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Home , Cholangiocarcinoma, Pancreatic tumor

JOP. J (Online) 2011 May 6; 12(3):255-258.

CASE REPORT

Simultaneous Non-Functioning Neuroendocrine of the Pancreas and Extra-Hepatic . A Case of Early Diagnosis and Favorable Post-Surgical Outcome

Simone Maurea1, Antonio Corvino1, Massimo Imbriaco1, Giuseppe Avitabile1, Pierpaolo Mainenti1, Luigi Camera1, Gennaro Galizia2, Marco Salvatore1

1Department of Biomorphological and Functional Sciences (DSBMF), University Federico II of Napoli (UNINA), Biostructures and Bioimages Institution (IBB), National Research Council (CNR); SDN Foundation (IRCCS). 2Divisions of Surgical , F Magrassi A Lanzara Department of Clinical and Experimental Medicine and , Second University of Naples School of Medicine. Naples, Italy

ABSTRACT Context Thanks to the wide use of diagnostic imaging modalities, multiple primary are being diagnosed more frequently and different associations of malignancies have been reported in this setting. Case report In this paper, we describe the case of a patient with non-functioning well-differentiated neuroendocrine carcinoma of the head of the pancreas associated with extra-hepatic cholangiocarcinoma, in which an early diagnosis using magnetic resonance imaging allowed a good outcome. Conclusion The simultaneous association of neuroendocrine pancreatic tumors and cholangiocarcinoma has not yet been described; however, this association should be considered and, due to the high contrast of magnetic resonance imaging, this technique is recommended in such patient in order to reach an accurate diagnosis.

INTRODUCTION CASE REPORT

To the best of our knowledge, simultaneous cholangio- A 55-year-old male with a previous history of recurrent and neuroendocrine pancreatic tumors in , and a significant increase in the same patient have not yet been reported. However, cholestasis laboratory indices underwent ERCP with the occurrence of two or more primary malignant positioning of a biliary in the middle third of the tumors arising in the same patient is the well-accepted extra-hepatic common since a significant definition of multiple primary malignancies; the biliary stenosis had been found. Four months later, the of these lesions is being increasingly noted patient was admitted to our institution without evidence due to the wide use of diagnostic imaging modalities of significant clinical symptoms to account for the and different associations of tumor lesions have been nature of the biliary stenosis. Since the patient was reported [1, 2]. stented, an initial evaluation revealed no obstructive We describe the case of a patient with extra-hepatic jaundice; the conjunctivae were anicteric in the absence cholangiocarcinoma associated with a non-functioning of hepatomegaly; his abdomen was soft, non-tender well-differentiated neuroendocrine carcinoma of the and not distended with normal bowel sounds; the head of the pancreas with low grade , in was not palpable and Murphy’s sign was which MR imaging detected both tumor lesions and led negative. The remaining physical examination was to the decision to perform surgery. unremarkable. He had no significant comorbidities; Received February 7th, 2011 - Accepted March 25th, 2011 conventional laboratory evaluation as well as tumor Key words Diagnostic Imaging; Magnetic Resonance Imaging; markers (CA 19-9, CA 125, CEA, and alpha- , Multiple Primary fetoprotein) were normal. The patient initially Correspondence Simone Maurea underwent abdominal ultrasound which demonstrated Dipartimento di Scienze Biomorfologiche e Funzionali; Università slightly intra-hepatic bile duct dilatation especially in degli Studi di Napoli Federico II; via S. Pansini; 80131 Naples; the left ; the was dilated (10.4 Italy Phone: +39-81.746.3560/2039; Fax: +39-81.545.7081 mm) and the presence of the previously positioned E-mail: [email protected] stent was visible; the liver echo-pattern appeared Document URL http://www.joplink.net/prev/201105/13.html normal.

JOP. Journal of the Pancreas - http://www.joplink.net - Vol. 12 No. 3 - May 2011. [ISSN 1590-8577] 255 JOP. J Pancreas (Online) 2011 May 6; 12(3):255-258.

Figure 2. Cross-sectional T2-weighted fat-suppressed images. Axial T2-weighted turbo spin eco short-time inversion recovery (STIR) sequences show a circumferential wall-thickening of the common Figure 1. Conventional turbo spin eco T2-weighted coronal (a.) and bile duct with a firm component projecting into the lumen. cholangiopancreatography (b.) magnetic resonance sequences. MR views show a lengthy stricture with abrupt and asymmetric narrowing in the middle and lower third of the common bile duct; the contrast medium, the lesion did not show significant proximal biliary tree is dilated. enhancement in the arterial phase; however, late-phase images showed non-homogeneous enhancement MR imaging was successively performed to evaluate (Figure 3). There was no evidence of positive lymph and characterize the nature of the biliary stenosis by nodes or metastatic disease; the characteristics of the acquiring axial and coronal T1- and T2-weighted MR images were suggestive of a malignant primary with/without fat saturation images integrated with stenosis probably by extra-hepatic cholangiocarcinoma. MRCP T2-weighted hydro-cholangiographic sequences. Furthermore, MR views demonstrated mild In particular, the patient received 900 mL of enlargement of the pancreas associated with a non- superparamagnetic oral contrast material (Lumirem®, homogeneous signal intensity of the pancreatic tissue Guerbet, Paris, France) 20 min before the study. Post- contrast acquisition was performed after the intra- venous administration of gadolinium diethylenetriamine pentaacetic acid (DTPA) in a volume of 20 mL with 2 mL/s acquiring T1 fast-field echo short-time inversion recovery (FFE-STIR) images. In particular, cross- sectional T1- and T2-weighted and MR cholangio- graphy sequences showed dilatation of the biliary tree including the intrahepatic ducts, primarily of the left hepatic lobe and the . Furthermore, MR images showed a lengthy stricture with luminal flow-signal preserved, irregular margins as well as abrupt and asymmetric narrowing in the middle third and intra-pancreatic segment of the Figure 3. T1-weighted fast-field echo short-time inversion recovery common bile duct (Figure 1). A solid lesion along the (FFE STIR) post-contrast image shows a solid lesion with common bile duct, at same level of the stricture, inhomogeneous late-phase enhancement (at the level of the intra- appearing as circumferential wall-thickening with a pancreatic ); moreover, MRI demonstrates mild enlargement diffusely involving the head of the pancreas associated firm component projecting into the duct lumen, was with inhomogeneous signal intensity of the pancreatic tissue due to also detected (Figure 2); after the administration of the presence of a hypointense nodule (arrow).

JOP. Journal of the Pancreas - http://www.joplink.net - Vol. 12 No. 3 - May 2011. [ISSN 1590-8577] 256 JOP. J Pancreas (Online) 2011 May 6; 12(3):255-258. due to the presence of a hypointense nodule (Figure 3). cholangiocarcinoma as well as of small pancreatic A second ERCP examination was subsequently nodules and, thus, significant enough to suggest performed, which revealed a stricture immediately surgical treatment. above and at the level of the intra-pancreatic common The first report regarding multiple primary bile duct and the biliary stent was removed; brush malignancies was in 1889 by Billroth who described a cytology did not reveal atypical cells and the final patient with a spinocellular epithelioma of the right ear report was not indicative of malignancy. and a gastric carcinoma [3]. Since that time, multiple Although no definite demonstration of malignancy was primary malignancies have been the object of medical obtained, on the basis of MR findings which were research [2]; in particular, the technical innovation of highly suggestive of a malignant stenosis, the patient diagnostic imaging has been employed in this setting underwent surgical treatment: a Whipple’s pancreatico- and, thus, several distinct associations have been duodenectomy with end-to-side gastrojejunostomy, T- described [4]. L hepaticojejunostomy and T-L pancreaticojejuno- The occurrence of a second tumor in patients with stomy were carried out. The resected specimens were pancreatic is described [5, 6, 7, 8]; in particular, submitted to the Department of Surgical Pathology for in these studies, patients with intraductal papillary histological evaluation; they included the distal mucinous carcinoma had second malignancies in other stomach, the duodenum, part of the proximal jejunum, organs in percentages ranging from 7 to 30%; however, part of the pancreas (head, neck and uncinate process) only a single case of simultaneous cholangiocarcinoma and the distal biliary tree (distal common hepatic duct, was reported [8]. Conversely, the most frequently gallbladder and cystic duct). Histological examination associated tumors were gastric and colorectal , revealed well-differentiated distal common bile duct followed by pulmonary neoplasms. The tumor , which was confined to the muscular association that we observed in our report is different wall without infiltrating the pancreatic head and other since the pancreatic lesion consisted of a different surrounding tissues; the margins were tumor free and histological type represented by neuroendocrine tissue. there was no vascular invasion; all loco-regional lymph In the case presented, MR imaging detected the two nodes were negative for malignancy. According to the tumor lesions which were located in the same TNM classification system, the tumor was staged as anatomical region, the superior abdomen; in particular, pT1 N0 M0, stage 1A. Macroscopically, a solid, yellow the small neuroendocrine was barely ochre, well-defined lesion measuring 0.4 cm was found visible only on the post-contrast T1-weighted images within the pancreatic head; the surgical margins were as a nodular area of hypo-intensity. This finding is not clear. Microscopic examination of the regional lymph surprising since the majority of such tumors after nodes near the mass revealed that they were all contrast administration show hyperintensity in the hyperplastic. Immunocytochemistry showed that the arterial phase because they are hypervascularized [9, tumor cells were positive for chromogranin A, 10, 11] but, in our patient, the post-contrast MR images synaptophysin and neuron-specific enolase; moreover, were acquired only in the late phase and thus the lesion the tumor tissue showed a negative reaction to appeared hypointense. On the other hand, MR images vimentin. The final pathology report classified the clearly demonstrated a malignant stenosis of the main tumor as a non-functioning well-differentiated biliary extra-hepatic duct with significantly reduced neuroendocrine carcinoma of the pancreas. After the biliary flow on T2-hydrographic sequences and surgical procedure, the patient was managed according abnormal concentric solid tissue at the same level. to standard postoperative procedure; the short-term Although brush cytology samples from ERCP were not postoperative course was complicated by diagnostic for biliary malignancy, the patient gastrointestinal bleeding requiring arterial embolization underwent a Whipple’s and intra-abdominal drainage. The patient was since the MR features were highly suspicious of a discharged one month after initial admission; the malignant biliary stenosis. Histological examination of patient has remained disease free for more than one the surgical specimens confirmed the MR suspicion of year after the initial diagnosis. malignant lesions represented by a neuroendocrine pancreatic tumor and an extra-hepatic cholangio- DISCUSSION carcinoma. In this paper, we report the particular case of a patient Regarding the ERCP management of our patient, some with multiple tumors in which a new association of observations need to be made. First, why was the malignancies was found; in fact, a small non- patient stented during his initial evaluation without a functioning neuroendocrine pancreatic tumor was precise diagnosis? The clinical explanation for this found simultaneously with an extra-hepatic procedure was the need to resolve the significant cholangiocarcinoma. In our patient, MR imaging was biliary stenosis; this approach is frequently performed able to detect both tumor lesions allowing appropriate in daily practice, but it is important to point out that and timely surgical treatment, although a proven biliary stenting without an exact diagnosis should be cytological diagnosis was not available; in this regard, avoided. Furthermore, in our patient, a delay of four the MR imaging characteristics were highly suggestive months between the first stenting and definitive of a malignant stenosis caused by an extra-hepatic treatment occurred. This is a certainly long interval for

JOP. Journal of the Pancreas - http://www.joplink.net - Vol. 12 No. 3 - May 2011. [ISSN 1590-8577] 257 JOP. J Pancreas (Online) 2011 May 6; 12(3):255-258. malignant disease and, hence, such a time gap should 3. Billroth T. Die allgemeine chirurgische Pathologie und Therapie be absolutely avoided in favor of timely appropriate in funfzig Vorlesungen. Ein Handbuch fur Studierende und Arzte. Berlin: Verlag von Georg Reimer 1863. Auflage, p. 908. treatment. Finally, why was ERCP repeated during the 4. Tammaro V, Spiezia S, D'Angelo S, Maurea S, Ciolli G, second clinical evaluation after MR imaging? In this Salvatore M. Diagnostic imaging techniques for synchronous regard, the invasive endoscopic procedure was multiple tumors. In Renda A, ed. Updates in Surgery. Multiple performed since MR findings suggested a malignant Primary Malignancies. Chapter 16. Springer-Verlag, 2009:231-244. biliary stenosis and a cytological confirmation was thus [ISBN 978-8847010949] required. 5. Sugiyama M, Atomi Y. Extrapancreatic neoplasms occur with In conclusion, a neuroendocrine pancreatic tumor and unusual frequency in patients with intraductal papillary mucinous tumors of the pancreas. Am J Gastroenterol 1999; 94:470-3. [PMID an extra-hepatic cholangiocarcinoma may occur 10022648] simultaneously; this association should thus be 6. Yamaguchi K, Yokohata K, Noshiro H, Chijiiwa K, Tanaka M. considered in multiple primary malignancies. In this Mucinous cystic of the pancreas intraductal papillary- setting, MR imaging is recommended since its high mucinous tumor of the pancreas. Eur J Surg 2000; 166:141-8. [PMID contrast capability allows the early detection of tumor 10724492] lesions enabling appropriate and timely treatment to be 7. Eguchi H, Ishikawa O, Ohigashi H, Tomimaru Y, Sasaki Y, carried out. Yamada T, et al. Patients with pancreatic intraductal papillary mucinous neoplasm are at high risk of development. Surgery 2006; 139:749-54. [PMID 16782429] Conflicts of interest The authors have no potential 8. Kamisawa T, Tu Y, Egawa N, Nakajima H, Tsuruta K, Okamoto conflicts of interest A. Malignancies associated with intraductal papillary mucinous neoplasm of the pancreas. World J Gastroenterol 2005; 11:5688-90. [PMID 16237766] References 9. Herwick S, Miller FH, Keppke AL. MRI of islet cell tumors of 1. De Angelis R, Grande E, Inghelmann R, Francisci S, Micheli A, the pancreas. AJR Am J Roentgenol 2006; 187:W472-80. [PMID Baili P, et al. Cancer estimates in Italy from 1970 to 17056877] 2010. Tumori 2007; 93:392-7. [PMID 17899871] 10. Graziani R, Brandalise A, Bellotti M, Manfredi R, Contro A, 2. Scotti A, Borrelli A, Tedesco G, Di Capua F, Cremone C, Iovino Falconi M, et al. Imaging of neuroendocrine gastroenteropancreatic MG, Renda A. Multiple primary malignancies: ''Non-codified'' tumours. Radiol Med 2010; 115:1047-64. [PMID 20221711] associations. In Renda A, ed. Updates in Surgery. Multiple Primary 11. Kalb B, Sarmiento JM, Kooby DA, Adsay NV, Martin DR. MR Malignancies. Chapter 13. Springer-Verlag, 2009:195-210. [ISBN imaging of cystic lesions of the pancreas. Radiographics 2009; 978-8847010949] 29:1749-65. [PMID 19959519]

JOP. Journal of the Pancreas - http://www.joplink.net - Vol. 12 No. 3 - May 2011. [ISSN 1590-8577] 258