A CASE REPORT Cystic Neuroendocrine Tumor of the Pancreas: A Rare Type of Pancreatic Cystic Lesion Accurately Diagnosed and Staged by EUS-FNA

by Amy Welch, Thomas McGarrity, Haresh Mani, Matthew Moyer

Cystic neuroendocrine tumors of the pancreas are extremely rare. The tumors are solitary, solid or cystic and occur predominately in the pancreatic head. The exception is in the setting of MEN-1 (multiple endocrine neoplasia type 1) where multiple tumors occur. We present the case of a 42 year-old male with multiple cystic lesions of the pancreas, diagnosed as a cystic neuroendocrine tumor on endoscopic ultrasound fine needle biopsy, and the diffuse nature of involvement resulting in the first reported total pancreatectomy.

Introduction ancreatic neuroendocrine tumors (NETs) setting of familial syndromes that occur at an early age represent about 2% of all pancreatic neoplasms. such as multiple endocrine neoplasia-1 (MEN-1), Von Although pancreatic NETs have been considered Hipple Lindau syndrome (VHL), neurofibromatosis P 3, 6, 10 to classically present with clinical syndromes related type 1 and tuberous sclerosis. We present a unique to hormone hypersecretion, up to 40% of all pancreatic case of multifocal cystic pancreatic NET. NETs are nonfunctioning (i.e. inactive, clinically silent or nonsyndromic).1 Nonfunctioning neuroendocrine Case Description tumors present with symptoms secondary to mass effects A 42 year-old white male presented with crampy of the tumor 3 or may present with features of pancreatitis. epigastric pain that had waxed and waned for one year; The most common symptoms include abdominal pain, this was associated with cough, nausea and mild weight usually epigastric or left upper quadrant radiating to the loss. His medical and family histories were significant back, and jaundice.3, 6 While not adequately specific to only for an 18 pack-year history of smoking and the be diagnostic, as they can be secreted by other tumors, use of omeprazole (40mg daily) for pain control. An NETs can secrete chromogranin A and B (90-100%), upper GI series was significant only for prominent pancreatic polypeptide (58%), alpha-HCG (human mucosal folds in the duodenal bulb with a possible chorionic gonadotropin) (40%) and Beta-HCG (20%).6 ulcer in the distal inferior duodenal bulb. His serum NETs usually present late with an average time to amylase was 217 U/L and serum lipase was 170 U/L. diagnosis from onset of symptoms of five years; 72% of A right upper quadrant abdominal ultrasound showed the lesions are greater than 5cm and hepatic metastasis a dilated common bile duct (5.5mm), gallbladder are present in 64-92% of cases at the time of diagnosis.6 polyp (7.7mm x 6.5mm x 8.8mm) and a cyst in the Sporadic pancreatic NETs are almost always solitary head of the pancreas measuring 1.25cm x 1.29cm x and well demarcated. Their texture varies from fleshy 1.37cm. Computed tomography (CT) scan and MRCP to fibrotic and they are rarely cystic.8 Multiple tumors (magnetic resonance cholangiopanctreatography) of the or diffuse pancreatic involvement usually occurs in a abdomen revealed multiple cystic lesions throughout the pancreas, the largest of which (2.9cm) was present Amy Welch, MD, MSN, MSc, Department of Internal in the tail (Figure 1). The pancreatic duct was dilated Medicine. Thomas McGarrity MD, Department of to 8mm with the common bile duct dilated to 1cm. A Gastroenterology and Hepatology. Haresh Mani, splenic cyst was also noted with a diameter of 8mm. MD, Department of Pathology. Matthew Moyer, The patient was scheduled for endoscopic MD, MS, Department of Gastroenterology and ultrasound and fine needle aspiration (EUS-FNA). Hepatology. Penn State Hershey Medical Center, PA Multiple cysts were noted throughout the head, body

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Figure 1. CT scan of the abdomen showing multiple cystic lesions Figure 2. EUS with multiple cystic lesions in the pancreas throughout the pancreas

Figure 3. EUS with 2.1cm cyst in the tail of the pancreas Figure 4. Intraoperative photo of the pancreas upon removal from the abdominal cavity and tail of the pancreas. Additional characteristics was 9.32, prolactin level was 8.0 and chromogranin A were multiple septations in some cysts and an irregular was 31.6. CT scan of the chest, abdomen and pelvis, pancreatic duct that measured 6mm in the head and evaluating for other lesions, was negative except for neck without filling defects. The largest lesion in the the noted pancreatic cystic lesions. tail was aspirated with a 22g FNA needle and sent for The patient subsequently underwent exploratory analysis of carcioembryonic antigen (CEA), amylase laparotomy, appendectomy, total pancreatectomy with and cytology (Figure 2). A second cyst in the body was splenectomy, hepaticojejunostomy, gastrojejunostomy drained and was targeted for additional testing due to and Braun enteroenterostomy (Figure 4). During the presence of a mural nodule (Figure 3). The cystic surgery, he had multiple small intussusceptions and fluid analysis revealed amylase levels of greater than an intraoperative enteroscopy was performed to look for 12,000, indicating ductal communication, and CEA lesions contributing to the intussusceptions. Examination levels of <5, excluding mucinous-type lesions. The to the mid-jejunum showed healthy mucosa except for cytology was positive for neoplastic cells consistent duodenitis and multiple small duodenal ulcers. Post- with a pancreatic neuroendocrine tumor. Further clinical operatively, his course was complicated by a chyle evaluation excluded multiple endocrine neoplasia leak, which required drain placement. This resolved syndromes. Laboratory values were significant for within one month with conservative management a pancreatic polypeptide level greater than 1600, and the drain was removed without problems. Final parathyroid hormone level of 43, corrected calcium (continued on page 34)

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Figure 5. A low power view of one of the lesions shows a cyst with Figure 6. Higher magnification shows the characteristic trabecular a solid component in the wall and acinar architecture of a neuroendocrine tumor. The nuclei are relatively uniform with stippled (so-called “salt and pepper”) chromatin

pathologic evaluation of removed tissue displayed well- considered when there are solid areas within the cyst differentiated pancreatic neuroendocrine neoplasm as well as when multiple cysts are present. Abdominal (stage IB; pT2N0) with less than 2 mitoses per high- ultrasound has a reported sensitivity of <20% to 80% powered field and Ki-67 index less than 2% (Figures 5 depending on the location of the lesion.10 Therefore, and 6). The tumor was confined to the pancreas and all historically, the only definitive way to differentiate these 37 regional lymph nodes were negative for metastasis cystic lesions was through open biopsy of the cyst wall and the microscopic margins were clear. due to the inability of ultrasound and CT to differentiate At present, one year later, the patient has well these lesions definitively.7 As demonstrated by our case managed insulin-dependent diabetes, feels well and however, EUS-FNA effectively evaluates these cystic is being monitored closely by surgical oncology lesions and offers a minimally invasive option to obtain and hematology/oncology. He has not received any an accurate tissue diagnosis thus allowing appropriate oncologic treatment as it was felt that his tumor had medical and surgical intervention.7, 9, 10 n favorable characteristics and the entire tumor was removed with clear margins. References 1. Kloppel G, Heitz PU. Pancreatic endocrine tumors. Pathol Res Pract 1988; 183:155-68. Conclusion / Discussion 2. Winston, Jr. JH. Malignant islet cell adenoma in a pancreatic cyst. Journal of the National Medical Association. 1965. 57(3):203-4. The differential diagnosis of pancreatic cystic neoplasms 3. Thompson, NW; et al. Cystic neuroendocrine neoplasms of the includes pseudocysts, mucinous cystic neoplasm, pancreas and liver. Annals of Surgery. 1984. 199(2):158-64. 4. Pogany, AC; Kerlan, Jr. RK; Le Quesne, LF; and Ring, EJ. Cystic intraductal papillary mucinous neoplasm, serous Insulinoma. American Journal of Radiology. 1984. 142:951-2. cystadenoma and solid pseudopapillary tumor. Cystic 5. Sohaib, SAA; Reznek, RH; Healy, JC; and Besser, GM. 2, 3, 4, 5 Cystic Islet Cell Tumors of the Pancreas. American Journal of neuroendocrine tumors are very rare with the first Radiology. 1998. 170:217. case reported by Thigpen in 1940.2 Nonfunctioning 6. Jensen, Robert T. “Chapter 344. Endocrine tumors of the gas- trointestinal tract and pancreas” (Chapter). Fauci AS, Brauwald cystic neuroendocrine tumors have a typical radiologic E, Kasper DL, Hauser SL, Longo DL, Jameson JL, Loscalzo J: appearance 80% of the time.10 On ultrasound, the Harrison’s Principles of Internal Medicine, 17e: http://www. accessmedicine.com/content/aspx?aID=2886966. lesions are well-circumscribed, hypoechoic masses 7. Heller, SJ; Ferrari, AP; Carr-Locke, DL; Lichtenstein, DR; Van with smooth margins. On CT scan, the lesions are Dam, J; and Banks, PA. Pancreatic duct stricture caused by islet cell tumors. American Journal of Gastroenterology. 1996. 91(1):147-9. well circumscribed and in 90% of cystic lesions the 8. Graziana R, Brandalise A, Bellotti M, et al. Imaging of neuroen- rim is hypervascular.10 Multiple cystic lesions occur docrine gastroenteropancreatic tumours. Radiologic Medicine. 2010. 115(7):1047-64. in a very small subset of patients and require close 9. Pais SA, Al-Haddad, Mohamadnejad M et al. EUS for pancre- investigation to make an accurate diagnosis as they atic neuroendocrine tumors: a single center 11 year experience. 10 Gastrointestinal Endoscopy. 2010. 71(7):1185-93. closely resemble other pancreatic neoplasms. 10. Lewis RB, Lattin GE, Paal E. Pancreatic endocrine tumors:radiologic-clinicopathologic correlation. Radiographics. Pancreatic cystic neuroendocrine lesions should be 2010. 30(6):1445-64.

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