310 J La state Med soc VoL 162 november/December 2010

Journal of the Louisiana State Medical Society

clinical case oF the month

heterotopic Pancreas

Maneesh K. Gupta, MD; Jordan J. Karlitz, MD; Daniel L. Raines, MD; Sander S. florman, MD; and fred A. Lopez, MD (Section Editor)

inTRoDucTion

Heterotopic pancreas (HP) is typically an asymptomatic malformation that can present anywhere along the gastrointestinal tract. It is often found incidentally as a single focal mass in patients with abdominal complaints undergoing routine diagnostic testing. HP occasionally presents symptomatically, and the manifestations vary depending on the location of the lesion. We describe the first reported case of symptomatic jejunal HP which presents as a circumferential infiltrative lesion with multiple foci rather than a single focal mass. This is accompanied by a review of the current literature regarding the pathogenesis, clinical manifestations, and treatment of HP.

cAse RePoRT

A 37-year-old woman with a history of systemic lupus erythematosus and cadaveric kidney transplant in 1997 was referred to our institution for recurrent nausea, vomiting, diarrhea, and abdominal pain of two years duration. Her symptoms occurred in discrete episodes requiring repeated hospitalizations for dehydration and abdominal pain. On physical exam, her abdomen was tender to palpation in the left upper quadrant and epigastrum, with voluntary guarding but no rebound tenderness.

Extensive evaluation including laboratory studies, abdominal ultrasound, upper endoscopy, and colonoscopy were unrevealing. An abdominal computed tomographic (CT) scan with oral and intravenous contrast demonstrated an area of abnormal small bowel localized to the proximal jejunum (Figure 1). Capsule endoscopy was subsequently performed to evaluate the small bowel and was unremarkable. Due to persistent symptoms, the patient underwent single bowel enteroscopy (SBE) to visualize directly and to biopsy the abnormal jejunal segment seen on CT.

Examination by SBE revealed a 6cm grossly edematous and circumferentially ulcerated segment of mucosa located approximately 100cm distal to the Ligament of Treitz (Figure 2). The lesion was biopsied; however, pathological examination only revealed mild vascular congestion. The patient was eventually taken for surgical resection. Intraoperatively, the lesion was visualized. In addition, a separate ulcerated lesion was seen in the small bowel 10cm proximal to the original lesion. Both lesions were resected, and histological examination revealed heterotopic pancreatic tissue involving the adventitia, muscularis propria, and submucosa extending to the muscularis mucosa (Figure 3). There was no evidence of vasculitis. The patient experienced symptoms of abdominal pain and nausea postoperatively but these symptoms resolved completely within one month.

figure 1. Axial computed tomographic image of the abdomen demonstrating gross thickening of a jejunal segment (arrows).

J La state Med soc VoL 162 november/December 2010 311

Discussion

Heterotopic pancreas (HP) is defined as pancreatic tissue that lacks an anatomic or vascular communication with the normal body of the pancreas.1-3 Although HP can occur throughout the entire gastrointestinal tract, it is most commonly found in the stomach (25%-38%), duodenum (17%-36%), and jejunum (15%-21%).4 Rare cases have described HP in the esophagus, biliary tract, gallbladder, spleen, and mesentery. HP can be pathologically subdivided into four subtypes. Type 1 heterotopia consists of typical pancreatic tissue. The remaining subtypes consist of specific components of normal pancreatic tissue such as pancreatic ducts only (type II), acinar tissue only (type III), or islet cells only (type IV).5 Heterotopic pancreatic tissue can be found in patients of any age and is slightly more common in men.4

The development of heterotopic pancreatic tissue is unclear. The two predominant theories of origin of HP involve misplacement of pancreatic tissue during development versus tissue metaplasia. Embryologically, the pancreas develops from invaginations of endodermal tissue in the primitive duodenum. The ventral aspect forms the head of the pancreas and the dorsal aspect forms the body and tail. The misplacement theory proposes that, during rotation of the foregut, several elements of the primitive pancreas become separated and eventually form mature pancreatic tissue along the length of the gastrointestinal tract.2 The metaplasia theory states that pancreatic heterotopia arises from areas of pancreatic metaplasia of the endoderm which migrate to the submucosa during embryogenesis.6

Heterotopic pancreatic tissue is a common incidental finding in patients undergoing laparotomy for other indications or at autopsy. The reported frequency of this finding during laparotomy is 0.5% and at autopsy is 1.7%.7

Despite the relatively frequent occurrence of HP, the vast majority of these cases are asymptomatic.8 When present, symptoms vary depending on the anatomical location and size of the lesion. Abdominal pain, nausea, vomiting, and gastrointestinal bleeding are the most commonly reported symptoms and are most likely to be seen with lesions greater than 1.5cm in diameter.2 Pain associated with HP may be related to the local secretion of hormones and enzymes resulting in tissue inflammation or chemical irritation.4

Pain may also be related to mechanical obstruction of the intestinal lumen, especially when associated with nausea or vomiting. Gastric lesions are the most likely to be symptomatic, presenting with either epigastic pain or symptoms of gastric outlet obstruction due to a pre-pyloric mass.9 Rarely, jejunal lesions may result in intestinal obstruction or intussusception.10-12 Even after finding an HP lesion in a patient with the above mentioned symptoms, other causes must be ruled out before the symptoms can be attributed to the HP.8,10,13,14

HP also may present with symptoms related to complications similar to those normally associated with the pancreas. Cases of pancreatitis due to gastric lesions have been reported.15,16 Pseudocyst formation complicating duodenal lesions is another known complication.17,18

Malignant transformation of heterotopic pancreas can rarely occur with up to 15 cases reported.19,20 In order to be identified as malignancy derived from HP, the malignant

figure 2. Endoscopic image of the lumen of the proximal jejunum seen on single balloon enteroscopy. The mucosa in this segment is circumferentially edematous. The segment was marked with india ink in preparation for surgical resection.

figure 3. Microscopic pathology of the resected segment of intes-tine. Heterotopic pancreatic tissue is seen involving the adventitia, muscularis propria and submucosa (arrow).

312 J La state Med soc VoL 162 november/December 2010

Journal of the Louisiana State Medical Society

tissue must be within or in close proximity to the heterotopic focus. Additionally, a transition between the carcinoma and normal pancreatic structures must exist. Fully developed ducts and acini in the non-neoplastic heterotopic pancreatic tissue must also be seen. Overall, adenocarcinoma arising from HP has a better prognosis than malignancy which arises from the normally located pancreas.8

HP has several characteristic radiographic and endoscopic features that aid in its identification. Gastric HP classically presents as a rounded filling defect with a central indentation on barium studies or as a broad based, umbilicated, submucosal lesion on endoscopy.8 This central umbilication results from a subjacent pancreatic duct.21

However, these features are not always present, leading to a difficulty in diagnosis. In 1999, Hsia et al reported that only 3 of 17 cases of HP presented preoperatively with the endoscopic finding of a submucosal lesion with a central indentation.22 Various imaging tests can be used to identify heterotopic pancreas in the gastrointestinal tract. It is important to stress that these tests are almost always performed to evaluate more common causes of abdominal symptoms, and the finding of HP is usually incidental. Computed tomographic findings are usually nonspecific although heterotopic pancreatic tissue can enhance to the same degree as normal pancreas with intravenous contrast. Newer technologies such as capsule endoscopy and single bowel enteroscopy are being used to detect lesions in the small bowel which were previously inaccessible without

surgery.8 Even when lesions are identified endoscopically, biopsies are often too superficial to reveal the submucosal lesions, and show only chronic inflammation, as in this case.23 Endoscopic ultrasound (EUS) is the standard test to evaluate submucosal lesions of the gastrointestinal tract. In the gastric antrum, EUS can diagnose submucosal heterotopic pancreas (pancreatic rests) ranging from 0.5-2cm in diameter, and when combined with fine needle aspiration the cytological evaluation has a sensitivity of 80%-100%.24

The management of HP is a controversial topic. Surgical resection of HP should be performed in symptomatic patients after more common causes of abdominal complaints such as peptic ulcer disease, gastro-esophageal reflux disease, and biliary disease have been ruled out. Benign asymptomatic lesions generally do not require surgical intervention. Ormarsson et al followed 32 patients with HP of the stomach or small bowel for 13 years and found that there was no malignant transformation in any of the patients over this time. The literature is divided on the management of asymptomatic and incidental lesions. Some state that management should include frequent endoscopy, while others suggest that there is no need for increased surveillance. In lesions with malignant changes or in which malignancy is uncertain, surgical resection is required.4,17,25

Although heterotopic pancreas is not uncommon, this is the first reported case of jejunal HP that presents as a circumferential mural infiltration with multiple foci rather than a single focal mass. This patient had two separate jejunal lesions which involved the adventitia, muscularis propria, and submucosa resulting in symptoms of recurrent intestinal obstruction. Additionally, this case highlights the difficulty in making a diagnosis of HP even with the aid of newer techniques such as capsule endoscopy and SBE. Although an area of gross inflammation was located endoscopically in the jejunum, a diagnosis of HP could not be made until the specimen was surgically excised.

RefeRences

Fam S, O’Briain DS, Borger JA. Ectopic pancreas with acute inflammation. J Pediatr Surg 1982;17:86-87.Armstrong CP, King PM, Dixon JM, et al. The clinical significance of heterotopic pancreas in the gastrointestinal tract. Br J Surg 1981;68:384-387. Margulis AR, Burhenne HJ. Alimentary Tract Roentgenology. St. Louis, MO: Mosby; 1973.Ormarsson OT, Gudmundsdottir I, Marvik R. Diagnosis and treatment of gastric heterotopic pancreas. World J Surg 2006;30:1682-1689.Gaspar-Fuentes A, Campos-Tarrech JM, Fernandez-Burgui JL, et al. Pancreatic ectopias. Rev Esp Enferm Apar Dig 1973;39:255-268.Chandan VS, Wang W. Pancreatic heterotopia in the gastric antrum. Arch Pathol Lab Med 2004;128:111-112.Barbosa J, Dockerty MB, Waugh JM. Pancreatic heterotopia review of the literature and report of 41 authenticated surgical cases. Surg Gynecol Obstet 1946; 82;527-542.

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J La state Med soc VoL 162 november/December 2010 313

Christodoulidis G, Zacharoulis D, Barbanis S, et al. Heterotopic pancreas in the stomach: a case report and literature review. World J Gastroenterol 2007;13:6098-6100.Pang LC. Pancreatic heterotopia: a reappraisal and clinicopathologic analysis of 32 cases. South Med J 1988; 81:1264-1275.Hirasaki S, Kubo M, Inoue A, et al. Jejunal small ectopic pancreas developing into jejunojejunal intussusception: a rare cause of ileus. World J Gastroenterol 2009;15: 3954-3956.Chandra N, Campbell S, Gibson M, et al. Intussusception caused by heterotopic pancreas. JOP 2004;5:476-479.Gurbulak B, Kabul E, Dural C, et al. Heterotopic pancreas as a leading point for small-bowel intussusceptions in a pregnant woman. JOP 2007;8:584-587.Rana SS, Bhasin DK, Nada R, et al. Heterotopic pancreas in the jejunum presenting as a submucosal lesion on endoscopy. JOP 2009;10:419-420.Erkan N, Vardar E, Vardar R. Heterotopic pancreas: report of two cases. JOP 2007;8:588-591.Hirasaki S, Tanimizu M, Moriwaki T, et al. Acute pancreatitis occurring in gastric aberrant pancreas. Intern Med 2005;44:1169-1973.Green PH, Barratt PJ, Percy JP, et al. Acute pancreatitis occurring in gastric aberrant pancreatic tissue. Dig Dis Sci 1970;22:734-740.Sharma DK, Agarwal S, Saran R, et al. Pseudocyst of ectopic pancreas of the duodenal wall masquerading as malignant cystic tumor of pancreas. Saudi J Gastroenterol 2009;15: 271-273.Chung JP, Lee SI, Kim KW, et al. Duodenal ectopic pancreas complicated by chronic pancreatitis and pseudocyst formation. J Korean Med Sci 1994;9:351-356.Eisenberger CF, Gocht A, Knoefel WT, et al. Heterotopic pancreas-clinical presentation and pathology with review of the literature. Hepatogastroenterology 2004;51:854-858.Tanaka K, Tsunoda T, Eto T, et al. Diagnosis and management of heterotopic pancreas. Int Surg 1993; 78:32-35.Tsurumaru D, Utsunomiya T, Kayashima K, et al. Heterotopic pancreas of the jejunum diagnosed by double baloon enteroscopy. Gastrointest Endosc 2007; 66:1026-1027.Hsia CY, Wu CW, Lui WY. Heterotopic pancreas: a difficult diagnosis. J Clin Gastroenterol 1999;28:144-147.Hsu SD, Chan DC, Hsieh HF, et al. Ectopic pancreas presenting as ampulla of vater tumor. Am J Surg 2008; 195:498-500.Chak A, Canto MI, Rosch T, et al. Endosonographic differentiation of benign and malignant stromal cell tumors. Gastrointest Endosc 1997;45:468-473.Yuan Z, Chen J, Zheng Q, et al. Heterotopic pancreas in the tract. World J Gastroenterol 2009;15:3701-3703.

Dr. Gupta is a first-year internal medicine resident at Louisiana State University Health Sciences Center, new orleans. Dr. karlitz is an assistant professor of clinical medicine in the Department of Medicine, Section of Gastroenterology at Tulane University Medical Center, new orleans. Dr. Raines is an assistant professor of clinical medicine in the Department of Medicine, Section of Gastroenterology at Louisiana State University Health Sciences Center, new orleans. Dr. florman is a professor of surgery at Mount Sinai Medical Center and director of the Recanati/Miller Transplant institute in new York. Dr. Lopez is the Richard Vial Professor of medical education at Louisiana State University Health Sciences Center in new orleans.

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