Single-institution validation of the international consensus guidelines for treatment of branch duct intraductal papillary mucinous neoplasms of the pancreas

Background

The international consensus guidelines (the guidelines) for management of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas recommend surgical resection of branch duct IPMNs with any of the following features: cyst size >30 mm, mural nodules, main pancreatic duct diameter >6 mm, positive cytology, and symptoms. The aim of this study was to evaluate the usefulness of these guidelines for resection of branch duct IPMNs.

Methods

We reviewed 84 consecutive patients with branch duct IPMNs who underwent surgical resection at our hospital between January 1984 and December 2007.

Results

Sixty-nine patients had indications for resection according to the guidelines. Malignant IPMNs had significantly larger cysts than benign tumors (P = 0.026). Patients with malignant IPMNs had significantly more indications for resection than those with benign IPMNs (2.6 ± 1.0 vs. 1.7 ± 0.9, P < 0.001), and 36 of the 37 patients with malignant IPMNs had indications. The sensitivity of the guidelines for predicting malignancy was 97.3%. One of 15 patients without indications had malignancy, and the specificity was low (29.8%).

Conclusions

The guidelines show a high sensitivity for predicting malignancy of branch duct IPMNs, but the specificity is low. The cyst size and the total number of indications in each patient should be taken into account when predicting the risk of malignancy for branch duct IPMNs.     

Characterization of K-ras gene mutations in association with mucinous hypersecretion in intraductal papillary-mucinous neoplasms

Background/Purpose

Intraductal papillary-mucinous neoplasms (IPMNs) of the pancreas have a favorable prognosis. However, invasive ductal carcinomas of the pancreas show a rapid progression. The aim of this study was to investigate gene mutations in pure pancreatic juice from IPMN patients and to define these genetic mutations in relation to the histopathological and clinical features of IPMNs.

Methods

Twenty-two patients with IPMN, 21 patients with ductal carcinoma, and 20 patients with normal pancreas or chronic pancreatitis were recruited for this study. We measured the main pancreatic duct’s largest diameter and the maximum size of a dilated branch was assessed by ultrasonography or endoscopic ultrasonography. Pure pancreatic juice was collected and was investigated for K-ras, p16, and p53 mutations.

Results

Mutant K-ras gene was detected in 13 of the 22 patients (59.1%) with IPMNs. Different kinds of mutations were detected in the same patient in 4 cases. In the 13 patients with mutant K-ras gene, the diameter of the most dilated part of the main pancreatic duct was 2–8 mm (average, 4.5 mm) and in 7 patients with wild-type K-ras gene, the diameter was 2–5 mm (average, 2.7 mm). There was a significant difference in the diameter of the main pancreatic duct between patients with and without the mutant K-ras gene (P = 0.0323).

Conclusions

The incidence of K-ras mutation may be associated with the hypersecretion of mucin.     

Intraductal papillary mucinous neoplasm of the pancreas: diagnosis and treatment

Intraductal papillary mucinous neoplasm (IPMN) is characterized by cystic dilatation of the main and/or branch pancreatic duct. Only one-third of all patients are symptomatic, and others are diagnosed by chance. IPMNs are classified into 3 types: main duct, branch duct, and mixed IPMN. Most branch-type IPMNs are benign, while the other 2 types are frequently malignant. The presence of large mural nodules increases the possibility of malignancy in all types. Presence of a large branch-type IPMN and marked dilatation of the main duct indicate, at the very least, the existence of adenoma. Ultrasonography, endosonography, and intraductal ultrasonography clearly demonstrate ductal dilatation and mural nodules, and magnetic resonance pancreatography best visualizes the entire outline of IPMN. Not infrequently, synchronous or metachronous malignancy develops in various organs, including the pancreas. Prognosis is excellent after complete resection of benign and noninvasive malignant IPMNs. Asymptomatic branch-type IPMNs without mural nodules may be followed up without resection. Malignant IPMNs displaying acquired aggressiveness after parenchymal invasion require adequate lymph node dissection. Total pancreatectomy is needed for some IPMNs; its benefits, however, must be balanced against operative and postoperative risks because most IPMNs are slow growing and affect elderly people, and prognosis is favorable for IPMN patients with even malignant neoplasms.     

Management of intraductal papillary mucinous neoplasm of the pancreas

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a distinct entity characterized by papillary proliferations of mucin-producing epithelial cells with excessive mucus production and cystic dilatation of the pancreatic ducts. IPMNs have malignant potential and exhibit a broad histologic spectrum, ranging from adenoma to invasive carcinoma. IPMNs are classified into main duct and branch duct types, based on the site of tumor involvement. IPMN patients have a favorable prognosis if appropriately treated. The postoperative 5-year survival rate is nearly 100% for benign tumors and noninvasive carcinoma, and approximately 60% for invasive carcinoma. A main duct type IPMN should be resected. Surgical treatment is indicated for a branch duct IPMN with suspected malignancy (tumor diameter ≥ 30 mm, mural nodules, dilated main pancreatic duct, or positive cytology) or positive symptoms. Malignant IPMNs necessitate lymph node dissection (D1). IPMNs are associated with a high incidence of extrapancreatic malignancies and pancreatic ductal carcinoma.     

Patterns of recurrence and long-term outcomes in patients who underwent pancreatectomy for intraductal papillary mucinous neoplasms with high grade dysplasia: implications for surveillance and future management guidelines

Background

While intraductal papillary mucinous neoplasms (IPMNs) with high-grade dysplasia (HGD) are thought to represent non-invasive, high-risk lesions, its natural history following resection is unknown.

The distance of tumor spread in the main pancreatic duct of an intraductal papillary-mucinous neoplasm: where to resect and how to predict it

Background

The surgical decision regarding where to resect the pancreas is an important judgement that is directly linked to the surgical procedure. An appropriate surgical margin to resect intraductal papillary-mucinous neoplasm (IPMN) of the pancreas based on the distance of tumor spread (DTS) in the main pancreatic duct has not been adequately documented. We analyzed the appropriate surgical margin based on the DTS in the main pancreatic duct of IPMN and the positive rate at the pancreatic cut end margin.

Methods

Forty patients with main duct- or mixed-type IPMN diagnosed histopathologically who underwent surgery at Tokai University Hospital between 1991 and 2008 were retrospectively analyzed. The resection line was determined to achieve a 2-cm surgical margin in patients with main duct- or mixed-type IPMN and as limited a resection as possible to remove the dilated branch duct in patients with branch duct-type IPMN according to macroscopic type. The dysplastic state of the epithelium was judged as positive for carcinoma in situ (high-grade dysplasia) or adenoma (very low to moderate dysplasia) and judged as negative for hyperplasia or normal.

Results

The mean DTS in the main pancreatic duct was 41.6 ± 30.0 mm, and that of the distance of tumor absence was 13.6 ± 12.4 mm. The positive rate at the pancreatic cut end margin in frozen sections was 29.7%. The final positive rate at the pancreatic cut end margin was 26.2%. There has been no evidence of local recurrence in the remnant pancreas. DTS in the main pancreatic duct of IPMN was correlated with the maximum diameter of the duct (R = 0.678).

Conclusion

Distance of tumor spread offered important insights about the appropriate site to resect the pancreas and the positive rate at the cut end margin in IPMN.     

Imaging IPMN: take home messages and news

IPMN is a frequent disease involving pancreatic duct. This disease could be malignant (parenchymal invasive adenocarcinoma), particularly if the main pancreatic duct is involved (this involvement is considered present if > 6 mm), if this enlargement reaches 10 mm or more, and if the pathological phenotype is biliopancreatic or intestinal (malignancy is less frequent if gastric one). Invasiveness is suspected if hypodense parenchymal lesion is present, particularly near a cystical lesion or MPD, a mural nodule of the wall, or if MPD wall has got a contrast uptake. Mural nodules inside cystic branch duct are associated with in situ grade 3 malignancies. MPD IPMN must be resected to prevent malignancy. The follow-up of isolated branch duct cysts relies upon MDCT and MRI, every two years if lesion is less than 1cm. Every one year if bigger, particularly if more than to 3 cm.     

Increased K-ras mutation and expression of S100A4 and MUC2 protein in the malignant intraductal papillary mucinous tumor of the pancreas

Purpose

The purpose of this study was to document the biological changes during the progression of intraductal papillary mucinous neoplasm of the pancreas (IPMN) and to identify biological markers capable of differentiating benign and malignant IPMN.

Methods

Forty-one patients with IPMN who underwent resection between 1994 and 2003 were enrolled in this study. The paraffin-embedded tumors from 27 with benign IPMNs and from 14 with IPMCs were subjected to immunohistochemical staining and DNA extraction. Direct DNA sequencing analysis for K-ras mutation and immunohistochemical staining using 17 biological markers was performed.

Results

K-ras mutations at codon 12 and 13 were detected in 13 of 37 (38.2%) of the IPMNs: in 5 of 24 (20.8%) of benign IPMNs, and in 8 of 13 (61.5%) of malignant IPMNs (p = 0.028). The expression of S100A4 and MUC2 were increased in malignant IPMNs. S100A4 was expressed in 2 (7.4%) of 27 benign IPMNs, and 6 (42.9%) of 14 malignant IPMNs (p = 0.007). MUC2 was expressed in 2 (7.4%) benign IPMNs, and in 9 (64.3%) malignant IPMNs (p < 0.001).

Conclusion

K-ras mutation and the expression of S100A4 and MUC2 (especially in intestinal subtype) were found to be related to malignancy in IPMN, and may be useful for the diagnosis and for assessing the biological behavior of IPMN.     

Endoscopic ultrasonographic findings predict the risk of carcinoma in branch duct intraductal papillary mucinous neoplasms of the pancreas

BackgroundThe preoperative diagnosis of branch duct intraductal papillary mucinous neoplasm (IPMN) of the pancreas can be very difficult, since low-risk and high-risk lesions can be difficult to differentiate even after cytological analysis. The purpose of this study was to evaluate the preoperative diagnostic value of endoscopic ultrasonography (EUS) in differentiating low-risk and high-risk IPMNs.MethodsWe retrospectively identified 36 patients who underwent preoperative EUS for branch duct IPMNs. The pathological diagnosis after surgical resection was low-grade dysplasia (n = 26), moderate dysplasia (n = 1), high-grade dysplasia or carcinoma in situ (n = 5), and invasive carcinoma (n = 4). We divided the patients into two groups: low risk (low-grade dysplasia or moderate dysplasia) and high risk (high-grade dysplasia or carcinoma). We focused on the diameter of the cystic dilated branch duct, the main pancreatic duct, and the mural nodule as measured using the EUS findings.ResultsThe cystic dilated branch duct diameter (31.5 mm vs. 41.9 mm, P = 0.0225) was significantly correlated with low-risk and high-risk IPMNs, but the main pancreatic duct diameter (5.37 mm vs. 5.44 mm, P = 0.9418) was not significantly correlated with the low-risk and high-risk IPMNs. The mural nodule diameter of the papillary protrusions (4.3 mm vs. 16.4 mm, P < 0.0001) and the width diameter of the mural nodule (5.7 mm vs. 23.2 mm, P < 0.0001) were significantly correlated with low-risk and high-risk IPMNs.ConclusionsThe mural nodule of papillary protrusions diameter and width diameter observed using EUS was a reliable preoperative diagnostic finding capable of distinguishing low-risk and high-risk IPMNs.     

Clinical aspects of intraductal papillary mucinous neoplasm of the pancreas

Intraductal papillary mucinous neoplasm (IPMN) is a spectrum of neoplasia in the pancreatic duct epithelium characterized by cystic dilation of the main and/or branch pancreatic duct. According to the site of involvement IPMNs are classified into three categories, i.e., main duct type, branch duct type, and combined type. Most branch duct IPMNs are benign, whereas the other two types are often malignant. A large size of branch duct IPMN and marked dilation of the main pancreatic duct indicate the presence of adenoma at least. The additional existence of large mural nodules increases the possibility of malignancy in all types. Of recent interest is the relatively high prevalence of synchronous and/or metachronous malignancy in various organs, including the pancreas. The prognosis is favorable after complete resection of benign and noninvasive malignant IPMNs. Malignant IPMNs acquiring aggressiveness after parenchymal invasion necessitate adequate lymph node dissection. On the other hand, asymptomatic branch duct IPMNs without mural nodules can be observed without resection for a considerably long time. This review addresses available data, current understanding, controversy, and future directions.     

Optimal management of the branch duct type intraductal papillary mucinous neoplasms of the pancreas

GOALS: To determine the optimal management of the intraductal papillary mucinous neoplasms (IPMNs) according to the morphologic type based on distinguishing between benign and malignant diseases. BACKGROUNDS: IPMNs are increasingly recognized clinicopathologic entity. Extended pancreatic resection with radical lymph node dissection has been recommended for treatment. STUDY: A retrospective clinicopathologic study was carried out of the 57 cases with IPMNs who were treated between 1985 and 2001. Forty-three patients with IPMNs underwent resection, and 14 patients with small IPMNs were observed without resection. RESULTS: Among the 43 resected IPMNs, 25 were benign and 18 were malignant. Malignant tumors were significantly greater in diameter than benign tumors (52.9 vs. 30.2 mm, P< 0.05). All main duct type tumors with mural nodules were malignant. All branch duct type tumors less than 30 mm in diameter and without mural nodules were benign. Twelve branch duct type IPMNs size less than 30 mm were not resected and have not progressed. CONCLUSION: These results suggest that the branch duct type IPMNs less than 30 mm and without mural nodules is benign and might be treatable with limited resection or careful observation.     

Suppressive effect of sulindac on branch duct-intraductal papillary mucinous neoplasms

Backgound

When considering surgery for branch duct-intraductal papillary mucinous neoplasms (BD-IPMNs) with suspected malignancy, it should be recognized that these lesions are frequently multifocal and are usually found in elderly patients with potential comorbidities that could affect the outcome of surgery. Clinical trials of chemoprevention have been conducted for a wide variety of malignancies.

Methods

Twenty-two BD-IPMN patients participated in the trial at our institution from June 2004 to January 2007. Ten of the 22 patients who rejected surgical therapy although their lesions or clinical symptoms met the criteria for surgical resection of the International Association of Pancreatology guidelines were assigned to the treatment group. Sulindac (150 mg twice daily) and omeprazole (20 mg once daily) were administered to these patients for 18 months. The remaining 12 patients comprised the control group. Branch duct diameter and mural nodule heights were monitored by either magnetic resonance cholangiopancreatography (MRCP) or computed tomography (CT) and by endoscopic ultrasonography (EUS).

Results

Both branch duct diameter and mural nodule height of BD-IPMNs in the treatment group were significantly reduced, while those in the control group were unchanged. Immunohistochemical staining for cyclooxygenase-1 and -2 was negative in hyperplasia, adenoma and carcinoma portions of resected pancreatic specimens but was clearly positive for glutathione-S-transferase π (GST-π), suggesting that GST-π is a putative target molecule for sulindac.

Conclusions

Although a larger scale randomized controlled study is needed in future, the present results suggest the promise of chemoprevention of carcinoma derived from BD-IPMNs by sulindac.     

Magnetic resonance (MR) for mural nodule detection studying Intraductal papillary mucinous neoplasms (IPMN) of pancreas: Imaging-pathologic correlation

PurposeMagnetic Resonance (MR) is recommended to diagnose Intraductal Papillary Mucinous Neoplasms (IPMN) and in the follow-up of borderline lesions. The purpose of this work is to evaluate the diagnostic accuracy of dynamic MR with Diffusion Weighted Imaging (DWI) in the identification of mural nodules of pancreatic IPMN by using pathological analysis as gold standard.Materials and methodsNinety-one preoperative MR with histopathological diagnosis of IPMN were reviewed by two radiologists. Presence, number and size of mural nodule, signal intensity of the nodule on T1-weighted imaging (T1-WI) after contrast medium administration and on DWI. Inter-observer agreement was evaluated.ResultsSignificant correlation (p < 0.0001) were found for presence of nodules > 5 mm on MR and pathological specimen, size and number of mural nodules evaluated on pathological review and degree of dysplasia, size and number of mural nodules evaluated on MR and tumoral dysplasia, presence of nodule > 5 mm with enhancement after contrast medium administration and hyperintensity on DWI and degree of dysplasia. Interobserver agreement was moderate for the presence of mural nodule (K = 0.56), for the presence of high signal intensity on DWI (K = 0.57) and enhancement of mural nodule (K = 0.58). Apparent Diffusion Coefficient (ADC) map histogram analysis showed a correlation between Entropy of the entire cystic lesion and the degree of dysplasia (p < 0.034).ConclusionsMR with dynamic and DWI sequences was an accurate method for the identification of ≥ 5 mm solid nodules of the IPMNs and correlate with the lesion malignancy. Entropy, calculated from the histogram analysis of the IPMN ADC map, correlated with the lesion dysplasia.     

Inferior head resection of the pancreas for intraductal papillary mucinous neoplasms

Background

Previous reports have suggested that patients with intraductal papillary mucinous neoplasm (IPMN) have a favorable prognosis after surgical resection. Thus, a variety of types of partial pancreatic resections have been advocated for treating these low-grade malignant tumors. However, the surgical outcome of IPMN after such limited pancreatectomy has not been fully clarified.

Methods

We performed a retrospective review of the clinicopathologic features and surgical outcome in 15 patients who underwent inferior head resection for IPMN at the Chiba University Hospital and National Cancer Center Hospital East between July 1994 and January 2007.

Results

There were 13 patients with noninvasive IPMNs (10 adenomas and 3 noninvasive carcinomas) and 2 patients with minimally invasive intraductal papillary mucinous carcinoma (minimally invasive IPMN). Complete tumor removal (R0 resection) was performed in four patients (80%) with intraductal papillary mucinous carcinoma. Subsequent pancreatoduodenectomy was performed in one patient because of noninvasive carcinoma with multiple mucous lakes in the pancreatic parenchyma. Values for N-benzoyl-l-tyrosyl-p-aminobenzoic acid excretion test results before (n?=?13) and after (n?=?13) the operation were 70.7 and 66.1, showing no significant difference. The 2-h glucose levels in the 75?g oral glucose tolerance test before (n?=?13) and after (n?=?13) the operation were 133 and 146?mg/dl, respectively, showing no significant difference. Pancreatic fistula occurred in 7 (47%) patients. Overall morbidity and mortality rates were 67 and 0%, respectively. The overall 1-, 3-, 5-, and 10-year survival rates for the 15 patients were 100, 79, 79, and 71%, respectively. The 1-, 3-, 5-, and 10-year survival rates for patients with noninvasive IPMN (n?=?13) and those with minimally invasive IPMN (n?=?2) were 100, 92, 92, and 83%; and 100, 0, 0, and 0%, respectively. There was a significant difference in survival between patients with noninvasive IPMN and those with minimally invasive IPMN (p?=?0.0005). No patient with noninvasive IPMN developed recurrent disease. One patient with minimally invasive IPMN died of recurrent peritoneal dissemination 18?months after margin-positive R1 resection. Two patients died of pancreatic ductal adenocarcinoma, 30 and 78?months after inferior head resection.

Conclusions

Pancreatic endocrine and exocrine function was well preserved after inferior head resection. Pancreatic fistula occurred more frequently after inferior head resection than with conventional pancreatoduodenectomy. Patients with noninvasive IPMN had favorable survivals after this procedure. However, one patient with minimally invasive IPMN with margin-positive R1 resection died of recurrent disease. Thus, margin-negative R0 resection should be performed for IPMN.     

A resected case of two branch duct-type intraductal papillary mucinous neoplasms showing different clinical courses after a two-year follow-up

The patient was a 60-year-old man without any particular complaints, but he underwent abdominal computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP) due to a fatty liver, which revealed two similar cystic lesions regarded as branch duct-type intraductal papillary mucinous neoplasm (BD-IPMN) in the pancreatic body [BD-IPMN (b), 16 mm in size] and tail [BD-IPMN (t), 13 mm in size] without a “high-risk stigmata” or “worrisome features”. He subsequently received follow-up by MRCP every 6 months. Two years later, MRCP showed prominent dilation of the main pancreatic duct (MPD) and mural nodule formation within the dilated MPD adjacent to the BD-IPMN (b). Distal pancreatectomy specimens revealed that the BD-IPMN (b) was lined by low-papillary gastric mucinous epithelium with low-to-intermediate-grade dysplasia and involved the MPD, forming a malignant mural nodule showing pancreatobiliary-type IPMN. In contrast, the BD-IPMN (t) was lined by flat, monolayer columnar gastric mucinous epithelium without atypia, which suggested the possibility of a “simple mucinous cyst”. A genetic analysis showed KRAS mutation only in BD-IPMN (b). Differences in the histological and genetic findings between two similar BD-IPMNs in the present case may suggest what kinds of examinations should be performed in patients with BD-IPMNs without any worrisome features.     

Preoperative evaluation of malignancy in intraductal papillary mucinous neoplasms of the pancreas, especially in relation to dysplastic epithelial changes

BACKGROUND/AIMS: Intraductal papillary mucinous neoplasms have a better prognosis than ductal adenocarcinomas of the pancreas. The aim of this study was to evaluate the malignant potential of IPMNs by their preoperative images. METHODOLOGY: Forty-three intraductal papillary mucinous neoplasms were divided into 3 duct ectatic types using preoperative images (the main duct type, the branch duct type, and the mixed type), and into 2 groups using resected specimens (the malignant group including severe dysplasia based on the WHO classification and the benign group). The diameters of the tumor, main pancreatic duct and mural nodule were measured on the images. RESULTS: Two thirds of main duct type cases were in the malignant group. For the branch duct and mixed types, the diameters of the tumor and detectable mural nodules were larger in the malignant group than in the benign group. A tumor diameter larger than 3.5cm and a mural nodule diameter larger than 6mm were risk factors for malignancy (p < 0.05). CONCLUSIONS: The main duct type, a tumor larger than 3.5cm of the branch duct or mixed type, and a mural nodule larger than 6mm were all indicators of malignancy risk.     

Evaluation of the International Consensus Guidelines for the Surgical Resection of Intraductal Papillary Mucinous Neoplasms

Background

International consensus guidelines for intraductal papillary mucinous neoplasms (IPMNs) were revised in 2012.

Aims

We aimed to evaluate the clinical utility of each predictor in the 2006 and 2012 guidelines and validate the diagnostic value and surgical indications.

Methods

Forty-two patients with surgically resected IPMNs were included. Each predictor was applied to evaluate its diagnostic value.

Results

The 2012 guidelines had greater accuracy for invasive carcinoma than the 2006 guidelines (64.3 vs. 31.0%). Moreover, the accuracy for high-grade dysplasia was also increased (48.6 vs. 77.1%). When the main pancreatic duct (MPD) size ≥8 mm was substituted for MPD size ≥10 mm in the 2012 guidelines, the accuracy for high-grade dysplasia was 80.0%.

Conclusions

The 2012 guidelines exhibited increased diagnostic accuracy for invasive IPMN. It is important to consider surgical resection prior to invasive carcinoma, and high-risk stigmata might be a useful diagnostic criterion. Furthermore, MPD size ≥8 mm may be predictive of high-grade dysplasia.

     

Can the location of the mural nodule indicate benign or malignant in branch duct-type intraductal papillary mucinous neoplasm of the pancreas?

Background/ObjectivesIntraductal papillary mucinous neoplasms (IPMNs) are classified into main duct (MD)-type IPMNs, branch duct (BD)-type IPMNs, and mixed type IPMNs. While MD-type IPMN has a high risk of malignancy and should therefore be considered for resection if the patient is fit, BD-type IPMN needs to be carefully judged for surgical indication. The decision to resect BD-type IPMN is often based on international consensus Fukuoka guidelines 2017, but further investigation is required. In this study, we focused on whether the location of the mural nodule (MN) could be an indicator of malignancy.MethodsWe enrolled 17 cases who had been diagnosed BD-type IPMNs which were surgically resected from January 2016 to December 2019. These cases were classified into benign and malignant group. Subsequently, a clinicopathological study was conducted based on the localization of MN (MN-central type or MN-peripheral type).ResultsAlthough MN was found in 57% (4/11) in the benign group, 88% (7/8) was noted in the malignant group, indicating the presence of MN to be more common in the malignant group. Those with MN consisted of 6 cases of MN-central type and 5 cases of MN-peripheral type. All cases of central type were malignant compared to only one case of the peripheral group being confirmed on histology as cancer.ConclusionBD-IPMN with central mural nodule should be considered high risk for malignancy.     

Pancreatic juice cytology in IPMN of the pancreas.

BACKGROUND: Intraductal papillary-mucinous neoplasm (IPMN) of the pancreas is a disease ranging from adenoma to borderline (with moderate dysplasia) and further to carcinoma (noninvasive and invasive) and surgical strategy is different by the grades of dysplasia. METHODS: Preoperative pancreatic juice cytology in IPMN was reviewed in 71 patients with IPMN who underwent surgical resection. RESULTS: The IPMN was adenoma in 48 patients, borderline in 13 and carcinoma (invasive) in 10. The sensitivity of pancreatic juice cytology in malignant IPMN was 40% (4/10). In 4 patients with the 48 IPM adenomas, diagnosis of pancreatic juice cytology was class IV or V. One of the 4 cases was considered to be an overdiagnosis of cytology, but the other 3 cases were considered to be a consequence of accompanying carcinoma in situ (or PanIN-3) (2 patients) or invasive ductal adenocarcinoma (1 patient) apart from IPMN. Sensitivity of pancreatic juice cytology was higher in IPMN of the main duct type with mucin hypersecretion and with mural nodules. CONCLUSIONS: These findings suggest that pancreatic juice cytology in IPMN is useful especially in the main duct type with mucin hypersecretion and mural nodules. When the diagnosis of pancreatic juice cytology is malignant in otherwise benign-looking IPMNs, coexistence of pancreatic carcinoma should be suspected.     

Different subtypes of intraductal papillary mucinous neoplasm in the pancreas have distinct pathways to pancreatic cancer progression

Background

Intraductal papillary mucinous neoplasm (IPMN) is recognized as a precursor lesion to pancreatic cancer, a unique pathological entity. IPMN has subtypes with different clinical characteristics. However, the molecular mechanisms of cancer progression from IPMN remain largely unknown. In this study we examined the differences in genetic alteration(s) among the IPMN subtypes.

Methods

Surgically resected IPMNs (n?=?25) were classified into four subtypes by hematoxylin and eosin (H&;E) and mucin immunostaining. Mutations in KRAS, BRAF, and PIK3CA genes and expression of CDKN2A, TP53, SMAD4, phospho-ERK, and phospho-SMAD1/5/8 proteins were examined.

Results

There were 11 gastric, 11 intestinal, one pancreatobiliary, and two oncocytic types in this study. We then compared the two major subtypes, gastric-type and intestinal-type IPMN. Gastric-type IPMN showed a significantly higher incidence of KRAS mutations (9/11, 81.8%) compared with intestinal type (3/11, 27.3%; p?p?KRAS mutations showed phospho-ERK immunostaining. In contrast, intestinal type (9/11, 81.8%) showed more frequent SMAD1/5/8 phosphorylation compared with gastric-type IPMN (3/11, 27.3%; p?Conclusions There may be distinct mechanisms of pancreatic cancer progression in the different subtypes of IPMN. In particular, KRAS mutation and bone morphogenetic protein-SMAD signaling status may be crucial diverging steps for the two representative pathways to pancreatic cancer in IPMN patients.