ABSTRACT Context Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas have been detected with increasing frequency as a result of the progression of diagnostic modalities. Recently, invasive ductal carcinoma of the pancreas concomitant with IPMNs has been the focus of attention. Case report We report the case of a 57-year-old man with multifocal ductal carcinomas of the pancreas concomitant with IPMNs detected by intraoperative cytology. During a follow-up for branch duct IPMNs, a stenotic lesion of the main duct in the pancreatic body was found by ERCP, and brush cytology of the stenosis revealed an adenocarcinoma. A distal pancreatectomy was proposed; however, intraoperative pancreatic juice cytology from the pancreatic head also revealed adenocarcinoma, and a total pancreatectomy was finally carried out. Pathological examination of the resected specimen showed multifocal ductal carcinomas and IPMNs in the distal pancreas, and invasive ductal carcinoma in the pancreatic head which had not been detected by preoperative imaging studies. Conclusions Surgeons should be aware of the possibility of multifocal carcinomas in patients with concomitant IPMNs. Intraoperative pancreatic juice cytology should always be performed in order to confirm the absence of carcinoma in the pancreas to be left in place after planned resection

Junji Ueda

Kosuke Tsutsumi

Masafumi Nakamura

Masao Tanaka

Shunichi Takahata

Takaharu Yasui

Takao Ohtsuka

Yasuhisa Mori

Yoshihiko Sadakari

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JOP. J Pancreas (Online) 2010 Jul 5; 11(4):389-392. 
JOP. Journal of the Pancreas - http://www.joplink.net - Vol. 11, No. 4 - July 2010. [ISSN 1590-8577] 389
CASE REPORT 
 
 
Multifocal Pancreatic Ductal Adenocarcinomas Concomitant with 
Intraductal Papillary Mucinous Neoplasms of the Pancreas Detected 
by Intraoperative Pancreatic Juice Cytology. A Case Report 
 
 
Yasuhisa Mori, Takao Ohtsuka, Kosuke Tsutsumi, Takaharu Yasui, Yoshihiko Sadakari, 
Junji Ueda, Shunichi Takahata, Masafumi Nakamura, Masao Tanaka 
 
 
Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University. 
Fukuoka, Japan 
 
 
ABSTRACT 
Context Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas have been detected with increasing frequency as a result 
of the progression of diagnostic modalities. Recently, invasive ductal carcinoma of the pancreas concomitant with IPMNs has been 
the focus of attention. Case report We report the case of a 57-year-old man with multifocal ductal carcinomas of the pancreas 
concomitant with IPMNs detected by intraoperative cytology. During a follow-up for branch duct IPMNs, a stenotic lesion of the 
main duct in the pancreatic body was found by ERCP, and brush cytology of the stenosis revealed an adenocarcinoma. A distal 
pancreatectomy was proposed; however, intraoperative pancreatic juice cytology from the pancreatic head also revealed 
adenocarcinoma, and a total pancreatectomy was finally carried out. Pathological examination of the resected specimen showed 
multifocal ductal carcinomas and IPMNs in the distal pancreas, and invasive ductal carcinoma in the pancreatic head which had not 
been detected by preoperative imaging studies. Conclusions Surgeons should be aware of the possibility of multifocal carcinomas in 
patients with concomitant IPMNs. Intraoperative pancreatic juice cytology should always be performed in order to confirm the 
absence of carcinoma in the pancreas to be left in place after planned resection. 
 
INTRODUCTION 
 
Intraductal papillary mucinous neoplasms (IPMNs) of 
the pancreas were first reported in 1982 by Ohashi et 
al. [1] and have been detected with increasing 
frequency as a result of the progression of diagnostic 
modalities. Recently, invasive ductal carcinoma of the 
pancreas concomitant with IPMNs has been the focus 
of attention [2], and ductal carcinoma of the pancreas 
in addition to IPMN has been reported to develop in 
9.2% of patients with IPMNs [3]. We herein report the 
case of a patient having multifocal ductal carcinomas 
concomitant with IPMNs which were detected by 
intraoperative pancreatic juice cytology and were 
treated by total pancreatectomy. 
 
CASE REPORT 
 
A 57-year-old man was admitted to our hospital in 
2003 due to cystic lesions in the pancreas which had 
been detected by health screening ultrasonography. He 
had had a past history of diabetes mellitus but did not 
have a family history of malignancy. Laboratory tests 
including blood cell counts, blood chemistry and tumor 
markers, carcinogenic embryonic antigen (CEA) and 
carbohydrate antigen 19-9 (CA 19-9) were all within 
normal limits. Enhanced computed tomography (CT) 
showed a low density mass measuring 10 mm in the 
tail of the pancreas. Magnetic resonance cholangio-
pancreatography demonstrated two small cystic 
lesions, 10 mm in diameter in the pancreatic tail and 5 
mm in the pancreatic head. Endoscopic retrograde 
cholangiopancreatography revealed a cystic dilatation 
of the branch duct measuring 10 mm in the tail of the 
pancreas without dilation of the main pancreatic duct. 
Cytologic examination of the pancreatic juice collected 
by the use of secretin (ChiRhoStimTM, ChiRhoClin, 
Inc., Burtonsville, MD, USA) during ERCP 
demonstrated no malignant cells (Class II). Based on 
these results, a diagnosis of multiple benign branch 
duct IPMNs was made, and follow-up observations 
were scheduled for every 6 months. In 2006, CT and 
MRI revealed that the size of the IPMN in the 
Received May 12th, 2010 - Accepted May 18th, 2010 
Key words Carcinoma, Pancreatic Ductal; Neoplasms, Cystic, 
Mucinous, and Serous; Pancreatectomy; Pancreatic Juice /cytology 
Correspondence Masao Tanaka 
Department of Surgery and Oncology, Graduate School of 
Medical Sciences, Kyushu University, 3-1-1 Maidashi, Fukuoka
812-8582, Japan 
Phone: +81-92.642.5444; Fax: +81-92.642.5458 
E-mail: masaotan@surg1.med.kyushu-u.ac.jp 
Document URL http://www.joplink.net/prev/201007/10.html 
JOP. J Pancreas (Online) 2010 Jul 5; 11(4):389-392. 
JOP. Journal of the Pancreas - http://www.joplink.net - Vol. 11, No. 4 - July 2010. [ISSN 1590-8577] 390
pancreatic tail had slightly increased to 15 mm in 
diameter; however, cytology of the pancreatic juice 
during ERCP showed no atypical cells (Class II) and, 
therefore, the patient continued to be followed up. 
The findings of CT and MRI in 2009 showed no 
remarkable change; however, ERCP demonstrated 
dilatation of the orifice of the duodenal papilla with 
mucin excretion and a irregular stenotic lesion 
measuring 5 mm in the main pancreatic duct of the 
pancreatic body (Figure 1). Both brush cytology from 
the stenotic lesion and subsequent pancreatic juice 
cytology collected by a balloon catheter placed in the 
pancreatic head demonstrated adenocarcinoma (Class 
V). At this time, the serum CEA level was normal 
while the CA 19-9 level was slightly elevated to 38.4 
U/mL (reference range: 37.0 U/mL). A distal 
pancreatectomy was proposed with a diagnosis of 
pancreatic ductal carcinoma concomitant with branch 
duct IPMNs. Hypersecretion of mucin was considered 
to be from the IPMN in the pancreatic tail, and was 
expected to be resected. However, to avoid the 
possibility of co-existent pancreatic cancer in the 
remnant pancreas, intraoperative pancreatic juice 
cytology in the remnant pancreas was also planned. 
During surgery, there was neither peritoneal 
dissemination nor liver metastasis. The pancreas was 
cut above the portal vein, and then a 4 French tube was 
inserted into the main pancreatic duct of the remnant 
pancreas about 2 cm from the cut margin. Fluid for 
cytology was obtained by saline irrigation through the 
tube with a syringe. Although the surgical cut margin 
was pathologically negative for cancer cells, cytologies 
of the pancreatic juice obtained 3 times from the 
remnant pancreas proved to be positive. Therefore, a 
total pancreatectomy was performed, followed by 
hepaticojejunostomy and duodenojejunostomy in the 
Billroth-II fashion. Operating time was 10 hours and 
blood loss was 1,185 g. 
Pathological examination of the resected specimen 
revealed that there were two invasive carcinomas in the 
head and tail of the pancreas, and two non-invasive 
ductal carcinomas as shown in Figure 2. The sizes of 
the two invasive carcinomas in the pancreatic head and 
tail were 12 mm and 3 mm, respectively. Those lesions 
had no definitive communication with each other. 
There were two cystic dilations of the branch ducts in 
the body and tail of the pancreas, both of which were 
intraductal papillary mucinous adenomas. A regional 
lymph node on the posterior surface of the pancreatic 
head contained carcinoma cells. The postoperative 
course was uneventful, and the patient has received 
chemotherapy using gemcitabine for 6 months to date 
without any sign of recurrence. The patient had also 
been treated to control pancreatic diabetes with a 
satisfactory nutrient status and quality of life.  
DISCUSSION  
It is well known that an IPMN is often accompanied by 
malignant diseases including gastric, colon and lung 
cancers [4]. In addition to such extrapancreatic cancers, 
we previously stated that attention should be paid to the 
possible presence of ductal carcinoma of the pancreas 
because 7 of the 76 (9.2%) patients of our series of 
patients with IPMNs had ductal carcinoma of the 
pancreas [5]. Using the latest technology, we have 
recently reported that concomitant ductal carcinoma 
was detected synchronously or metachronously in 22 of 
236 patients with IPMN (9.3%) [3]. Of note, all of 
these 22 patients had a benign branch duct IPMN, and 
our patient also had two branch duct IPMNs. We have 
also demonstrated that a worsening of diabetes mellitus 
and elevated serum CA 19-9 levels are indicators for 
coexisting ductal carcinoma during a follow-up of 
IPMNs, although these were not observed in the 
current patient. The precise mechanisms of the 
coexistence of ductal carcinoma with branch duct 
IPMNs of the pancreas remains unknown. In addition, 
multifocal ductal carcinomas concomitant with IPMNs 
are a very rare condition, and, in our experience, this is 
first case to date. Further clinical and molecular-based 
investigations are necessary to elucidate the 
mechanism of the development of ductal carcinoma 
and an IPMN in the same pancreatic organ. However, 
an IPMN could be an indicator of coexisting pancreatic 
ductal carcinoma, and careful attention should be paid 
to the possibility of concomitant malignant diseases 
including pancreatic ductal carcinoma, even when the 
existing IPMN is diagnosed as benign. 
Eguchi et al. and Ishikawa et al. [6, 7] demonstrated 
that intraoperative pancreatic juice cytology as well as 
frozen-section histology during resection of an IPMN 
are necessary to detect continuous or skip lesions. They 
collected the pancreatic juice from the pancreatic head, 
body and tail by the use of a balloon catheter, in 
Figure 1. a. Computed tomogram showing a low density mass in the
tail of the pancreas, the size of which had slightly increased to 15
mm in diameter (arrow). b. Magnetic resonance cholangio-
pancreatogram demonstrating two small cystic lesions; 10mm in
diameter in the pancreatic tail (long arrow) and 5mm in the
pancreatic head (short arrow). c. ERCP showing a cystic lesion
measuring 10 mm in the tail of the pancreas (arrow with broken line),
and stenotic lesions in the main duct of the pancreatic body (arrows).
d. Endoscopic photograph of the dilated orifice of the duodenal
papilla with mucin excretion. 
JOP. J Pancreas (Online) 2010 Jul 5; 11(4):389-392. 
JOP. Journal of the Pancreas - http://www.joplink.net - Vol. 11, No. 4 - July 2010. [ISSN 1590-8577] 391
addition to frozen-section histology of the surgical 
margin, during pancreatectomy for IPMNs, and 
showed that 42% of the patients required additional 
pancreatic resection for intraductal carcinomas. At our 
institution, intraoperative irrigation cytology is 
routinely performed three times during a 
pancreatectomy for IPMN, when there are IPMN(s) in 
the remnant pancreas or preoperative pancreatic juice 
cytology is positive for cancer cells. Although the two 
IPMNs were included in the initially resected side in 
our patient, preoperative pancreatic juice cytology was 
positive for cancer cells and, therefore, intraoperative 
cytology was also performed. As a result, we could 
detect the ductal carcinoma in the pancreatic head, 
which had not been detected by any preoperative 
imaging studies. We previously reported two patients 
having a branch duct IPMN with a concomitant 
carcinoma in situ which was likewise not detected by 
imaging studies but was diagnosed by pancreatic juice 
cytology preoperatively [8]. The reason for carrying 
out irrigation cytology three times is to negate the 
possibility of migration of the floating cancer cells in 
the resected side into the portion to be left unremoved. 
During collection of the pancreatic juice, operators 
should pay attention to leakage of the pancreatic juice 
into the abdominal cavity to prevent later possible 
dissemination. 
Total pancreatectomy was first introduced in 1943 by 
Rockey [9]; however, the indication for such a 
procedure has been limited to date because of its high 
morbidity and mortality. Recently, several reports have 
shown the efficacy and safety of total pancreatectomy 
in selected patients [10, 11, 12, 13]. Reddy et al. [14] 
demonstrated that operative mortality after total 
pancreatectomy decreased over time from 40.0% to 
1.9%. Our patient had an uneventful postoperative 
course and his postoperative nutrition and quality of 
life have been satisfactory due to the control of the 
pancreatic diabetes. Total pancreatectomy seems to 
have become a feasible procedure in selected patients, 
and should be considered when the oncological 
situation leaves no choice. 
In conclusion, careful attention should be paid to the 
possible presence of ductal carcinoma in patients with 
IPMNs. During surgery for IPMN(s), intraoperative 
irrigation cytology from the remnant pancreas could be 
useful in detecting the lesions which were not observed 
in the preoperative imaging studies. If this is the case, 
Figure 2. Upper panel. Schematic representation of the location of intraductal papillary mucinous neoplasms (IPMNs) and non-invasive and 
invasive ductal carcinomas. Lower panel. Microscopic photographs corresponding to the lesions are also shown (H&E; left x40; middle x200; right
x40, insert x100). 
JOP. J Pancreas (Online) 2010 Jul 5; 11(4):389-392. 
JOP. Journal of the Pancreas - http://www.joplink.net - Vol. 11, No. 4 - July 2010. [ISSN 1590-8577] 392
then total pancreatectomy should be considered when 
the oncological situation leaves no choice. 
 
 
Conflict of interest The authors have no potential 
conflict of interest 
 
 
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