REFERENCES

1. Norton JA, Jensen RT. Resolved andunresolved controversies in the surgicalmanagement of patients with Zollinger-Ellisonsyndrome. Ann Surg. 2004;240:757Y773.

2. Norton JA, Alexander HR, Fraker DL, et al.Possible primary lymph node gastrinoma:occurrence, natural history, and predictivefactors: a prospective study. Ann Surg.2003;237:650Y7.

3. Zhou H, Schweikert H-U, Wolff M, et al.Primary peripancreatic lymph node gastrinomain a woman with MEN1. J HepatobiliaryPancreat Surg. 2006;13:477Y481.

4. Norton JA, Fraker DL, Alexander HR, et al.Surgery to cure the Zollinger-Ellisonsyndrome. N Engl J Med. 1999;341:635Y644.

5. Thompson NW, Pasieka J, Fukuuchi A.Duodenal gastrinomas, duodenotomy, andduodenal exploration in the surgicalmanagement of Zollinger-Ellison syndrome.World J Surg. 1993;17:455Y462.

6. Herrmann ME, Ciesla MC, Chejfec G, et al.Primary nodal gastrinomas. Arch PatholLab Med. 2000;124:832Y835.

7. Perrier ND, Batts KP, Thompson GB, et al.An immunohistochemical survey forneuroendocrine cells in regional pancreaticlymph nodes: a plausible explanation forprimary nodal gastrinomas? Surgery.1995;118:957Y965.

Pancreatic Adenocarcinomain a Patient WithMultiple Endocrine

Neoplasia 1 Syndrome

To the Editor:

W e present the rare occurrence of aconcurrent pancreatic neuroendo-

crine tumor (pNET) and pancreatic ductaladenocarcinoma (PDAC) in a patient withmultiple endocrine neoplasia 1 (MEN1)

syndrome. It is important for clinicians toconsider the possibility of PDAC in patientswith MEN1 because aggressive early sur-gical intervention provides the only chanceof cure.

Multiple endocrine neoplasia 1 is char-acterized by parathyroid adenomas, pNETs,and anterior pituitary tumors.1 Multiple en-docrine neoplasia 1Yassociated pNETs areusually slowly progressive and associatedwith low malignant potential. In the con-text of MEN1, pancreatic NET size corre-lates with prognosis and the presence ofmetastases,2 and lesions of more than 2 cmare associated with greater genetic instabil-ity and malignant behaviour.3

The European Neuroendocrine Tu-mour Society recommendations for man-agement of pancreatic lesions in a patientwith MEN1 state that early diagnosis andsurgical excision of MEN1-related pNETimprove survival, preventing or delaying thedevelopment of distant metastases.4 It ismandatory to operate on MEN1-related non-functioning pancreatic tumors with metas-tases, size of more than 2 cm, or yearlyincreased size of more than 0.5 cm. Man-agement of pNETs of less than 2 cm iscontroversial, current recommendation be-ing intensive surveillance to avoid repeatedintervention where lesions are typically mul-tiple and behave in an indolent fashion.

CASE HISTORYA 46-year-old man was under sur-

veillance in a tertiary referral neuroen-docrine tumor unit for a diagnosis ofMEN1 syndrome. Medical history includedZollinger-Ellison syndrome with resectionof primary gastrinoma from the tail of thepancreas, primary hyperparathyroidism, andchronic hypercalcemia.

Fifteen years following his diagno-sis of MEN1, he presented with anorexia,nausea, and jaundice and was treated for

biliary sepsis. Computed tomography (CT)scan and endoscopic retrograde cholangio-pancreatography (ERCP) showed intrahepaticand pancreatic duct dilation. Endoscopicstent placement was performed, and thepatient improved.

Three months later, his symptomsrecurred, and he underwent a further ERCPat which point a blocked stent was replacedwith symptomatic improvement. Biochemi-cal testing showed an extremely high car-bohydrate antigen 19-9 (CA-19-9) tumormarker of 4520 U/mL (46 U/mL 2 monthspreviously). Cross-sectional imaging showeda 2.8 � 2.2-cm mass in the head/uncinateprocess of the pancreas with associated ductobstruction. Cytological brushings from theERCP demonstrated synaptophysin immu-nopositivity, indicating the presence of neu-roendocrine tumor; however, gallium 68DOTA octreotate positron emission tomog-raphy (Ga-68 PET) scanning did not showany uptake in the pancreas. Endoscopic ul-trasound demonstrated the double duct signand confirmed a mass in the head of thepancreas. In view of these findings, in asso-ciation with a raised CA-19-9, a Whipplepancreatoduodenectomy was performed.Histology demonstrated a 30-mm moder-ately differentiated ductal adenocarcinomaof the head of the pancreas, invading to themucosal surface of the duodenum and peri-pancreatic adipose tissue, pT3 N0M0 (stageIIA). Also present was a concurrent 9-mmwell-differentiated grade 1 pNET, with 5 of19 lymph nodes positive for metastatic neu-roendocrine tumor (pT1 N1). Immunohis-tochemistry of the pNET was positive forchromogranin and synaptophysin, andKi-67 was less than 1%. Figure 1 illustrateshistopathologic features of both tumors.

DISCUSSIONIn this case, the use of serum tumor

markers (a significantly raised CA-19-9)

FIGURE 1. A, Hematoxylin-eosinYstained section, original magnification �4: head of the pancreas with a moderately differentiatedpancreatic ductal-type adenocarcinoma (upper half of the picture) closely juxtaposed to a well-differentiated neuroendocrineneoplasm of low grade (lower half of the picture). B, Immunohistochemistry for Ki-67, X4: the proliferative rate with Ki-67 is lowin the well-differentiated neuroendocrine neoplasm compared with the high proliferative rate seen in the pancreatic adenocarcinoma.C, Immunohistochemistry for synaptophysin, X4: a diffuse and strong positivity is seen in the well-differentiated neuroendocrineneoplasm, and complete negativity is seen in the adenocarcinoma.

Pancreas & Volume 42, Number 4, May 2013 Letters to the Editor

* 2013 Lippincott Williams & Wilkins www.pancreasjournal.com 725

Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

and negative functional imaging (Ga-68PET) of the pancreatic mass raised the sus-picion of an alternative diagnosis to the ex-pected pNET.

CA-19-9 is the most frequently uti-lized biochemical marker for pancreatic ade-nocarcinoma, with median sensitivity fordiagnosis of 79% (70%Y90%) and speci-ficity of 82% (68%Y91%).5 Specificity fallsin jaundice. Recommendations for evalua-tion of suspected pancreatic adenocarcino-ma involve endoscopic ultrasound and CTassessment, and note that CA-19-9 is oflimited diagnostic value but of use toguide treatment and follow-up.6

The use of functional and somatostatinreceptor imaging is important in the evaluationof suspected neuroendocrine tumors; how-ever, all modalities are limited by reducedsensitivity for lesions of less than 1 cm.Gallium 68 PET scan is more sensitive thanother modalities; however, its role in theassessment of patients with MEN1 has notyet been determined.7 In our case, lack ofuptake in the pancreas on Ga-68 PET despitea 3-cm lesion being visualized on CT raisedthe suspicion of nonneuroendocrine malig-nancy. The small (9 mm) neuroendocrinetumor was below the resolution thresholdof the Ga-68 PET and therefore was notvisualized.

CONCLUSIONSWe have presented a rare concurrence

of PDAC with pNET in a patient withMEN1 syndrome. This case highlights theimportance of relevant imaging and bio-chemical biomarkers and questions thecurrent practice of surveillance for smallpancreatic masses in patients with MEN1syndrome.

No specific funding was providedfor this work. Two of the authors (A.K.and C.Th.) are funded by Cancer ResearchUK and the Raymond and Beverley SacklerFoundation.

The authors declare no conflict ofinterest.

Anna Karpathakis, MRCPNeuroendocrine UnitRoyal Free Hospital

and University College LondonCancer Institute

London, United Kingdoma.karpathakis@cancer.ucl.ac.uk

Marinos Pericleous, MRCPNeuroendocrine UnitRoyal Free Hospital

London, United Kingdom

Tu Vinh Luong, MDHistopathology Department

Royal Free HospitalLondon, United Kingdom

Bernard Khoo, MD, PhDNeuroendocrine UnitRoyal Free Hospital

London, United Kingdom

Christina Thirlwell, MRCP, PhDNeuroendocrine UnitRoyal Free Hospital

and University College LondonCancer Institute

London, United Kingdom

Christos Toumpanakis, MD, PhD

Martyn E. Caplin, FRCP, MDNeuroendocrine UnitRoyal Free Hospital

London, United Kingdom

REFERENCES

1. Thakker RV. Multiple endocrineneoplasiaVsyndromes of the twentiethcentury. J Clin Endocrinol Metab.1998;83(8):2617Y2620.

2. Triponez F, Dosseh D, Goudet P, et al.Epidemiology data on 108 MEN 1 patientsfrom the GTE with isolated nonfunctioningtumors of the pancreas. Ann Surg.2006;243(2):265Y272.

3. Triponez F, Goudet P, Dosseh D, et al. Issurgery beneficial for MEN1 patients withsmall (G or = 2 cm), nonfunctioningpancreaticoduodenal endocrine tumor?An analysis of 65 patients from the GTE.World J Surg. 2006;30(5):654Y662;discussion 654Y663.

4. Falconi M, Bartsch DK, Eriksson B, et al.ENETS consensus guidelines for themanagement of patients with digestiveneuroendocrine neoplasms of the digestivesystem: well-differentiated pancreaticnon-functioning tumors. Neuroendocrinology.2012;95(2):120Y134.

5. Goonetilleke KS, Siriwardena AK.Systematic review of carbohydrate antigen(CA 19-9) as a biochemical marker in thediagnosis of pancreatic cancer. Eur J SurgOncol. 2007;33(3):266Y270.

6. Cascinu S, Falconi M, Valentini V, et al.Pancreatic cancer: ESMO Clinical PracticeGuidelines for diagnosis, treatment andfollow-up. Ann Oncol. 2010;21(suppl 5):v55Yv58.

7. Jensen RT, Cadiot G, Brandi ML, et al.ENETS consensus guidelines for themanagement of patients with digestiveneuroendocrine neoplasms: functionalpancreatic endocrine tumor syndromes.Neuroendocrinology. 2012;95(2):98Y119.

Masking Effect of ChronicPancreatitis in theInterpretation of

Somatostatin ReceptorPositron Emission

Tomography in PancreaticNeuroendocrine Tumors

To the Editor:

T he pancreatic neuroendocrine tumors(pNETs) represent a small percentage

of all pancreatic tumors (1.3%), but theirincidence is rising.1 Neuroendocrine tumorsusually overexpress somatostatin receptorson their cell surface; therefore, somatostatinreceptor imaging could be used to evalu-ate these tumors. Somatostatin receptorpositron emission tomography/computedtomography (SMSR-PET/CT) using differentsomatostatin analogs (such as DOTANOC,DOTATOC, DOTATATE) labeled withgallium-68 is a valuable diagnostic toolfor staging and restaging patients withNETs, including patients with pNET.2,3

We present a patient with a multifo-cal pNET in whom the coexistence ofchronic pancreatitis has hampered the cor-rect functional characterization of tumorallesions at SMSR-PET/CT.

CASE REPORTA 49-year-old woman underwent

magnetic resonance imaging (MRI) foronset of abdominal pain. Magnetic reso-nance imaging showed a large encapsulatedexophytic mass arising from the pancreatictail, with heterogeneous hyperintensity onaxial T2-weighted image caused by necroticareas. Magnetic resonance imaging alsoshowed smaller lesions distributed in allpancreatic segments that appear variablyhyperintense related to cystic compo-nents in axial T2-weighted images (Fig. 1).The patient underwent an endoscopicultrasonographyYguided fine-needle tissueacquisition of the largest lesion in the pan-creatic tail. Fine-needle aspiration cytologyshowed small monomorphic cells form-ing loosely structured groups positive forchromogranin A at immunohistochemistryand highly suspected for NET cells (Fig. 1).Based on the morphologic suspicion ofa multifocal pNET, the patient underwentSMSR-PET/CTwith gallium-68YDOTANOCfor staging. The SMSR-PET/CT imagesshowed diffuse and intense radiopharma-ceutical uptake distributed in all the pan-creatic segments, and a correct interpretationand functional evaluation of the pancreaticlesions detected at MRI were not possible.

This is an open access article distributed underthe Creative Commons Attribution License,which permits unrestricted use, distribution, andreproduction in any medium, provided the origi-nal work is properly cited.

Letters to the Editor Pancreas & Volume 42, Number 4, May 2013

726 www.pancreasjournal.com * 2013 Lippincott Williams & Wilkins

Copyright © 2013 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.