clinical presentation. They can be predominantly cystic or can result from cystic degeneration of a solid tumor. In one large series, incorrect diagnosis of cystic neoplasms delayed appropriate surgical treatment or led to an inappropriate intervention in up to 37% of cases. 2Warshaw A.L. Compton C.C. Lewandrowski K. et al.Cystic tumors of the pancreas. New clinical, radiologic and pathologic observations in 67 patients.Ann Surg. 1990; 212: 432-435Google Scholar Among neoplastic cystic pancreatic lesions, serous cystadenomas, mucinous cystic neoplasms, and intraductal mucinous neoplasms are the most common tumors seen in practice. Other cystic tumors include the rarer papillary mucinous tumors and cystic islet cell tumors. Serous cystadenomas originally were termed microcystic adenomas, referring to the small (<2 cm) cystic compartments that make up the tumors. The term microcystic adenoma still is used synonymously with serous cystadenomas but has been criticized because of reports of macrocystic serous tumors. 3Lewandrowski K. Warshaw A. Compton C. Macrocystic serous cystadenoma of the pancreas a morphologic variant differing from microcystic adenoma.Hum Pathol. 1992; 23: 871-875Google Scholar Serous cystadenomas occur more commonly in women, with typical age at presentation in the 60s. These tumors generally represent approximately one third of cystic pancreatic lesions in surgical series. Although nearly always benign, malignant serous cystadenocarcinomas rarely have been described (to our knowledge, <10 have been reported in the literature). 4Sarr M.G. Murr M. Smyrk T.C. et al.Primary cystic neoplasms of the pancreas: neoplastic disorders of emerging importance: current state-of-the-art and unanswered questions.J Gastrointest Surg. 2003; 7: 417-428Google Scholar Serous cystadenomas generally are slowly growing tumors that are symptomatic in as many as 50% of patients. They may present with vague abdominal or back pain, nausea, or weight loss; jaundice and pancreatitis are quite rare. It is not uncommon for these tumors to be discovered by palpation at the time of an abdominal examination in an asymptomatic patient because these tumors can grow to a considerable size. Similar to pancreatic neuroendocrine tumors, 5Lubensky I.A. Pack S. Ault A. et al.Multiple neuroendocrine tumors of the pancreas in von Hippel-Lindau disease histopathological and molecular genetic analysis.Am J Pathol. 1998; 153: 223-231Google Scholar serous cystadenomas have an increased incidence in patients with von Hippel-Lindau disease, occurring in 35%–75% of patients. 6Hammel P.R. Wilgrain W. Terris B. Penfornis A. Sauvanet A. Correeas J.M. Chauveau D. Balaian A. Beigelman C. O’Toole D. Bernades P. Ruszniewski P. Richard S. Pancreatic involvement in von Hippel-Lindau disease.Gastroenterology. 2000; 119: 1087-1095Abstract Full Text Full Text PDF Scopus (297) Google Scholar Recent studies suggest that these patients may harbor allelic losses on selected chromosomes, with loss of heterozygosity on chromosomes 3p (the location of the von Hippel-Lindau or VHL tumor suppressor gene) and 10q. 7Moore P.S. Zamboni G. Brighenti A. et al.Molecular characterization of pancreatic serous microcystic adenomas. Evidence for a tumor suppression gene on chromosome 10q.Am J Pathol. 2001; 158: 317-321Google Scholar These tumors are well-circumscribed masses enclosed in a fibrous capsule containing numerous, small, fluid-filled cysts arranged in a classic honeycomb pattern. 8Pyke C.M. van Heerden J.A. Colby T.V. et al.The spectrum of serous cystadenoma of the pancreas. Clinical, pathologic, and surgical aspects.Ann Surg. 1992; 215: 132-139Google Scholar Fibrous bands within the lesions often converge, centrally forming a stellate scar that may calcify, giving a pathognomonic sunburst appearance on CT scan. 9Procacci C. Graziani R. Bicego E. et al.Serous cystadenoma of the pancreas report of 30 cases with emphasis on the imaging findings.J Comput Assist Tomogr. 1997; 21: 373-382Google Scholar Mucinous cystic neoplasms represent nearly half of the tumors removed in contemporary surgical series. These have been classified into benign, borderline (low-grade malignant), and malignant. However, this World Health Organization classification has been challenged as incompletely predictive of clinical outcomes. 10Sarr M.G. Carpenter H.A. Prabhakar L.P. et al.Clinical and pathologic correlation of 84 mucinous cystic neoplasms of the pancreas can one reliably differentiate benign from malignant (or premalignant) neoplasms?.Ann Surg. 2000; 231: 205-212Google Scholar Intraductal papillary mucinous neoplasms (IPMNs) are similar lesions that characteristically communicate with the main pancreatic duct as their main point of distinction. Mucinous tumors are much more common in women (>75%), with the age at diagnosis typically in the 60s. Although the patient may present with pain, an abdominal mass, or weight loss, up to one third of contemporary surgical series report discovery by cross-sectional imaging for unrelated reasons. Ninety percent of these tumors occur in the pancreatic body or tail. 4Sarr M.G. Murr M. Smyrk T.C. et al.Primary cystic neoplasms of the pancreas: neoplastic disorders of emerging importance: current state-of-the-art and unanswered questions.J Gastrointest Surg. 2003; 7: 417-428Google Scholar Mucinous cystic tumors are characterized by a thick fibrous capsule that encircles the cystic spaces. A characteristic spindle-cell stroma containing epithelioid cells similar to ovarian stroma surrounds the tumor. The cyst lining is comprised of mucin-producing duct-like cells frequently exhibiting a papillary architecture. However, the epithelial lining may be denuded, leading to misdiagnosis of pseudocyst on limited tissue samples such as surgical frozen sections. The prognosis for mucinous cystic neoplasms is defined by the presence or absence of invasive adenocarcinoma. Cancer has been described in approximately one third of tumors, and these patients have a variable prognosis, with 5-year survival ranging from poor outcomes similar to ductal adenocarcinoma up to 60%. 10Sarr M.G. Carpenter H.A. Prabhakar L.P. et al.Clinical and pathologic correlation of 84 mucinous cystic neoplasms of the pancreas can one reliably differentiate benign from malignant (or premalignant) neoplasms?.Ann Surg. 2000; 231: 205-212Google Scholar, 11Brugge W.R. Lauwers G.Y. Sahani D. Fernandez-del Castillo C. Warshaw A.L. Cystic neoplasms of the pancreas.N Engl J Med. 2004; 351: 1218-1226Google Scholar One explanation for the disparate literature may be variability in tissue sampling because the invasive component may be only a small part of the lesion. These increasingly recognized lesions are characterized by intraductal dysplastic epithelium resembling colorectal villous adenomas, with papillae covered by columnar epithelium with occasional goblet cells and extensive mucin production. IPMNs represent nearly 20% of mucinous cystic lesions in surgical series. This category includes several previously used terms: mucinous ductal ectasia, intraductal mucin-producing tumor, intraductal cystadenoma, and pancreatic duct villous adenoma. These tumors always exhibit at least low-grade dysplasia, and should be considered premalignant in all clinical situations. 11Brugge W.R. Lauwers G.Y. Sahani D. Fernandez-del Castillo C. Warshaw A.L. Cystic neoplasms of the pancreas.N Engl J Med. 2004; 351: 1218-1226Google Scholar However, the natural history with regard to progression to cancer is not well characterized. IPMNs principally occur in men, with a mean age of diagnosis in the mid-60s. The lesions are frequently (50%) confined to the head, and a typical presenting symptom complex is recurrent unexplained pancreatitis with ductal dilation or symptoms similar to chronic pancreatitis, typically without disease risk factors. 11Brugge W.R. Lauwers G.Y. Sahani D. Fernandez-del Castillo C. Warshaw A.L. Cystic neoplasms of the pancreas.N Engl J Med. 2004; 351: 1218-1226Google Scholar IPMNs may involve the main duct and/or side branches. In the latter case, it may be confused with a mucinous cystic tumor. However, the absence of the characteristic stroma differentiates the lesions. 4Sarr M.G. Murr M. Smyrk T.C. et al.Primary cystic neoplasms of the pancreas: neoplastic disorders of emerging importance: current state-of-the-art and unanswered questions.J Gastrointest Surg. 2003; 7: 417-428Google Scholar It has been proposed that the side branch type has a better prognosis than the variant that involves the main duct. Surgical resection must consider the extent of intraductal growth to achieve a negative margin and prevent recurrence. In the absence of carcinoma, prognosis is excellent with definitive surgical resection. Imaging techniques that have findings characteristic of IPMN include CT and endoscopic retrograde cholangiopancreatography. A patulous papilla at endoscopic retrograde cholangiopancreatography with mucous extruding is pathognomonic, with a pancreatogram showing profound ductal dilation for main branch disease. In the side branch variant, ductal communication with multiple cystic lesions is present. Islet cell tumors of the pancreas are quite rare, representing approximately 3%–5% of all cystic pancreatic neoplasms. 12Buetow P.C. Parrino T.V. Buck J.L. et al.Islet cell tumors of the pancreas pathologic-imaging correlation among size, necrosis and cysts, calcification, malignant behavior, and functional status.AJR Am J Roentgenol. 1995; 165: 1175-1179Google Scholar They usually are associated with an excess hormone-production syndrome but symptoms may not be evident or the tumors may be nonfunctional. They are typically larger than their solid islet-cell counterparts (mean diameter, 8.4 cm) and are associated with calcification, local and vascular invasion, and distant metastases. 12Buetow P.C. Parrino T.V. Buck J.L. et al.Islet cell tumors of the pancreas pathologic-imaging correlation among size, necrosis and cysts, calcification, malignant behavior, and functional status.AJR Am J Roentgenol. 1995; 165: 1175-1179Google Scholar The prognosis for patients with solid and cystic islet-cell tumors is good, with curative resection occurring in a significant proportion of patients and with some patients surviving years despite metastatic disease. 13Schwartz R.W. Munfakh N.A. Zweng T.N. et al.Nonfunctioning cystic neuroendocrine neoplasms of the pancreas.Surgery. 1994; 115: 645-649Google Scholar Papillary cystic tumors of the pancreas represent less than 5% of pancreatic cystic neoplasms. Histologically, papillary cystic tumors are made up of uniform cells arranged around delicate fibrovascular septae with loss of cellular cohesion resulting in a classic pseudopapillary pattern. 15Klimstra D.S. Heffess C.S. Oertel J.E. et al.Acinar cell cystadenocarcinoma of human pancreas. A clinical pathologic study of 28 cases.Am J Surg Pathol. 1992; 16: 815-837Google Scholar Although most of these tumors are benign, up to 15% may be malignant. 16Sperti C. Pasquali C. Constantino V. Perasole A. Liessi G. Pedrazzoli S. Solitary true cyst of the pancreas in adults. Report of three cases and review of literature.Int J Pancreatol. 1995; 18: 161-167Google Scholar The vast majority of papillary cystic neoplasms present in women (∼90%), most often in the third decade. Although frequently arising in the tail, they can occur in any part of the pancreas and frequently grow to a large size (mean diameter, 10 cm) before producing symptoms. Greater than 90% of tumors are completely or partially cystic. Grossly, the tumors are enclosed by a fibrous capsule and internally are made up of multiple cystic components without well-defined septae and lacking the organization of serous cystadenomas. Calcification of papillary cystic tumors has been reported, but in contrast to serous cystadenomas occurs peripherally in the fibrous capsule. 15Klimstra D.S. Heffess C.S. Oertel J.E. et al.Acinar cell cystadenocarcinoma of human pancreas. A clinical pathologic study of 28 cases.Am J Surg Pathol. 1992; 16: 815-837Google Scholar Most centers recommend surgical resection owing to the difficulty in distinguishing benign from malignant disease. Prognosis in resected malignant disease is excellent. A number of other entities have been reported as primary cystic neoplasms of the pancreas including cystic lymphangiomas and other tumors of mesenchymal origin. 11Brugge W.R. Lauwers G.Y. Sahani D. Fernandez-del Castillo C. Warshaw A.L. Cystic neoplasms of the pancreas.N Engl J Med. 2004; 351: 1218-1226Google Scholar Definitive surgical resection is recommended owing to malignant potential or confusion with lesions with malignant potential in most cases. Lymphangiomas may be found in asymptomatic patients or those with abdominal pain. The mass may appear multiloculated or single and the diagnosis typically is confirmed by resection. Cystic metastatic tumors in the pancreas are rare. Solitary true cysts of the pancreas are felt to be extremely rare but may need to be considered in the asymptomatic patient with an incidentally found cyst. 16Sperti C. Pasquali C. Constantino V. Perasole A. Liessi G. Pedrazzoli S. Solitary true cyst of the pancreas in adults. Report of three cases and review of literature.Int J Pancreatol. 1995; 18: 161-167Google Scholar High-resolution CT using thin sections with both enhanced and unenhanced technique provides detailed information about cyst structure (Figure 1) and may facilitate differentiation from mucin-secreting tumors of the pancreas. 17Buetow P.C. Rao P. Thompson L.D. Mucinous cystic neoplasms of the pancreas radiologic-pathologic correlation.Radiographics. 1998; 18: 433-449Google Scholar Magnetic resonance imaging has the potential added advantage of determining communication between the cyst and pancreatic duct. The presence of a central scar is a highly diagnostic feature of serous lesions, but is seen in only 1 in 5 patients. The role of positron emission tomography (PET) remains under investigation. 4Sarr M.G. Murr M. Smyrk T.C. et al.Primary cystic neoplasms of the pancreas: neoplastic disorders of emerging importance: current state-of-the-art and unanswered questions.J Gastrointest Surg. 2003; 7: 417-428Google Scholar Despite the high quality of contemporary CT and magnetic resonance imaging, their ability to distinguish neoplastic from nonneoplastic cystic pancreatic lesions remains imperfect. Because of this, EUS imaging has emerged as a useful tool in the differential diagnosis of these lesions. Although some enthusiastic publications reported that assessment of the endosonographic architecture of the lesion provides an accuracy of more than 90% in differentiating benign neoplasms from malignant neoplastic tumors and from nonneoplastic cysts, other reports emphasize that the technique is not sufficiently accurate to differentiate between benign and malignant lesions unless there is evidence of a solid mass or invasive tumor outside the pancreas. 18Brugge W.R. The role of EUS in the diagnosis of cystic lesions of the pancreas.Gastrointest Endosc. 2000; 52: S18-S22Abstract Full Text Full Text PDF Scopus (87) Google Scholar, 19Ahmad N.A. Kochman M.L. Lewis J.D. Ginsberg G.G. Can EUS alone differentiate between malignant and benign cystic lesions of the pancreas?.Am J Gastroenterol. 2001; 96: 3295-3300Google Scholar The presence of septation and solid components of the lesion can be observed for both benign and malignant lesions as well as nonneoplastic cysts. Furthermore, although EUS is quite sensitive in the detection and evaluation of cyst morphology, it is highly operator dependent. Typically, EUS of serous cystadenomas shows numerous small cysts with thin-walled septae (Figure 2) and possibly calcification in the central portion of the septae. 20Kaneto H. Endo T. Ozeki I. et al.Macrocystic serous cystadenoma of the pancreas importance of co-existent tiny cysts depicted by EUS.J Gastroenterol. 2000; 35: 472-475Google Scholar Mucinous tumors typically are macrocystic and can be unilocular or multilocular (Figure 3). They also may have septations and/or an adjacent mass, usually considered features concerning for malignancy. IPMN findings at EUS may include mural ductal nodules that show invasive features used to target fine-needle aspiration (FNA); however, inflammatory changes may compromise staging accuracy. 4Sarr M.G. Murr M. Smyrk T.C. et al.Primary cystic neoplasms of the pancreas: neoplastic disorders of emerging importance: current state-of-the-art and unanswered questions.J Gastrointest Surg. 2003; 7: 417-428Google ScholarFigure 3EUS appearance of a septated mucinous cystic lesion (septum within cystic lesion denoted by arrow). sv, splenic vein.View Large Image Figure ViewerDownload (PPT) Nonfunctioning islet-cell tumors of the pancreas typically are quite large by the time of clinical presentation and may be detected reliably with conventional imaging modalities including transabdominal ultrasound and CT. Useful CT findings include the presence of a hypervascular rim or images of cysts within cysts. 21Ligneau B. Lombard-Bohas C. Partensky C. et al.Cystic tumors of the pancreas Clinical, radiologic, and histopathologic features in 13 cases.Am J Surg Pathol. 2001; 25: 752-760Google Scholar Papillary cystic and solid tumors of the pancreas appear as well-defined, encapsulated masses on CT. By definition, they contain cystic and solid components with variable presence of calcification. Regions of cystic degeneration are usually nonenhancing unless they contain blood, which shows high attenuation. Magnetic resonance imaging reportedly shows these tumors as well-demarcated lesions containing central high-signal intensity on T1-weighted images, which represents hemorrhagic necrosis. 22Buetow P.C. Buck J.L. Pantongrag-Brown L. et al.Solid and papillary epithelial neoplasm of the pancreas imaging-pathologic correlation on 56 cases.Radiology. 1996; 199: 707-711Google Scholar The endosonographic appearance of these tumors is similar to the CT findings. Although EUS morphology alone has limitations regarding definitive diagnosis, aspiration and characterization of cyst fluid contents have shown somewhat greater promise. EUS-guided cyst aspiration (Figure 4) is well tolerated and safe in the hands of an experienced operator, with a complication rate of less than 1% of bleeding, perforation, or infection. Most experts use periprocedural antibiotics to decrease the risk for infection, and limit the number of needle passes and remove as much fluid as possible to decrease the risk for bacterial inoculation of the fluid. 23Levy M.J. Clain J.E. Evaluation and management of cystic pancreatic tumors emphasis on the role of EUS FNA.Clin Gastroenterol Hepatol. 2004; 2: 639-653Google Scholar Aspirated fluid has been evaluated by cytology and chemical measurements of amylase and tumor markers. Characterization of cyst fluid is best used to differentiate those with malignant potential, mucinous cysts, from serous and nonneoplastic pseudocysts. A large prospective study, the Cooperative Pancreatic Cyst Study, assessed a large number of cyst fluid tumor markers, and concluded that carcinoembryonic antigen was most useful. By using receiver operator curve analysis, the optimal cut-off level of 192 ng/mL was 79% accurate for differentiating mucinous from nonmucinous lesions. The accuracy of cytology was poor (59%). No combination of tests, including EUS appearance, was more accurate than carcinoembryonic antigen alone in that study. 24Brugge W.R. Lewandrowski K. Lee-Lewandrowski E. et al.Diagnosis of pancreatic cystic neoplasms a report of the Cooperative Pancreatic Cyst Study.Gastroenterology. 2004; 126: 1330-1336Google Scholar Although characteristic findings on FNA for serous cystadenomas includes low tumor carcinoembryonic antigen level, low amylase level, cyst fluid cytology, even surgical frozen sections have a diagnostic accuracy as low as 50% unless the characteristic cuboidal cells are seen. 4Sarr M.G. Murr M. Smyrk T.C. et al.Primary cystic neoplasms of the pancreas: neoplastic disorders of emerging importance: current state-of-the-art and unanswered questions.J Gastrointest Surg. 2003; 7: 417-428Google Scholar In a patient with characteristic morphology on EUS, the incremental value of FNA to confirm clinical impression may have potential value but should be individualized for every patient given the small but measurable risk for FNA. Considerations include the size of the lesion because aspirates may be very limited for small lesions. An estimate of the cyst fluid volume can by made from cyst size by the formula 4r3, r being the radius of the cyst. 23Levy M.J. Clain J.E. Evaluation and management of cystic pancreatic tumors emphasis on the role of EUS FNA.Clin Gastroenterol Hepatol. 2004; 2: 639-653Google Scholar Citing a low surgical mortality and excellent prognosis for cystic tumors of the pancreas, many advocate an aggressive surgical approach, specifically a Whipple procedure for tumors of the head and a distal pancreatectomy for tumors in the body or tail. 11Brugge W.R. Lauwers G.Y. Sahani D. Fernandez-del Castillo C. Warshaw A.L. Cystic neoplasms of the pancreas.N Engl J Med. 2004; 351: 1218-1226Google Scholar The mortality rate among patients undergoing resection in specialized centers is less than 2%. With this approach, all symptomatic cystic tumors and asymptomatic small tumors that cannot be characterized clearly in acceptable surgical candidates are removed. The argument has been made that the costs of surveillance imaging may approach surgical costs over time; however, this should be tempered by the risk for mortality after surgery, particularly if the patient’s lesion has no malignant potential. 25Spinelli KS, Fromwiller TE, Daniel RA, Kiely JM, Nakeeb A, Komorowski RA, Wilson SD, Pitt HA. Cystic pancreatic neo-plasms: observe or operate. Ann Surg 3004;239:651-659.Google Scholar A conservative surgical approach using enucleation rather than pancreatectomy led to re-operation in 4 of 8 patients owing to complications 26Pyke C.M. van Heerden J.A. Colby T.V. et al.The spectrum of serous cystadenoma of the pancreas. Clinical, pathologic, and surgical aspects.Ann Surg. 1992; 215: 132-139Google Scholar and has led most experts to recommend pancreatectomy when intervention is undertaken. A recent report of middle pancreatectomy by Warshaw et al 27Warshaw A.L. Rattner D.W. Fernandez-del Castillo C. Z’graggen K. Middle segment pancreatectomy a novel technique for conserving pancreatic tissue.Arch Surg. 1998; 133: 327-331Google Scholar suggests that this may be an alternative for patients with tumors of the neck and body. In this study, 12 benign tumors (including 5 patients with serous cystadenoma) ranging in size from 0.9 to 5.2 cm were treated with a limited resection of the middle portion of the pancreas. No patient became diabetic or required pancreatic enzyme supplements and all were free of recurrence after a mean follow-up period of 18 months. The prognosis for patients with a complete resection of a mucinous cystic neoplasm without transmural invasion is nearly 100%, and for patients with intraductal papillary mucinous tumors containing cancer, the 5-year survival is over 50% with surgical resection. 28Chari S.T. Yadav D. Smyrk T.C. et al.Study of recurrence after surgical resection of intraductal papillary mucinous neoplasm of the pancreas.Gastroenterology. 2002; 123: 1500-1507Google Scholar There are limited prospective data to support this approach, which is particularly attractive in the patient with an incidentally identified lesion. Surveillance in well-documented serous cystadenomas may be justified, but approached cautiously given reports of malignant serous lesions. In a large series of 398 cases of cystadenomas including 170 serous cystadenomas, 26 patients with nonresected serous cystadenomas were followed-up for a mean of 38 months with no patient requiring surgery. 29Le Borgne J. de Calan L. Partensky C. French Surgical AssociationCystadenomas and cystadenocarcinomas of the pancreas.Ann Surg. 1999; 230: 152-161Google Scholar In a series of patients prospectively assessed with EUS-guided aspirate analysis, with surgery reserved for all symptomatic or confirmed mucinous tumors, no need for resection was noted in the 52 of 87 patients not resected at 1-year follow-up evaluation. 30Walsh R.M. Henderson J.M. Vogt D.P. Baker M.E. O’Malley C.M. Herts B. Zuccaro Jr, G. Vargo J.J. Dumot J.A. Conwell D.L. Biscotti C.V. Brown N. Prospective preoperative determination of mucinous pancreatic cystic neoplasms.Surgery. 2002; 132: 628-634Google Scholar Similar results from a cancer center, mainly of incidentally found lesions, showed that for those with benign radiographic features who were selected for nonsurgical management (average cyst diameter, 2.5 cm) the median change in cyst diameter was 0 cm over 31 months of follow-up evaluation. None of the 6 patients with a change in cyst diameter had malignancy: 3 were pseuodcysts, 2 were nondysplastic IPMNs, and 2 were serous cystadenomas—with increases in cyst diameter of 3, 4, and 4 cm, respectively. 31Allen P.J. Jaques D.P. D’Angelica M. Bowne W.B. Conlon K.C. Brennan M.F. Cystic lesions of the pancreas selection criteria for operative and nonoperative management in 209 patients.J Gastrointest Surg. 2003; 7: 970-977Google Scholar Size alone as a poor predictor of risk for malignancy is emphasized by a single-center retrospective study based on serial imaging with CT and magnetic resonance imaging. Although cyst size did not predict neoplasia, symptoms and age over 70 years did. Notably, of the 15 patients in that series with increasing size (change of 0.2 cm by CT), 11 of 15 had malignancies, including 3 unresectable cancers. 25Spinelli KS, Fromwiller TE, Daniel RA, Kiely JM, Nakeeb A, Komorowski RA, Wilson SD, Pitt HA. Cystic pancreatic neo-plasms: observe or operate. Ann Surg 3004;239:651-659.Google Scholar The patient described has no prior history of pancreatic disease or symptoms. The pretest likelihood is high that this is a neoplastic cyst. The key question is how likely this cyst will be to cause the patient symptoms (either owing to growth or malignant behavior) in the future. The lesion is relatively large, but unlikely to cause biliary obstruction because of its location. Given the broad differential diagnosis and the lack of prospective data to guide management, I would recommend an EUS to characterize the lesion further. I would inform the patient that if the lesion has the characteristic microcystic appearance by EUS, I would observe the lesion with serial imaging at 6-month intervals over 2 years and then yearly thereafter (Figure 5). I question the value of FNA as a confirmatory test given the risk for FNA and its poor negative predictive value. This would come with the understanding that a very low risk for malignancy could not be excluded. If the lesion were macrocystic, I would offer the patient FNA of cyst fluid because one could obtain fluid easily from a lesion this size, and I would send it for carcinoembryonic antigen testing and cytology. If the findings were consistent with mucinous tumor, I would recommend resection. Because the location of the tumor may lead to a challenging surgery, I favor cyst fluid characterization to confirm the mucinous fluid characteristics, notwithstanding the limitations of the test discussed earlier. The approach to the patient with a pancreatic cystic lesion begins with a detailed history, and consideration of the major diagnostic considerations (Table 1). A history to suggest prior pancreatitis or trauma is important. A careful review for symptoms of a hormone-excess state should be sought. In the absence of a history of pancreatitis, pseudocyst is quite unlikely and the concern of a cystic neoplasm is paramount. In general, all symptomatic lesions and all mucinous lesions should proceed to appropriate surgical resection. If preoperative characterization of the lesion will change management, EUS ± FNA for cytology and fluid analysis may provide information of diagnostic and prognostic value. For those patients with benign-appearing lesions, such as classic appearance of a serous cystadenoma, a decision regarding the patient’s willingness to observe the lesion should be developed in collaboration with a pancreatic surgeon. In many circumstances, selected use of EUS ± FNA with cytology and fluid measurement can provide further evidence to support the approach of watchful waiting. Patients then can be monitored carefully with serial examinations to exclude change in size. Watchful waiting clearly represents a trade-off between the development of unresectable disease with delayed surgery and unnecessary surgical morbidity and mortality.Table 1Cystic Pancreatic LesionsSerous cystadenomaMucinous cystadenomaIPMNPseudocystClinical SexFemale (2–3:1)Female (≈100%)Male (3–4:1)Male Age60sAdenoma (50s–60s)60sVariableCarcinoma (60s–70s) Ethanol abuseNo associationNo associationNo associationYes Pancreatitis historyYes (uncommon)Yes (uncommon)Yes (uncommon)Yes (uncommon) Malignant potentialNo (rare)YesYesNo LocationEvenly distributedBody/tailHeadHeadImaging studies SeptaeYesYesNoVariable LocularityMultiple small (usually)Multilocular (usually)Multilocular (usually)Unilocular (usually) CalcificationsYes (central sunburst or stellate)Yes (peripheral, curvilinear)NoaExcept in the minority of patients with associated chronic pancreatitis, and typically within the nontumorous or noncystic portion of the pancreas.NoaExcept in the minority of patients with associated chronic pancreatitis, and typically within the nontumorous or noncystic portion of the pancreas.Modified from Levy and Clain.23Levy M.J. Clain J.E. Evaluation and management of cystic pancreatic tumors emphasis on the role of EUS FNA.Clin Gastroenterol Hepatol. 2004; 2: 639-653Google Scholara Except in the minority of patients with associated chronic pancreatitis, and typically within the nontumorous or noncystic portion of the pancreas. Open table in a new tab