Synchronous primary epithelial tumors of the pancreas

Abstract

INTRODUCTION

Pancreatic incidentalomas are diagnosed at increased rates due to advanced pancreatic imaging. Coexistence of such lesions with another pancreatic pathology, however, is uncommon and their management might be perplexed by the anatomical location and the histological features of the lesion.

PRESENTATION OF CASE

A patient with obstructive jaundice was diagnosed with adenocarcinoma of the pancreatic head and underwent routine pancreatic imaging (CT) which revealed the coexistence of a small cystic lesion at the pancreatic body. Further investigation with MRCP and ERCP was unable to confirm a benign lesion and total pancreatoduodenectomy was performed. Histological examination showed a rare type of mixed serous–mucinous cystadenoma of borderline malignancy at the pancreatic body coexistent with an adenocarcinoma of the pancreatic head.

DISCUSSION

Coexistence of a peripheral pancreatic cystic tumor with a ductal adenocarcinoma of the pancreatic head is a very rare incidence in medical literature. The management of the peripheral lesion is not straightforward and there can be uncertainty as to the extent of the pancreatic resection that may be required.

CONCLUSION

Appropriate preoperative imaging has a significant impact on the definitive management of synchronous pancreatic tumors. Implications of a common pathogenetic pathway are also raised for this rare occurrence of two primary epithelial pancreatic tumors.

1. Introduction

Pancreatic tumors can be categorized into ductal and peripheral, depending on their origin within the pancreatic parenchyma. Peripheral cystic tumors do not communicate with the main pancreatic duct (MPD) and include two main histological types: serous cystadenoma/cystadenocarcinoma and mucinous cystadenoma/cystadenocarcinoma. Differentiation of these cystic tumors from other benign peripheral cystic lesions, such as pancreatic pseudocysts, is important to determine their correct management. Various combinations of investigations including CT, MRI and transabdominal ultrasound are often utilized. Endoscopic ultrasound (EUS) with fine needle aspiration (FNA) and cyst fluid sampling can sometimes be helpful in making a definitive diagnosis.¹

Synchronous primary pancreatic tumors are rare and reports of various combinations of benign and malignant tumors of the exocrine or endocrine pancreas have been published.^2–5 Autopsy studies have reported an association between neoplastic cystic lesions or pancreatic adenocarcinoma and endocrine tumors of the pancreas.^4,6 Due to the relatively small number of cases, however, pathogenic pathways have not been yet elucidated and in most cases the coexistence of multiple pancreatic tumors is thought to represent a distinct and possibly unrelated tumor growth.

We encountered a case of pancreatic adenocarcinoma with a synchronous peripheral lesion which could not be characterized on preoperative imaging, posing a significant diagnostic and therapeutic dilemma. This case is of further interest because of the coexistence of an extremely rare variant of a cystadenoma. The coexistence per se has only rarely been reported and raises important implications for possible common pathogenetic alterations.

2. Presentation of case

A 53-year-old man presented with anorexia, vomiting, yellow discoloration of the skin and sclera and associated mild epigastric pain with radiation to the right upper quadrant (RUQ) since few days. The patient remained apyrexial and no previous medical history was reported. On physical examination the patient was jaundiced with mild tenderness at deep palpation of the epigastrium and the RUQ. Laboratory examination revealed elevated total (7.42 mg/dL) and conjugated (6.32 mg/dL) bilirubin levels in serum along with a four to five fold increase in serum alkaline phosphatase (1322 U/L) and γ-glutamyl transpeptidase (251 U/L) levels above normal. The cause of extrahepatic cholestasis was initially investigated with liver and biliary ultrasound scan which confirmed distension of the gallbladder and dilation of the common bile duct (CBD, d = 20.5 mm), the intrahepatic biliary tree and the main pancreatic duct (MPD, d = 5.6 mm), excluding cholelithiasis or choledocholithiasis. Upper abdominal contrast-enhanced computed tomography (CT) revealed the presence of a mass at the pancreatic head (Fig. 1, white arrow) and a small hypodense cystic lesion at the lateral border of the pancreatic body (Fig. 1, yellow arrow), showing enhancement of thin septa within the lesion during the distribution phase. In an effort to differentiate between a neoplastic and a non-neoplastic cyst, a magnetic resonance cholangiopancreatography (MRCP) was conducted which showed marked dilation of the MPD in close relationship with the lesion (Fig. 2, yellow arrow). Subsequent endoscopic retrograde cholangiopancreatography (ERCP) to define a possible communication between the lesion and the MPD was not feasible due to complete obstruction of the MPD at the pancreatic head.

Fig. 1.

Synchronous pancreatic tumors. A solid mass at the pancreatic head (white arrow) and a small hypodense cystic lesion at the lateral border of the pancreatic body (yellow arrow) are visible on abdominal CT scan. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 2.

Magnetic resonance cholangiopancreatography (MRCP) showing a dilated main pancreatic duct in close relationship to the lesion of the pancreatic body, without excluding a possible communication between them. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

The patient underwent total pancreatoduodenectomy with choledochojejunostomy and gastrojejunostomy. Histological examination of the surgical specimen showed two distinct epithelial tumors: a pancreatic ductal adenocarcinoma (max. d = 2.7 cm) with variably sized tubular structures (Fig. 3a) at the pancreatic head and a mixed serous–mucinous cystadenoma (max. d = 1.3 cm) of borderline malignancy (Fig. 3b) at the lateral border of the pancreatic body without communication with the MPD.

Fig. 3.

(a) Ductal adenocarcinoma of the pancreatic head with tubular structures (HE ×20; inset HE ×100). (b) Borderline mixed serous–mucinous cystadenoma of the pancreatic body (HE ×20; inset HE ×100).

3. Discussion

Cystic tumors of the pancreas are often detected incidentally (pancreatic incidentalomas) owing to small size and asymptomatic course. Differentiation of these tumors from other cystic lesions of the pancreas, such as pseudocysts, nonneoplastic true cysts and cystic degeneration of solid tumors, is essential for proper follow-up and management. Upper abdominal CT provides information about the location, size, unilocular or multilocular structure and relationship with the MPD. The latter is better investigated with MRCP and/or ERCP which further distinguish between peripheral tumors (absence of communication with the MPD) and ductal tumors, i.e. intraductal papillary mucinous neoplasia.

Histological classification of cystic pancreatic neoplasia has been discussed by various authors and generally includes three main types of neoplastic lesions: serous cystadenoma (SCA), mucinous cystadenoma (MCA) and intraductal papillary mucinous neoplasia (IPMN) of either main pancreatic duct type or branch duct type. SCA is considered a benign tumor arising from centroacinar cells, does not communicate with the MPD and carries a very low malignant potential as opposed to mucinous cystic neoplasms (MCNs) and IPMN. In our case, an extremely rare type of mixed serous–mucinous cystadenoma of the pancreas was detected.⁷ Moderate dysplastic changes of this borderline tumor were attributed to the mucinous component. The presence of a common developmental precursor of pancreatic epithelial cells and associated oncogenic mutations might provide some evidence for deviation from typical differentiation.⁸ Significant implications arise regarding the optimal management of small cystic pancreatic tumors based on imaging studies alone. Current recommendations dictate periodical follow-up with repeat imaging for SCA unless the tumor becomes symptomatic and surgical resection for histologically documented MCA and IPMN.⁹

In our case, however, the operative strategy was determined by the presence of a synchronous ductal adenocarcinoma and a standard pancreaticoduodenectomy (Whipple's procedure) was initially planned. However, a safe pancreaticojejunostomy would not be possible due to the small distance of the cystic lesion from the pancreatic neck, as seen on the CT scan. In this case, the anastomotic suture line would certainly interfere with the right border of the cystic lesion, increasing the possibility of an anastomotic leak. Based on these preoperative considerations, further investigation by EUS-guided aspiration cytology was not deemed necessary as it would not change the operative plan. Thus a total pancreatectomy was performed.

Coexistence of a peripheral pancreatic cystic tumor with a pancreatic ductal adenocarcinoma is a very rare incidence in medical literature.^10,11 Despite the different histological origin of these neoplastic lesions, i.e. centroacinar cells and ductal cells respectively, molecular analysis data have suggested that allelic losses on chromosome 10q, observed in both pancreatic SCA (50% of cases) and ductal adenocarcinoma, might partly account for synchronous development of these tumors at distinct sites of the pancreas and exclude coincidental presentation in the same patient.¹² Mutations of the phosphatase and tensin homolog gene, a tumor suppressor gene located on 10q, have been implicated in the development of both SCA and pancreatic ductal adenocarcinoma and might represent a common pathogenetic pathway.¹³ On the other hand, important genetic alterations commonly found in pancreatic cancer, such as K-ras or p53 gene mutations, are absent in SCA.¹² These data suggest a complex sequence of genetic events that lead to deviation from normal differentiation of a common precursor of these lesions or the presence of an underlying genetic defect that leads to the development of distinct tumors of the exocrine pancreas. Moreover, in our case emphasis is given on the occurrence of an extremely rare combination of a pancreatic ductal adenocarcinoma and a mixed-type cystadenoma, which, to our knowledge, has no precedent.

Conflict of interest statement

The authors have no conflict of interest to state.

Funding

None.

Ethical approval

I declare that the patient has given a written consent to be included in this scientific paper as an interesting case report. The consent is available upon request.

Author contributions

Nikolaos P. Karidis contributed in draft preparation and final review of the manuscript, Panoraia Paraskeva contributed in data collection and organization, and Dimitrios Mantas contributed in final review of the manuscript.