Ultrasonographic Characteristics of Intraductal Papillary Mucinous Neoplasm of the Pancreas

Ke Lü,Qing Dai*,Zhong-hui Xu,Yi-xiu Zhang,Li Tan,Yan Yuan,and Yu-xin Jiang

Department of Ultrasound,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences &Peking Union Medical College,Beijing 100730,China

INTRADUCTAL papillary mucinous neoplasm (IPMN)of the pancreas is a rare pancreatic tumor.Along with the further understanding of IPMN and the development of medical imaging technology,there were more cases of IPMN reported.However,there were few researches in the diagnostic value of ultrasonography for IPMN.We analyzed the clinical and ultrasonographic imaging features of IPMN of pancreas in order to assess the applicability of transabdominal ultrasonography in diagnosing IPMN.

PATIENTS AND METHODS

Patients

Between May 2005 and December 2008,12 cases of IPMN undergoing surgery were identified pathologically in Peking Union Medical College Hospital,including 4 (33.3%) adenomas and 8 (66.7%) adenocarcinomas.A retrospective review of clinical and ultrasonographic findings of these cases was conducted.

Transabdominal ultrasonography

Transabdominal ultrasonography was performed with 2-5 MHz curved array transducer using Philips HDI-5000,Philips iU22,and GE LOGIQ9.

The patients fasted for at least 8 hours before the abdominal ultrasonic examinations.Supine position was taken to obtain images of the pancreatic area.Images were saved in the hard disk for further analysis.

Based on the sonographic findings,the lesions of IPMN were classified into 3 types:main duct,branch duct,and combined type.The lesions of IPMN predominantly involving the main pancreatic duct with main duct dilation were classified as main duct type,while lesions mainly involving a branch duct without nodules in the main duct were classified as branch duct type,and those involving both main and branch ducts were classified as combined type.

All clinical presentations and ultrasonographic imaging results were reviewed and the correlation between ultrasonographic findings and histopathological results was analyzed.

Statistical analysis

Continuous variables were expressed as means±SD.Statistical analysis was carried out using SPSS 9.0.Descriptive data were reported.

RESULTS

Clinical presentations

There were 9 (75.0%) men and 3 (25.0%) women with a mean age of 60.1±9.6 years (range,32-73).Of the 12 patients with IPMN,9 (75.0%) had experienced symptoms including epigastric discomfort and/or pain and backache,7 had medical history of acute pancreatitis.Among the 8 malignant cases,5 presented diabetes and 2 presented steatorrhea.Three (25.0%) cases did not display any symptom and the lesions were found during routine check,among which one lesion was adenoma located in the tail of the pancreas and the other two were adenocarcinomas located in the body and the neck of the pancreas,respectively.Raised serum CA19-9 level was only presented in 4(33.3%) patients with adenocarcinomas.One patient with malignant IPMN had adenocacinoma of colon simultaneously.General information and major clinical features of both benign and malignant cases are shown in Table 1.

Ultrasonographic findings

Both dilation of the main pancreatic ducts and lesions of the IPMNs were demonstrated by transabdominal ultrasound.The mean diameter of all the lesions was 4.6±3.6 cm(range,0.5-20.0) with dilated main duct of 1.9±0.8 cm(range,0.2-3.4).The mean diameter of the lesions in adenomas was 1.4±0.8 cm (range,0.5-2.0) with main duct dilation of 1.0±0.8 cm (range,0.2-1.9).The mean diameter of the lesions in adenocarcinomas was 6.3±6.0 cm(range,2.0-20.0) with main duct dilation of 1.6±1.0 cm(range,0.7-3.4).

Six lesions of the IPMN,including 2 adenomas and 4 adenocarcinomas,were demonstrated as multicystic or mixed cystic with solid echogenic components by ultrasound (Figs.1-3).One adenoma and three adenocarcinomas presented as projecting nodules within the dilated main duct.The other adenoma and an adenocarcinoma were demonstrated as echoic masses located at the head of the pancreas,and the lesion of adenocarcinoma was inhomogenous.Among the 4 adenomas,3 (75.0%) were classified as branch type,and 1 (25.0%) as main duct type.Among the 8 adenocarcinomas,5 (62.5%) cases were classified as main duct type,and 3 (37.5%) as combined type.Mural nodules were found within 7 malignant lesions(adenocarcinomas) (7/8,87.5%),and 5 of them showed abundant color flow signals within the mural nodules (Fig.3B).On the contrary,mural nodules were found in 2 of the 4 adenomas (2/4,50.0%) but no color signal was detected within them.

Table 1.General information and major clinical features of both benign and malignant cases of IPMN§

Figure 1.In one case of adenoma,transabdominal ultrasonography shows a cystic lesion (left arrow) and dilated main duct (right arrow).This IPMN,located in the tail of the pancreas and extruding to the pancreatic parenchyma,is classified as branch duct type.

Figure 2.In one case of adenocarcinoma involving the main pancreatic duct,transabdominal ultrasonography shows the obviously dilated pancreatic duct and multiple mural nodules.This IPMN is classified as main duct type.

Figure 3.In one case of adenocarcinoma,transabdominal ultrasonography shows obviously dilated pancreatic main and branch ducts (A),and color Doppler reveals the multilocular mixed cystic-solid structure and a few color signals within the mural nodules and walls(B).IPMN in this case is classified as combined type.

DISCUSSION

IPMNs of the pancreas have been defined and classified by the World Health Organization in 1996.IPMNs have malignant potential and undergo transformation from adenoma to borderline neoplasms,followed by carcinomain situand then invasive carcinoma.Histologically,IPMN displays as neoplastic mucin-producing cells arranged in a papillary pattern.Mucin production by the cells leads to intraductal mucin accumulation and subsequent cystic dilation of the main or branch ducts.1Recently,IPMNs have been increasingly detected.According to the report of Furuta et al,2IPMN accounts for 0.5% of all pancreatic neoplasms diagnosed clinically,and 16.3% of pancreatic neoplasms surgically resected.The distinction between benign and malignant IPMNs has become more important since the complete resection is favorable for improving the prognosis of malignant IPMN and that benign IPMN can be followed up without resection.In this study,we analyzed the ultrasonographic characteristics of IPMN combined with the clinical presentations in order to further improve the understanding of IPMN,and help diagnose IPMN at the early stage.

In our study,most patients with IPMN were elderly male,with a mean age of 60.1±9.6 years.Moreover,most patients have experienced clinical symptoms.Some of them had symptoms of acute pancreatitis,which may be caused by the partial or complete occlusion of the main pancreatic duct with viscid mucin.3Persistent occlusion may result in pancreatic insufficiency,which may present as diabetes and steatorrhea.In particular,patients with serious clinical symptoms were all diagnosed histologically as adenocarcimomas in our study.Jaundice may follow the obstruction of bile duct due to the invasion of malignant IPMN although the patients with benign IPMN may also develop obstructive jaundice owing to mucin within the papilla or a fistula extrude into the bile duct.4Serum CA19-9 level was elevated only in malignant IPMN in this study and that in the benign group was all in the normal range.However,some patients with IPMN are asymptomatic,which is probably due to the relatively inactive production of mucin and/or the location of the tumor away from the head of the pancreas.5

Although the differences between benign and malignant lesions of IPMN were not of statistically significance in our study,as limited by the case number,the malignant lesions did have bigger size and more dilated pancreatic duct than the benign lesions,half of the IPMN lesions located in the head of the pancreas.Moreover,mural nodules and color flow signal within the nodules were more often detected in the lesions of adenocarcinomas than in those of adenomas.Those findings are consistent with previous reports,4,6-12which consider the main duct ≥7-15 mm,diameter of lesions ≥30 mm,and mural nodules within the tumors as predictive factors for malignant IPMNs.However,mural nodules are difficult to demonstrate accurately.It remains difficult to discriminate mucin plugs from mural nodules even in ultrasonography with the intraductal probe.5Itoh et al13pointed out that contrast-enhanced ultrasonography may be helpful for distinguishing benign from malignant lesions.According to that study,the quantitative change in intensity with contrast enhancement is probably a useful parameter for differentiation of benign and malignant IPMNs.

The imaging findings have played a more important role in classifying subtypes of IPMN,which may be helpful for differential diagnosis of IPMN.It was reported that main duct and mixed-type IPMNs are more frequently malignant,while most branch-type IPMNs are benign.6Furthermore,it is recommended that resection should be done if any of the following five factors are present:a cyst >3 cm in diameter,mural nodules,dilation of the main pancreatic duct >6 mm in diameter,positive cytological finding,and symptoms attributable to tumors.14However,Nagai et al15suggested that the cyst size and number of indications per patient should be taken into account when predicting malignancy of branch duct IPMNs because the specificity of the guidelines for predicting malignancy of those lesions is low.

In our study,the dilated main duct as well as the location and extension of IPMNs were all revealed by transabdominal ultrasonographic imaging,indicating that transabdominal ultrasonography did play an important role in detecting and diagnosing IPMNs.Of all the imaging modalities,transabdominal ultrasonography and CT scan have advantages in demonstrating the entire lesions of IPMNs,but usually fail to depict small cystic tumors of branch ducts as well as mural nodules in less than 10% of patients.However,both ultrasound and CT have lower sensitivity than magnetic resonance cholangiopancreatography and endoscopic ultrasonography do.Endoscopic retrograde cholangiopancreatography failed to detect branch duct ectasia in 12% of patients and occasionally some dilated main ducts because of abundant intraductal or intracystic mucin.6Therefore,combining the findings of multiple methods will be helpful for estimating the characteristics of the lesions.

Differentiating IPMN from other cystic lesions of the pancreas is relatively easy.Radiological imaging of pseudocysts frequently shows a single cystic lesion,with no locular or solid components,and with a wall <4 mm.Endocrine tumours of the pancreas do not develop cystic areas secondary to pancreatic necrosis presumably because of their better blood supply.Cyst formation is usually unilocular,but may occasionally be microcystic in nature.16Notably,it is important to differentiate IPMN from mucinous cystic neoplasm (MCN).Although IPMN and MCN both produce a large amount of mucin,MCN is predominantly found in middle-aged women in the tail of the pancreas,and the tumor appears as a spherical multilocular cyst with a considerably thick,smooth wall and does not show communication with the pancreatic duct.5It has been suggested that ovarian-type stroma is a characteristic histological feature of MCN.

IPMN has been found to be associated with a high incidence (23.6%-32.0%) of malignant non-pancreatic neoplasms.5,17However,this association was not found to be predictive of malignant or invasive IPMN.5We should know that an IPMN may be an indicator of development of non-pancreatic cancers and a thorough examination would be needed for the patients.

In conclusion,IPMN is often found in elderly men and presents with clinical symptoms,especially epigastric discomfort.Cystic or cystic-solid lesions and dilated ducts of the pancreas can be observed by transabdominal ultrasonography.Therefore,transabdominal ultrasonography may be helpful for making diagnosis and appropriate management of IPMN.

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