This rare tumor is characterized by a proliferation of mucinous type epithelium lining the pancreatic ducts causing dilatation. It is a slow growing tumor with a low malignancy rate.
Pathogenesis Laboratory/Radiologic/Other Diagnostic Testing Gross Appearance and Clinical Variants Histopathological Features and Variants Special Stains/
Differential Diagnosis Prognosis Treatment Commonly Used Terms Internet Links
PATHOGENESIS CHARACTERIZATION CHROMOSOMAL ABNORMALITIES
Pancreatic mucinous noncystic (colloid) carcinomas and intraductal papillary mucinous carcinomas are usually microsatellite stable.
Luttges J, Beyser K, Pust S, Paulus A, Ruschoff J, Kloppel G.
Department of Pathology, University of Kiel, Germany.
Mod Pathol. 2003 Jun;16(6):537-42. Abstract quote
Pancreatic mucinous noncystic (colloid) carcinomas (MNCC) differ from the usual ductal adenocarcinomas in their mucin expression profile and share with many extrapancreatic mucinous carcinomas the expression of MUC2. Because mucinous carcinomas are frequently associated with mutations of the DNA mismatch repair genes, causing them to exhibit the so-called mutator phenotype, we decided to investigate whether MNCCs of the pancreas are characterized by microsatellite instability (MSI).
Twelve carcinomas with a mucinous phenotype (8 mucinous noncystic carcinomas, 3 intraductal papillary-mucinous carcinomas with an invasive muconodular component, and 1 ductal adenocarcinoma with an extensive mucinous noncystic component) and 11 ductal adenocarcinomas were immunostained with monoclonal antibodies to the mismatch repair gene products hMLH1, hMSH2, and hMSH6. For MSI analysis, DNA was isolated from microdissected tissue, and five primary microsatellites (BAT 25, BAT 26, D5S346, D17S250, and D2S123) were analyzed. MSI was diagnosed in case a novel allele was found, compared with the normal tissue. The criterion for LOH was a 75% signal reduction. All carcinomas tested exhibited nuclear expression of mismatch repair gene products, except for one MNCC that also showed MSI at the molecular level.
The data suggest that pancreatic carcinomas with a mucinous phenotype (MUC2+/MUC1-) do not appear to normally exhibit mutations in the mismatch repair genes and therefore differ in their carcinogenesis from those in other organs.
Dpc4 Protein in Mucinous Cystic Neoplasms of the Pancreas Frequent Loss of Expression in Invasive Carcinomas Suggests a Role in Genetic Progression
Christine A. Iacobuzio-Donahue, M.D., Ph.D.; Robb E. Wilentz, M.D.; Pedram Argani, M.D.; Charles J. Yeo, M.D.; John L. Cameron, M.D.; Scott E. Kern, M.D.; Ralph H. Hruban, M.D.
From the Departments of Pathology (C.I.D., R.E.W., P.A., S.E.K., R.H.H.), Surgery (C.J.Y., J.L.C.), and Oncology (C.J.Y., J.L.C., S.E.K., R.H.H.), The Johns Hopkins Medical Institutions, Baltimore, Maryland, U.S.A.
Am J Surg Pathol 2000;24:1544-1548 Abstract quote
DPC4 (MADH4, SMAD4) is a nuclear transcription factor shown to be genetically inactivated in over half of infiltrating ductal adenocarcinomas of the pancreas. Immunohistochemical labeling for the DPC4 gene product using a monoclonal antibody has recently been shown to be an extremely sensitive and specific marker for DPC4 gene alterations in pancreatic adenocarcinomas. Mucinous cystic neoplasms (MCNs) are a biologically less aggressive subtype of pancreatic neoplasm that may show benign, borderline, or overtly malignant features. However, the role of DPC4 inactivation in the development of MCNs has not been examined.
The immunohistochemical expression of Dpc4 protein was therefore examined in 36 mucinous cystic neoplasms using this previously characterized monoclonal antibody.
The 36 mucinous cystic neoplasms studied included 23 adenomas, 1 tumor with borderline potential, 5 tumors with carcinoma in situ, and 7 invasive carcinomas. Twenty-nine (100%) of the 29 noninvasive mucinous cystic neoplasms strongly expressed Dpc4 in the neoplastic epithelium. In striking contrast, only one (14%) of seven infiltrating carcinomas expressed Dpc4 in the neoplastic epithelium (p = 0.0001). The adjacent stroma retained expression of this protein in all 36 cases. In invasive MCNs with loss of Dpc4 expression, areas of carcinoma in situ were identified in the same paraffin sections, and these areas of carcinoma in situ retained expression of Dpc4.
The frequent loss of Dpc4 expression in invasive MCNs indicates that genetic inactivation of Dpc4 occurs late in the neoplastic progression of these tumors and suggests a relationship to the development of invasion.
- Distinct progression pathways involving the dysfunction of DUSP6/MKP-3 in pancreatic intraepithelial neoplasia and intraductal papillary-mucinous neoplasms of the pancreas.
Furukawa T, Fujisaki R, Yoshida Y, Kanai N, Sunamura M, Abe T, Takeda K, Matsuno S, Horii A.
1Department of Molecular Pathology, Tohoku University School of Medicine, Sendai, Japan.
Mod Pathol. 2005 Aug;18(8):1034-42. Abstract quote
DUSP6/MKP-3 is identified as a candidate tumor suppressor gene for pancreatic cancer.
The aim of this study was to elucidate the roles of DUSP6 in the pancreatic carcinogenesis through the pancreatic intraepithelial neoplasia and/or intraductal papillary-mucinous neoplasms, both of which are considered to be precursor lesions of invasive carcinoma of the pancreas, by comparing with involvements of other major tumor suppressive pathways.
Expressions of DUSP6, CDKN2A, TP53, and SMAD4 were investigated by immunohistochemistry in a total of 206 lesions of dysplastic ductal precursors and carcinomas retrieved from 52 pancreata with invasive ductal carcinomas and 51 of those with intraductal papillary-mucinous neoplasms. The intensity of staining was evaluated in lesions at different atypical grades and statistically compared among them. Mutations of KRAS2 were analyzed by methods of the allele-specific oligonucleotide hybridization and nucleotide sequencing. In pancreata with invasive ductal carcinomas, expressions of DUSP6 were abrogated exclusively in the invasive carcinoma cells in contrast to its fairly preserved expressions in pancreatic intraepithelial neoplasia.
In pancreata with intraductal papillary-mucinous neoplasms, abrogated expressions of DUSP6 were observed in a relatively small fraction of intraductal adenoma/borderlines and intraductal carcinomas. Most of the intraductal adenoma/borderline lesions with abrogation of DUSP6 harbored mutations of KRAS2. None of the molecules was associated with each other in any grade of lesions. Morphological variations of papillae of the intraductal papillary-mucinous neoplasms were evaluated and analyzed for their associations with abrogations of the molecules, which resulted in finding of no significant associations.
Our results suggest that the abrogation of DUSP6 is associated exclusively with progression from pancreatic intraepithelial neoplasia to the invasive ductal carcinoma while it is potentially associated with initiation of intraductal papillary-mucinous neoplasms with mutated KRAS2, which is independent of other major tumor suppressive pathways in both types of neoplasms.
K-ras MUTATIONS These have been reported in atypical and simple ductal hyperplasia and may be an early but not sufficient change for neoplastic transformation Wnt-SIGNALING PATHWAY
- Expression of Wnt-signaling pathway proteins in intraductal papillary mucinous neoplasms of the pancreas: a tissue microarray analysis.
Chetty R, Serra S, Salahshor S, Alsaad K, Shih W, Blaszyk H, Woodgett JR, Tsao MS.
Department of Pathology, University Health Network/Toronto Medical Laboratories, University of Toronto, Toronto, Ontario, Canada M5G 2M9.
Hum Pathol. 2006 Feb;37(2):212-7. Abstract quote
Abrogation of the Wnt-signaling pathway is implicated in the carcinogenesis of several malignancies, especially colorectal cancer where up to 90% of cases are thought to have impaired Wnt signaling. It is less frequently involved in conventional ductal pancreatic adenocarcinoma. This pathway has not been explored in intraductal papillary mucinous neoplasms (IPMNs) of the pancreas previously and formed the basis of this study.
A tissue microarray of 18 cases of IPMN was stained for proteins involved in the Wnt pathway: adenomatous polyposis coli (APC), pan-beta-catenin, axin 2, glycogen synthase 3alphabeta and 3beta, c-myc, E-cadherin, and cyclin D1. The IPMNs were classified as 8 adenomas, 3 borderline, and 7 cases with carcinoma in situ and/or invasive carcinoma, occurring in 13 females, and the overall age range was 45 to 73 years. Immunohistochemical analysis showed nuclear beta-catenin staining in 7 (39%) of the 18 cases.
The cases with nuclear beta-catenin localization included 1 adenoma, 2 borderline IPMN, and 4 carcinomas in situ and/or invasive carcinomas. Seven cases showed absence of APC immunostaining and these included 4 cases with nuclear beta-catenin localization. Fourteen cases displayed marked diffuse up-regulation of c-myc protein, and 12 cases also showed diffuse cyclin D1 protein overexpression. E-cadherin expression was intense and membrane in location (comparable to normal tissue) in 6 of 8 adenomas (no tissue was available in 1 case). Decreased E-cadherin staining was noted in 8 cases where tissue was available for assessment. There was progressive decrease in membrane staining of E-cadherin in 2 of 3 borderline lesions, 1 of 2 carcinomas in situ, and 4 of 5 invasive carcinomas. All other immunostains were either normal in distribution or did not show any correlation with beta-catenin or clinicopathologic parameters. In conclusion, 7 (39%) of 18 cases of IPMN in this study demonstrated abnormal localization of beta-catenin, 4 of which also lacked APC expression. Of 5 carcinomas arising in IPMN, 4 displayed a decrease in E-cadherin expression. There was also a trend for the higher grades of IPMN to show nuclear localization of beta-catenin.
These findings suggest that a proportion of cases of IPMN may show abnormalities in the Wnt-signaling pathway with consequent altered expression of downstream related proteins.
CHARACTERIZATION General Divided into:
Adenoma (no atypia)
Borderline (moderate atypia)
Carcinoma in situ
- Intraductal Papillary Mucinous Neoplasm (IPMN) of the Pancreas: Its Histopathologic Difference Between 2 Major Types.
Departments of *Pathology paragraph signSurgery, Saitama Medical School daggerDepartment of Surgery, Sakadocyuuou Hospital, Saitama section signDepartment of Pathology, Kyoto University Hospital, Kyoto parallelDepartment of Pathology, Fujita Health University School of Mecicine, Aichi double daggerGastrointestinal Pathology Service, Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
- Am J Surg Pathol. 2006 Dec;30(12):1561-1569 Abstract quote
Intraductal papillary mucinous neoplasm (IPMN) is a unique pancreatic neoplasm developing in the ductal system. Two major histologic subtypes have been reported, that is the gastric type and the intestinal type. However, their histopathologic features, especially those of the gastric type, have not been fully described.
To evaluate the features of these two types and refine their differences, we analyzed 80 IPMNs including 50 cases of the gastric type and 30 cases of the intestinal type with mucin immunohistochemistry. By defining a main duct-type lesion as predominantly involving the main pancreatic duct with or without branch ducts, and a branch duct-type lesion as exclusively centered on branch ducts or consisting of a collection of small cystic lesions, gastric-type IPMNs were mostly branch duct-type lesions (98%), whereas the intestinal-type IPMNs were usually main duct type (73%).
The histologic grade of the intestinal type was generally higher than that of the gastric type. The intestinal type was also characterized by frequent intraluminal nodular growth, and severe atrophy and fibrosis of the surrounding parenchyma with mucous lake formation. In contrast, pyloric glandlike structures at the base of the papillae and pancreatic intraepithelial neoplasia (PanIN)-like complexes were more frequently observed in the gastric type. A significant difference was observed between the gastric type and the intestinal type with regard to all the above features (P<0.05). Seven cases (23%) of the intestinal type were associated with an invasive adenocarcinoma (6 mucinous and 1 ductal), versus only 1 case (2%) of the gastric type (invasive ductal carcinoma).
All cases of both gastric and intestinal types expressed MUC5AC; however, high immunolabeling scores for MUC2 were mostly observed in the intestinal type (P<0.05). In conclusion, gastric and intestinal types of IPMNs have distinct histopathologic features and mucin profiles, suggesting that they may follow different biologic pathways.
An Illustrated Consensus on the Classification of Pancreatic Intraepithelial Neoplasia and Intraductal Papillary Mucinous Neoplasms.
Hruban RH, Takaori K, Klimstra DS, Adsay NV, Albores-Saavedra J, Biankin AV, Biankin SA, Compton C, Fukushima N, Furukawa T, Goggins M, Kato Y, Kloppel G, Longnecker DS, Luttges J, Maitra A, Offerhaus GJ, Shimizu M, Yonezawa S.
Am J Surg Pathol. 2004 Aug;28(8):977-987. Abstract quote
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.
Pathologically and Biologically Distinct Types of Epithelium in Intraductal Papillary Mucinous Neoplasms: Delineation of an "Intestinal" Pathway of Carcinogenesis in the Pancreas.
Adsay NV, Merati K, Basturk O, Iacobuzio-Donahue C, Levi E, Cheng JD, Sarkar FH, Hruban RH, Klimstra DS.
*Departments of Pathology, Karmanos Cancer Institute and Wayne State University, Detroit, MI; daggerMemorial Sloan-Kettering Cancer Center, New York, NY; and double daggerJohns Hopkins University Hospitals, Baltimore, MD.
Am J Surg Pathol. 2004 Jul;28(7):839-848. Abstract quote
Although general characteristics of intraductal papillary mucinous neoplasms (IPMNs) and their delineation from other pancreatic tumors have been well established, several issues regarding their biology and management remain unresolved.
It has been noted briefly by us and other authors that there are different types of papillae in IPMNs; however, their frequency, biologic significance, and clinical relevance are unknown.
In this study, the association of different papillary patterns with clinical, pathologic, and biologic parameters was studied in 74 IPMNs, and the expression profile of CDX2 (a specific marker and one of the key determinants of intestinal "programming," and a tumor suppressor) was determined immunohistochemically in addition to MUC1 (a marker of an "aggressive" phenotype in pancreatic neoplasia) and MUC2 ("intestinal type mucin," a marker of the "indolent" phenotype, and a tumor suppressor). The patterns of papillae identified and their association with these parameters were as follows: 1) The intestinal-type (Yonezawa's dark-cell type), similar to villous adenomas, was seen in 26 of 74 (35%) cases. The majority harbored carcinoma in situ (85%) or borderline atypia (15%). They tended to be large (mean, 5.5 cm). Most expressed CDX2 (95%) and MUC2 (92%) but not MUC1 (8%). This type was more commonly associated with colloid-type invasion (14 of 16 invasive carcinomas were of colloid type). 2) The pancreatobiliary type, characterized by arborizing papillae lined by cuboidal cells resembling papillary neoplasms of the biliary tract, was present in 22% of the cases. These were mostly graded as carcinoma in situ (94%); they rarely expressed CDX2 (6%) or MUC2 (19%) but often showed MUC1 labeling (44%). This pattern was more commonly associated with the tubular type of invasive carcinoma and had a slight tendency for a more aggressive clinical course. 3) The null type was characterized by abundant apical mucin and basally located nuclei, similar to the gastric foveolar epithelium. Thirty-one percent of IPMNs had this type of papillae, but this pattern was also present in the background of other IPMNs and in the cystic components of most cases as well. Most pure null-type IPMNs were devoid of complexity and consequently classified as adenoma (48%). They tended to be small (mean, 2.6 cm), were often negative for CDX2, MUC1, and MUC2, and were rarely associated with invasive carcinoma. 4) Some IPMNs (12%) exhibited features that were difficult to classify, and 2 cases had a mixture of pancreatobiliary and intestinal types of papillae. In conclusion, IPMNs include pathologically and biologically distinct epithelial patterns. CDX2 and MUC2 expression is relatively specific for the intestinal type papillae, confirming that these IPMNs indeed exhibit intestinal differentiation. Their close association with colloid carcinoma, which also shows consistent MUC2 and CDX2 expression, supports the existence of an intestinal pathway of carcinogenesis.
This "metaplastic" pathway may reflect different genetic events in the development of these IPMNs, and the presence of intestinal differentiation may potentially be used in prognostication and stratification of patients into appropriate treatment categories.
Pathologic Features of Mucin-producing Bile Duct Tumors: Two Histopathologic Categories as Counterparts of Pancreatic Intraductal Papillary-mucinous Neoplasms
Shibahara, Hiroaki MD*†; Tamada, Shugo MD*; Goto, Masamichi MD*; Oda, Koji MD†; Nagino, Masato MD†; Nagasaka, Tetsuro MD‡; Batra, Surinder K PHD§; Hollingsworth, Michael A PHD§; Imai, Kohzoh MD¶; Nimura, Yuji MD†; Yonezawa, Suguru MD*
From the *Department of Human Pathology, Field of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan; †Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan; ‡Division of Pathology, Clinical Laboratory, Nagoya University Hospital, Nagoya, Japan; §Departments of Biochemistry and Molecular Biology, Eppley Institute for Reseach in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE; and ¶Department of Internal Medicine, Sapporo Medical College, Sapporo, Japan
The American Journal of Surgical Pathology : Volume 28(3) March 2004 pp 327-338 Abstract quote
Tumors with clinically recognizable mucin production arising from bile duct have been reported as mucus producing bile duct carcinoma,25 mucin-producing cholangiocarcinoma,31,32 mucin-producing cholangiocellular carcinoma,10 mucin-producing biliary papillomatosis,28 mucin ball-producing extrahepatic bile duct carcinoma,17 intraductal mucosal-spreading mucin-producing peripheral cholangiocarcinoma,22 mucin-hypersecreting intrahepatic biliary neoplasms,21 mucin-hypersecreting bile duct tumor,19 and mucin-hypersecreting papillary cholangiocarcinoma20 as clinical entities. Sakamoto et al reported a characteristic feature of mucin-producing cholangiocarcinoma, which showed an apparent mucin production radiographically with cystic or ductectatic tumor growth pattern.31,32 The clinical entities of these mucin-producing tumors in the bile duct can be named as mucin-producing bile duct tumors (MPBTs). However, MPBTs have not been studied yet for their pathologic features and classification in details.
On the other hand, recently, an entity of intraductal papillary-mucinous neoplasms (IPMN) was created in mucin-producing cystic tumors of the pancreas.23,36 IPMN of the pancreas has been given a variety of names such as intraductal carcinoma, intraductal papillary cystic tumor of the pancreas, intraductal papillary neoplasm of the pancreas, and other names as we discussed previously,29 since the first report by Ohhashi et al who called it mucous secreting pancreatic cancer.27 We first reported that IPMN showed MUC1-negative and MUC2-positive expression in contrast to invasive ductal carcinoma which showed MUC1 positive and MUC2-negative expression.29
Recently, we proposed a new classification of pancreatic IPMN by mucin expression profiles: IPMN with MUC2-positive expression composed of dark columnar cells and IPMN with MUC2-negative expression composed of clear columnar cells.26 Adsay et al2 also reported that the papillae of IPMNs could be divided into two types: intestinal type and pancreaticobiliary type morphologically. The dark cells type in our classification is the same as the intestinal type in Adsay's classification. The highly atypical areas of the clear cell type in our classification is very similar to the pancreaticobiliary type in Adsay's classification.
The clinical findings of MPBTs have a lot of similarities to those of pancreatic IPMNs. Thus, we had a hypothesis that MPBTs could be classified as counterparts of pancreatic IPMNs.
In the present study, we report that MPBTs can be classified into two distinct categories by the histopathologic findings, and demonstrated that there are significant differences in the clinicopathological findings including macroscopic findings, morphometric data, mucin expression profiles, and cell proliferative activity (Ki-67 labeling) between the two groups. For the study of mucin expression, we examined not only MUC1 and MUC2, which have been investigated in the series of our previous studies,14,26,29,39,41 but also MUC4, MUC5AC, and MUC6, since they were expressed in the pancreatic neoplastic or preneoplastic lesions.4,18,37 According to those data, we propose two histopathologic categories in the MPBTs.
Intraductal Papillary-Mucinous Neoplasm of the Pancreas The Findings and Limitations of Cytologic Samples Obtained by Endoscopic Ultrasound–Guided Fine-Needle Aspiration
Edward B. Stelow, MD, Michael W. Stanley, MD, Ricardo H. Bardales, MD, Shawn Mallery, MD, Rebecca Lai, MD, Bradley M. Linzie, MD, and Stefan E. Pambuccian, MD
Am J Clin Pathol 2003;120:398-404 Abstract quote
All clinically and ultrasonographically suspected examples of intraductal papillary-mucinous neoplasm (IPMN) aspirated during a 17-month period were reviewed and analyzed for follow-up.
We identified 18 cases of suspected IPMN in patients 52 to 87 years old. All patients had dilated pancreatic ducts, with 3 showing sonographically apparent intraductal papillary lesions; 5 had adjacent cystic or solid pancreatic masses. Cytologic preparations showed thick, glistening, viscid, abnormal mucus in all cases. Aspirates from 13 lesions (72%) were acellular or sparsely cellular, but entrapped single or loosely cohesive neoplastic cells were identified in 16 cases (89%). Goblet cell morphologic features were common (6/18 [33%]), but papillary clusters and dysplastic changes were infrequent (3 [17%] each). In keeping with current therapeutic thinking, confirmatory histologic follow-up was available for only 4 patients (22%), as most people with lesions clinically, sonographically, and cytologically consistent with IPMN are elderly and often have comorbid conditions.
Although endoscopic ultrasound–guided fine-needle aspiration has important limitations, gross and cytologic findings can aid in confirming the suspected diagnosis, and integration of complete clinical, sonographic, and cytologic information may be the best way to reach the most accurate diagnosis possible.
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
B. Terris; P. Ponsot; F. Paye; P. Hammel; A. Sauvanet; G. Molas; P. Bernades; J. Belghiti; P. Ruszniewski; J. F. Fléjou
From the Departments of Pathologic Anatomy (B.T., G.M., J.F.F.), Gastroenterology (P.P., P.H., P.B., P.R.), and Digestive Surgery (F.P., A.S., J.B.), Hôpital Beaujon, Clichy, France.
Am J Surg Pathol 2000;24:1372-1377 Abstract quote
Intraductal papillary mucinous tumors (IPMTs) of the pancreas are rare tumors characterized by a malignant potential. Because of the progress of imaging procedures, smaller cystic pancreatic lesions are now detected and some of them correspond to IPMTs that involve ectatic pancreatic branch ducts but spare the main pancreatic duct.
To investigate differences in morphology and clinical behavior of branch and main duct types of IPMT, a surgical series of 43 cases was studied.
All pathologic specimens of IPMT, surgically resected in our institution between October 1987 and July 1998, were analyzed. In all cases, the entire pancreatic specimen was systematically examined. IPMT of the branch type was found in 13 (30%) patients, whereas IPMT of main pancreatic duct type that involved the main pancreatic duct and branch ducts was observed in 30 (70%) patients. Patients with IPMT of the branch type were younger (median age, 55 yrs vs 64 yrs), and all but one of the lesions were located in the head and neck of the pancreas (vs 17 of 30 patients with the main duct type). The size of the cysts ranged from 4 to 55 mm, and the major duct showed a mild dilation in most cases.
In contrast to the main pancreatic duct type, which showed invasive carcinoma and in situ carcinoma in 11 (37%) of 30 patients and 6 (20%) of 30 patients, respectively, IPMT of the branch type showed significantly less aggressive histologic lesions with five (39%) patients with simple hyperplasia, six (46%) patients with atypical hyperplasia, and two (15%) patients with in situ carcinoma. No invasive carcinoma was observed in this group. IPMT of the branch type occurs in younger patients and is associated with less aggressive histologic features than is the main pancreatic duct type.
Our findings raise the difficult issue of clinical management of IPMT of the branch type as a distinctive group.
The mucin profile of noninvasive and invasive mucinous cystic neoplasms of the pancreas.
Luttges J, Feyerabend B, Buchelt T, Pacena M, Kloppel G.
Department of Pathology, University of Kiel, Kiel, Germany.
Am J Surg Pathol 2002 Apr;26(4):466-71 Abstract quote
Recently, it was shown that ductal adenocarcinomas and intraductal papillary-mucinous neoplasms of the pancreas differ in their expression of the mucin markers MUC1 and MUC2 while both tumors express MUC5AC. It is not known whether mucinous cystic neoplasms of the pancreas have their own mucin profile.
To clarify this issue, 22 mucinous cystic neoplasms were examined immunohistologically for their expression of MUC1, MUC2, MUC5AC, and MUC6 and also for the protein products of the tumor suppressor genes p53 and DPC4 and the mismatch repair genes. Noninvasive mucinous cystic neoplasms, regardless of the degree of cellular atypia, were all positive for MUC5AC and negative for MUC1, with the exception of the cyst-lining epithelium of a single case with eosinophilic cytology (case no. 16). Only in cases with an invasive component was MUC1 expression observed. MUC2 expression was restricted to goblet cells scattered within the epithelium of the mucinous cystic neoplasms and was often accompanied by endocrine cells, a further indication of intestinal differentiation. DPC4 expression was maintained in all tumors, except for three invasive carcinomas. p53 nuclear reactivity was found in one borderline tumor and four invasive mucinous cystic carcinomas.
The results suggest that the epithelium of noninvasive mucinous cystic neoplasms does not differ in its expression of MUC5AC from ductal adenocarcinomas, intraductal papillary-mucinous neoplasms, and metaplastic pancreatic duct epithelium. The fact that noninvasive mucinous cystic neoplasms lack MUC1 expression (except for an eosinophilic variant) but express it when they become invasive might be used as a marker indicating the step of progression from noninvasiveness to invasiveness.
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES MUCINOUS NONNEOPLASTIC CYST
Mucinous Nonneoplastic Cyst of the Pancreas: A Novel Nonneoplastic Cystic Change?
Markus Kosmahl, M.D., Naoto Egawa, M.D., Sören Schröder, M.D., Fatima Carneiro, M.D., Jutta Lüttges, M.D. and Günter Klöppel, M.D.
Department of Pathology, University of Kiel (MK, JL, GK), Kiel, Germany; Department of Internal Medicine, Tokyo Metropolitan Komagome Hospital (NE), Tokyo, Japan; Institute of Pathology (SS), Hamburg, Germany; and Institute of Pathology, University of Porto (FC), Porto, Portugal
Mod Pathol 2002;15:154-158 Abstract quote
Cystic lesions and neoplasms of the pancreas are uncommon, but they are of special interest because they can usually be cured by resection. During the last decade, the spectrum of these tumors has increased considerably.
We present a series of five cystic lesions of the pancreas that differ from all categories described so far. The patients affected by these tumors were three men and two women (mean age, 57 y). Four lesions were unifocal and involved the head of the pancreas; one was multifocal and involved the pancreatic head and tail.
Grossly, these tumors presented as unilocular or multilocular thin-walled cysts that contained turbid fluid, or, in two cases, blood, and lacked any communication with the duct system.
Microscopically, the cysts were lined by cuboidal to columnar mucin-producing cells, supported by a small band of dense fibrous stroma. Immunocytochemically, the epithelial cells were positive for cytokeratins 7, 8, 18, 19, and 20 (except one), and Ca 19-9 but were negative for trypsin, CEA, synaptophysin, chromogranin A, calretinin, and -inhibin. In four of the five lesions, the epithelial cells expressed MUC5AC, and in one of the five, MUC1. MUC2 and MUC6 were not expressed in any of the lesions. The stromal cells lacked the nuclear progesterone positivity that is typical of mucinous cystic neoplasms. During a mean follow-up period of 2 years, there were no recurrences or cases of malignant transformation after resection.
The results suggest that these cystic lesions are distinct from mucinous cystic neoplasms, the most important entity in the differential diagnosis. Because they may represent a nonneoplastic cystic change of the pancreas, we propose the descriptive term mucinous nonneoplastic cyst for these tumors of unknown pathogenesis.
PROGNOSIS AND TREATMENT CHARACTERIZATION PROGNOSTIC FACTORS GENERAL Tumors confined to the secondary ducts show less aggressive pathologic features compared to those involving the main duct Am J Surg Pathol 2000;24:1372-1377
PANCREATIC INTRAEPITHELIAL NEOPLASIA Pancreatic Intraepithelial Neoplasia in Association With Intraductal Papillary Mucinous Neoplasms of the Pancreas: Implications for Disease Progression and Recurrence.
Biankin AV, Kench JG, Biankin SA, Lee CS, Morey AL, Dijkman FP, Coleman MJ, Sutherland RL, Henshall SM.
*Cancer Research Program, Garvan Institute of Medical Research, St. Vincent's Hospital, Darlinghurst; daggerInstitute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead; double daggerDivision of Surgery and section signDepartment of Anatomical Pathology, St. Vincent's Hospital Campus, Darlinghurst; and the paragraph signDepartment of Anatomical Pathology, Royal Prince Alfred Hospital, and Department of Pathology, University of Sydney, Camperdown, NSW Australia.
Am J Surg Pathol. 2004 Sep;28(9):1184-1192. Abstract quote
The development of pancreatic cancer (PC) several years after curative resection for noninvasive intraductal papillary mucinous neoplasm (IPMN) and the presence of PC distant from IPMN suggest that PC may develop independently of the IPMN.
Here, we identified pancreatic intraepithelial neoplasia (PanIN) lesions, the putative precursors of PC, in the ducts of pancreata resected for IPMN and assessed the frequency of molecular aberrations common to PanIN and PC, within these lesions. The protein expression of p53, p21, cyclin D1, p16 and DPC4/Smad4 were examined by immunohistochemistry in 267 PanIN lesions from a cohort of 23 patients with IPMN. Overexpression of p21 was present in PanIN-1A and -1B lesions and increased in frequency in PanIN-2 and PanIN-3. Overexpression of p53 and cyclin D1, and loss of p16 expression were detected in PanIN-2 and PanIN-3 lesions. Loss of DPC4/Smad4 expression occurred only in the PanIN-3 lesions. PanIN lesions that were more dysplastic than the coincident IPMN were identified in 5 of 12 patients, and 2 of these contained a greater number of aberrations in protein expression than the IPMN.
PanIN lesions seen in association with IPMN demonstrate molecular and histologic changes identical to PanIN lesions found in association with PC and, in some cases, are more advanced than the associated IPMN.
These data suggest that PanIN lesions found in the ducts of a pancreas with IPMN may be relevant to the development of PC either coincident with IPMN or in the remnant pancreas after curative resection of IPMN.
Treatment Surgical resection
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Basic Principles of Disease
Learn the basic disease classifications of cancers, infections, and inflammation
Commonly Used Terms
This is a glossary of terms often found in a pathology report.
Learn how a pathologist makes a diagnosis using a microscope
Surgical Pathology Report
Examine an actual biopsy report to understand what each section means
Understand the tools the pathologist utilizes to aid in the diagnosis
How Accurate is My Report?
Pathologists actively oversee every area of the laboratory to ensure your report is accurate
Recent teaching cases and lectures presented in conferences
Pathologists Who Make A Difference
Search for a Physician Specialist
Last Updated December 4, 2006
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