The immunohistochemical mucin expression pattern distinguishes different types of intraductal papillary mucinous neoplasms of the pancreas and determines their relationship to mucinous noncystic carcinoma and ductal adenocarcinoma.

Intraductal papillary-mucinous neoplasms of the pancreas seem to comprise various types, whose relationship to ductal adenocarcinoma and mucinous noncystic carcinoma is unclear. We analyzed the mucin immunophenotype and the DPC4/SMAD4 expression in intraductal papillary-mucinous neoplasms, ductal carcinomas, and mucinous noncystic carcinomas to define features that may help to distinguish between different types of intraductal papillary-mucinous neoplasms and to establish their relationship to other neoplasms of the exocrine pancreas. A series of 51 intraductal papillary-mucinous neoplasms, three mucinous noncystic carcinomas (two with an intraductal component), and 35 ductal adenocarcinomas were screened immunohistochemically for their expression of MUC1, MUC2, MUC5, and DPC4/SMAD4. All intraductal papillary-mucinous neoplasms and mucinous noncystic carcinomas were positive for MUC5. Thirty-two intraductal papillary-mucinous neoplasms and three mucinous noncystic carcinomas abundantly expressed MUC2 but no (or only little) MUC1. The remaining intraductal papillary-mucinous neoplasms showed either mainly MUC1 expression or focal MUC1 and MUC2 expression. All ductal carcinomas but one were MUC2 negative and MUC1 and MUC5 positive. DPC4 was not expressed in two intraductal papillary-mucinous neoplasms that showed a tubular invasion pattern. Twelve of 23 ductal adenocarcinomas were DPC4 positive. Intraductal papillary-mucinous neoplasms can be divided into at least three different mucin immunophenotypes. The first and largest group of intraductal papillary-mucinous neoplasms and mucinous noncystic carcinomas is MUC1 negative and MUC2 positive and probably forms one tumor entity. The second group seems to be related to ductal carcinoma because of its MUC1 positivity in the absence or very weak MUC2 staining. The third group shows focal MUC1/MUC2 expression and is characterized by oncocytic histology.     

The expression of several types of mucin is related to the biological behavior of pancreatic neoplasms

Background/Purpose: Mucins are high molecular weight glycoproteins that have oligosaccharides attached to the apomucin protein backbone by O-glycosidic linkages. Here, we report the expression of MUC1 mucin (membrane-bound mucin), MUC2 mucin (intestinal-type secretory mucin), and MUC5AC mucin (gastric-type secretory mucin) in invasive ductal carcinomas (IDCs; n= 46) and intraductal papillary-mucinous neoplasms (IPMNs; n= 33) of the pancreas, and the relationship of this expression with malignant potential. Methods: To clarify the precise expression pattern of mucins in IPMNs, we classified IPMNs into three histologic subtypes; IPMN-dark cell type (n= 19), IPMN-clear cell type (n= 10), and IPMN-compact cell type (n= 4). Results: IDC, with a poor outcome, showed a pattern of MUC1(+), MUC2(−), and MUC5AC(+ or −). In contrast, IPMN-dark cell type tumors, with a fairly favorable outcome, showed a pattern of MUC1(−), MUC2(+), and MUC5AC(+), and IPMN-clear cell type tumors, with a favorable outcome, showed a pattern of MUC1(−), MUC2(−), and MUC5AC(+). On the other hand, IPMN-compact cell type tumors showed a pattern of MUC1(+), MUC2(−), and MUC5AC(+). In IPMN-dark cell type tumors with carcinomatous change showing invasive growth, the invasive areas acquired a characteristic of MUC1 expression that was usually seen in IDC, although their main noninvasive lesions showed no MUC1 expression. The IPMN-compact cell type tumors usually showed high cellular atypia and frequent MUC1 expression, even in the noninvasive areas. Conclusions: Our study of the mucin expression pattern in IDC and IPMN shows that this pattern may be related to the biological behavior of pancreatic tumors and their malignant potential. Received: May 11, 2001 / Accepted: September 26, 2001     

Mucin expression profile in pancreatic cancer and the precursor lesions

In this review article, we demonstrate the mucin expression profile in normal tissue, invasive ductal carcinoma (IDC), two subtypes of intraductal papillary–mucinous neoplasm (IPMN dark cell type and IPMN clear cell type), pancreatic intraepithelial neoplasia (PanIN), and mucinous cystic neoplasm (MCN) of the pancreas. In MUC1, there are various glycoforms, such as poorly glycosylated MUC1, sialylated MUC1, and fully glycosylated MUC1. IDCs showed high expression of all the glycoforms of MUC1. IPMNs dark cell type showed no expression or low expression of all the glycoforms of MUC1. IPMNs clear cell type showed low expression of poorly glycosylated MUC1, but expression of sialylated MUC1 and fully glycosylated MUC1. Expression of MUC2 was negative in IDCs, high in IPMNs dark cell type and low in IPMNs clear cell type. MUC5AC was highly expressed in IDCs, IPMNs dark cell type, and IPMNs clear cell type. MUC6 expression was higher in IPMNs clear cell type than in IDCs and IPMNs dark cell type. Our recent study demonstrated that high expression of MUC4 in IDCs is correlated with a poor outcome for patients. In PanINs, expression of both MUC5AC and MUC6 are an early event, whereas up-regulation of MUC1 is a late event. MCNs do not look as if they will show a specific mucin expression profile according to the literature review.     

Mucinous cystic neoplasm of the pancreas or intraductal papillary-mucinous tumour of the pancreas.

OBJECTIVE: To compare clinicopathological findings in patients with mucinous cystic neoplasms and intraductal papillary-mucinous tumours. DESIGN: Retrospective study. SETTING: University department of surgery, Japan. SUBJECTS: 21 patients with mucinous cystic neoplasms (group 1) and 48 with intraductal papillary-mucinous tumours (group 2). RESULTS: The mean age was younger in group 1 (53(3.4) years) than in group 2 (65(1) years, p < 0.0001). The male:female ratio was smaller in group 1 than in group 2, being 0.17 (3/18) and 1.4 (28/20), respectively, (p = 0.0007). The main sites of the lesions were also significantly different: in group 1 four (19%) were located in the head and 17 in the body or tail, while 32 (67%) were in the head of the pancreas and 16 (33%) in the body or tail in group 2 (p = 0.0007). A unique endoscopic finding, excretion of mucin from the patulous orifice of the papilla, was present in two (9%) of the 21 mucinous cystic tumours and in 21 (45%) of the 47 intraductal papillary-mucinous tumours examined (p = 0.006). Metachronous or synchronous malignant diseases were found in the pancreas or other organs in one (5%) of the 21 patients with mucinous cystic neoplasm and in 13 (27%) of the 48 with intraductal papillary-mucinous tumours (p = 0.03). The three- and five-year survival rates of 11 patients with mucinous cystadenocarcinoma were 45% and 27%, while those of 15 with intraductal papillary-mucinous carcinoma were 85% and 42%. CONCLUSIONS: These findings suggest that mucinous cystic neoplasm and intraductal papillary-mucinous tumours are different clinicopathological entities. Aggressive surgery with peripancreatic lymph node dissection is recommended, particularly for mucinous cystadenocarcinoma, and postoperative follow-up with attention given to the presence of other malignancy is necessary as well as to local recurrence and haematogenous spread.     

An illustrated consensus on the classification of pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasms

Invasive pancreatic ductal adenocarcinoma is an almost uniformly fatal disease. Several distinct noninvasive precursor lesions can give rise to invasive adenocarcinoma of the pancreas, and the prevention, detection, and treatment of these noninvasive lesions offers the potential to cure early pancreatic cancers. Noninvasive precursors of invasive ductal adenocarcinoma of the pancreas include pancreatic intraepithelial neoplasias (PanINs), intraductal papillary mucinous neoplasms (IPMNs), and mucinous cystic neoplasms. Diagnostic criteria, including a distinct ovarian-type stroma, and a consistent nomenclature are well established for mucinous cystic neoplasms. By contrast, consistent nomenclatures and diagnostic criteria have been more difficult to establish for PanINs and IPMNs. Because both PanINs and IPMNs consist of intraductal neoplastic proliferations of columnar, mucin-containing cells with a variable degree of papilla formation, the distinction between these two classes of precursor lesions remains problematic. Thus, considerable ambiguities still exist in the classification of noninvasive neoplasms in the pancreatic ducts. A meeting of international experts on precursor lesions of pancreatic cancer was held at The Johns Hopkins Hospital from August 18 to 19, 2003. The purpose of this meeting was to define an international acceptable set of diagnostic criteria for PanINs and IPMNs and to address a number of ambiguities that exist in the previously reported classification systems for these neoplasms. We present a consensus classification of the precursor lesions in the pancreatic ducts, PanINs and IPMNs.     

Clinical and pathologic correlation of 84 mucinous cystic neoplasms of the pancreas: can one reliably differentiate benign from malignant (or premalignant) neoplasms?

OBJECTIVE: To determine whether the long-term behavior of cystic mucinous neoplasms of the pancreas could be predicted using a novel, precisely defined classification of benign mucinous cystadenomas, noninvasive proliferative cystic mucinous neoplasms, and invasive mucinous cystadenocarcinomas. The primary interest was to obtain long-term follow-up after complete resection to determine the recurrence rates based on this objective classification. BACKGROUND: Current understanding is that all cystic mucinous neoplasms of the pancreas are potentially malignant and that mucinous cystadenomas, when completely removed, are biologically benign. Cystadenocarcinomas are thought to be less aggressively malignant than ordinary ductal adenocarcinoma, but reported recurrence rates vary widely and are unpredictable. METHODS: All patients who underwent "curative" resection for cystic mucinous neoplasms at Mayo Clinic Rochester from 1940 to 1997 were identified. All available pathology slides, gross specimens, and clinical records were reviewed, eliminating patients with inadequate documentation. Neoplasms were reclassified as mucinous cystadenomas, noninvasive proliferative mucinous cystic neoplasms, or invasive cystadenocarcinomas based on specific histologic criteria. RESULTS: Of 84 patients (70 women, 14 men) with cystic mucinous neoplasms of the pancreas, 54 were classified as cystadenomas, 23 as noninvasive proliferative cystic mucinous neoplasms, and only 7 as cystadenocarcinomas. Recurrent disease developed in none of the 77 patients without invasion, but 5 of the 6 patients surviving resection for cystadenocarcinomas died of recurrent cystadenocarcinoma within 5 years. CONCLUSIONS: When the neoplasm is completely resected and subjected to adequate histopathologic examination based on these objective criteria, absence of tissue invasion predicts a curative operation and detailed follow-up may be unnecessary. In contrast, a histologic diagnosis of invasive cystadenocarcinoma portends a dismal prognosis, similar to that of typical ductal adenocarcinoma of the pancreas.     

Clinical importance of precursor lesions in the pancreas

Three distinct noninvasive precursor lesions to invasive ductal adenocarcinoma of the pancreas have been described. These include the mucinous cystic neoplasm, intraductal papillary mucinous neoplasm, and pancreatic intraepithelial neoplasia. The early detection and treatment of these lesions can interrupt the progression of a curable noninvasive precursor to an almost uniformly deadly invasive cancer.     

Immunohistochemical staining in the diagnosis of pancreatobiliary and ampulla of Vater adenocarcinoma: application of CDX2, CK17, MUC1, and MUC2

Pancreatobiliary and ampulla of Vater adenocarcinomas frequently metastasize to regional lymph nodes, liver, or lung and are difficult to diagnose because they lack specific immunohistochemical markers. We studied the expression of cytokeratin 7 (CK7), cytokeratin 17 (CK17), cytokeratin 20 (CK20), CDX2, mucin 1 (MUC1), mucin 2 (MUC2), and mucin 5AC (MUC5AC) in 46 cases of pancreatic ductal carcinoma, 18 ampulla of Vater adenocarcinomas, and 24 intrahepatic cholangiocarcinomas. The expression of MUC1 and CK17 was restricted to pancreatic ductal carcinoma (41 of 46, 89%; 38 of 46, 83%, respectively), the ampullary carcinoma of pancreatobiliary origin (6 of 6, 100%; 5 of 6, 83%, respectively), and intrahepatic cholangiocarcinoma (20 of 24, 83%; 17 of 24, 71%, respectively). More than 50% of cases of pancreatobiliary adenocarcinomas showed diffuse cytoplasmic CK17 positivity. In contrast, less than 5% cases (8 of 184) of extra-pancreatobiliary nonmucinous adenocarcinomas expressed CK17, and only 3 of them showed diffuse CK17 positivity. The expression of MUC2 and CDX2 was restricted to the intestinal, mucinous, and signet-ring cell-type adenocarcinomas of duodenal papillary origin (9 of 11, 82%; 11 of 11, 100%, respectively). MUC2 was rarely expressed in pancreatic ductal carcinoma (1 of 46, 2%) and was negative in the ampullary carcinoma of pancreatobiliary origin and in intrahepatic cholangiocarcinoma. A heterogeneous CDX2 staining pattern was seen in 1 of 6 cases of the ampullary carcinoma of pancreatobiliary origin (17%), 5 of 24 intrahepatic cholangiocarcinomas (21%), and 10 of 46 (22%) pancreatic ductal carcinomas. In contrast, all 11 cases of the intestinal, mucinous, and signet-ring cell-type adenocarcinomas of duodenal papillary origin showed homogeneous CDX2 nuclear positivity. We concluded that CK17 is a useful marker in separating pancreatobiliary adenocarcinomas from extra-pancreatobiliary nonmucinous adenocarcinomas, including adenocarcinomas from the colon, breast, gynecologic organs, stomach, lung, prostate, thyroid, kidney, and adrenal gland, and malignant mesothelioma. MUC1+/CK17+ can be used as positive markers for pancreatic ductal carcinomas, the ampullary carcinoma of pancreatobiliary origin, and cholangiocarcinomas with positive predictive values of 76%, 83%, and 58%, respectively. MUC2+/CDX2+ can be used as positive markers for the intestinal-type adenocarcinoma of duodenal papillary origin with a positive predictive value of 82%.     

Immunohistochemical studies of mucin antigens in pancreas and intrahepatic bile-duct tumors

Our previous studies of pancreatic and intrahepatic bile-duct tumors revealed that MUC2 mucin (“secretory mucin”, detected by a polyclonal antibody, anti-MRP) was highly expressed in intraductal papillary-mucinous tumors of the pancreas (IPMTs) and bile duct cystadenocarcinomas of the liver (BDCs) with expansive growth pattern and favorable prognosis, whereas it was rarely or not expressed in invasive ductal carcinomas of the pancreas (IDCs) and cholangiocarcinomas of the liver (CCs) with invasive growth pattern and poor prognosis. In contrast, MUC1 mucin (“membrane-bound mucin” detected by the monoclonal antibody, DF3) was rarely or not expressed in IPMTs and BDCs, but was always expressed in IDCs and CCs (Cancer 71:2191–2199, 1993;Int J Cancer 55:82–91, 1993). The results of these studies suggest that the difference in the expression of MUC1 and MUC2 mucins is a useful indicator of malignant potential in neoplasms of the pancreas and intrahepatic bile duct. This article is a review of our previous studies described above. In addition, we present longer-term follow-up data for the cases reported in our previous studies as well as demonstrating pathological prognostic factors, such as lymph node status, lymphatic infiltration, and perineural invasion. We also examined several additional cases of IPMTs and analyzed the same prognostic factors. We could confirmed the findings of our previous studies, and found that most IPMTs and BDCs with a MUC1(−) and MUC2(+) expression pattern showed less aggressive pathological factors than most IDCs and CCS with a MUC1(+) and MUC2(−) expression pattern.     

Similarities and differences between intraductal papillary tumors of the bile duct with and without macroscopically visible mucin secretion

Intraductal papillary neoplasms of the bile duct (IPNB) have been recently proposed as the biliary counterpart of intraductal papillary mucinous neoplasms of the pancreas (IPMN-P). However, in contrast to IPMN-P, IPNB include a considerable number of the tumors without macroscopically visible mucin secretion. Here we report the similarities and differences between IPNB with and without macroscopically visible mucin secretion (IPNB-M and IPNB-NM). Surgically resected 27 consecutive cases with IPNB were divided into IPNB-M (n=10) and IPNB-NM (n=17), and their clinicopathologic features were examined. Clinically, both tumors were similar. Pathologically, the most frequent histopathologic types were pancreatobiliary in IPNB-NM and intestinal in IPNB-M. Various degrees of cytoarchitectural atypia within the same tumor were exhibited in 8 IPNB-M, but only 3 in IPNB-NM. Although the tumor size was similar, 9 IPNB-NM were invasive carcinoma, whereas all but 1 IPNB-M with carcinoma were in situ or minimally invasive. Immunohistochemically, positive MUC2 expression was significantly more frequent in IPNB-M than in IPNB-NM, whereas MUC1 tended to be more frequently expressed in IPNB-NM compared with IPNB-M. Among IPNB-NM with positive MUC1 expression, 3 had negative MUC2 and MUC5AC expressions. These tumors showed a tubulopapillary growth with uniform degree of cytoarchitectural atypia. All IPNB-M were negative for p53, and the frequency of positive p53 protein in IPNB-NM was at the middle level of that in IPNB-M and nonpapillary cholangiocarcinoma. In conclusion, IPNB-M showed striking similarities to IPMN-P, but IPNB-NM contained heterogeneous disease groups.     

Mucin-producing neoplasms of the pancreas. Intraductal papillary and mucinous cystic neoplasms.

OBJECTIVE: The authors compared the clinicopathologic features of the intraductal papillary and mucinous cystic neoplasms of the pancreas and clarified the similarities as well as the differences between these two tumors. In addition, they reviewed 104 cases of the intraductal papillary neoplasm in the English literature to provide a global view of the condition. SUMMARY BACKGROUND DATA: Controversy about the term and clinicopathologic entity still exist regarding intraductal papillary neoplasm of the pancreas. Currently, with only a few cases of this rare tumor in each report, there continues to be inadequate knowledge available regarding the tumor and methods by which to distinguish it from the mucinous cystic neoplasm. METHODS: Multiple demographic and clinicopathologic parameters were compared between intraductal papillary and mucinous cystic neoplasms identified from 1985 to 1994 in the Medical Center, Veterans General Hospital--Taipei. RESULTS: There were four intraductal papillary adenocarcinomas and 10 mucinous cystic neoplasms (8 cystadenocarcinoma and 2 cystadenoma). The sex, age, size, tumor location, and pathologic findings were quite different between these two groups. Clinical presentation of intraductal papillary adenocarcinomas were similar to those of periampullary tumors. The most common presentations of mucinous cystic neoplasm were epigastric pain and abdominal mass. All four intraductal papillary adenocarcinoma showed mucin secretion from a patulous orifice of the ampulla of Vater and filling defects in the dilated main pancreatic duct by endoscopic retrograde cholangiopancreatography (ERCP). Accurate preoperative diagnosis was not easy regarding either group. Serum carbohydrate antigen 19-9 (CA 19-9) was more useful for diagnosis in both groups. CONCLUSIONS: The intraductal papillary neoplasm is a unique clinical entity but not a variant of mucinous cystic neoplasm in terms of sex, age, size, tumor location, or pathologic picture. The pathognomonic findings of ERCP should lead to diagnosis. Very aggressive surgical procedures should be attempted for these two mucin-producing neoplasms with low-grade malignancy.     

p16 and p53 gene alterations and accumulations in the malignant evolution of intraductal papillary-mucinous tumors of the pancreas

Abstract. Background/Purpose: In general, intraductal papillary-mucinous tumors of the pancreas have a favorable prognosis. However, some invasive carcinomas show a rapid progression and a poor prognosis, such as invasive ductal carcinomas of the pancreas. The aim of this study was to clarify the genetic backgrounds underlying the evolution necessary for these tumors to become invasive carcinomas. Methods: Twenty-three patients with intraductal papillary-mucinous tumors, including 9 adenomas, 5 borderline tumors, 3 noninvasive carcinomas, and 6 invasive carcinomas, along with 24 patients with invasive ductal carcinomas were studied. After microdissection, K-ras mutation and loss of heterozygosity (LOH) of the p16 and p53 genes were investigated. Results: In the intraductal papillary-mucinous tumors, K-ras mutations were frequently seen, without a relationship to histological grade. LOH of the p16 gene was observed increasingly with increasing degrees of histological atypia. LOH of the p53 gene was seen only in invasive carcinomas. The frequency of each genetic alteration in invasive carcinomas was the same as that in invasive ductal carcinomas. The accumulation of genetic alterations was as common in invasive carcinomas, as they were in invasive ductal carcinomas. Conclusions: The p16 and p53 gene alterations and accumulations observed are crucial events during the carcinogenesis and malignant progression of intraductal papillary-mucinous tumors of the pancreas. Received: October 4, 2001 / Accepted: November 16, 2001     

Intraductal tubular adenoma of the pancreas, pyloric gland type: a clinicopathologic and immunohistochemical study of 6 cases

The intraductal tubular adenoma (ITA), pyloric gland type, of the pancreas is an uncommon benign tumor, akin to the pyloric gland type adenoma of the gallbladder. We report 6 cases of ITA of the pancreas: 3 male and 3 female aged 50 to 79 years (mean, 63.5 years; median, 65 years); all were examined clinicopathologically. Four patients showed no symptoms, but appetite loss and/or general fatigue presented in two. Grossly, all tumors formed a localized polypoid mass protruding into the lumen of the dilated pancreatic duct. Five of the six tumors were found within the main duct, and the other arose within the branch duct of the pancreas. Microscopically, the tumors were composed of closely packed tubular glands resembling pyloric type glands. They were lined by columnar or cuboidal epithelial cells with foci of mild to moderate dysplastic change. In 2 cases, the adjacent pancreas showed foci of intraductal papillary-mucinous adenoma. Histochemically, the tumors largely showed neutral mucin with a lesser amount of acidic mucin made up mainly of sialomucin. Endocrine cells were found in five tumors. Immunohistochemically, all tumors were labeled with M-GGMC-1 and MUC6, whereas MUC1 and MUC2 stains were negative. Pepsinogen II was positive in 5 tumors; thus, the results displayed a pattern of differentiation similar to those of ordinary gastric pyloric or metaplastic pyloric glands. DPC4 expression was maintained in all tumors and p53-positive nuclei were hardly encountered. All patients are alive with no evidence of disease 3 to 10.5 years after surgical resection.     

Current understanding of precursors to pancreatic cancer

Precursors to pancreatic cancer have been investigated for a century. Previous studies have revealed three distinct precursors, i.e. mucinous cystic neoplasm (MCN), intraductal papillary mucinous neoplasm (IPMN), and pancreatic intraepithelial neoplasia (PanIN), harboring identical or similar genetic alterations as does invasive pancreatic carcinoma. The current understanding of precursors to pancreatic cancer can be illustrated by progressive pathways from noninvasive MCN, IPMN, and PanIN toward invasive carcinoma. MCNs consist of ovarian-type stroma and epithelial lining with varying grades of atypia, and are occasionally associated with invasive adenocarcinoma. The epithelium of noninvasive IPMNs shows a variety of different directions of differentiation, including gastric, intestinal, pancreatobiliary (PB), and oncocytic types. IPMNs can also harbor varying grades of architectural and cytologic atypia. IPMNs confined to branch ducts are mostly the gastric type, and IPMNs involving the main ducts are often intestinal type, while PB and oncocytic types are rare. Small (<1 cm) IPMNs of the gastric type are not always morphologically distinguishable from low-grade PanINs. Mucin expression profiles suggest intestinal-type IPMNs progress to mucinous noncystic (colloid) carcinoma, while PB-type IPMNs progress toward ductal adenocarcinoma. It is a well-described paradigm that PanIN lesions progress toward ductal adenocarcinoma through step-wise genetic alterations. The activation of Hedgehog and Notch signaling pathways in PanIN lesions as well as in pancreatic adenocarcinoma suggest that developmental pathways may be disregulated during carcinogenesis of the pancreas. Further study is needed to elucidate the pathways from precursors toward invasive carcinoma of the pancreas.     

Endoscopic diagnosis and staging of mucinous cystic neoplasms and intraductal papillary-mucinous tumors

Background/Purpose. The number of patients with cystic neoplasms of the pancreas as detected using various types of imaging techniques has been steadily increasing. Among the cystic neoplasms, mucinous cystic neoplasms (MCNs) and intraductal papillary-mucinous tumors (IPMTs) were comparatively more frequently encountered. We used imaging techniques to focus on the differential diagnosis of MCNs and IPMTs, and tumor staging.Methods. Fifteen patients with MCNs with ovarian-like stroma and 109 patients with IPMTs were experienced. We examined the image findings for the differential diagnosis and stage diagnosis of these two types of cystic neoplasms.Results. Endoscopic ultrasonography could reveal detailed images of internal structure and was effective for the diagnosis of MCNs. Other endoscopic imaging modalities could not give specific findings for MCNs. Endoscopic retrograde cholangiopancreatography (ERCP; including duodenoscopic findings and pancreatogram) and pancreatoscopy showed the characteristic and specific findings of IPMTs. Also, endoscopic ultrasonography and intraductal ultrasonography were found to have high sensitivity and diagnostic accuracy for their differential diagnosis of neoplastic/nonneoplastic and invasive/noninvasive lesions in IPMTs.Conclusions. Endoscopic imaging techniques are capable of revealing the detailed structure of pancreatic cystic lesions. They are effective for differential diagnosis, for assessing the degree of malignancy, and for deciding upon an appropriate treatment in patients with IPMTs.     

Intraductal papillary mucinous neoplasms of the pancreas: an increasingly recognized clinicopathologic entity

OBJECTIVE: To assess the authors' experience with intraductal papillary mucinous neoplasms of the pancreas (IPMNs). SUMMARY BACKGROUND DATA: Intraductal papillary mucinous neoplasms of the pancreas are being recognized with increasing frequency. METHODS: All patients who underwent pancreatic resection for an IPMN at the Johns Hopkins Hospital between January 1987 and December 2000 were studied. The data were compared with those of 702 concurrent patients with infiltrating ductal adenocarcinoma of the pancreas not associated with an IPMN resected by pancreaticoduodenectomy. RESULTS: In the 13-year time period, 60 patients underwent pancreatic resection for IPMNs, with 40 patients undergoing resection in the past 3 years. Mean age at presentation was 67.4 +/- 1.4 years. The most common presenting symptom in patients with IPMNs was abdominal pain (59%). Most IPMNs were in the head of the pancreas or diffusely involved the gland, with 70% being resected via pancreaticoduodenectomy, 22% via total pancreatectomy, and 8% via distal pancreatectomy. Twenty-two patients (37%) had IPMNs with an associated infiltrating adenocarcinoma. In a subset of IPMNs immunohistochemically stained for the Dpc4 protein (n = 50), all of the intraductal or noninvasive components strongly expressed Dpc4, whereas 84% of associated infiltrating cancers expressed Dpc4. The 5-year survival rate for all patients with IPMNs (n = 60) was 57%. CONCLUSION: Intraductal papillary mucinous neoplasms represent a distinct clinicopathologic entity being recognized with increasing frequency. IPMNs are clinically, histologically, and genetically disparate from pancreatic ductal adenocarcinomas. The distinct clinical features, the presumably long in situ or noninvasive phase, and the good long-term survival of patients with IPMNs offer a unique opportunity for early diagnosis, curative resection, and further studies of the molecular genetics and natural history of these unusual neoplasms.     

Systematic review of the utility of 18-FDG PET in the preoperative evaluation of IPMNs and cystic lesions of the pancreas

BackgroundThe aim of this systematic review is to assess the role of 18-fluorodeoxyglucose positron emission tomography in the preoperative evaluation of intraductal papillary mucinous neoplasms and cystic lesions of the pancreas.MethodsA computerized PubMed search was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify studies evaluating positron emission tomography in the preoperative evaluation of pancreatic cystic lesions.ResultsA total of 14 studies evaluated the role of 18-fluorodeoxyglucose positron emission tomography/positron emission tomography-computed tomography, 9 of which evaluated only intraductal papillary mucinous neoplasms and 5 evaluated all pancreatic cystic lesions, including intraductal papillary mucinous neoplasms. Pooled analysis was carried out for studies evaluating intraductal papillary mucinous neoplasms only and studies evaluating all cystic lesions. Imaging with 18-fluorodeoxyblucose positron emission tomography had a positive predictive value, negative predictive value, sensitivity, specificity, and accuracy of 90%, 91%, 85%, 95%, and 91% in identifying malignancy (defined as either invasive and/or high-grade dysplasia) in intraductal papillary mucinous neoplasms and a positive predictive value, negative predictive value, sensitivity, specificity, and accuracy of 85%, 81%, 79%, 86%, and 88% in identifying malignancy in other cystic lesions. Pooled analysis reported the positive predictive value, negative predictive value, sensitivity, specificity, and accuracy of Sendai consensus guidelines (SCG) criteria as 69%, 69%, 68%, 55%, and 58%. The Fukuoka consensus guidelines (FCG) only had sensitivity, specificity, and accuracy reported as 61%, 52%, and 52%, respectively.ConclusionThe 18-fluorodeoxyblucose positron emission tomography had a high degree of accuracy of detecting malignancy in intraductal papillary mucinous neoplasm and cystic lesion of the pancreas. Comparison of the utility of positron emission tomography with the Fukuoka consensus guidelines and the Sendai consensus guidelines suggest that positron emission tomography is superior to present guidelines in detecting malignant intraductal papillary mucinous neoplasm and cystic lesion of the pancreas. Further studies in larger patient cohorts may be required to corroborate these findings and to determine the place of positron emission tomography in the management of intraductal papillary mucinous neoplasm and cystic lesions of the pancreas.