SCImago Journal & Country Rank
This journal is a member of, and subscribes to the principles of, the Committee on Publication Ethics (COPE)
[ Abstract ] [ PDF ] [ E-Mail to Author ] [ E-Mail to Editor ]
DOI: 10.5146/tjpath.2017.01386
Intraductal Neoplasms of the Pancreas: An Update
Gökçe AŢKAN1, Pelin BAĐCI2, Bahar MEMÝŢ3, Olca BAŢTÜRK1
1Department of Pathology, 1Memorial Sloan Kettering Cancer Center, NEW YORK, NY, USA
2Department of Pathology, Marmara University School of Medicine, ÝSTANBUL, TURKEY
3Department of Pathology, Emory University School of Medicine, ATLANTA, GA, USA
With improvements in imaging to detect silent pancreatic lesions and increases in the number of centers now performing pancreatic surgery, more surgeries have been performed for indications other than invasive carcinoma. This has enormously added to our knowledge of the intraductal neoplasms of the pancreas. In addition, our understanding of the genetics of these lesions has expanded with the introduction of routine molecular genetic analyses. In this review, we provide an update into the most common intraductal neoplasms, namely intraductal papillary mucinous neoplasm and intraductal tubulopapillary neoplasm. We first focus on their clinicopathologic and molecular features of relevance to the practicing pathologist and then discuss their differential diagnoses.
Intraductal neoplasms of the pancreas have become increasingly more common as recent developments in imaging techniques have led to increased detection of clinically silent tumors, many of which are detected incidentally during work-up for other diseases1-5. Therefore, within the last decade, their histomorphologic, and especially molecular features have been studied in detail.

This article reviews the currently available information on the clinicopathological/molecular features, differential diagnosis, and biological behavior of intraductal neoplasms of the pancreas namely; intraductal papillary mucinous neoplasm (IPMN) (including intraductal oncocytic neoplasm) as well as intraductal tubulopapillary neoplasm (ITPN).

Intraductal Papillary Mucinous Neoplasms
The term intraductal papillary mucinous neoplasm (IPMN) was first described by Klöppel et al. in 1994 as grossly visible, mucin-producing, predominantly papillary, epithelial neoplasm arising from the main pancreatic duct or branch ducts, with varying degrees of duct dilatation6. As per the international guidelines7, which was also endorsed by the 2010 WHO Classification System8, greater than 1 cm diameter by radiologic/gross examination is required to distinguish IPMNs from large pancreatic intraepithelial neoplasms (PanINs).

Clinical Features
IPMNs occur slightly more frequently in men than in women with a male to female ratio of 3 to 2. The mean age at the time of diagnosis ranges between 62 and 67 years8-12. Most patients diagnosed with IPMNs are asymptomatic13,14 and when associated with symptoms, it can mimic chronic pancreatitis11,15-18. The etiology of IPMNs is not so clear, however, a previous history of diabetes, especially with insulin use, smoking, and a family history of pancreatic ductal adenocarcinoma are regarded as risk factors10,19. Interestingly, the rate of extrapancreatic malignant tumors (colonic, gastric, bile duct, breast and prostate carcinoma) is reported to be higher in patients with IPMN than in those with pancreatic ductal adenocarcinoma (PDAC)11,12,20-24.

Diagnostic Imaging Techniques
Typical signs on computed tomography (CT) are a diffusely distended pancreatic duct with filling defects and cystic lesions with connection to the pancreatic duct system12,25-27. However, magnetic resonance imaging (MRI) seems superior to CT in terms of characterizing the lesion28. Endoscopic retrograde cholangiopancreatography (ERCP) also usually reveals a dilated pancreatic duct with filling defects12,29,30.

IPMNs are currently classified based on their radiologic (and also macroscopic) appearance, cell type, and grade of dysplasia31. Most IPMNs are localized, but they can diffusely involve the entire gland.

Radiologic (and Also Macroscopic) Classification
All IPMNs connect to larger pancreatic duct(s); however, not all IPMNs arise in the main pancreatic duct. Therefore, they are classified as branch duct-type and main duct-type12.

Branch duct-type IPMN (BD-IPMN) is one of the most common “incidentalomas” due to the recent widespread use of imaging modalities32. It arises in younger patients and is more likely to involve the uncinate process12,16,33. BD-IPMN manifests either as a cyst or a cluster of cysts without dilation of the main pancreatic duct. The cysts are usually not larger than 1-2 cm with smooth and glistening cyst lining (Figure 1A)10,15,26,31. Many BD-IPMNs lack nodular formation and commonly contain inspissated mucinous material34.

Click Here to Zoom
Figure 1: A) Branch duct-type IPMN with smooth and glistening cyst lining. B) Main duct-type IPMN involving the main pancreatic duct with friable papillary projections.

Main duct-type IPMN (MD-IPMN) is usually located in the head of the pancreas. It is characterized by a markedly dilated (average diameter, 4.1 cm), tortuous main pancreatic duct that may be filled with mucin or solid but friable mass12,31,35,36 (Figure 1B).

Microscopic Classification
IPMNs differ in the cell type that composes the papillary epithelium, allowing their classification into gastric, intestinal, pancreatobiliary, and oncocytic subtypes37 based on the histomorphologic features and the immunohistochemical characteristics. Although the oncocytic-type was originally described as a separate entity (intraductal oncocytic papillary neoplasm) (See below)38, the current (2010) WHO puts this neoplasm under the general category of IPMNs, due to overlap between the clinicopathologic features of IOPNs and other subtypes of IPMNs39.

In gastric-type, the papillae are lined by simple epithelium that resembles gastric foveolar epithelium. BD-IPMNs often show gastric foveolar differentiation12,40-42 (Figure 2A). The tumor cells have low proliferative activity, and rarely exhibit malignant transformation. Intestinal-type IPMNs have papillae lined by pseudostratified columnar cells with cigar-shaped nuclei and apical goblet like mucin resembling colonic villous adenomas (Figure 2B). Most main duct IPMNs are of intestinal type12,41,43,44. Pancreatobiliary-type IPMNs usually involve the main pancreatic duct and are characterized by more complex, interconnecting papillae lined by atypical cuboidal cells that have little intracellular mucin, enlarged round nuclei, and prominent eccentric nucleolus (Figure 2C)10,41. This type epithelium is often seen in an intimate association with less atypical gastric type epithelium, and for this reason, some observers believe that it represents the high-grade dysplastic version of gastric type rather than a specific type of its own42. Of note, both intestinaland pancreatobiliary-types of IPMN may have areas lined by gastric-type epithelium; however, it is extremely uncommon to find both intestinal- and pancreatobiliarytype papillae within the same IPMN.

Click Here to Zoom
Figure 2: A) IPMN of gastric type. The papillae are lined by simple epithelium that resembles gastric foveolar epithelium (H&E; x100). B) IPMN of intestinal type. The papillae lined by pseudostratified columnar cells with cigar-shaped nuclei, apical goblet like mucin resembling colonic villous adenomas (H&E; x200). C) IPMN of pancreatobiliary type with more complex, interconnecting papillae lined by atypical cuboidal cells that have little cytoplasmic mucin and enlarged round nuclei (H&E; x100).

Microscopically, IPMNs also exhibit various degrees of dysplasia. Based on the degree of architectural and cytological atypia, the current (2010) WHO classification system subclassifies these neoplasms as IPMN with lowgrade, intermediate-grade, and high-grade dysplasia8. In this 3-tiered grading system, low-grade dysplasia is defined as neoplastic cells that form a single layer of well oriented, have small and uniform nuclei, lack of nucleoli and mitoses (Figure 3A). Intermediate-grade dysplasia is defined as tumor cells with nuclear stratification, high nuclear to cytoplasmic ratio, loss of polarity, enlarged nuclei and pleomorphism, but papillae still have fibrovascular cores. High-grade dysplasia has more complex architecture with nuclear pleomorphism, increased mitotic figures, atypia, and cribriforming additional to these features (Figure 3B)43. In a given case, the final grade of IPMN is based on the highest grade, no matter how small it is45.

Click Here to Zoom
Figure 3: A) IPMN with low grade dysplasia. The neoplastic cells form a single layer of well oriented, small and uniform nuclei and lack of frequent mitoses (H&E; x100). B) IPMN with high grade dysplasia has more complex architecture with cribriform pattern, nuclear pleomorphism, and increased mitotic figures (H&E; x100)

However, lately it has been shown that IPMNs with lowgrade or intermediate-grade dysplasia have low progression rate compared to ones with high-grade dysplasia45-51. Also, the goal of clinical management is to observe lowgrade and intermediate-grade precursor lesions and to resect high-grade precursor lesions in order to decrease the risk of invasive cancer. Therefore, at a recent international consensus meeting held in Baltimore to revise the grading system and reporting of precursor lesions in pancreas, a 2-tiered classification scheme was felt to be more in line with practical consequences: low-grade and intermediate-grade dysplasia likely has no immediate clinical consequences, whereas high-grade dysplasia usually requires clinical attention. According to this new 2-tiered grading system, intermediate-grade is now categorized as low-grade, and high-grade is used only for most advanced dysplastic lesions52.

Invasive Carcinoma Associated with IPMNs
The most important determinant of outcome in the management of patients with IPMNs is whether an associated invasive carcinoma is present or not1,11,13,16,53-57. Approximately 40-60% of resected IPMNs have had an associated invasive carcinoma, either of the colloid-type or ductal-type11,58. Various authors have reported that MD-IPMNs have a higher potential of having invasive disease, compared to BD-IPMNs13,43,59,60.

Gastric-type IPMNs rarely have an invasive carcinoma61; however, when a carcinoma develops, it is typically ductal-type and has aggressive behavior62. Intestinaltype IPMNs tend to be large, complex, and prone to have invasive carcinoma, and when they are associated with an invasive carcinoma, it is typically of colloid type (Figure 4A) characterized by nodules of stromal mucin that contain relatively scant clusters of carcinoma cells10,41,63-65. This form of invasive carcinoma has to be distinguished from benign spillage of mucin into the stroma called pseudoinvasion. In contrast to invasive carcinoma, benign spillage of mucin does not contain neoplastic cells and is usually associated with an inflammatory response at the periphery. In some cases, it can be very difficult to distinguish pseudoinvasion from true invasive colloid carcinoma. For such cases, the diagnosis of “indeterminate for invasion” may have to be rendered45. Invasive carcinoma associated with pancreatobiliary-type IPMNs is usually tubular type, characterized by infiltrating small to medium tubular units separated by desmoplastic stroma with all the morphologic features of PDAC (Figure 4B) (10,16,24,54,66-68).

Click Here to Zoom
Figure 4: A) Invasive carcinoma of colloid type characterized by abundant mucin with floating epithelial cells and (H&E; x40), B) Tubular type, characterized by infiltrating small to medium tubular units separated by desmoplastic stroma (H&E; x40).

First of all, every attempt should be made to measure the diameter of the main pancreatic duct. Then, for unifocal but multilocular lesions, overall size of locules; for multifocal lesions, the range of the foci should be documented45. Some IPMNs have very thin-walled cysts that can rupture during gross examination. Therefore, for such IPMNs, the true size needs to be determined by close correlation with radiologic findings. Documenting the gross size of any solid or gelatinous component is also required as invasive carcinomas are often solid or gelatinous and this component often corresponds to ‘‘mural nodule'' detected by imaging preoperatively69. More importantly, it should be kept in mind that an invasive carcinoma arising in association with an IPMN can only be definitely excluded by thorough evaluation of not only the entire lesion but also the uninvolved pancreas as well45,70,71.

Frozen Section
Evaluation of margins by frozen section may be indicated in some cases of IPMNs. The presence of low-grade dysplasia at the resection margin does not need further resection, while involvement by high-grade dysplasia or invasive carcinoma is important as it usually means more aggressive surgery72-74. Although intestinal- and oncocytic-type IPMNs are easy to distinguish from PanIN, gastric- or pancreatobiliary-type IPMNs are virtually indistinguishable from PanIN. For this reason, it is recommended that lowgrade intraductal mucinous lesions in pancreatic margins be reported as ‘‘No high-grade dysplasia or invasive carcinoma is identified; low-grade mucinous epithelium is present (differential diagnoses include low-grade PanIN or low-grade IPMN).'' Similarly, high-grade intraductal mucinous lesions should be reported as ‘‘High-grade mucinous epithelium is present (differential diagnoses include high-grade PanIN or high-grade IPMN).

Evaluation of denuded duct epithelium is also problematic on frozen section. For such cases, deeper sections are suggested to find whether any adherent epithelium is present. If deeper sections are also similar, the case may be reported as “denuded epithelium, cannot assess for neoplastic process”45,53

In reporting IPMNs, if there is no associated invasive carcinoma, it is recommended that the diagnosis should start with the name of the precursor lesions, followed by the grade, morphologic subtype and size (i.e. IPMN with low-grade dysplasia, intestinal type, 2 cm). If there is any associated invasive carcinoma, the pathology report should separately document the characteristics of both precursor and invasive lesions. The term “IPMN with invasive carcinoma” or “invasive carcinoma with an associated IPMN” may be used. The terms “malignant IPMN” or “minimally invasive IPMN” should not be used as these terms are non-specific and potentially misleading. If the invasive carcinoma is unifocal, the largest diameter of the invasive focus should be measured. If it is multifocal, it is recommended that both the diameter of the largest invasive focus and the overall estimated size of all foci in aggregate be provided in the comment of the report45,52.

Immunohistochemical Features
All IPMNs express cytokeratin (AE1/AE3, CAM5.2, CK7, 8,18,19), and except for the intestinal type, all are negative for CK2075,76. Different patterns of MUC expression are seen in IPMNs and correlate with morphologic differentiation (Table I)24,41,44. MUC5AC is detected in most IPMNs, regardless of the type. The gastric-type just labels with MUC5AC, while the pancreatobiliarytype IPMNs also label with MUC1 and is negative for MUC212,41,42,44,77-80. Intestinal-type IPMNs express the intestinal lineage markers such as MUC2, and CDX2 that are not expressed in the normal pancreas or other IPMN types11,12,24,41,44,78. When pancreatobiliary- and intestinal-type IPMNs are associated with invasive carcinoma, the invasive component also expresses the same markers as noninvasive component does. It should be noted that scattered goblet cells can be seen in non-intestinal types of IPMNs rendering the tumor focal positivity for MUC2, CDX2, and CK2034. Immuno labeling can also reveal scattered chromogranin positive cells at the base of the neoplastic epithelium81.

Click Here to Zoom
Table I: Immunohistochemical profile of IPMNs (including IOPNs)

Molecular Features
Whole-exome sequencing of IPMNs revealed about 26 mutations per IPMN82,83. The most common mutations seen in IPMNs are KRAS, GNAS and RNF43 genes. KRAS mutation is identified in approximately 80% of IPMNs, while GNAS mutation is seen in approximately 60%, and RNF43 in approximately 75%. KRAS mutation is most commonly seen in gastric-, and secondly in pancreatobiliary-type 84-86. GNAS mutation is commonly identified in intestinaltype of IPMNs and if the neoplasm is associated with invasive carcinoma this mutation is seen in both invasive and noninvasive component87. Although KRAS mutation is common in both IPMN and PDAC, GNAS mutation is not identified in PDAC and the frequency of RNF43 mutation in PDAC is not known84. Less common alterations seen in IPMNs involves PIK3CA, AKT1, CDKN2a/p16, SMAD4, TP53, BRAF, CTNNB1/β-catenin, IDH1, STK11, PTEN, ATM, CDH1, and FGFR3 genes54,82,88,89.

Nowadays, IPMNs represent the 10-30% of all resectable pancreatic tumors and the treatment of MD-IPMNs has not changed much over the past three decades. Most patients with MD-IPMNs who fit for surgery, undergo tumor resection. BD-IPMNs measuring >3 cm in diameter, even without mural nodules is also recommended for resection according to Sendai guidelines although Fukuoka guidelines include more conservative criteria for resection7

Malignant progression is more closely associated with older age (>70 years) and female gender90. Not surprisingly, invasive carcinoma stage is the most significant predictor of survival followed by the invasive carcinoma histological subtype55,91-93 and half of those with an associated invasive carcinoma die of the disease15,66 94-98. In a relatively recent study comparing stage matched IPMNassociated colloid carcinoma, IPMN-associated tubular carcinoma, and conventional pancreatic adenocarcinoma, the colloid carcinoma was found to have a more favorable survival outcome than the tubular carcinoma (The 5-year estimated survival rates for colloid carcinoma and tubular carcinoma were 87% and, 55%, respectively (p=0.01)). Also, patients with invasive tubular IPMN had no statistically significant difference in survival as matched patients with conventional ductal pancreatic carcinoma (The 3-year estimated survival rates were 61% and, 21%, respectively (p=0.87))99.

Series from large centers also allow the conclusion that non-invasive IPMNs recur in up to 13% after resection. The recurrence rate is higher (28-60%) for IPMNs with invasive component100,101. Invasive carcinoma may also develop in the remnants after partial pancreatectomy for IPMNs. This is likely related to the multicentricity of IPMNs102 that is why careful examination of the remaining pancreas by the surgeon is as important as extensive, if not total, sampling of the resected pancreas by the pathologists.

Differential Diagnosis
The most common problem is to distinguish IPMNs from MCNs. IPMNs are defined as mucin producing tumors arising from the main or branch pancreatic ducts8, while MCNs are characterized by de-novo mucin-producing tumors with ovarian-type type stroma (Figure 5) (i.e. MCNs don't have any communication with pancreatic ductal system)103. They have different clinical, gross and microscopic findings (Table II). For example, MCNs generally involve the tail of the pancreas in perimenopausal women, while IPMNs are seen in older men and involve the head of the pancreas. Grossly, the most important finding that favors MCN over IPMN is the lack of communication with pancreatic duct system11,14,77,103-105. Microscopically, both neoplasms are lined by mucinous epithelium, but MCNs have distinct ovarian-type stroma, which is positive for estrogen, and progesterone receptors as well as smooth muscle actin (SMA), inhibin and calponin12,103-113. The cyst lining of both lesions might be papillary or flat, and sometimes be almost entirely denuded, which makes rendering the diagnosis difficult. In this situation, additional sectioning is recommended to identify the epithelial lining104,114,115. The epithelial cells of MCNs label with CK7, 8, 18, 19, CAM 5.2, as well as MUC5AC. MUC6 expression is also reported114,116. MUC1 expression can be identified in the invasive component. Unlike IPMNs, MCNs do not show intestinal differentiation, so they generally do not express CDX2 and CK20115,117.

Click Here to Zoom
Figure 5: Mucinous cystic neoplasm characterized by mucin producing columnar epithelium surrounded by ovarian type stroma (H&E; x100).

Click Here to Zoom
Table II: The comparison of IPMNs and MCNs

The other problematic issue is to distinguish IPMNs from PanIN. If the IPMN is gastric- or pancreatobiliary-type, it may be impossible to distinguish IPMNs extending to smaller ducts from independent, incidental PanIN43,54. If the tumor is grossly and microscopically less than 0.5 cm, PanIN is favored as IPMN is, by definition, larger than 1 cm in size10,43,73. Also, the papillae of IPMNs are taller and more complex than those of PanIN, and the tumors cells may express MUC2 in IPMNs, while they are negative in PanIN43. Some PDACs with large invasive glands, a.k.a large duct-type PDAC, may also resemble IPMNs, but the irregular contours and flat epithelial lining of the glands and presence of necrotic debris within their lumen favor PDAC118,119.

Of note, larger than 1 cm pancreatic cysts lined by nonpapillary mucinous epithelium without ovarian-type stroma (i.e. mucinous cysts that do not have characteristic features of intraductal papillary mucinous neoplasms or mucinous cystic neoplasms) may pose diagnostic challenges120. The term “simple mucinous cyst” was recently proposed for these lesions52. Since KRAS mutations can be detected in these typically bland cysts, and in rare instances, focal high-grade dysplasia may be present, these cysts should be viewed as neoplastic and treated similarly to other neoplastic mucinous pancreatic cysts120.

Intraductal Oncocytic Papillary Neoplasm
The term intraductal oncocytic papillary neoplasm (IOPN) was first described by Adsay et al in 1996, as a grossly cystic epithelial neoplasm composed of oxyphilic cells that grow within the pancreatic ducts (38). However, the current (2010) WHO classification puts this neoplasm under the general IPMN category39.

Clinical Features
IOPN is usually seen during the seventh decade of life58,121,122 with equal male to female ratio58,121,122. Patients are either asymptomatic or have non-specific symptoms, similar to IPMNs.

Pathologic Features
Macroscopically, IOPNs usually involve the head of the pancreas and present as cystic lesions with soft friable papillary structures involving the main pancreatic duct. The mean tumor size is 6 cm38,122-124.

Microscopically, they are characterized with papillary projections lined by stratified cuboidal or columnar cells. The cells have distinctive oncocytic cytoplasm and nuclei with single, prominent, nucleoli58,121 (Figure 6A,B). Intracellular lumens are also seen38,121-123,125,126. Despite highly complex morphology and atypical cytology, most examples are devoid of invasive carcinoma, and, if present, invasion is usually limited in amount121,124. The invasive component can be oncocytic, mucinous (colloid-like), sarcomatoid/undifferentiated, or even neuroendocrine type38,123,125,127,128. Similar to IPMNs, features of both invasive and non-invasive components should be documented separately121.

Click Here to Zoom
Figure 6: A) The characteristic appearance of IOPN with complex papillae and distinctive granular cytoplasm (H&E; x100) and B) Nuclei with single prominent, eccentric nucleoli. Intracellular lumens are also present (H&E; x200).

Immunohistochemical Features
The tumor cells usually express MUC1 and MUC661,77,121,129,130, while are negative for MUC2, and CDX2. More importantly, neuroendocrine and acinar differentiation markers are both negative.

Molecular Features
Recent molecular studies showed that IOPNs have distinct molecular features compared to IPMNs as they do not reveal KRAS, GNAS, or RNF43 mutations, which are commonly seen in IPMNs131.

Prognosis and Treatment
The long-term follow-up of patients with IOPN reveals that the recurrence rate is high (up to 40%)132. However, survival outcomes are still favorable despite the second resection. Also, even though these intraductal neoplasms may develop invasive carcinoma, usually in the form of invasive oncocytic or mucinous (colloid-like) carcinoma, they still have more indolent course than conventional PDAC16,31,38,40,71,121,124,126,133.

Intraductal Tubulopapillary Neoplasm
First reported by Tajiri et al in 2004134, intraductal tubulopapillary neoplasm (ITPN) was classified by WHO as a distinct type of pancreatic intraductal neoplasm in 20108.

Clinical Features
ITPNs are rare neoplasms seen at an average age of 53 years, with equal female to male ratio31,135. The patients usually present with non-specific symptoms such as abdominal pain, vomiting, weight loss, and steatorrhea. Unlike PDAC, there is no jaundice135. The tumor is usually characterized by solid and cystic areas on imaging; pre-operative diagnosis of IPMN might be rendered for some cases.

Pathologic Features
On gross examination, the tumors are multinodular, with the mean tumor size of 4.5 cm and one might see soft, polypoid masses within dilated pancreatic ducts135. About 50% of the ITPNs involve the head of the pancreas, and 30% involves the entire gland. Cyst formation is generally uncommon, and the adjacent pancreatic tissue is usually sclerotic136. Because of their intraductal growth pattern, it is difficult to differentiate ITPNs from IPMNs grossly8,137.

Microscopically, these neoplasms have a nodular growth pattern (Figure 7A). Intraductal location of at least some of the tumor nodules is identified in every case as there is continuity of the neoplastic epithelium with histologically normal-appearing ductal epithelium. However, many tumor nodules show no residual non-neoplastic ductal epithelium at the periphery135. The nodules are composed of either back to back tubular glands or punctuated sheets of tumor cells (Figure 7B)54,134,138. Despite the entity's name, the predominant growth pattern is tubular in ITPNs with papilla formation seen only focally in rare cases135,139. Although small foci of necrosis are common, rare cases might even reveal comedo-like necrosis as shown here within the nodules. The cuboidal tumor cells have modest amount of cytoplasm without obvious intracellular mucin content. The nuclei are small, round to oval, and moderately to markedly atypical with readily identifiable mitotic figures135.

Click Here to Zoom
Figure 7: A) Intraductal tubulopapillary neoplasm with a nodular growth pattern within the fibrotic stroma (H&E; x100), and B) The nodule is composed of back to back tubular glands or punctuated solid areas (H&E; x200).

Approximately 70% cases have invasive carcinoma component ranging from minute (representing less than 10% of the tumor) to extensive (more than 50% of the tumor)135. However, because7,134 many of the individual tumor nodules lack a peripheral rim of nonneoplastic ductal epithelium, it is often very difficult to determine whether invasive carcinoma is present24,138. Foci in which there are thin strands of cells extending away from the edges of the nodules are regarded to represent stromal invasion (Figure 8). In some cases, there are individual malignant glands clearly infiltrating into the stroma135.

Click Here to Zoom
Figure 8: Foci in which there are thin strands of cells extending away from the edges of the nodules are regarded as stromal invasion (H&E; x40).

Immunohistochemical Features
The immuno profile for ITPNs is interesting. The tumor cells are positive with CK7,8,18,19, and MUC1 and MUC6, while MUC2 and MUC5AC are generally negative. Most cases also express CA19.9, which is typically expressed in ductal epithelial cells and ductal neoplasms135.

Molecular Features
Although their intraductal nature and some of clinicopathological feature similar to those of IPMNs, ITPNs appear to have distinguishing molecular characteristics. For example, in a recent study based on targeted nextgeneration sequencing for a panel of 51 cancer-associated genes, no mutations were identified in three ITPNs analyzed88. Similarly, in another study analyzing eleven ITPNs by targeted next-generation sequencing for a panel of 300 cancer-associated genes, our group showed that ITPNs do not harbor the majority of the previously reported IPMNrelated mutations. In fact, only three specific genes were mutated in more than one ITPN: MLL2, MLL3, and BAP1 (chromatin remodeling genes)140. Further analysis of genetic alterations in biologically distinct pathway(s) will likely shed new light on the mechanisms of intraductal tumor formation in the pancreas.

Although ITPN is relatively newly defined entity, preliminary data suggest that the overall clinical course of these neoplasms was indolent. Interestingly, there seems to be no clinical course and invasion correlation135,139. However, this is most likely, due to sampling phenomenon. Therefore, careful sampling and evaluation is warranted.

Differential Diagnosis
The differential diagnosis includes other fundamentally intraductal tumors such as IPMNs as well as other pancreatic neoplasms that may rarely grow within the ducts (acinar cell carcinoma and pancreatic neuroendocrine neoplasm). Although IPMNs may have some limited tubular growth, especially at the periphery of the involved ducts, all show extensive intraductal papilla formation, and complete obliteration of the ductal profiles is distinctly unusual.

The back-to-back tubules of intraductal tubular carcinoma, each of which has a relatively small lumen, closely simulate the pattern of acinar neoplasms of the pancreas. Most acinar cell carcinomas are large solid lesions and demonstrate no involvement of the native pancreatic ducts. However, rare cases have been described in which an intraductal growth pattern is present either focally or extensively. Some in fact show papillary formations within the native ducts137,141,142. Acinar cell carcinomas with intraductal spread can be difficult to distinguish from ITPN by routine microscopy, but immunohistochemistry is very helpful. Acinar cell carcinomas consistently express pancreatic enzymes such as trypsin, chymotrypsin, and lipase and generally lack expression of CK19141-144.

Finally, pancreatic neuroendocrine neoplasms can rarely show an intraductal growth pattern. Usually, these are solid neoplasms, although gland formation can occur in pancreatic neuroendocrine neoplasms. Again, immunohistochemistry is extremely helpful, as there is diffuse positivity for chromogranin and/or synaptophysin in pancreatic neuroendocrine neoplasms. In should be kept in mind that some ITPNs have a minor population of neuroendocrine cells (as can be seen in any type of exocrine pancreatic neoplasm), but these are generally arranged individually, and diffuse labeling for neuroendocrine markers is not found135,139.

  • Top
  • Abstract
  • Introduction
  • Conclusion
  • References
  • Conclusion
    Intraductal neoplasms of the pancreas are precursor lesions for pancreatic ductal adenocarcinoma and IPMNs are the most common type among these. The most important determinant of outcome in the management of patients with these intraductal neoplasms is whether an associated invasive carcinoma is present or not and the tumor size/ stage is the most significant predictor of survival followed by the histological subtype. That is why the careful and extensive, if not complete, sampling is necessary (8,13,16, 53,55-57).

    Differential diagnoses of IPMN include PanIN, IOPN, ITPN, MCN, and large duct type PDAC. In addition to imaging and histomorphologic findings, immunohistochemistry and even genetic tests summarized in this article might be used to establish the final diagnosis.

    This work has been supported by the Cancer Center Support Grant (CCSG) / Core Grant / P30 CA008748.

    The authors thank to Ms. Tanisha Daniel and Ms. Dana Haviland for their assistance during manuscript preparation and Ms. Allyne Manzo and Ms. Lorraine Corsale for their assistance with the figures.

    The authors declare no conflict of interest.

  • Top
  • Abstract
  • Introduction
  • Conclusion
  • References
  • References

    1) Klöppel G, Kosmahl M. Cystic lesions and neoplasms of the pancreas. The features are becoming clearer. Pancreatology. 2001;1:648-55.

    2) Kosmahl M, Pauser U, Peters K, Sipos B, Lüttges J, Kremer B, Klöppel G. Cystic neoplasms of the pancreas and tumorlike lesions with cystic features: A review of 418 cases and a classification proposal. Virchows Arch. 2004;445:168-78.

    3) Adsay NV. Cystic neoplasia of the pancreas: Pathology and biology. J Gastrointest Surg. 2008;12:401-4.

    4) Spinelli KS, Fromwiller TE, Daniel RA, Kiely JM, Nakeeb A, Komorowski RA, Wilson SD, Pitt HA. Cystic pancreatic neoplasms: Observe or operate. Ann Surg. 2004;239:651-7; discussion 657-9.

    5) Fernández-del Castillo C, Targarona J, Thayer SP, Rattner DW, Brugge WR, Warshaw AL. Incidental pancreatic cysts: Clinicopathologic characteristics and comparison with symptomatic patients. Arch Surg. 2003;138:427-3; discussion 433-4.

    6) Sessa F, Solcia E, Capella C, Bonato M, Scarpa A, Zamboni G, Pellegata NS, Ranzani GN, Rickaert F, Klöppel G. Intraductal papillary-mucinous tumours represent a distinct group of pancreatic neoplasms: An investigation of tumour cell differentiation and K-ras, p53 and c-erbB-2 abnormalities in 26 patients. Virchows Arch. 1994;425:357-67.

    7) Tanaka M, Chari S, Adsay V, Fernandez-del Castillo C, Falconi M, Shimizu M, Yamaguchi K, Yamao K, Matsuno S; International Association of Pancreatology. International consensus guidelines for management of intraductal papillary mucinous neoplasms and mucinous cystic neoplasms of the pancreas. Pancreatology. 2006;6:17-32.

    8) Adsay NV, Kloppel G, Fukushima N. WHO classification for tumors of the digestive system. In: Bosman FT, Carneiro F, Hruban RH, editors. Intraductal neoplasms of the pancreas. Lyon:WHO;2010. 304-313.

    9) Ingkakul T, Warshaw AL, Fernández-Del Castillo C. Epidemiology of intraductal papillary mucinous neoplasms of the pancreas: Sex differences between 3 geographic regions. Pancreas. 2011;40:779-80.

    10) Fernández-del Castillo C, Adsay NV. Intraductal papillary mucinous neoplasms of the pancreas. Gastroenterology. 2010;139:708-13, 713.e1-2.

    11) Adsay NV. The “new kid on the block”: Intraductal papillary mucinous neoplasms of the pancreas: Current concepts and controversies. Surgery. 2003;133:459-63.

    12) Katabi N, Klimstra DS. Intraductal papillary mucinous neoplasms of the pancreas: Clinical and pathological features and diagnostic approach. J Clin Pathol. 2008;61:1303-13.

    13) Nagai K, Doi R, Kida A, Kami K, Kawaguchi Y, Ito T, Sakurai T, Uemoto S. Intraductal papillary mucinous neoplasms of the pancreas: Clinicopathologic characteristics and longterm follow-up after resection. World J Surg. 2008;32:271-8; discussion 279-80.

    14) Ferrone CR, Correa-Gallego C, Warshaw AL, Brugge WR, Forcione DG, Thayer SP, Fernández-del Castillo C. Current trends in pancreatic cystic neoplasms. Arch Surg. 2009;144:448-54.

    15) Salvia R, Fernández-del Castillo C, Bassi C, Thayer SP, Falconi M, Mantovani W, Pederzoli P, Warshaw AL. Main-duct intraductal papillary mucinous neoplasms of the pancreas: Clinical predictors of malignancy and long-term survival following resection. Ann Surg. 2004;239:678-85; discussion 685-7.

    16) Sohn TA, Yeo CJ, Cameron JL, Hruban RH, Fukushima N, Campbell KA, Lillemoe KD. Intraductal papillary mucinous neoplasms of the pancreas: An updated experience. Ann Surg. 2004;239:788-97; discussion 797-9.

    17) Jang JW, Kim MH, Jeong SU, Kim J, Park DH, Lee SS, Seo DW, Lee SK, Kim JH. Clinical characteristics of intraductal papillary mucinous neoplasm manifesting as acute pancreatitis or acute recurrent pancreatitis. J Gastroenterol Hepatol. 2013;28:731-8.

    18) Valsangkar NP, Morales-Oyarvide V, Thayer SP, Ferrone CR, Wargo JA, Warshaw AL, Fernández-del Castillo C. 851 resected cystic tumors of the pancreas: A 33-year experience at the Massachusetts General Hospital. Surgery. 2012;152:S4-12.

    19) Capurso G, Boccia S, Salvia R, Del Chiaro M, Frulloni L, Arcidiacono PG, Zerbi A, Manta R, Fabbri C, Ventrucci M, Tarantino I, Piciucchi M, Carnuccio A, Boggi U, Leoncini E, Costamagna G, Delle Fave G, Pezzilli R, Bassi C, Larghi A; Italian Association for Study of Pancreas (AISP); Intraductal Papillary Mucinous Neoplasm (IPMN) Study Group. Risk factors for intraductal papillary mucinous neoplasm (IPMN) of the pancreas: A multicentre case-control study. Am J Gastroenterol. 2013;108:1003-9.

    20) Lubezky N, Ben-Haim M, Lahat G, Marmor S, Solar I, Brazowski E, Nackache R, Klausner JM. Intraductal papillary mucinous neoplasm of the pancreas: Associated cancers, family history, genetic predisposition? Surgery. 2012;151:70-5.

    21) E guchi H, Ishikawa O, Ohigashi H, Tomimaru Y, Sasaki Y, Yamada T, Tsukuma H, Nakaizumi A, Imaoka S. Patients with pancreatic intraductal papillary mucinous neoplasms are at high risk of colorectal cancer development. Surgery. 2006;139:749-54.

    22) R iall TS, Stager VM, Nealon WH, Townsend CM Jr, Kuo YF, Goodwin JS, Freeman JL. Incidence of additional primary cancers in patients with invasive intraductal papillary mucinous neoplasms and sporadic pancreatic adenocarcinomas. J Am Coll Surg. 2007;204:803-13; discussion 813-4.

    23) Baumgaertner I, Corcos O, Couvelard A, Sauvanet A, Rebours V, Vullierme MP, Hentic O, Hammel P, Lévy P, Ruszniewski P. Prevalence of extrapancreatic cancers in patients with histologically proven intraductal papillary mucinous neoplasms of the pancreas: A case-control study. Am J Gastroenterol. 2008;103:2878-82.

    24) Adsay NV, Merati K, Andea A, Sarkar F, Hruban RH, Wilentz RE, Goggins M, Iocobuzio-Donahue C, Longnecker DS, Klimstra DS. The dichotomy in the preinvasive neoplasia to invasive carcinoma sequence in the pancreas: Differential expression of MUC1 and MUC2 supports the existence of two separate pathways of carcinogenesis. Mod Pathol. 2002;15:1087-95.

    25) Silas AM, Morrin MM, Raptopoulos V, Keogan MT. Intraductal papillary mucinous tumors of the pancreas. AJR Am J Roentgenol. 2001;176:179-85.

    26) Sahani DV, Kadavigere R, Blake M, Fernandez-Del Castillo C, Lauwers GY, Hahn PF. Intraductal papillary mucinous neoplasm of pancreas: Multi-detector row CT with 2D curved reformations- -correlation with MRCP. Radiology. 2006;238:560-9.

    27) O gawa H, Itoh S, Ikeda M, Suzuki K, Naganawa S. Intraductal papillary mucinous neoplasm of the pancreas: Assessment of the likelihood of invasiveness with multisection CT. Radiology. 2008;248:876-86.

    28) W aters JA, Schmidt CM, Pinchot JW, White PB, Cummings OW , Pitt HA, Sandrasegaran K, Akisik F, Howard TJ, Nakeeb A, Zyromski NJ, Lillemoe KD. CT vs MRCP: Optimal classification of IPMN type and extent. J Gastrointest Surg. 2008;12:101-9.

    29) Yamao K, Nakamura T, Suzuki T, Sawaki A, Hara K, Kato T, Okubo K, Matsumoto K, Shimizu Y. Endoscopic diagnosis and staging of mucinous cystic neoplasms and intraductal papillarymucinous tumors. J Hepatobiliary Pancreat Surg. 2003;10:142-6.

    30) Basturk O, Coban I, Adsay NV. Pancreatic cysts: Pathologic classification, differential diagnosis, and clinical implications. Arch Pathol Lab Med. 2009;133:423-38.

    31) Klöppel G, Basturk O, Schlitter AM, Konukiewitz B, Esposito I. Intraductal neoplasms of the pancreas. Semin Diagn Pathol. 2014;31:452-66.

    32) W inter JM, Cameron JL, Lillemoe KD, Campbell KA, Chang D, Riall TS, Coleman J, Sauter PK, Canto M, Hruban RH, Schulick RD, Choti MA, Yeo CJ. Periampullary and pancreatic incidentaloma: A single institution's experience with an increasingly common diagnosis. Ann Surg. 2006;243:673-80; discussion 680-3.

    33) Pelaez-Luna M, Chari ST, Smyrk TC, Takahashi N, Clain JE, Levy MJ, Pearson RK, Petersen BT, Topazian MD, Vege SS, Kendrick M, Farnell MB. Do consensus indications for resection in branch duct intraductal papillary mucinous neoplasm predict malignancy? A study of 147 patients. Am J Gastroenterol. 2007;102:1759-64.

    34) Xiao SY. Intraductal papillary mucinous neoplasm of the pancreas: An update. Scientifica (Cairo). 2012;2012:893632.

    35) Sohn TA, Yeo CJ, Cameron JL, Iacobuzio-Donahue CA, Hruban RH, Lillemoe KD. Intraductal papillary mucinous neoplasms of the pancreas: An increasingly recognized clinicopathologic entity. Ann Surg. 2001;234:313-21; discussion 321-2.

    36) Siech M, Tripp K, Schmidt-Rohlfing B, Mattfeldt T, Görich J, Beger HG. Intraductal papillary mucinous tumor of the pancreas. Am J Surg. 1999;177:117-20.

    37) Tanaka M. Thirty years of experience with intraductal papillary mucinous neoplasm of the pancreas: From discovery to international consensus. Digestion. 2014;90:265-72

    38) Adsay NV, Adair CF, Heffess CS, Klimstra DS. Intraductal oncocytic papillary neoplasms of the pancreas. Am J Surg Pathol. 1996;20:980-94.

    39) Bosman FT, Carneiro F, Hruban RH. WHO classification for tumors of the digestive system. Bosman FT, Carneiro F, Hruban RH, editors. Geneva:WHO; 2010.417.

    40) Adsay NV, Klimstra DS, Compton CC. Cystic lesions of the pancreas. Introduction. Semin Diagn Pathol. 2000;17:1-6.

    41) Adsay NV, Merati K, Basturk O, Iacobuzio-Donahue C, Levi E, Cheng JD, Sarkar FH, Hruban RH, Klimstra DS. Pathologically and biologically distinct types of epithelium in intraductal papillary mucinous neoplasms: Delineation of an “intestinal” pathway of carcinogenesis in the pancreas. Am J Surg Pathol. 2004;28:839-48.

    42) Ban S, Naitoh Y, Mino-Kenudson M, Sakurai T, Kuroda M, Koyama I, Lauwers GY, Shimizu M. Intraductal papillary mucinous neoplasm (IPMN) of the pancreas: Its histopathologic difference between 2 major types. Am J Surg Pathol. 2006;30:1561-9.

    43) 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, Klöppel G, Longnecker DS, Lüttges J, Maitra A, Offerhaus GJ, Shimizu M, Yonezawa S. An illustrated consensus on the classification of pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasms. Am J Surg Pathol. 2004;28:977-87.

    44) Furukawa T, Klöppel G, Volkan Adsay N, Albores-Saavedra J, Fukushima N, Horii A, Hruban RH, Kato Y, Klimstra DS, Longnecker DS, Lüttges J, Offerhaus GJ, Shimizu M, Sunamura M, Suriawinata A, Takaori K, Yonezawa S. Classification of types of intraductal papillary-mucinous neoplasm of the pancreas: A consensus study. Virchows Arch. 2005;447:794-9.

    45) Adsay V, Mino-Kenudson M, Furukawa T, Basturk O, Zamboni G, Marchegiani G, Bassi C, Salvia R, Malleo G, Paiella S, Wolfgang CL, Matthaei H, Offerhaus GJ, Adham M, Bruno MJ, Reid MD, Krasinskas A, Klöppel G, Ohike N, Tajiri T, Jang KT, Roa JC, Allen P, Fernández-del Castillo C, Jang JY, Klimstra DS, Hruban RH; Members of Verona Consensus Meeting, 2013. Pathologic evaluation and reporting of intraductal papillary mucinous neoplasms of the pancreas and other tumoral intraepithelial neoplasms of pancreatobiliary tract: Recommendations of Verona Consensus Meeting. Ann Surg. 2016;263:162-77.

    46) Shimizu Y, Yamaue H, Maguchi H, Yamao K, Hirono S, Osanai M, Hijioka S, Hosoda W, Nakamura Y, Shinohara T, Yanagisawa A. Predictors of malignancy in intraductal papillary mucinous neoplasm of the pancreas: Analysis of 310 pancreatic resection patients at multiple high-volume centers. Pancreas. 2013;42:883-8.

    47) O hno E, Itoh A, Kawashima H, Ishikawa T, Matsubara H, Itoh Y, Nakamura Y, Hiramatsu T, Nakamura M, Miyahara R, Ohmiya N, Ishigami M, Katano Y, Goto H, Hirooka Y. Malignant transformation of branch duct-type intraductal papillary mucinous neoplasms of the pancreas based on contrastenhanced endoscopic ultrasonography morphological changes: Focus on malignant transformation of intraductal papillary mucinous neoplasm itself. Pancreas. 2012;41:855-62.

    48) Hwang DW, Jang JY, Lim CS, Lee SE, Yoon YS, Ahn YJ, Han HS, Kim SW, Kim SG, Yun YK, Han SS, Park SJ, Lim TJ, Kang KJ, Sim MS, Choi SH, Heo JS, Choi DW, Hur KY, Lee DS, Yun SS, Kim HJ, Cho CK, Kim HJ, Yu HC, Cho BH, Song IS. Determination of malignant and invasive predictors in branch duct type intraductal papillary mucinous neoplasms of the pancreas: A suggested scoring formula. J Korean Med Sci. 2011;26:740-6.

    49) Tomimaru Y, Takeda Y, Tatsumi M, Kim T, Kobayashi S, Marubashi S, Eguchi H, Tanemura M, Kitagawa T, Nagano H, Umeshita K, Wakasa K, Doki Y, Mori M. Utility of 2-(18F) fluoro-2-deoxy-D-glucose positron emission tomography in differential diagnosis of benign and malignant intraductal papillary-mucinous neoplasm of the pancreas. Oncol Rep. 2010;24:613-20.

    50) Mimura T, Masuda A, Matsumoto I, Shiomi H, Yoshida S, Sugimoto M, Sanuki T, Yoshida M, Fujita T, Kutsumi H, Ku Y, Azuma T. Predictors of malignant intraductal papillary mucinous neoplasm of the pancreas. J Clin Gastroenterol. 2010;44:e224-9.

    51) Shimamoto T, Tani M, Kawai M, Hirono S, Ina S, Miyazawa M, Shimizu A, Uchiyama K, Yokoyama S, Tsutsumi M, Yamaue H. MUC1 is a useful molecular marker for malignant intraductal papillary mucinous neoplasms in pancreatic juice obtained from endoscopic retrograde pancreatography. Pancreas. 2010;39:879-83.

    52) Basturk O, Hong SM, Wood LD, Adsay NV, Albores-Saavedra J, Biankin AV, Brosens LA, Fukushima N, Goggins M, Hruban RH, Kato Y, Klimstra DS, Klöppel G, Krasinskas A, Longnecker DS, Matthaei H, Offerhaus GJ, Shimizu M, Takaori K, Terris B, Yachida S, Esposito I, Furukawa T; Baltimore Consensus Meeting. A Revised Classification System and Recommendations From the Baltimore Consensus Meeting for Neoplastic Precursor Lesions in the Pancreas. Am J Surg Pathol. 2015;39:1730-41.

    53) Hruban R, Pitman MB, Klimstra DS. Tumors of the Pancreas. AFIP atlas of tumor pathology. Washington, DC: American Registry of Pathology;2007.

    54) Adsay NV, Conlon KC, Zee SY, Brennan MF, Klimstra DS. Intraductal papillary-mucinous neoplasms of the pancreas: An analysis of in situ and invasive carcinomas in 28 patients. Cancer. 2002;94:62-77.

    55) Grützmann R, Post S, Saeger HD, Niedergethmann M. Intraductal papillary mucinous neoplasia (IPMN) of the pancreas: Its diagnosis, treatment, and prognosis. Dtsch Arztebl Int. 2011;108:788-94.

    56) R aut CP, Cleary KR, Staerkel GA, Abbruzzese JL, Wolff RA, Lee JH, Vauthey JN, Lee JE, Pisters PW, Evans DB. Intraductal papillary mucinous neoplasms of the pancreas: Effect of invasion and pancreatic margin status on recurrence and survival. Ann Surg Oncol. 2006;13:582-94.

    57) Chari ST. Intraductal Papillary Mucinous Neoplasm. Curr Treat Options Gastroenterol. 2002;5:339-344.

    58) 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.

    59) Klöppel G, Kosmahl M, Lüttges J. Intraductal neoplasms of the pancreas: Cystic and common. Pathologe. 2005;26:31-6.

    60) Kim YI, Shin SH, Song KB, Hwang DW, Lee JH, Park KM, Lee YJ, Kim SC. Branch duct intraductal papillary mucinous neoplasm of the pancreas: Single-center experience with 324 patients who underwent surgical resection. Korean J Hepatobiliary Pancreat Surg. 2015;19:113-20.

    61) Basturk O, Khayyata S, Klimstra DS, Hruban RH, Zamboni G, Coban I, Adsay NV. Preferential expression of MUC6 in oncocytic and pancreatobiliary types of intraductal papillary neoplasms highlights a pyloropancreatic pathway, distinct from the intestinal pathway, in pancreatic carcinogenesis. Am J Surg Pathol. 2010;34:364-70.

    62) Ideno N, Ohtsuka T, Kono H, Fujiwara K, Oda Y, Aishima S, Ito T, Ishigami K, Tokunaga S, Ohuchida K, Takahata S, Nakamura M, Mizumoto K, Tanaka M. Intraductal papillary mucinous neoplasms of the pancreas with distinct pancreatic ductal adenocarcinomas are frequently of gastric subtype. Ann Surg. 2013;258:141-51.

    63) Adsay NV, Merati K, Nassar H, Shia J, Sarkar F, Pierson CR, Cheng JD, Visscher DW, Hruban RH, Klimstra DS. Pathogenesis of colloid (pure mucinous) carcinoma of exocrine organs: Coupling of gel-forming mucin (MUC2) production with altered cell polarity and abnormal cell-stroma interaction may be the key factor in the morphogenesis and indolent behavior of colloid carcinoma in the breast and pancreas. Am J Surg Pathol. 2003;27:571-8.

    64) Adsay NV, Pierson C, Sarkar F, Abrams J, Weaver D, Conlon KC, Brennan MF, Klimstra DS. Colloid (mucinous noncystic) carcinoma of the pancreas. Am J Surg Pathol. 2001;25:26-42.

    65) Seidel G, Zahurak M, Iacobuzio-Donahue C, Sohn TA, Adsay NV, Yeo CJ, Lillemoe KD, Cameron JL, Hruban RH, Wilentz RE. Almost all infiltrating colloid carcinomas of the pancreas and periampullary region arise from in situ papillary neoplasms: A study of 39 cases. Am J Surg Pathol. 2002;26:56-63.

    66) Shimada K, Sakamoto Y, Sano T, Kosuge T, Hiraoka N. Invasive carcinoma originating in an intraductal papillary mucinous neoplasm of the pancreas: A clinicopathologic comparison with a common type of invasive ductal carcinoma. Pancreas. 2006;32:281-7.

    67) Schnelldorfer T, Sarr MG, Nagorney DM, Zhang L, Smyrk TC, Qin R, Chari ST, Farnell MB. Experience with 208 resections for intraductal papillary mucinous neoplasm of the pancreas. Arch Surg. 2008;143:639-46; discussion 646.

    68) Falconi M, Salvia R, Bassi C, Zamboni G, Talamini G, Pederzoli P. Clinicopathological features and treatment of intraductal papillary mucinous tumour of the pancreas. Br J Surg. 2001;88:376-81.

    69) Jr CM, Dixon E. Intraductal papillary mucinous neoplasm: Coming of age. World J Gastrointest Surg. 2010;2:299-305.

    70) Cuillerier E, Cellier C, Palazzo L, Devičre J, Wind P, Rickaert F, Cugnenc PH, Cremer M, Barbier JP. Outcome after surgical resection of intraductal papillary and mucinous tumors of the pancreas. Am J Gastroenterol. 2000;95:441-5.

    71) D'Angelica M, Brennan MF, Suriawinata AA, Klimstra D, Conlon KC. Intraductal papillary mucinous neoplasms of the pancreas: An analysis of clinicopathologic features and outcome. Ann Surg. 2004;239:400-8.

    72) Nara S, Shimada K, Sakamoto Y, Esaki M, Kosuge T, Hiraoka N. Clinical significance of frozen section analysis during resection of intraductal papillary mucinous neoplasm: Should a positive pancreatic margin for adenoma or borderline lesion be resected additionally? J Am Coll Surg. 2009;209:614-21.

    73) Matthaei H, Hong SM, Mayo SC, dal Molin M, Olino K, Venkat R, Goggins M, Herman JM, Edil BH, Wolfgang CL, Cameron JL, Schulick RD, Maitra A, Hruban RH. Presence of pancreatic intraepithelial neoplasia in the pancreatic transection margin does not influence outcome in patients with R0 resected pancreatic cancer. Ann Surg Oncol. 2011;18:3493-9.

    74) Fujii T, Kato K, Kodera Y, Kanda M, Nagai S, Yamada S, Kanzaki A, Sugimoto H, Nomoto S, Takeda S, Morita S, Nakamura S, Nakao A. Prognostic impact of pancreatic margin status in the intraductal papillary mucinous neoplasms of the pancreas. Surgery. 2010;148:285-90.

    75) Nishigami T, Onodera M, Torii I, Sato A, Tao LH, Kushima R, Kakuno A, Kishimoto M, Katsuyama E, Fujimori T, Hirano H, Satake M, Kuroda N, Nishiguchi S, Fujimoto J, Tsujimura T. Comparison between mucinous cystic neoplasm and intraductal papillary mucinous neoplasm of the branch duct type of the pancreas with respect to expression of CD10 and cytokeratin 20. Pancreas. 2009;38:558-64.

    76) Tobi M, Hatfield J, Adsay V, Galagan K, Kozarek R, Inagaki M, Kasai S, Tokusashi Y, Obara T, Hruban RH, Lough J, Barkun AN, Jabbari M, Sheikh R, Ruebner B, Lawson MJ, Ben-Josef E, Fligiel S. Prognostic significance of the labeling of Adnab-9 in pancreatic intraductal papillary mucinous neoplasms. Int J Pancreatol. 2001;29:141-50.

    77) Lüttges J, Zamboni G, Longnecker D, Klöppel G. 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. Am J Surg Pathol. 2001;25:942-8.

    78) Nakamura A, Horinouchi M, Goto M, Nagata K, Sakoda K, Takao S, Imai K, Kim YS, Sato E, Yonezawa S. New classification of pancreatic intraductal papillary-mucinous tumour by mucin expression: Its relationship with potential for malignancy. J Pathol. 2002;197:201-10.

    79) Yonezawa S, Taira M, Osako M, Kubo M, Tanaka S, Sakoda K, Takao S, Aiko T, Yamamoto M, Irimura T, Kim YS, Sato E. MUC- 1 mucin expression in invasive areas of intraductal papillary mucinous tumors of the pancreas. Pathol Int. 1998;48:319-22.

    80) Levi E, Klimstra DS, Andea A, Basturk O, Adsay NV. MUC1 and MUC2 in pancreatic neoplasia. J Clin Pathol. 2004;57:456-62.

    81) Terada T, Ohta T, Kitamura Y, Ashida K, Matsunaga Y, Kato M. Endocrine cells in intraductal papillary-mucinous neoplasms of the pancreas. A histochemical and immunohistochemical study. Virchows Arch. 1997;431:31-6.

    82) Furukawa T, Kuboki Y, Tanji E, Yoshida S, Hatori T, Yamamoto M, Shibata N, Shimizu K, Kamatani N, Shiratori K. Wholeexome sequencing uncovers frequent GNAS mutations in intraductal papillary mucinous neoplasms of the pancreas. Sci Rep. 2011;1:161.

    83) O dze RD, Goldblum JR. Odze and Goldblum surgical pathology of the GI tract, liver, biliary tract and pancreas. 3rd ed. Philadelphia, PA: Saunders; 2014.

    84) W u J, Matthaei H, Maitra A, Dal Molin M, Wood LD, Eshleman JR, Goggins M, Canto MI, Schulick RD, Edil BH, Wolfgang CL, Klein AP, Diaz LA Jr, Allen PJ, Schmidt CM, Kinzler KW, Papadopoulos N, Hruban RH, Vogelstein B. Recurrent GNAS mutations define an unexpected pathway for pancreatic cyst development. Sci Transl Med. 2011;3:92ra66.

    85) Xiao HD, Yamaguchi H, Dias-Santagata D, Kuboki Y, Akhavanfard S, Hatori T, Yamamoto M, Shiratori K, Kobayashi M, Shimizu M, Fernandez-Del Castillo C, Mino-Kenudson M, Furukawa T. Molecular characteristics and biological behaviours of the oncocytic and pancreatobiliary subtypes of intraductal papillary mucinous neoplasms. J Pathol. 2011;224:508-16.

    86) Mohri D, Asaoka Y, Ijichi H, Miyabayashi K, Kudo Y, Seto M, Ohta M, Tada M, Tanaka Y, Ikenoue T, Tateishi K, Isayama H, Kanai F, Fukushima N, Tada M, Kawabe T, Omata M, Koike K. Different subtypes of intraductal papillary mucinous neoplasm in the pancreas have distinct pathways to pancreatic cancer progression. J Gastroenterol. 2012;47:203-13.

    87) Tan MC, Basturk O, Brannon AR, Bhanot U, Scott SN, Bouvier N, LaFemina J, Jarnagin WR, Berger MF, Klimstra D, Allen PJ. GNAS and KRAS mutations define separate progression pathways in intraductal papillary mucinous neoplasmassociated carcinoma. J Am Coll Surg. 2015;220:845-54.e1.

    88) Amato E, Molin MD, Mafficini A, Yu J, Malleo G, Rusev B, Fassan M, Antonello D, Sadakari Y, Castelli P, Zamboni G, Maitra A, Salvia R, Hruban RH, Bassi C, Capelli P, Lawlor RT, Goggins M, Scarpa A. Targeted next-generation sequencing of cancer genes dissects the molecular profiles of intraductal papillary neoplasms of the pancreas. J Pathol. 2014;233:217-27.

    89) Bailey P, Chang DK, Nones K, Johns AL, Patch AM, Gingras MC, Miller DK, Christ AN, Bruxner TJ, Quinn MC, Nourse C, Murtaugh LC, Harliwong I, Idrisoglu S, Manning S, Nourbakhsh E, Wani S, Fink L, Holmes O, Chin V, Anderson MJ, Kazakoff S, Leonard C, Newell F, Waddell N, Wood S, Xu Q, Wilson PJ, Cloonan N, Kassahn KS, Taylor D, Quek K, Robertson A, Pantano L, Mincarelli L, Sanchez LN, Evers L, Wu J, Pinese M, Cowley MJ, Jones MD, Colvin EK, Nagrial AM, Humphrey ES, Chantrill LA, Mawson A, Humphris J, Chou A, Pajic M, Scarlett CJ, Pinho AV, Giry-Laterriere M, Rooman I, Samra JS, Kench JG, Lovell JA, Merrett ND, Toon CW, Epari K, Nguyen NQ, Barbour A, Zeps N, Moran-Jones K, Jamieson NB, Graham JS, Duthie F, Oien K, Hair J, Grützmann R, Maitra A, Iacobuzio-Donahue CA, Wolfgang CL, Morgan RA, Lawlor RT, Corbo V, Bassi C, Rusev B, Capelli P, Salvia R, Tortora G, Mukhopadhyay D, Petersen GM; Australian Pancreatic Cancer Genome Initiative, Munzy DM, Fisher WE, Karim SA, Eshleman JR, Hruban RH, Pilarsky C, Morton JP, Sansom OJ, Scarpa A, Musgrove EA, Bailey UM, Hofmann O, Sutherland RL, Wheeler DA, Gill AJ, Gibbs RA, Pearson JV, Waddell N, Biankin AV, Grimmond SM. Genomic analyses identify molecular subtypes of pancreatic cancer. Nature. 2016;531:47-52.

    90) Tanno S, Nakano Y, Sugiyama Y, Nakamura K, Sasajima J, Koizumi K, Yamazaki M, Nishikawa T, Mizukami Y, Yanagawa N, Fujii T, Obara T, Okumura T, Kohgo Y. Incidence of synchronous and metachronous pancreatic carcinoma in 168 patients with branch duct intraductal papillary mucinous neoplasm. Pancreatology. 2010;10:173-8.

    91) Furukawa T, Hatori T, Fujita I, Yamamoto M, Kobayashi M, Ohike N, Morohoshi T, Egawa S, Unno M, Takao S, Osako M, Yonezawa S, Mino-Kenudson M, Lauwers GY, Yamaguchi H, Ban S, Shimizu M. Prognostic relevance of morphological types of intraductal papillary mucinous neoplasms of the pancreas. Gut. 2011;60:509-16.

    92) Mino-Kenudson M, Fernández-del Castillo C, Baba Y, Valsangkar NP, Liss AS, Hsu M, Correa-Gallego C, Ingkakul T, Perez Johnston R, Turner BG, Androutsopoulos V, Deshpande V, McGrath D, Sahani DV, Brugge WR, Ogino S, Pitman MB, Warshaw AL, Thayer SP. Prognosis of invasive intraductal papillary mucinous neoplasm depends on histological and precursor epithelial subtypes. Gut. 2011;60:1712-20.

    93) W hite R, D'Angelica M, Katabi N, Tang L, Klimstra D, Fong Y, Brennan M, Allen P. Fate of the remnant pancreas after resection of noninvasive intraductal papillary mucinous neoplasm. J Am Coll Surg. 2007;204:987-93; discussion 993-5.

    94) Yamada S, Fujii T, Shimoyama Y, Kanda M, Nakayama G, Sugimoto H, Koike M, Nomoto S, Fujiwara M, Nakao A, Kodera Y. Clinical implication of morphological subtypes in management of intraductal papillary mucinous neoplasm. Ann Surg Oncol. 2014;21:2444-52.

    95) Koh YX, Chok AY, Zheng HL, Tan CS, Goh BK. Systematic review and meta-analysis comparing the surgical outcomes of invasive intraductal papillary mucinous neoplasms and conventional pancreatic ductal adenocarcinoma. Ann Surg Oncol. 2014;21:2782-800.

    96) De Moor V, Arvanitakis M, Nagy N, Coppens E, Delhaye M, Closset J. Intraductal papillary mucinous neoplasms of the pancreas: Clinicopathological features and long term outcome related to histopathological group. Hepatogastroenterology. 2012;59:565-9.

    97) W aters JA, Schnelldorfer T, Aguilar-Saavedra JR, Chen JH, Yiannoutsos CT, Lillemoe KD, Farnell MB, Sarr MG, Schmidt CM. Survival after resection for invasive intraductal papillary mucinous neoplasm and for pancreatic adenocarcinoma: A multi-institutional comparison according to American Joint Committee on Cancer Stage. J Am Coll Surg. 2011;213:275-83.

    98) Yamaguchi K, Kanemitsu S, Hatori T, Maguchi H, Shimizu Y, Tada M, Nakagohri T, Hanada K, Osanai M, Noda Y, Nakaizumi A, Furukawa T, Ban S, Nobukawa B, Kato Y, Tanaka M. Pancreatic ductal adenocarcinoma derived from IPMN and pancreatic ductal adenocarcinoma concomitant with IPMN. Pancreas. 2011;40:571-80.

    99) Yopp AC, Katabi N, Janakos M, Klimstra DS, D'Angelica MI, DeMatteo RP, Fong Y, Brennan MF, Jarnagin WR, Allen PJ. Invasive carcinoma arising in intraductal papillary mucinous neoplasms of the pancreas: A matched control study with conventional pancreatic ductal adenocarcinoma. Ann Surg. 2011;253:968-74.

    100) Bassi C, Sarr MG, Lillemoe KD, Reber HA. Natural history of intraductal papillary mucinous neoplasms (IPMN): Current evidence and implications for management. J Gastrointest Surg. 2008;12:645-50.

    101) Simons JP, Ng SC, Shah SA, McDade TP, Whalen GF, Tseng JF. Malignant intraductal papillary mucinous neoplasm: Are we doing the right thing? J Surg Res. 2011;167:251-7.

    102) Ishida M, Egawa S, Sakata N, Mikami Y, Motoi F, Abe T, Fukuyama S, Sunamura M, Furukawa T, Unno M. Intraductal papillary-mucinous adenocarcinoma in the remnant pancreas after pancreatoduodenectomy for cancer of Vater's papilla associated with intraductal papillary-mucinous adenoma. J Hepatobiliary Pancreat Surg. 2007;14:522-5.

    103) Klimstra DS. Cystic, mucin-producing neoplasms of the pancreas: The distinguishing features of mucinous cystic neoplasms and intraductal papillary mucinous neoplasms. Semin Diagn Pathol. 2005;22:318-29.

    104) Tanaka M, Fernández-del Castillo C, Adsay V, Chari S, Falconi M, Jang JY, Kimura W, Levy P, Pitman MB, Schmidt CM, Shimizu M, Wolfgang CL, Yamaguchi K, Yamao K; International Association of Pancreatology. International consensus guidelines 2012 for the management of IPMN and MCN of the pancreas. Pancreatology. 2012;12:183-97.

    105) Jang KT, Park SM, Basturk O, Bagci P, Bandyopadhyay S, Stelow EB, Walters DM, Choi DW, Choi SH, Heo JS, Sarmiento JM, Reid MD, Adsay V. Clinicopathologic characteristics of 29 invasive carcinomas arising in 178 pancreatic mucinous cystic neoplasms with ovarian-type stroma: Implications for management and prognosis. Am J Surg Pathol. 2015;39:179-87.

    106) Masia R, Mino-Kenudson M, Warshaw AL, Pitman MB, Misdraji J. Pancreatic mucinous cystic neoplasm of the main pancreatic duct. Arch Pathol Lab Med. 2011;135:264-7.

    107) Izumo A, Yamaguchi K, Eguchi T, Nishiyama K, Yamamoto H, Yonemasu H, Yao T, Tanaka M, Tsuneyoshi M. Mucinous cystic tumor of the pancreas: Immunohistochemical assessment of “ovarian-type stroma”. Oncol Rep. 2003;10:515-25.

    108) Fukushima N, Zamboni G. Mucinous cystic neoplasms of the pancreas: Update on the surgical pathology and molecular genetics. Semin Diagn Pathol. 2014;31:467-74.

    109) Fukushima N, Fukayama M. Mucinous cystic neoplasms of the pancreas: Pathology and molecular genetics. J Hepatobiliary Pancreat Surg. 2007;14:238-42.

    110) Nguyen BN, Edgecombe A, Gomes M, Soucy G, Marginean CE, Mai KT. Comparative immunohistochemical study of the stroma of serous and mucinous cystic neoplasms: Possible histopathogenetic relationship of the 2 entities. Pancreas. 2011;40:37-41.

    111) Fukushima N, Sato N, Prasad N, Leach SD, Hruban RH, Goggins M. Characterization of gene expression in mucinous cystic neoplasms of the pancreas using oligonucleotide microarrays. Oncogene. 2004;23:9042-51.

    112) Yeh MM, Tang LH, Wang S, Robert ME, Zheng W, Jain D. Inhibin expression in ovarian-type stroma in mucinous cystic neoplasms of the pancreas. Appl Immunohistochem Mol Morphol. 2004;12:148-52.

    113) W ilentz RE, Albores-Saavedra J, Hruban RH. Mucinous cystic neoplasms of the pancreas. Semin Diagn Pathol. 2000;17:31-42.

    114) Thompson LD, Becker RC, Przygodzki RM, Adair CF, Heffess CS. Mucinous cystic neoplasm (mucinous cystadenocarcinoma of low-grade malignant potential) of the pancreas: A clinicopathologic study of 130 cases. Am J Surg Pathol. 1999;23:1-16.

    115) Zamboni G, Scarpa A, Bogina G, Iacono C, Bassi C, Talamini G, Sessa F, Capella C, Solcia E, Rickaert F, Mariuzzi GM, Klöppel G. Mucinous cystic tumors of the pancreas: Clinicopathological features, prognosis, and relationship to other mucinous cystic tumors. Am J Surg Pathol. 1999;23:410-22.

    116) O hta T, Nagakawa T, Fukushima W, Mori K, Kayahara M, Akiyama T, Kanno M, Ueno K, Miyazaki I, Terada T, et al. Immunohistochemical study of carcinoembryonic antigen in mucinous cystic neoplasm of the pancreas. Eur Surg Res. 1992;24:37-44.

    117) 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;26:466-71.

    118) Bagci P, Andea AA, Basturk O, Jang KT, Erbarut I, Adsay V. Large duct type invasive adenocarcinoma of the pancreas with microcystic and papillary patterns: A potential microscopic mimic of non-invasive ductal neoplasia. Mod Pathol. 2012;25:439-48.

    119) Kloppel G. Clinicopathologic view of intraductal papillarymucinous tumor of the pancreas. Hepatogastroenterology. 1998;45:1981-5.

    120) Krasinskas AM, Oakley GJ, Bagci P, Jang KT, Kuan SF, Reid MD, Erbarut I, Adsay V. Simple Mucinous Cyst of the Pancreas: A clinicopathologic analysis of 39 examples of a diagnostically challenging entity distinct from intraductal papillary mucinous neoplasms and mucinous cystic neoplasms. Am J Surg Pathol. 2017;41:121-127.

    121) Basturk O, Chung SM, Hruban RH, Adsay NV, Askan G, Iacobuzio-Donahue C, Balci S, Zee SY, Memis B, Shia J, Klimstra DS. Distinct pathways of pathogenesis of intraductal oncocytic papillary neoplasms and intraductal papillary mucinous neoplasms of the pancreas. Virchows Arch. 2016;469:523-532.

    122) R eid MD, Stallworth CR, Lewis MM, Akkas G, Memis B, Basturk O, Adsay V. Cytopathologic diagnosis of oncocytic type intraductal papillary mucinous neoplasm: Criteria and clinical implications of accurate diagnosis. Cancer Cytopathol. 2016;124:122-34.

    123) Nobukawa B, Suda K, Suyama M, Ariyama J, Beppu T, Futagawa S. Intraductal oncocytic papillary carcinoma with invasion arising from the accessory pancreatic duct. Gastrointest Endosc. 1999;50:864-6.

    124) Askan G, Klimstra D, Adsay A, Allen P, Memis B, Sigel C, Basturk O. Oncocytic-type of intraductal papillary mucinous neoplasm (IPMN): An analysis of 25 cases. Laboratory Investigation. 2016;96 suppl 1: 439A.

    125) Shima Y, Yagi T, Inagaki M, Sadamori H, Tanaka N, Horimi T, Hamazaki S. Intraductal oncocytic papillary neoplasm of the pancreas with celiac artery compression syndrome and a jejunal artery aneurysm: Report of a case. Surg Today. 2005;35:86-90.

    126) Jyotheeswaran S, Zotalis G, Penmetsa P, Levea CM, Schoeniger LO, Shah AN. A newly recognized entity: Intraductal “oncocytic” papillary neoplasm of the pancreas. Am J Gastroenterol. 1998;93:2539-43.

    127) Abue M, Suzuki M, Onodera H, Suzuki S, Noguchi T, Uchimi K, Nomura E, Fujiya T, Yamanami H, Tateno H. A case of pancreatic endocrine tumor developing from intraductal papillary mucinous neoplasm (IPMN). Nihon Shokakibyo Gakkai Zasshi. 2009;106:1070-7.

    128) Hashimoto Y, Murakami Y, Uemura K, Hayashidani Y, Sudo T, Ohge H, Sueda T, Shimamoto F, Hiyama E. Mixed ductalendocrine carcinoma derived from intraductal papillary mucinous neoplasm (IPMN) of the pancreas identified by human telomerase reverse transcriptase (hTERT) expression. J Surg Oncol. 2008;97:469-75.

    129) Inoue H, Furukawa T, Sunamura M, Takeda K, Matsuno S, Horii A. Exclusion of SMAD4 mutation as an early genetic change in human pancreatic ductal tumorigenesis. Genes Chromosomes Cancer. 2001;31:295-9.

    130) Terris B, Dubois S, Buisine MP, Sauvanet A, Ruszniewski P, Aubert JP, Porchet N, Couvelard A, Degott C, Fléjou JF. Mucin gene expression in intraductal papillary-mucinous pancreatic tumours and related lesions. J Pathol. 2002;197:632-7.

    131) Basturk O, Tan M, Bhanot U, Allen P, Adsay V, Scott SN, Shah R, Berger MF, Askan G, Dikoglu E, Jobanputra V, Wrzeszczynski KO, Sigel C, Iacobuzio-Donahue C, Klimstra DS. The oncocytic subtype is genetically distinct from other pancreatic intraductal papillary mucinous neoplasm subtypes. Mod Pathol. 2016;29:1058-69.

    132) Marchegiani G, Mino-Kenudson M, Ferrone CR, Warshaw AL, Lillemoe KD, Fernández-del Castillo C. Oncocytic-type intraductal papillary mucinous neoplasms: A unique malignant pancreatic tumor with good long-term prognosis. J Am Coll Surg. 2015;220:839-44.

    133) Crippa S, Fernández-Del Castillo C, Salvia R, Finkelstein D, Bassi C, Domínguez I, Muzikansky A, Thayer SP, Falconi M, Mino-Kenudson M, Capelli P, Lauwers GY, Partelli S, Pederzoli P, Warshaw AL. Mucin-producing neoplasms of the pancreas: An analysis of distinguishing clinical and epidemiologic characteristics. Clin Gastroenterol Hepatol. 2010;8:213-9.

    134) Tajiri T, Tate G, Kunimura T, Inoue K, Mitsuya T, Yoshiba M, Morohosh T. Histologic and immunohistochemical comparison of intraductal tubular carcinoma, intraductal papillarymucinous carcinoma, and ductal adenocarcinoma of the pancreas. Pancreas. 2004;29:116-22.

    135) Basturk O, Adsay V, Askan G, Dhall D, Zamboni G, Shimizu M, Cymes K, Carneiro F, Balci S, Sigel C, Reid MD, Esposito I, Baldaia H, Allen P, Klöppel G, Klimstra DS. Intraductal tubulopapillary neoplasm of the pancreas: A clinicopathologic and immunohistochemical analysis of 33 cases. Am J Surg Pathol. 2016 (Epub ahead of print).

    136) Königsrainer I, Glatzle J, Klöppel G, Königsrainer A, Wehrmann M. Intraductal and cystic tubulopapillary adenocarcinoma of the pancreas--a possible variant of intraductal tubular carcinoma. Pancreas. 2008;36:92-5.

    137) Basturk O, Zamboni G, Klimstra DS, Capelli P, Andea A, Kamel NS, Adsay NV. Intraductal and papillary variants of acinar cell carcinomas: A new addition to the challenging differential diagnosis of intraductal neoplasms. Am J Surg Pathol. 2007;31:363-70.

    138) Yamaguchi K, Watanabe M, Nakamura M, Konomi H, Tanaka M. Intraductal papillary-mucinous neoplasm of the pancreas. Nihon Rinsho. 2006;64:52-9.

    139) Klimstra DS, Adsay NV, Dhall D, Shimizu M, Cymes K, Basturk O, Klöppel G. Intraductal tubular carcinoma of the pancreas: Clinicopathologic and immunohistochemical analysis of 18 cases. Mod Pathol. 2007;20 suppl 2: 285A.

    140) Bhanot U, Basturk O, Berger M, Shah R, Scott R, Cott S, Adsay NV, Askan G, Carneiro F, Klimstra DS. Molecular characteristics of the pancreatic intraductal tubulopapillary neoplasm. Mod Pathol. 2015; 28 suppl 2: 440A.

    141) Klimstra DS, Heffess CS, Oertel JE, Rosai J. Acinar cell carcinoma of the pancreas. A clinicopathologic study of 28 cases. Am J Surg Pathol. 1992;16:815-37.

    142) Klimstra DS, Adsay V. Acinar neoplasms of the pancreas-A summary of 25 years of research. Semin Diagn Pathol. 2016;33:307-18.

    143) Hashimoto M, Matsuda M, Watanabe G, Mori M, Motoi N, Nagai K, Ishibashi M. Acinar cell carcinoma of the pancreas with intraductal growth: Report of a case. Pancreas. 2003;26:306-8.

    144) La Rosa S, Sessa F, Capella C. Acinar cell carcinoma of the pancreas: Overview of clinicopathologic features and insights into the molecular pathology. Front Med (Lausanne). 2015;2:41.

  • Top
  • Abstract
  • Introduction
  • Conclusion
  • References
  • [ Top ] [ Abstract ] [ PDF ] [ E-Mail to Author ] [ E-Mail to Editor ]