Nonfunctioning Pancreatic Endocrine Neoplasm Presenting As Asymptomatic, Isolated Pancreatic Duct Stricture: A Case Report and Review of the Literature
By Powell, Anathea C Hajdu, Cristina H; Megibow, Alec J; Shamamian, Peter
Morphologic irregularities of the pancreatic duct are often noted on abdominal imaging studies obtained for unrelated symptoms or conditions. We report the case of a patient who was found to have an incidental, isolated pancreatic duct dilatation on multiple imaging studies and who was found to have a nonfunctioning pancreatic endocrine neoplasm at resection. His prognosis is excellent based on the histology of the lesion and a curative resection. This case highlights the importance of fully investigating incidental pancreatic duct abnormalities regardless of the setting in which they are found. INCIDENTAL FINDINGS OF segmental changes in the caliber of the pancreatic duct are becoming more common as patients undergo frequent abdominal imaging to evaluate other symptoms and conditions and as these imaging modalities improve. These serendipitous discoveries represent an opportunity to detect neoplastic pancreatic disease at an early stage. We report the case of a patient who was referred for evaluation of an incidental segmental pancreatic duct dilatation seen on CT. This was seen to be an isolated stricture on magnetic cholangiopancreatography (MRCP) and endoscopic ultrasound (EUS), but cytology of an adjacent mass seen on the EUS was nondiagnostic. The patient was found to have a nonfunctioning pancreatic endocrine neoplasm (PEN) at resection. Our case highlights the importance of carefully evaluating pancreatic duct morphologic changes. Despite advances in imaging, small pancreatic neoplasms can still evade some of these diagnostic techniques. It is important to maintain a high index of suspicion regarding pancreatic duct morphologic changes, and pancreatic duct stricture in the face of an otherwise normal pancreas should be considered malignancy.
Case Report
A 62-year-old man underwent CT for hematuria and a dilated pancreatic duct in the body of the gland was fortuitously identified. He denied abdominal pain or trauma, past episodes of pancreatitis, and symptoms of pancreatic endocrine or exocrine insufficiency. His medical history was significant for Crohn’s disease, hypertension, a myocardial infarction, and stable angina. He had undergone a right colon resection 5 years earlier for Crohn’s disease as well as a laparoscopic cholecystectomy. Medications included lowdose oral steroids, mesalamine, methotrexate, and antihypertensives. He denied smoking and reported only minimal alcohol use. He was anicteric and had no abdominal masses or tenderness. There were no skin changes. Laboratory studies were unremarkable, including complete blood count and liver chemistries.
A MRCP was obtained to evaluate the dilated pancreatic duct seen on CT. This revealed a pancreatic duct stricture in the neck with leftward dilatation of the main pancreatic duct and a normal- caliber duct to the right of the stricture. At the level of the stricture, there was no mass, signal alteration, or extrapancreatic abnormality (Fig. 1). The common bile duct was normal. An EUS again demonstrated the pancreatic duct stricture and also suggested an associated 8-mm hypoechoic mass. Fine needle aspiration cytology of the mass was nondiagnostic.
The patient underwent an uncomplicated pancreaticoduodenectomy. The specimen revealed a 7-mm endocrine neoplasm in the pancreatic neck, growing into and obstructing the main pancreatic duct lumen and extending to the peripancreatic adipose tissue. Perineural invasion was present but there was no lymphovascular invasion. The lesion stained positive for chromogranin A, synaptophysin, and CD56 but negative for AE1/AE3 (Fig. 2). Focal positivity for glucagon was seen throughout the mass and the proliferation index (MIB-I) was less than 2 per cent. Focal pancreatitis was also seen around the lesion. The findings were interpreted as being consistent with a nonfunctioning PEN. Eight months later, he is doing well and remains asymptomatic.
Fig. 1. (A) Single image from three-dimensional magnetic resonance cholangiopancreatography examination (MRCP) acquired with respiratory gating reveals a focal stricture in the neck of the pancreatic duct. The downstream duct is normal caliber. (B) Single image from fat-suppressed, gadolinium-enhanced T1-weighted gradient- recalled echo sequence at the level of the stricture fails to reveal a mass. The signal intensity of the pancreatic parenchyma is uniform.
Discussion
Improved imaging technology has allowed routine visualization of normal pancreatic ducts with cross-sectional techniques and has increased the detection of pancreatic duct morphological changes. Cases of minute pancreatic neoplasms inciting elastic tissue and fibroblastic proliferation surrounding the duct and producing stenosis have been reported.1 Based on retrospective data, it has been suggested that morphological changes of either local dilatation and/or cutoff of the pancreatic duct may be the earliest detectable imaging findings suggesting pancreatic neoplasm.2 Although most commonly seen in patients with ductal adenocarcinoma, pancreatic duct obstruction has been reported in patients with PEN.3
It is difficult to differentiate strictures resulting from chronic pancreatitis from those caused by a neoplasm. Inoue et al. reported that strictures arising from neoplasms produced a higher discrepancy between the leftward and rightward pancreatic duct segments in patients with neoplasm as opposed to those with chronic pancreatitis.4 When a dilated pancreatic duct traverses a mass, as shown by MRCP, there is a high likelihood that the mass will be inflammatory. Alternatively, when the duct abruptly terminates, a pancreatic neoplasm is likely.5
A recent retrospective review of 355 cases of pancreatic duct strictures detected by endoscopic retrograde cholangiopancreatography (ERCP) investigated characteristics that predict malignancy.6 Of 218 isolated strictures, 27 (12%) were found to be malignant and the strongest predictor of malignancy was location of the stricture (head/neck; odds ratio, 41.7). A history of pancreatitis or the discovery of irregular ductal side branches strongly suggested benign disease. The investigators developed a prognostic equation based on these variables. Extrapolating this model to our patient’s MRCP, the isolated neck stricture with no irregular side branches and no history of pancreatitis would convey a malignancy risk of 0.937.
Based on the evidence reviewed of pancreatic duct strictures harboring malignancy, the decision was made for resection despite the nondiagnostic cytology. We did not proceed with ERCP because we did not feel information gained from it would change our decision for resection. An ERCP may have provided another opportunity for evaluation of the stricture and aspiration of the mass seen on EUS. However, MRCP had already unequivocally demonstrated a stricture of the neck of the main pancreatic duct. Positive cytology from the ERCP would only have confirmed our decision to resect and nondiagnostic cytology would not have kept us from resection in the face of this isolated stricture. Pathological examination of the resection specimen confirmed a neoplasm and revealed an unusual diagnosis of a PEN.
The annual incidence of PENs has been reported as four persons per million.7 Nonfunctioning neoplasms comprise between 25 and 67 per cent in selected series of pancreatic islet cell neoplasms.8-11 These lesions usually present in the fourth and fifth decades of life12 and are determined to be “nonfunctioning” by the absence of a clinically recognizable syndrome. Despite their lack of endocrine symptoms, they may still be biologically active and produce multiple amines and peptides such as chromogranin, pancreatic peptide, the alpha-subunit of human chorionic gonadotropin, and neuron-specific enolase.7,12
Fig. 2. (A) Pancreatic neck involved by pancreatic endocrine neoplasm with pancreatic duct stricture (arrow, slice 2) and upstream ductal dilatation (slices 3 and 4). (B) Pancreatic endocrine neoplasm growing around main pancreatic duct (MPD) and extending into peripancreatic adipose tissue (hematoxylin & eosin x 10). (C) Chromogranin A highlights clusters of neuroendocrine cells abutting MPD epithelium ( x 40). (D) Perineural invasion (hematoxylin & eosin x 400).
Given the lack of an endocrine syndrome, many patients present only when symptoms of mass effect develop.12 However, in a recent series of 184 patients, 35 per cent of the cases were diagnosed incidentally in asymptomatic patients.13 The tumors are usually located in the head of the pancreas, although they can occur in the body and tail of the gland.13,14 Intraluminal growth of these neoplasms is rare but has been reported. In 2004, Akatsu et al. reported the case of a nonfunctioning endocrine neoplasm that grew within the main pancreatic duct without invading the pancreatic duct epithelium and completely obstructed the lumen. Their review of the literature found 18 previously reported cases of a PEN completely obstructing the main pancreatic duct at ERCP and three cases, including their own, of intraductal growth of PENs.15
CT, MRI, ERCP, MRCP, and EUS have been reviewed for accuracy in localizing PENs. Using currently available imaging technology, CT and MRI sensitivities have been reported as between 71 to 82 per cent and 85 to 94 per cent, respectively, for islet cell tumors.16 ERCP and MRCP have been shown to have high accuracy in the diagnosis of pancreatic adenocarcinoma17 but may miss small islet cell tumors.17,18 EUS is considered the test of choice for localizing small islet cell tumors17-19 with one series reporting a sensitivity of 84 per cent for tumors 0.5 to 2.5 cm.19 Malignant characteristics of PENs include evidence of metastases, histologic findings of tumor necrosis; high mitotic activity20; and vascular, lymphatic, or perineural invasion.14 The rate of malignancy is reported to vary between 64 and 92 per cent.7 The 5-year survival rate for patients undergoing curative resections of a localized, nonfunctioning PEN has recently been reported to be 72 to 80 per cent.13,14
In conclusion, pancreatic duct strictures may represent both nonneoplastic and neoplastic disease. Investigation of these lesions may include many different imaging modalities; findings that highly suggest neoplasm include abrupt termination of the pancreatic duct5 at MRCP and a stricture located in the head or neck of the gland6 at ERCP. Although PENs do not usually involve the duct, they may rarely arise within the duct itself or, more commonly, compress the duct, causing stricture. Given the hopeful survival data for PEN in contrast to the dismal prognosis of pancreatic adenocarcinoma, identification of asymptomatic patients such as our patient with nonfunctioning PENs presents an opportunity for early intervention and improved outcomes. This case demonstrates the importance of investigating pancreatic strictures even when they are asymptomatic. Strictures, particularly those located in the head and neck of the gland, in the absence of pancreatitis should be regarded as malignancy and require definitive determination of etiology.
Acknowledgments
We thank David McAneny, MD, for assistance with editing.
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ANATHEA C. POWELL, M.D.,* CRISTINA H. HAJDU, M.D.,[dagger] ALEC J. MEGIBOW, M.D.[double dagger] PETER SHAMAMIAN, M.D.*[section]
From the Departments of * Surgery, tPathology, and [double dagger] Radiology, New York University School of Medicine,
New York, New York; and the [section] Veterans Administration New York Harbor Healthcare System
(New York Campus), New York, New York
Address correspondence and reprint requests to Peter Shamamian, M.D., New York University School of Medicine, Department of Surgery, 530 First Avenue, Suite 6D, New York, NY 10016. E-mail: peter.shamamian@med.nyu.edu.
Copyright Southeastern Surgical Congress Feb 2008
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