the malignant potential of intraductal papillary - mucinous neoplasm ( ipmn ) of the pancreas has been estimated based on three viewpoints : histologic grades ( adenoma , carcinoma and their borderline lesion ) , localization ( main duct - type and branch duct - type ) , and histologic subtypes ( gastric type , intestinal type , pancreatobiliary type , and oncocytic type ) [ 1 , 2 ] . these viewpoints have a deep connection for each other , such as , the gastric type , which occurs in the periphery of the pancreatic parenchyma , corresponds to the branch duct type , and which usually shows a multicystic lesion with less invasive pattern , adenoma . then , branch - type ipmn ( ipmn - br ) has been usually an object for just follow up . however , recent guidelines indicated operative indication as the followings : symptoms attributable to the cyst , dilation of the main pancreatic duct ( mpd ) over 10 mm , cyst size over 30 mm with the intramural nodule , or cystic fluid with cytological malignancy . in fact , relative surgical indications were applied for cases with disease development such as pancreatitis , positive cytology , or solid mass formation in the followup term for ipmn - br [ 4 , 5 ] . by contrast , there was no report describing the ipmn - br to show morphologic change and transformation to the main duct . in the present , our experienced ipmn - br case , which is visualized for transition gradually from branch to mpd in three years followup images , was found to include several patterns of subtypes by histopathological study . this phenomenon might be critical to estimate the malignant potential or surgical indication for ipmn - br . a continuous image of 64-year - old man , who was referred to the department of medicine at our hospital for further evaluation of gallbladder stones , was shown in figure 1 . a magnetic resonance cholangiopancreatography ( mrcp ) showed a multilocular cystic lesion for 20 mm in diameter in the head of the pancreas . the main pancreatic duct was noted smoothly except for the head adjacent to the multilocular cyst . although these findings suggested a cystic neoplasm such as serous cystadenoma , the existence of duct - cyst connection ( arrow ) strongly suggested that the most likely diagnosis was intraductal papillary - mucinous neoplasm ( ipmn ) mainly located in the branch ducts . followup mrcp revealed gradual increase of the cystic components and its sizes , from 2.0 cm to 3.8 cm with dilation of mpd over 10 mm until 2005 . in 2006 , since intraductal nodule with elevation of serum amylase appeared , surgical indication was evaluated . the levels of serum tumor marker , such as carcinoembryonic antigen ( cea ) or carcinohydrate antigen 19 - 9 ( ca19 - 9 ) , were in normal range . the cytological study for pancreatic juice showed findings for high - grade intraductal papillary - mucinous carcinoma ( ipmc ) ; therefore , surgical procedure was selected . on laparotomy , a cystic mass , 4.0 cm in diameter , was identified in the pancreatic head . macroscopically , cystic dilation of mpd was filled with soft papillary tumor producing mucin . and solid tumor in mpd and communicating branch ducts was visualized with different components : gastric - type adenoma showing closely packed tubular glands similar as pyloric gland - like morphology and dark eosinophilic cells with marked pseudostratificatied spindle nuclei for an intestinal - type carcinoma . in branch ducts , components of intestinal - type carcinoma showed irregular arborizing growth . adjacent to the branch duct , a minimal invasion was observed as a dilated mucouslake containing scanty cancer cells floating in the abundant mucin , indicating mucinous carcinoma . under consideration for the invasive components existed with the distance of less than 5 mm schematic presentation of histologic distribution in the present case is shown in figure 3 ( left column ) .   to estimate the malignant potential , additional immunohistochemistry ( ihc ) was performed by using primary antibodies as followed : ki67 ( clone mib-1 , nichirei , 1:200 ) , proliferating cell nuclear antigen ( clone pcna , dakocytomation , 1:200 ) , and c - met ( clone c - met , santa cruz biotechnology inc , 1:200 ) , as described in previous report . these molecules have been reported to be involved in the early events of carcinogenesis , formation of in situ carcinoma in the stepwise progression of ipmn and ordinary pancreatic ductal carcinoma . the expression of the three molecules was independently evaluated by two investigators ( y s and s k ) . evaluation of the staining was determined based on the following criteria . in ki67 and pcna , stained cells were accounted for less than 10% regarding for negative ( 0 ) , and 10% or more for positive with further classified 10% to 30% ( 1 + ) and over 30% ( 2 + ) . for c - met , positivity was rated for 1 + or 2 + under 30% cut - off line , respectively . ki67 and pcna were focally stained in the intestinal - type carcinoma in the mpd . in branch ducts , intestinal - type carcinoma components showed diffuse staining for ki67 and pcna . in addition , pcna was focally stained in gastric - type adenoma components in branch ducts , but not in the mpd . c - met was diffusely expressed in the intestinal - type carcinoma , whereas gastric - type adenoma components showed focal and thin staining both in the mpd and branch ducts . the microscopic and immunohistochemical findings indicated a diagnosis of combined type ipmc with minimal invasion from branch duct . although the nodular growth of ipmn cells was observed adjacent to the resection margin of the mpd , the epithelium of the mpd at the resection margin was lined with normal epithelial cells . in common , the indication of surgical procedures for ipmn - br was accepted for the presence of symptom , solid mass formation , or positive cytology , suggesting the mucinous cystic neoplasm . otherwise , followup regimens based on clinical experiences have no strong evidence , according to the past report , once a year evaluation for lesions fewer than 10 mm , 6 to 12 months for 10 to 20 mm , and 3 to 6 months for over 20 mm . despite ipmn - br was known for less invasive comparing to the main - duct type , its malignant morphology was also demonstrated . in fact , carcinoma in situ or invasive carcinoma was detected in 22% of resected ipmn - br . in the present case , the cystic mass grew up gradually year by year and the size was 3.8 mm at the time of operation after 36 months followup . according to the past report for 66 conservative cases , 11 ipmn - br were decided for surgical procedure after a median follow - up of 41 months ; 9 of the 11 patients had malignancy , including 4 carcinoma in situ and 5 invasive carcinomas . waters et al . enhanced the critical role of mrcp for followup to provide the favorite information of ipmn with matching actual pathology . in the present case also , the connection of cystic components to the mpd was clearly detected due to mrcp , and the cystic lesion was found to change its feature to grow up to the mpd . however , among our referring to the past reports , the gradual infiltration from ipmn - br to the mpd during follow - up has not been described . the present case was found to have two independent subtypes , gastric - type and intestinal - type , supporting   the recognition for ipmn to compose a combination of over two subtypes . previously , we also described another case of ipmn with gastric - type adenoma and intestinal - type borderline lesion . the gastric - type adenoma of the ipmn is known to be localized just in the peripheral branches without any malignant potential [ 10 , 11 ] , supporting that the ipmn - br has to be applied for followup . then , the first mrcp offered clinical imaging course demonstrated no doubt for the present ipmn to rise from the peripheral branch . on the other hand , in the resected specimen , both gastric - type adenoma and intestinal - type carcinoma were detected in both the mpd and branch ducts , demonstrating the possibility for ipmn - br to change the malignant morphology . the present feature is usually not typical for ordinary gastric - type adenoma , and the distribution or histologic features in branch ducts of the present case differ from generally believed consensus in terms of the following viewpoints . second , minimally invasion was observed adjacent to a branch duct , not to the mpd . findings in the present case suggest that tumor cells in branch ducts possess malignant potential leading carcinogenesis . reported a case of gastric - typed ipmn - br with focal nodular growth to progress intraductal carcinoma of pancreatobiliary type . imaging features during follow - up support the idea that intraductal tumor cells in the mpd can be recognized as a later stage in the present case , harboring more malignant potential than those in branch ducts . intestinal - type carcinoma in the mpd is derived from the continuous progression that corresponds to the branch duct type showing low histologic grade ( adenoma ) .   to evaluate the further actions for malignant potential in ipmn - br ki67 and pcna were found to show positivity ratio increasing with increasing grade of atypism in ipmn [ 14 , 15 ] . in the present case , the most diffuse staining positively of ki67 and pcna was observed in the components of intestinal - type carcinoma of the present ipmn in branch duct , but not in the mpd ( table 1 ) .   taken together , the present tumor had intestinal type with high - grade malignant potential in early stage . pcna was also indicated to promote the proliferation of pancreatic ductal carcinoma with interaction of kiaa0101 and ki67 and then play a critical role in the regulation of cell cycle . these results suggest that tumor components with malignant potential in peripheral branch ducts develop the proliferation and formation of invasive potency . in addition , c - met is well known as a receptor of hepatocyte growth factor and is also associated with early events of carcinogenesis in the pancreas . and , the high expression of c - met was also found to involve in intestinal metaplasia of the bile duct epithelium , meaning its relation to the intestinal pathway during carcinogenesis . then , c - met expression was most diffusely noted in intestinal type carcinoma regardless of its localization ( the mpd or branch ducts ) , suggesting that the intestinal pathway is associated with the morphogenesis of ipmn progression in branch ducts .   in conclusion , the present clinical , regular histological , and immunohistochemical observations provided evidence that the components in branch ducts also might possess malignant potential leading invasive carcinoma . further ihc study to reveal the malignant potential will lead the extend strategy in the future .
a 64-year - old man underwent mrcp for further examination of gallbladder stones and ipmn of branch - type ( ipmn - br ) was pointed out . 
 yearly mrcp had revealed the gradual increase of the cystic components , marked dilation of the main pancreatic duct ( mpd ) , and filling defects in the mpd . 
 after follow - up 
 for three years , he underwent pancreatoduodenectomy . 
 histologically , the dilated mpd and connecting dilated branch ducts were filled with nodular growth of tumor cells consisting of gastric - type adenoma with pyloric gland - like structures . in the mpd , a transition from gastric - type adenoma to intestinal - type carcinoma was observed . 
 in addition , in a dilated branch duct , some components of intestinal - type carcinoma with marked arborizing structures were observed . 
 a minimally invasion was observed around branch ducts . 
 immunohistochemistry revealed diffuse nuclear accumulation of pcna and ki67 in the tumor cells of branch dusts . 
 our observations suggest that the secondary infiltration to the mpd of ipmn - br and ipmn - br possesses malignant potential for microinvasion .