Pancreatic tumors are uncommon in children and rarely result in biliary obstruction. A previously well 12-year old female presented with a one-week history of fatigue, pruritis, and painless jaundice. Abdominal ultrasound demonstrated a mass in the pancreatic head associated with dilation of the common bile duct. Further workup included abdominal MRI, CT and endoscopic retrograde pancreaticogram (ERCP) with biliary stenting. Octreotide scan did not reveal uptake in the pancreatic tumor. Percutaneous biopsies were consistent with a grade 2 pancreatic neuroendocrine tumor (NET). Preoperative imaging demonstrated involvement of the portal vein. The patient was brought the operating room for a pancreaticoduodenectomy and portal vein resection. Final pathology revealed a T3N1M0 pancreatic NET. The patient recovered uneventfully

Bertens, Kimberly A.

Bütter, Andreana

Leslie, Ken

Livingston, Michael

Quan, Douglas

Zorzi, Alexandra

English

Scholarship@Western

Western University Scholarship@Western Paediatrics Publications Paediatrics Department 1-1-2014 Neuroendocrine tumor of the pancreas causing biliary obstruction in a 12 year-old girl: A case report and literature review Kimberly A. Bertens Western University Michael Livingston Western University Douglas Quan Western University Ken Leslie Western University Alexandra Zorzi Western University See next page for additional authors Follow this and additional works at: https://ir.lib.uwo.ca/paedpub Citation of this paper: Bertens, Kimberly A.; Livingston, Michael; Quan, Douglas; Leslie, Ken; Zorzi, Alexandra; and Bütter, Andreana, "Neuroendocrine tumor of the pancreas causing biliary obstruction in a 12 year-old girl: A case report and literature review" (2014). Paediatrics Publications. 913. https://ir.lib.uwo.ca/paedpub/913 Authors Kimberly A. Bertens, Michael Livingston, Douglas Quan, Ken Leslie, Alexandra Zorzi, and Andreana Bütter This article is available at Scholarship@Western: https://ir.lib.uwo.ca/paedpub/913 Neuroendocrine tumor of the pancreas causing biliary obstruction ina 12 year-old girl: A case report and literature reviewqKimberly A. Bertens a, Michael Livingston a, Douglas Quan a, Ken Leslie a,Alexandra Zorzi c, Andreana Bütter a,b,*aDivision of General Surgery, London Health Sciences Centre, Western University, 800 Commissioners Rd East, London, Ontario, Canada N6A 5A5bDivision of Pediatric Surgery, Children’s Hospital, Western University, 800 Commissioners Road East, London, Ontario, Canada N6A 5W9cDivision of Pediatric Hematology/ Oncology, Children’s Hospital, Western University, 800 Commissioners Road East, London, Ontario, Canada N6A 5W9a r t i c l e i n f oArticle history:Received 1 July 2014Received in revised form13 August 2014Accepted 15 August 2014Key words:Neuroendocrine tumorPancreasChildrenBiliary obstructiona b s t r a c tPancreatic tumors are uncommon in children and rarely result in biliary obstruction. A previously well12-year old female presented with a one-week history of fatigue, pruritis, and painless jaundice.Abdominal ultrasound demonstrated a mass in the pancreatic head associated with dilation of thecommon bile duct. Further workup included abdominal MRI, CT and endoscopic retrograde pan-creaticogram (ERCP) with biliary stenting. Octreotide scan did not reveal uptake in the pancreatic tumor.Percutaneous biopsies were consistent with a grade 2 pancreatic neuroendocrine tumor (NET). Preop-erative imaging demonstrated involvement of the portal vein. The patient was brought the operatingroom for a pancreaticoduodenectomy and portal vein resection. Final pathology revealed a T3N1M0pancreatic NET. The patient recovered uneventfully. 2014 The Authors. Published by Elsevier Inc. All rights reserved.Pancreatic tumors are exceedingly rare in children and adoles-cents. Neuroendocrine tumors (NET) account for approximately25% of pediatric pancreatic masses [1,2]. NET arise from endocrinetissues of the pancreas and are classified as either non-functioningor functioning. Functioning NETs secrete various peptide hormones,which act at distant sites and can result in a variety of clinicalsyndromes. Pancreatic NETs can be benign or malignant, howeverthe majority of non-functioning tumors are malignant. Pancreatictumors in children rarely present with biliary obstruction, owing tothe expansive rather than infiltrative growth patterns of the com-mon pediatric pancreatic neoplasms [3,4].1. Case reportA 12 year-old female was referred to our center after presentingto her local emergency department with a one-week history offatigue, pruritis, and acholic stools. She was visibly jaundiced. Anabdominal ultrasound at her local hospital suggested a mass withinthe head of the pancreas. Her laboratory tests were: total bilirubin136 umol/L, direct bilirubin 84.6 umol/L, alkaline phosphatase543 U/L, alanine aminotransferase 172 U/L, and aspartate amino-transferase 75 U/L. Serum lipase was within normal limits.Following these investigations, the patient was transferred to ourinstitution for further workup in hospital.Magnetic resonance imaging (MRI) of the abdomen demon-strated extensive dilation throughout the intra and extrahepaticbiliary tree (Fig. 1). The common bile duct (CBD) measured 2.5 cmwith an abrupt transition at the pancreatic head. Within thepancreatic head there was a 3 cm solid, smoothly marginated mass.Computed tomography (CT) of the abdomen (Fig. 2) was also per-formed to better assess the surrounding vasculature. The lesionwasfound to be in direct contact with the portal vein (PV) with a nar-rowed segment, suspicious for tumor infiltration. Both the superiormesenteric artery (SMA) and superior mesenteric vein (SMV)appeared to be uninvolved. There also appeared to be 5  3 mmcalculus within the CBD. Because of the biliary obstruction andpossible CBD stone, the patient underwent endoscopic retrogradepancreaticochoangiogram (ERCP). This identified a tight stricture,1 cm from the ampulla, for a distance of 5 mm. No stone wasidentified and a plastic stent was placed for biliary drainage. ERCPq This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).* Corresponding author. Western University, Children’s Hospital, Room B1-188,800 Commissioners Road East, London, Ontario, Canada N6A 5W9. Tel.: þ1 519 6858401; fax: þ1 519 685 8421.E-mail addresses: andreana.butter@lhsc.on.ca, andreanabutter@gmail.com(A. Bütter).Contents lists available at ScienceDirectJournal of Pediatric Surgery CASE REPORTSjournal homepage: www.jpscasereports .com2213-5766/$ e see front matter  2014 The Authors. Published by Elsevier Inc. All rights reserved.http://dx.doi.org/10.1016/j.epsc.2014.08.008J Ped Surg Case Reports 2 (2014) 413e416was arranged prior to obtaining a tissue diagnosis because thepatient was highly symptomatic with pruritis.Tumor markers were sent in an attempt to determine the eti-ology of this mass. Serum carbohydrate antigen 19-9 (CA19-9) wasmildly elevated at 38 U/ml. Serum carbohydrate antigen 125(CA-125), b-human chorionic gonadotropin (b-HCG), alpha-fetoprotein (AFP) and Immunoglobulin 4 (IgG4) levels were withinnormal limits. Furthermore, serum gastrin, insulin and chromog-ranin A were also non-elevated. Twenty-four hour urine collectionrevealed normal levels of vanillylmandelic acid (VMA), homo-vanillic acid (HVA), and 5-hydroxyindole acetic acid (5-HIAA). Abone marrow aspirate was also normal, making the diagnosis ofleukemia unlikely. CT chest was also normal.This patient’s case was then reviewed in multi-disciplinarytumor board rounds with radiology, pediatric medical oncology,pathology, and pediatric surgery. A joint decision was made toproceed with a surgical biopsy, as the group felt that percutaneousbiopsies were less likely to result in adequate tissue for pathologicinterpretation and had a theoretical potential for seeding the tu-mor through the needle tract. She was brought to the operatingroom for laparoscopic biopsies of the pancreatic head. Tissuesamples sent to pathology for frozen sections revealed onlynormal pancreatic tissue. As a result, interventional radiology wasconsulted to perform ultrasound-guided, percutaneous biopsieswhile the patient was under the same general anesthetic. Thesespecimens demonstrated a grade 2 NET (2 mitoses per 10 highpower fields, Ki-67 index 12%). Unfortunately, the patient bledpost-biopsy and underwent angiographic embolization ofbranches of the pancreaticoduodenal artery. She tolerated thiswell and eventually recovered.An octreotide scintigraphic scan was then performed. Thisrevealed no significant octreotide uptake within the knownpancreatic tumor, and no evidence of octreotide-positivemetastaticdisease. Although not available in our center, but commonly utilizedin Europe, a 68Ga DOTATOC/68Ga DOTATATE PET scan would havebeen a good alternative imaging test for preoperative evaluation. Ifpositive, this would have provided an imaging modality forpostoperative surveillance.The patient was then reviewed in multi-disciplinary neuro-endocrine tumor board rounds. In conjunction with our adulthepatopancreaticobiliary surgeons, a decision was made to takethe patient to the operating room for a pancreaticoduodenectomy(Whipple’s procedure) with a plan for possible PV resection. Themass was visible in the pancreatic head, with firm nodes along theuncinate margin. The nodal tissue along the hepatic artery andposterior to the SMAwas cleared and sent with the specimen. Sheunderwent a standard pancreaticoduodenectomy with an end-to-side pancreaticojejunostomy, end-to-side hepaticojejunostomy,and a loop gastrojejunostomy. A frozen section of the pancreaticresection margin was sent to pathology before reconstruction,which was negative for malignancy (Fig. 3). A short segment(5 mm) of the PV was resected, due to significant tumor adher-ence, and reconstructed using an end-to-end anastomosis (Fig. 4).Total clamp time was 25 min. We elected to perform a primaryanastamosis of the PV rather than a vein graft due to the shortsegment of resection, and the fact that it came together under notension. On final pathology the PV was not infiltrated with tumorand therefore the dense adherence was likely desmoplasticreaction.Final pathology demonstrated a T3N1M0 grade 2 (World HealthOrganization Classification) pancreatic NET with negative resectionmargins. The tumor extended beyond the pancreas but did notinvolve the celiac axis or SMA. Lymphovascular and perineural in-vasion were present. The Ki-67 index ranged from 3% to 20%. Fiveout of nineteen lymph nodes were positive. She was again pre-sented at our neuroendocrine tumor board. Given her completeresection and the non-functionality of her tumor, no furthertreatment was recommended. Adjuvant treatment of completelyresected (R0) pancreatic neuroendocrine tumors is somewhatcontroversial, however after consultation with international ex-perts and a through literature review, it was felt that the potentialFig. 1. T2-weighted magnetic resonance imaging (MRI) demonstrating a mass in headof pancreas (1) causing massive dilatation of the common bile duct (2).Fig. 2. Coronal slice from computed tomography (CT) scan of the abdomen: pancreaticmass (1), portal vein (2), and dilated common bile duct (3).Fig. 3. Posterior view of specimen: gastric antrum (1), pancreatic tumor (2), bile duct(3), pancreatic neck margin (4), and duodenum (5).K.A. Bertens et al. / J Ped Surg Case Reports 2 (2014) 413e416414for toxicity in a young patient outweighed the questionable benefit.She will require pancreatic imaging every 3 months for the next 2years and continued long-term follow-up. Genetic screening formultiple endocrine neoplasia (MEN) and Von Hippel-Lindau (VHL)syndromes has been undertaken given the rarity of pancreatic NETand the implication on further screening.The patient recovered uneventfully post-operatively. Anasymptomatic portal vein thrombus was demonstrated onscreening ultrasound and anti-coagulation was initiated. The eti-ology of this thrombus was felt to be secondary to endothelialtrauma from the reconstruction. At 6 weeks, the PV thrombosis hadcompletely resolved and anti-coagulation was discontinued. At her3-month follow-up, she continued to do well with no signs ofrecurrence on CT.2. DiscussionPancreatic tumors in children and adolescents are exceedinglyrare, and as such, there is a paucityof data on this topic. The literatureconsists predominately of single institution case series carried outover long timeperiods. Investigators fromMemorial Sloan-Ketteringpublished a retrospective review of pediatric patients less than 21years of age with malignant pancreatic tumors [3]. Patients withMEN were excluded. They identified sixteen patients with pancre-atic neoplasms over a 35-year time period. Solid pseudopapillarytumors (SPT)were themost commonpathological subtype, followedclosely by pancreatoblastomas (PB) [3]. Only 2 patients (12.5%) hadNETs: one was non-functional and the other was a malignant vaso-active intestinal peptide-secreting neuroendocrine tumor (VIPoma).The largest case series published to date is from the Hospital for SickChildren inToronto, Canada. In this series 27patientswere identifiedover a 34-year time period (1986e2010). Again, SPT was the mostcommon pathology (66.7%) followed by NET (22.2%). There were nopatients with PB in this series [5]. Half of NETs were functional (2insulinomas, 1 glucogonoma) [5]. Preoperative biopsy was onlyperformed in a third of cases, however 80% of biopsies were diag-nostic, and no morbidity was attributed to biopsy [5].Other reports of pancreatic masses in children include: ductaladenocarcinoma, acinar cell carcinoma, peripheral neuro-ectodermal tumor (PNET), rhabdomyosarcoma, fibrosarcoma,Ewing sarcoma, lymphoma and teratoma [3,5e7]. Ductal adeno-carcinoma, the predominant tumor type in adults, is exceptionallyrare in the pediatric population. Non-neoplastic etiologies such asautoimmune pancreatitis are also possible [4].The majority of children or adolescents with pancreatic neo-plasms present with abdominal pain, emesis or a palpable mass[3,5]. Biliary obstruction is rare [3,4]. Unlike ductal adenocarci-noma, the majority of pediatric pancreatic tumors exhibit anexpansive growth pattern, and push nearby structures aside ratherthan invading them. Furthermore, they do not have a predilectionfor the pancreatic head, with only 38% found in this location in theseries from Memorial Sloan-Kettering [3]. In particular, NET have apredilection for the pancreatic tail [5].Complete surgical resection is the mainstay of treatment formalignant tumors of the pancreas in children. Due to the infrequentnature of these neoplasms and the histologic heterogeneity, the roleof chemotherapy and radiotherapy is anecdotal, and their role inthe adjuvant setting has yet to be clearly established [1,3]. Incontrast to the adult population, most children have resectabledisease at the time of presentation [3]. In a single-center retro-spective review of pediatric patients undergoing pancreatic resec-tion for mass lesions, 19 of 20 had an R0 resection [1]. There was noperi-operative mortality, but 25% of patients experienced peri-operative morbidity. The most common complication was apancreatic leak (15%) [1]. Median follow-up was 49.5 months andno patients experienced recurrence. Four patients (20%) developedpancreatic exocrine deficiency and one (5%) became diabeticpostoperatively. These results are similar to those reported fromMemorial Sloan-Kettering and MD Anderson [1,3,8].Extra-appendiceal NETs are rare in children, with an incidence of0.5 per million [9]. Approximately 25% of pediatric pancreaticneoplasms are NETs [1,2,5]. The WHO grading system for NET de-pends entirely on histopathologic criteria, including proliferationindex (Ki-67 index), mitotic count, and the presence or absence oftumor necrosis. The most common symptom at diagnosis isabdominal pain (85%) and weight loss (46%), while jaundice is rare[9]. The majority of pancreatic NETs in children and adolescents arenon-functioning tumors [9]. In some case series, up to 50% ofchildren had metastatic disease at presentation, and localized dis-ease is less common in pancreatic NET than with other sites ofextra-appendiceal NET [8,9]. These tumors may be associated withgenetic syndromes such as MEN, Von Hippel-Lindau syndrome,Neurofibromatosis type 1, or tuberous sclerosis [5,8]. It is unknownwhether high-grade tumors (WHO grade 2 or 3) are more commonin the pediatric population.The gold standard of treatment for extra-appendiceal NET iscomplete surgical resection. If complete surgical resection is notachieved, these tumors have a tendency to recur locally or metas-tasize [8]. NETs respond poorly to chemotherapy. Over-expressionof the somatostatin receptor is common in these tumors, so peptidereceptor radionucleotide therapy is possible [8]. There is no stan-dardized chemotherapy regimen in children, but in adults, bothstreptozotocin and fluorouracil are first-line treatments for stage IIIor greater [9]. Chemotherapy may have many adverse effects on thedeveloping child, including failure to thrive, infertility and a sig-nificant risk of secondary malignancy. The case series from MDAnderson estimated a 3-year overall survival rate for children withpancreatic NET of 75% (95% CI 13%e96%) [8].3. ConclusionsPancreatic tumors in children and adolescents are rare.Pancreatic NETs only represent 25% of these neoplasms. Unlikeadults, these tumors rarely present with biliary obstruction andhave a good prognosis if complete surgical resection can be ach-ieved. The preoperative work-up of a child with a pancreatic massshould include IgG4 levels as well as tumor markers (AFP, CA19-9,chromogranin A). Core biopsies should be strongly considered toavoid unnecessary surgical management in patients withFig. 4. Following removal of specimen: probe marking pancreatic duct (1), superiormesenteric vein (2), and liver (3).K.A. Bertens et al. / J Ped Surg Case Reports 2 (2014) 413e416 415autoimmune pancreatitis or lymphoma. Overall survival is signifi-cantly better among children with localized disease compared tothose with distant spread.References[1] Marchegiani G, Crippa S, Malleo G, Partelli S, Capelli P, Pederzoli P, et al. Surgicaltreatment of pancreatic tumors in childhood and adolescence: uncommonneoplasms with favorable outcome. Pancreatology 2011;11:383e9.[2] Yu DC, Kozakewich HP, Perez-Atayde AR, Shamberger RC, Weldon CB. Child-hood pancreatic tumors: a single institution experience. J Pediatr Surg 2009;44:2267e72.[3] Shorter NA, Glick RD, Klimstra DS, Brennan MF, LaQuaglia MP. Malignantpancreatic tumours in childhood and adolescence: the Memorial Sloan-Ket-tering experience, 1967 to present. J Pediatr Surg 2002;37(6):887e92.[4] Friedlander J, Quiros JA, Morgan T, Zhang Z, Tian W, Kehr E, et al. Diagnosis ofautoimmune pancreatitis vs neoplasms in children with pancreatic mass andbiliary obstruction. Clin Gastroenterol Hepatol 2012;10:1051e5.[5] van den Akker M, Angelini P, Taylor G, Chami R, Gerstle JT, Gupta A. Malignantpancreatic tumors in children: a single-institution series. J Pediatr Surg 2012;47:681e7.[6] Grosfeld JL, Van DW, Rescorla FJ, McGuire W, West KW. Pancreatic tumors inchildhood: analysis of 13 cases. J Pediatr Surg 1990;25:1057e62.[7] Eisenhuber E, Schoefl R, Weisbauer P, Bankier AA. Primary pancreatic lym-phoma presenting as acute pancreatitis in a child. Med Pediatr Oncol 2001;37:53e4.[8] Rojas Y, Warneke CL, Dhamne CA, Tsao K, Nuchtern JG, Lally KP, et al. Primarymalignant pancreatic neoplasms in children and adolescents: a 20 year expe-rience. J Pediatr Surg 2012;47:2199e204.[9] Redlich A, Wechsung K, Boxberger N, Leuschner I, Vorwerk P. Extra-appendicealneuroendocrine neoplasms in children-data from the GPOH-MET 97 study. KlinPadiatr 2013;225(06):315e9.K.A. Bertens et al. / J Ped Surg Case Reports 2 (2014) 413e416416

Neuroendocrine tumor of the pancreas causing biliary obstruction in a 12 year-old girl: A case report and literature review

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Neuroendocrine tumor of the pancreas causing biliary obstruction in a 12 year-old girl: A case report and literature review

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