Invasive MCNs show the pattern of either a DAC or an undifferentiated carcinoma with osteoclast-like giant cells. The stroma may also contain sarcomatous nodules. MCNs comprise approximately 1% in our series of pancreatic exocrine tumors and among the cystic neoplasms they account for approximately 7.6%. The higher frequencies that have been reported in some pre- vious studies are probably due to the fact that IPMNs and MCNs were not clearly distinguished from each other or were still interpreted as a single entity. The clear differentiation of MCNs from IPMNs also re- vealed that MCNs are extremely rare in men. The age at diagnosis ranges from 23 to 78 years, though patients with invasive carcinoma are often older than 50 years (Table 57.3). More than 60% of the patients experience abdominal discomfort or pain or present with a palpa- ble tumor. In the remaining patients the tumor is an incidental finding. The cyst fluid is usually rich in carcinoembryonic antigen (CEA) and CA-19-9 and contains columnar cells. The prognosis of MCNs has been found to be excel- lent if the tumors are completely resected, and this can be achieved today in more than 90% of cases. Two re- cent studies based on extensive tumor sampling have shown that recurrence and tumor-related death were features of deeply invasive MCNs only. MCNs of the pancreas resemble the same tumor cat- egory in the ovary. Like ovarian MCNs, the epithelial cells of pancreatic MCNs show gastroenteropancreatic differentiation and the stromal cells may express estro- gen and progesterone receptors as well as inhibin, which has been recommended as a marker of certain ovarian neoplasms including MCN. Because of this similarity between pancreatic and ovarian MCNs, the “genital ridge hypothesis” has been advanced, which infers that cellular stromal elements from the genital ridge may associate with the dorsal pancreatic anlage, or rarely the ventral anlage, and might thus later give rise to an MCN. The differential diagnosis of MCNs is with IPMNs especially. IPMNs, in contrast to MCNs, communi- cate with the duct system, are mainly localized in the pancreatic head, and occur more often in men than in women. Immunocytochemically, noninvasive MCNs are negative for MUC1 or MUC2 (except for single MUC2-positive goblet cells). Only in cases with an invasive component was MUC1 expression observed. PART IV 482 the seminal paper by Compagno and Oertel in 1978, there has been a debate about the prognosis and origin of these neoplasms. Two recent studies seem to have settled the first issue. On the second, a hypothesis has been advanced. More than 90% of MCNs occur in the body and tail of the pancreas, where they form large round cystic tu- mors (Fig. 57.2) showing a unilocular or multilocular cut surface and diameters between 2.7 and 23 cm. Mul- tilocularity, localization in the head region, and pres- ence of papillary projections and stromal nodules all correlate with an associated invasive component. The cystic spaces are lined by mucin-producing epithelial cells that are supported by an ovarian-like stroma which may be focally hyalinized. MCNs composed of cells exhibiting only minimal atypia are adenomas, whereas those with moderate or even severe atypia are borderline tumors and carcinomas respectively. Table 57.3 Clinicopathologic features of mucinous cystic neoplasms. Ratio of women to men: 9 : 1 Age range: 23–78 (mean 47) years Localization: > 90% in the body–tail region Morphology: mucinous cyst without duct communication Prognosis: excellent after complete resection Figure 57.2 Mucinous cystic adenoma in a 42-year-old woman: the multicystic tumor is well demarcated. CHAPTER 57 483 Serous cystic neoplasms: serous microcystic adenoma, serous oligocystic and ill-demarcated adenoma, and von Hippel–Lindau associated cystic neoplasm Serous microcystic adenoma (SMA), serous oligocystic and ill-demarcated adenoma (SOIA), and von Hippel– Lindau associated cystic neoplasm (VHL-CN) are com- posed of the same cell type. This cell is characterized by glycogen-rich cytoplasm and a ductal immunoprofile. However, despite these cytologic similarities, the three types of SCN differ in their localization in the pancreas, gross appearance, gender distribution, and genetic al- terations, suggesting that they represent different enti- ties (Table 57.4). The role of the solid variant of serous cystic adenoma and of serous cystadenocarcinoma in the spectrum of SCNs is not yet clear, mainly owing to the small number of cases that have been reported so far. In our series, SMAs equal MCNs in frequency (5.7% vs. 7.6% of cases). If SOIAs and VHL-CNs are added, the group of SCNs accounts for approximately 11% of all pancreatic cystic lesions and neoplasms. Most com- mon are SMAs, which make up 50% of all SCNs. They present as single, well-circumscribed, slightly bossel- ated round tumors, with diameters ranging from 2.5 to 16 cm. Their cut surface shows numerous small (hon- eycomb-like) cysts arranged around a (para)central stellate scar (Fig. 57.3), which may contain calcifica- tions. About two-thirds of SMAs occur in the body–tail region and almost all in women. They are usually found incidentally. SOIAs, which account for 35% of SCNs, are composed of few relatively large cysts (for which reason they have also been described as macrocystic serous adenoma), lack the stellate scar and round shape, and occur predominantly in the head of the pan- creas, where they may obstruct the common bile duct and cause jaundice. They show no sex predilection. In patients with VHL, the SCNs arise at multiple sites and in advanced stages of the disease they may merge and involve the entire pancreas. Because VHL-CNs affect the pancreas diffusely, they differ markedly from the gross features of both SMAs and SOIAs. Biologically, it is also important to note that patients with VHL, like those with SOIA but in contrast to those with SMA, are not predominantly female. This suggests that SMAs differ in their pathogenesis from VHL-CNs and SOIAs. Recently reported molecular data support this assump- tion. While VHL-CNs were found to be characterized by both loss of heterozygosity (LOH) at chromosome 3p (which contains the VHL gene) and a germline mu- tation of the VHLgene, only 40% of SMAs had LOH at chromosome 3p and of these tumors only two (22%) exhibited a somatic VHL gene mutation. Interestingly, more than 50% of SMAs showed LOH at 10q. It ap- pears therefore that alterations of the VHL gene are of minor importance in SMAs, while gene changes at 10q may play a major role. Whether the VHL gene is involved in the pathogenesis of SOIAs remains to be Table 57.4 Clinicopathologic features of serous cystic tumors of the pancreas. Serous microcystic adenoma Ratio of women to men: 9 : 1 Age range: 45–91 (mean 71) years Localization: more than 75% in body–tail region, stellate scar Prognosis: good Serous oligocystic adenoma Women and men alike Age range: 38–85 (mean 63) years Localization: head region (60%) Prognosis: good Von Hippel–Lindau associated cystic neoplasm Women and men alike Age range: 30–70 (mean 42) years Localization: diffuse involvement Prognosis: good Figure 57.3 Serous microcystic adenoma in a 69-year-old woman: well-demarcated multicystic tumor with central scar. PART IV 484 elucidated. The same also holds for the extremely rare serous cystadenocarcinoma. The differential diagnosis of SMAs is primarily with multiloculated MCNs, although their honeycomb appearance and stellate scar distinguish them quite clearly. SOIAs are more difficult to differentiate from other cystic lesions because of their variegated gross ap- pearance. Recently we found that inhibin is expressed in the epithelial cells of all types of SCNs, but not in the epithelial lining of MCNs (unpublished observation). In MCNs inhibin only occurs in stromal cells, making inhibin a good marker for use in differentiating SCNs from MCNs. Solid pseudopapillary neoplasm SPNs are round tumors whose diameters may range from 2 to 17 cm. They are found in any region of the pancreas or loosely attached to it. The cut surface typi- cally shows friable tan-colored tumor tissue, the center of which is undergoing hemorrhagic cystic degenera- tion, thereby forming irregular bloody cavities (Fig. 57.4). Usually SPNs appear to be demarcated by a pseudocapsule in which calcifications may occur. Histologically, there are three main features. First, solid areas merge with pseudopapillary, hemorrhagic, and pseudocystic structures. Second, the tumor tissue shows a delicate microvasculature that forms pseudorosettes or may be accompanied by hyalinized or myxoid stroma. The third feature concerns the tumor cell itself. It is unique because it does not resem- ble any of the known cell types in the pancreas. It shows eosinophilic or foamy cytoplasm (often containing PAS-positive globules) and a hybrid immuno- phenotype combining mesenchymal (vimentin, a 1 - antitrypsin), endocrine (neuron-specific enolase, synaptophysin, progesterone receptor), and epithelial (cytokeratin) differentiation. Once thought to be very rare, SPNs have distinctly increased in frequency as they came to be better recog- nized, and in our series they account for approximately 6% of all exocrine pancreatic tumors. If only cystic tu- mors are considered, SPNs (with cystic changes) are the most common type (21.2%). They occur predomin- antly in young women (15–35 years of age), but may occasionally be encountered in older women and also in men (Table 57.5). Many SPNs are detected inciden- tally. However, the patients may also present with sudden pain (because of bleeding into the tumor) or symptoms related to compression of adjacent organs. In 90% of the patients the prognosis of SPN is excel- lent. In the remaining patients, metastases (peri- toneum, liver) are present at the time of diagnosis or occur later after removal of the primary. Even if metas- tases have developed, many of them are amenable to re- section, usually resulting in long-term survival of the affected patients. There are still no prognostic factors that could help in the distinction between SPNs with or without malignant potential. It is therefore necessary to treat all SPNs by complete surgical resection. The pathogenesis of SPN is obscure. Because of its complex and hybrid immunoprofile, the cellular phenotype is not consistent with any of the known pancreatic cell types. In view of their striking female preponderance and the known close approximation of the genital ridges to the pancreatic anlage during embryogenesis, it has been hypothesized that SPNs, like MCNs, might derive from genital ridges/ovarian anlage-related cells, which were attached to the Figure 57.4 Solid pseudopapillary neoplasm in a 42-year-old woman: pseudocystic and partly hemorrhagic tumor in the tail of the pancreas. Table 57.5 Clinicopathologic features of solid pseudopapillary neoplasms. Ratio of women to men: 9:1 Age range: 11–73 (mean 30) years Localization: no preference Morphology: hemorrhagic pseudocyst in tumor Prognosis: rarely malignant (5–10%) pancreatic tissue during early embryogenesis. Recently it was found that most SPNs show nuclear expression of b-catenin, associated with mutations in exon 3 of the b-catenin gene. The differential diagnosis of cystic SPNs includes pseudocysts and cystic forms of endocrine tumors of the pancreas. Apart from the typical histologic features of SPNs, the expression of such markers as vimentin and neuron-specific enolase in the absence of chromo- granin A and the very faint expression of cytokeratin and synaptophysin distinguish this most enigmatic neoplasm of the pancreas from all other tumors. Ductal adenocarcinoma and variants with cystic features DACs and variants thereof showing cystic features are relatively frequent. In our series of cystic tumors they account for 7.6%. Three pathologic mechanisms may explain the development of cystic changes in these pri- marily solid neoplasms. Well-differentiated DACs may show ectatic duct-like structures that acquire a micro- cystic, grossly visible appearance. However, the cysts are usually no larger than 0.5 cm. The second mecha- nism by which DACs and their variants can become cystic is central tumor necrosis. This may occur in large tumors and especially in poorly differentiated or undif- ferentiated sarcomatoid carcinomas. Finally, DACs may obstruct not only the main pancreatic duct but also single secondary ducts, thereby producing small non- neoplastic retention cysts. While in the first and third cases the cystic changes are so subtle that they are usu- ally not revealed by imaging techniques, central tumor necrosis may produce a radiographically visible cystic cavity. Uncommon cystic neoplasms and lesions Among the uncommon cystic tumors of the pancreas are a variety of neoplastic and nonneoplastic changes. The neoplasms include such tumors as cystic acinar cell carcinomas, cystic endocrine tumors, cystic metastases (i.e., from renal cell carcinoma), dermoid cysts, and a number of cystic nonepithelial tumors. The rare benign cystic changes include lymphoepithelial cysts, paraam- pullary duodenal wall cysts usually associated with duodenal wall pancreatitis (also called groove pancre- CHAPTER 57 485 atitis), ciliated foregut cysts, enteric duplication cysts, dermoid cysts, multicystic hamartoma, congenital cysts, endometrial cysts, parasitic cysts, and the recently briefly mentioned mucinous nonneoplastic cyst and acinar cell cystadenoma. Although the prog- nosis of cystic epithelial neoplasms depends on the malignant potential of the respective type of tumor, the prognosis of nonneoplastic cystic lesions is good. Pseudocysts The frequent pancreatitis-associated pseudocyst be- longs to the nonneoplastic/nonepithelial group, indi- cating that it takes a benign course. A pseudocyst presents as a grossly visible and well-demarcated cystic lesion, which contains necrotic–hemorrhagic material and/or turbid fluid rich in pancreatic enzymes. The cys- tic contents are enclosed by a wall of inflammatory and fibrous tissue devoid of an epithelial cell lining. Pseudo- cysts usually occur attached to the pancreas and are a sequela of extensive confluent autodigestive tissue necrosis caused by alcoholic, biliary, or traumatic acute pancreatitis. Pseudocysts are thought to be the most common type of cystic lesion of the pancreas, with an estimated rela- tive frequency of 75%. In our series, pseudocysts ac- count for only 16.1% of the cases, most likely because this is a series from a referral center, which accumulates more tumors than pseudocyst cases. The correct preva- lence figures may therefore be higher than 16.1% but probably also lower than 75%, since the latter figure was generated at a time when only large cystic lesions in the pancreas were detected with certainty. Pseudocysts develop as a consequence of an episode of severe acute pancreatitis, usually in the setting of alcoholic pancreatitis. Most of the patients are men in the age range 31–62 years (Table 57.6). If children and Table 57.6 Clinicopathologic features of pancreatitis- associated pseudocysts in the pancreas. Ratio of men to women: 3 : 1 Age range: 31–62 years Localization: extrapancreatic > intrapancreatic Morphology: no epithelial lining, hemorrhagic debris Pathogenesis: caused by severe episodes of acute pancreatitis PART IV 486 adolescents are affected by pseudocysts, these are caused by hereditary or traumatic pancreatitis. The most common differential diagnosis of pseudo- cyst is with IPMN, MCN, and SPN, because the gross appearance of the latter may be similar to that of pseudocysts. Histologically and cytologically, howev- er, pseudocysts differ from the cystic neoplasms in that they lack any epithelial lining but display hemorrhagic debris and inflammatory cells. Moreover, pseudocysts contain pancreatic enzymes, such as amylase and li- pase, and lack elevated levels of CEA and CA-19-9. Recommended reading Abraham SC, Klimstra DS, Wilentz RE et al. Solid- pseudopapillary tumors of the pancreas are genetically distinct from pancreatic ductal adenocarcinomas and almost always harbor b-catenin mutations. Am J Pathol 2002;160:1361–1369. Adsay NV, Klimstra DS. Cystic Lesions of the Pancreas. Philadelphia: Saunders, 2000. Adsay NV, Longnecker DS, Klimstra DS. Pancreatic tumors with cystic dilatation of the ducts: intraductal papillary mucinous neoplasms and intraductal oncocytic papillary neoplasms. Semin Diagn Pathol 2000;17:16–30. Adsay NV, Pierson C, Sarkar F et al. Colloid (mucinous noncystic) carcinoma of the pancreas. Am J Surg Pathol 2001;25:26–42. Adsay NV, Merati K, Andea A et al. The dichotomy in the preinvasive neoplasia to invasive carcinoma sequence in the pancreas: differential expression of MUC1 and MUC2 sup- ports the existence of two separate pathways of carcinogen- esis. Mod Pathol 2002;15:1087–1095. Adsay NV, Hasteh F, Cheng JD et al. Lymphoepithelial cysts of the pancreas: a report of 12 cases and a review of the litera- ture. Mod Pathol 2002;15:492–501. Capella C, Solcia E, Klöppel G, Hruban RH. Serous cystic neoplasms of the pancreas. In: SR Hamilton, LA Aaltonen (eds) Pathology and Genetics of Tumours of the Digestive System. WHO Classification of Tumours. Lyon: IARC Press, 2000:231–233. Kimura W, Makuuchi M, Kuroda A. Characteristics and treatment of mucin-producing tumor of the pancreas. Hepatogastroenterology 1998;45:2001–2008. Klöppel G. Clinicopathologic view of intraductal papillary- mucinous tumor of the pancreas. Hepatogastroenterology 1998;45:1981–1985. Klöppel G. Pseudocysts and other non-neoplastic cysts of the pancreas. Semin Diagn Pathol 2000;17:7–15. Klöppel G, Hruban RH, Longnecker DS, Adler G, Kern SE, Partanen TJ. Ductal adenocarcinoma of the pancreas. In: SR Hamilton, LA Aaltonen (eds) Pathology and Genetics of Tumours of the Digestive System. WHO Classification of Tumours. Lyon: IARC Press, 2000:221–230. Klöppel G, Lüttges J, Klimstra D, Hruban R, Kern S, Adler G. Solid-pseudopapillary neoplasm. In: SR Hamilton, LA Aaltonen (eds) Pathology and Genetics of Tumours of the Digestive System. WHO Classification of Tumours. Lyon: IARC Press, 2000:246–248. Kosmahl M, Seada LS, Jänig U, Harms D, Klöppel G. Solid- pseudopapillary tumor of the pancreas: its origin revisited. Virchows Arch 2000;436:473–480. Longnecker DS, Adler G, Hruban RH, Klöppel G. Intraductal papillary-mucinous neoplasms of the pancreas. In: SR Hamilton, LA Aaltonen (eds) Pathology and Genetics of Tumours of the Digestive System. WHO Classification of Tumours. Lyon: IARC Press, 2000:237–240. Lüttges J, Zamboni G, Longnecker D, Klöppel G. The im- munohistochemical mucin expression pattern distinguishes different types of intraductal papillary mucinous neoplasms of the pancreas and determines their relationship to muci- nous noncystic carcinoma and ductal adenocarcinoma. Am J Surg Pathol 2001;25:942–948. Lüttges J, Feyerabend B, Buchelt T, Pacena M, Klöppel G. The mucin profile of noninvasive and invasive mucinous cystic neoplasms of the pancreas. Am J Surg Pathol 2002;26: 466–471. Mohr VH, Vortmeyer AO, Zhuang Z et al. Histopathology and molecular genetics of multiple cysts and microcystic (serous) adenomas of the pancreas in von Hippel–Lindau patients. Am J Pathol 2000;157:1615–1621. Moore PS, Zamboni G, Brighenti A et al. Molecular charac- terization of pancreatic serous microcystic adenomas. Evidence for a tumor suppressor gene on chromosome 10q. Am J Pathol 2001;158:317–321. Nakamura A, Horinouchi M, Goto M et al. New classification of pancreatic intraductal papillary-mucinous tumour by mucin expression: its relationship with potential for malig- nancy. J Pathol 2002;197:201–210. Rattner DW, Fernandez-del Castillo C, Warshaw AL. Cystic pancreatic neoplasms. Ann Oncol 1999;10(Suppl):S104– S106. Sugiyama M, Atomi Y. Extrapancreatic neoplasms occur with unusual frequency in patients with intraductal papillary mucinous tumors of the pancreas. Am J Gastroenterol 1999;94:470–473. Terris B, Ponsot T, Paye F et al. Intraductal papillary mucinous tumors of the pancreas confined to secondary ducts show less aggressive pathologic features as compared with those involving the main pancreatic duct. Am J Surg Pathol 2000;24:1372–1377. Wilentz RE, Albores-Saavedra J, Zahurak M et al. Pathologic examination accurately predicts prognosis in mucinous Zamboni G, Klöppel G, Hruban RH, Longnecker DS, Adler G. Mucinous cystic neoplasms of the pancreas. In: SR Hamilton, LA Aaltonen (eds) Pathology and Genetics of Tumours of the Digestive System. WHO Classification of Tumours. Lyon: IARC Press, 2000:234–236. Zamboni G, Terris B, Scarpa A et al. Acinar cell cystadenoma of the pancreas. A new entity? Am J Surg Pathol 2002;26:698–704. CHAPTER 57 487 cystic neoplasms of the pancreas. Am J Surg Pathol 1999; 23:1320–1327. Wilentz RE, Albores-Saavedra J, Hruban RH. Mucinous cystic neoplasms of the pancreas. Semin Diagn Pathol 2000;17:31–42. Zamboni G, Scarpa A, Bogina G et al. Mucinous cystic tumors of the pancreas. Clinicopathological features, prognosis and relationship to other mucinous cystic tumors. Am J Surg Pathol 1999;23:410–422. 488 Introduction The identification of cystic tumors of the pancreas has become clearer only in the past few years. Since first identified by Becourt in 1930, the major unsolved issue has been a definitive preoperative diagnosis. This clini- cal problem is obviously due to the fact that different cystic neoplasms require different treatment. The ini- tial differentiation of pancreatic cystic lesions is be- tween cystic tumors and nonneoplastic cystic lesions: this is based on the presence or absence of an epithelial lining inside the cystic wall and permits the exclusion of all simple cysts and pseudocysts. Once an epithelial lin- ing is detected, its characteristics define different kinds of tumors. This chapter attempts to resolve the diagnostic prob- lems and doubts that always affect clinicians and sur- geons in the management of pancreatic cystic tumors. Classification Our understanding of pancreatic cystic tumors is based on the WHO classification of tumors (Table 58.1). Laboratory findings There is no reliable serum tumor marker that can diag- nose serous cystic tumor (SCT) and spare some patients unnecessary operations. Nonetheless, positive carci- noembryonic antigen (CEA) serum marker status and/or the presence of more than two positive serum markers (CEA, CA-19-9, CA-125) indicates the presence of a mucinous cystic tumor (MCT) and can prevent delay in diagnosis. Positive CEA or presence of more than two markers suggests a definitely or potentially malignant tumor and can prevent delay in diagnosis. Serous cystic tumors Women in their fifties seem to be the population more affected by SCTs. Any portion of the pancreatic gland can be affected by SCTs but they are more frequently detected in the pancreatic head. At histology, SCTs take the form of multiple cysts lined with cuboid flat epithe- lium with clear cytoplasm rich in glycogen. Based on morphologic aspects these tumors can be divided into three types: microcystic, macrocystic or oligocystic (< 3% of cases), and mixed (micro-macrocystic). Serous cystic adenoma Clinical findings Serous cystic adenomas (SCAs) are mostly asympto- matic and are often detected incidentally during radio- logic investigations for symptoms that may not be related to the pancreas (Fig. 58.1). When present, the most common clinical complaint is some degree of abdominal discomfort or pain. Weight loss, palpable mass, jaundice, and obstruction of the upper gastroin- testinal tract are very rare and may correlate with ex- tensive growth of the lesion. Once detected, accurate characterization of a pancreatic mass as an SCA is of primary importance since this tumor, unlike the other cystic tumors of the pancreas, is benign and therefore a 58 Diagnosis and differential diagnosis of pancreatic cystic tumors Roberto Salvia, Isabella Frigerio, Claudio Bassi, Massimo Falconi, and Paolo Pederzoli tions of SCA. The diagnosis is easily made when ultra- sound shows a mass with multilobulated borders, no posterior acoustic enhancement, and an internal “hon- eycomb” architecture due to the presence of multiple septae that delimit small (< 2 cm diameter) cystic spaces. In 10–30% of cases, there can be calcifications within the septae and, even less frequently, a central cal- cified scar. The microcystic appearance is also seen in SCA associated with von Hippel–Lindau syndrome, although in these cases the tumor is multicentric or diffusely involves the whole gland. There are two circumstances where ultrasound may fail to recognize a microcystic SCA: in the presence of a sponge-like mass where the multiplicity of small cysts and thick fibrous stroma produce the false impression that the tumor is solid; and in the case of a mixed tumor when the macro- cystic component conceals the microcystic with the misdiagnosis of a macrocystic mass. The macrocystic type is easily detectable even when the size is small. The aspect is of a sharply marginated, hypoechoic mass; there might be sparse, thin, central septae and in this case the differential diagnosis from the other cystic mass is very difficult. In the mixed SCA, together with the microcysts, larger (> 2 cm) cystic spaces can be found at the periphery of the lesions resulting in a mixed pattern. The macrocyst can grow up to 8–10 cm, making it difficult to recognize the true nature of the tumor. The false-negative rate is low and is due to tumor location (tail) or patient characteristics (obesity, meteorism). The appearance of SCA on computed tomography (CT) depends on two factors: macroscopic features and timing of data acquisition. Microcystic tumors appear as an unenhanced mass affecting or deforming the pro- file of the gland. The density is homogeneous or slightly superior to that of water, isodense in respect to the parenchyma. When calcifications are present the loca- tion is always quite central, punctate, or globular, as opposed to the lamellar calcifications seen in MCTs. Usually a central fibrous scar is visible in the larger masses since it forms later. Maximal visualization of septae, as well as the honeycomb appearance, occurs in the pancreatic parenchymal phase. The presence of central calcification in conjunction with scars or septae definitively characterizes a cystic mass as an SCA. In the mixed forms peripheral macrocysts are even more easily recognizable than by ultrasound, thus making the diagnosis easier. In the delayed phase of contrast injection, recognition of septae is very difficult because CHAPTER 58 489 conservative approach should be the treatment of choice whenever possible. Despite the fact that symptoms are not helpful for diagnosis, overall they can guide the identification of a benign or malignant neoplasm. Suspicion of SCA should also arise in the presence of Von Hippel–Lindau syndrome, a genetic condition associated in 15% of cases with SCA. Radiology Ultrasound is usually the first step in diagnosis, and as a result of its widespread use in clinical practice it has sig- nificantly increased the number of incidental observa- Table 58.1 Histologic classification of pancreatic cystic tumors. Serous cystic tumors Serous cystadenoma Serous cystadenocarcinoma Mucinous cystic tumors Mucinous cystadenoma Mucinous cystadenoma with moderate dysplasia Mucinous cystadenocarcinoma Not infiltrating Infiltrating Intraductal papillary mucinous adenoma Intraductal papillary mucinous tumors with moderate dysplasia Intraductal papillary mucinous carcinoma Not infiltrating Infiltrating Figure 58.1 Macroscopic view of a serous cystic adenoma (microcystic pattern). of their resemblance to intracystic liquid. Macrocystic patterns are indistinguishable from other macrocystic masses of the pancreas (e.g., MCTs). Magnetic resonance imaging (MRI) is assuming an important role in the work-up of these tumors due to the accurate information it provides about the struc- ture of the lesion, in particular the presence of septae. In the microcystic pattern, MRI is able to demonstrate even a small amount of fluid within the dense septae of a “sponge-like” mass but has the disadvantage that it is insensitive to calcifications. In macro-microcystic cases the two components are easily recognizable. The tech- nique of magnetic resonance cholangiopancreatogra- phy (MRCP) provides even better evaluation of the spatial relationship between the mass and the biliary or pancreatic duct and thus can be used to discriminate the diagnosis with intraductal papillary mucinous neo- plasm (IPMN), particularly when the tumor is located on the head or in the uncinate process of the gland. MRCP should be carried out routinely in the staging of these tumors since it helps to distinguish micro- cystic SCA from intraductal tumor of the peripheral branches, which has a septate appearance. The absence of communication with the Wirsung duct confirms the diagnosis of SCA. MRI investigation of oligocystic forms is nonspecific and does not lead to a definitive dif- ferential diagnosis from mucinous forms. Serous cystic adenocarcinoma Serous cystic adenocarcinoma is a malignant form of SCT, all cases being described as microcystic forms. We concur that SCT should be basically considered a benign lesion and, if no complications or diagnostic doubts occur, conservative treatment and follow-up is the chosen policy. Differential diagnosis The finding of a mass with the described features in the pancreatic head of a female patient with no dilation of the duct, a normal parenchyma, and calcification leads to a definitive diagnosis of SCT. The diagnosis can be considered definite when the lesion shows a mixed as- pect with macrocysts in the periphery of a microcystic nucleus. Despite the microcystic aspect, the diagnosis is less certain when the cystic mass is located in the unci- nate process of a male patient and associated with main duct dilation: in this event, in order to make the dif- ferential diagnosis with IPMN of branch ducts, it is mandatory to demonstrate the relationship between the mass and the duct of Wirsung. MRCP is useful for this purpose, but in those cases where the lesion is very close to the main duct endoscopic retrograde cholan- giopancreatography (ERCP) is necessary. For different reasons, as we previously stressed, a mass can appear as a solid lesion therefore leading to misdiagnosis with other bright enhanced solid lesions, such as nonfunc- tioning neuroendocrine tumors. In these cases MRI will be able to detect the microcystic aspect. Since accurate radiologic characterization of macrocystic SCT is not possible using ultrasound, CT, or MRI, endoscopic ultrasound seems to be the only technique able to supply further information. Mucinous cystic tumors Epidemiology MCTs occur exclusively in women. These neoplasms are preferentially located in the body and tail and are characterized by unilocular/multilocular cysts that do not communicate with the ductal system. The tumor is encapsulated and lined by columnar mucin-producing cells overlying an ovarian-type stroma, thus explaining the exclusive incidence in a female population. The patient age range is huge, with an average that seems to depend on the degree of malignancy of the neoplasm: patients with malignant MCT appear to be older, sug- gesting a time-related degeneration from benign le- sions. Early diagnosis of malignant transformation of MCT is essential since the prognosis, once the malig- nant form occurs, is the same as for ductal adenocarci- noma, whereas in the in situ forms surgery could be curative. MCT is, at best, a premalignant lesion and it is there- fore important to distinguish it from other cystic lesions of the pancreas. Pathologically, all the different degrees of malignant transformation can be detected at the same time in the same lesion. This has a great relevance, suggesting an adenoma–carcinoma sequence. Clinical findings Once again symptoms are few, nonspecific, and do not help in the diagnostic process. Abdominal dis- comfort or pain is the most frequent in both benign and malignant lesions and, even if present, it is unusual PART IV 490 CHAPTER 58 491 for patients to complain about pancreatic-specific pain (radiation to the flanks); even early symptoms might not be of concern. However, nonspecific symptoms can also suggest malignant forms: weight loss, anorexia, and obstructive jaundice are common in malignancies. Radiology Radiologic investigations describe two patterns of MCT: macrocystic multilocular and macrocystic unilocular. The macrocystic multilocular pattern is not pathognomonic but is frequently located in the body–tail of the gland, appearing on ultrasound images as a sharply defined mass surrounded by a variably thickened wall. Thin septae delimit cystic spaces and calcifications are a common finding. On CT, the pre- contrast phase can easily detect calcifications. The den- sity of the content depends on the amount of mucin or fluid–fluid level from underlying bleeding. This pattern is clearly demonstrated by contrast medium: walls and septae display lower enhancement compared with the surrounding pancreatic parenchyma because of the fi- brous composition and minimal vascularization. The outer wall and septa have similar thickness. The macro- cystic unilocular pattern is less specific and simulates any kind of pancreatic cystic mass on both ultrasound and CT. As a consequence, differentiation cannot be made easily in cases with unique cysts having a thin wall, no calcifications, and no parietal nodules. From the radiologic point of view, thickened wall, presence of papillary proliferations arising from the wall or septae, evidence of peripheral calcifications, as well as invasion of surrounding vascular structure are considered the best signs of malignancy (Fig. 58.2). The diagnosis will be clearer if extracapsular extension of the lesion is detected on contrast-enhanced CT. When thick walls, thick septae, and calcifications are simulta- neously present, the probability of malignancy is 95%. When fewer than three signs are present, the probabil- ity of malignancy declines, being zero when there are no calcifications, no septae, and the wall is thin. Because calcifications cannot be detected by MRI, CT is the pri- mary imaging modality for these patients (Figs 58.3 & 58.4). The predominant fluid content of these masses ren- ders MCT brighter on T2-weighted MRI. The pres- ence, features, and distribution of internal septae are better seen with these techniques. T2-weighted images are optimal for the study of the Wirsung duct. When the mass clearly appears to be isolated from it, thereby Figure 58.2 Mucinous cystic tumor of the pancreatic tail with radiologic features suggesting malignancy: thick wall, papillary growth on the posterior wall, and collateral vessels from vascular compression/infiltration (computed tomography and magnetic resonance respectively). Figure 58.3 Computed tomography of a mucinous cystic tumor of the pancreatic tail showing intratumoral septae. [...]... lesions under real-time EUS guidance Doppler and color Doppler are also available and may be employed to identify vascular structures At present, different types of needles are available for EUS FNA The most commonly used in clinical practice are made by WilsonCook (Echotip EUSN-1, Echotip EUSN-19T, QuickCore EUSN 1-1 9QC: 19–22 gauge), GIP-Mediglobe (Sonotip: 19–22 gauge), and Olympus (NA-10J-1: 19 gauge)... antigen (CEA) and CA-7 2-4 to be elevated in the cyst aspirate of mucinous tumors but not in inflammatory or serous cysts (CA-7 2-4 : sensitivity 87.5%, specificity 94%) CA-1 9-9 has been found elevated in both benign and malignant lesions and does not appear to be useful in the evaluation of these 499 PART IV (a) (b) (c) Figure 59.1 (a) Serous cystadenoma: a microcystic tumor of the pancreas (cysts < 10 mm in... necrosis and abscess formation is reduced On the other hand, distal pancreatectomy with conservation of the splenic artery and vein is both time- and labor-consuming Dissecting the splenic vessels from the pancreas may be difficult to perform in the presence of tumors distorting and compressing the course of the vessels In this report we conducted a prospective study to evaluate the feasibility and outcome... 2002;19:507– 510 Fernández-Cruz L, Sáenz A, Astudillo E, Pantoja JP, Uzcátegui E, Navarro S Laparoscopic pancreatic surgery in patients with chronic pancreatitis Surg Endosc 2002;16:996 100 3 Fernández-Cruz L, Sáenz A, Astudillo E et al Outcome of laparoscopic pancreatic surgery: endocrine and non endocrine tumors World J Surg 2002;26 :105 7 106 5 Fernández-del Castillo C, Rattner DW, Warshaw L Standards for pancreatic... 497 PART IV Technique The EUS examination typically commences with use of the radial echoendoscope to identify the lesion and characterize its location, morphology (presence of septa, solid component, debris), and size and to establish a diagnosis of suspicion When clinically indicated, the cystic lesion of the pancreas is sampled and aspirated fluid sent for analysis EUS-guided cyst aspiration is performed... EUS is a very useful technique for detecting the presence of a pancreatic cystic lesion and for characterizing its nature EUS FNA permits cyst aspiration and fluid Special thanks to Michael J Levy MD and the Mayo Clinic, Rochester, MN, for their generous contribution with pictures from their personal archives 501 PART IV Table 59.3 Summary of clinical, endosonographic, and laboratory findings in pancreatic... methods For these reasons, EUS and EUS-guided fine-needle aspiration (FNA) have acquired in recent years a prominent role in the evaluation of patients with known or suspected pancreatic cystic lesions Equipment endoscope provided with an oblique forward viewing fiber or video optic system, and a high-frequency ultrasound transducer located at the tip of the scope Highresolution images of the gut wall and. .. EUS guidance, a 22 gauge fine needle is advanced into the cyst and fluid is aspirated for analysis (b) Macroscopic appearance of the pancreatic cyst at surgery Surgical pathology established a definitive diagnosis of serous cystadenoma Table 59.2 Laboratory findings in pancreas cyst aspirate Diagnosis Viscosity Amylase CA-7 2-4 CEA CA-1 5-3 CA-1 9-9 Pseudocyst Serous cystadenoma Mucinous cystadenoma Mucinous... another during the examination, modifying the depth of penetration and the degree of definition (e.g., higher ultrasound frequencies provide higher image resolution but lower penetration than the lower frequencies) The curved linear electronic array echoendoscope (Pentax EG-3630U, EG-3830UT, FG-34/36/38X: 5 10 MHz; Olympus GF-UC30P, GF-UCT160-OL5: 7.5 MHz) provides a sagittal scan parallel to the longitudinal... splenectomy group (28% and 11%) compared with the splenic preservation group (9% and 2%) Length of hospital stay was 9 days following splenectomy and 7 days following splenic preservation We encourage laparoscopic spleen-preserving pancreatectomy in order to prevent the potential long- and short-term complications associated with splenectomy The question is whether it should be performed with or without . are made by Wilson- Cook (Echotip EUSN-1, Echotip EUSN-19T, Quick- Core EUSN 1-1 9QC: 19–22 gauge), GIP-Mediglobe (Sonotip: 19–22 gauge), and Olympus (NA-10J-1: 19 gauge). 59 The role of endoscopic ultrasonography. reso- lution but lower penetration than the lower frequen- cies). The curved linear electronic array echoendoscope (Pentax EG-3630U, EG-3830UT, FG-34/36/38X: 5 10 MHz; Olympus GF-UC30P, GF-UCT160-OL5: 7.5. or side-branch IPMT. Several studies have shown carci- noembryonic antigen (CEA) and CA-7 2-4 to be elevat- ed in the cyst aspirate of mucinous tumors but not in inflammatory or serous cysts (CA-7 2-4 :