DOI: 10.1148/rg.262055056
RadioGraphics 2006;26:453-464
© RSNA, 2006
Multi–Detector Row CT of Pancreatic Islet Cell Tumors1
Karen M. Horton, MD,
Ralph H. Hruban, MD,
Charles Yeo, MD and
Elliot K. Fishman, MD
1 From the Russell H. Morgan Department of Radiology and Radiological Sciences (K.M.H., E.K.F.), the Department of Pathology (R.H.H.), and the Department of Surgery (C.Y.), Johns Hopkins Medical Institutions, 601 N Caroline St, JHOC 3253, Baltimore, MD 21287. Presented as an education exhibit at the 2004 RSNA Annual Meeting. Received March 18, 2005; revision requested May 9 and received July 14; accepted July 20. All authors have no financial relationships to disclose.
Address correspondence to K.M.H. (e-mail: kmhorton{at}jhmi.edu).
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Abstract
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Pancreatic islet cell tumors (ICTs) are neuroendocrine neoplasms that produce and secrete hormones to a variable degree. These neoplasms can present a diagnostic challenge, both clinically and radiologically. ICTs can be classified as either syndromic or nonsyndromic on the basis of their clinical manifestations. Multi–detector row computed tomography (CT) plays an important role in the diagnosis and staging of both syndromic and nonsyndromic ICTs. In general, syndromic ICTs are less than 3 cm in size. They are typically hyperenhancing and are usually best seen on CT scans obtained during the arterial phase. Nonsyndromic ICTs tend to be larger than syndromic ICTs at presentation and are more likely to be cystic or necrotic. It is important for the radiologist to be familiar with appropriate CT protocol for the evaluation of patients with suspected pancreatic ICT and to understand the variable CT appearances of these neoplasms.
© RSNA, 2006
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LEARNING OBJECTIVES
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After reading this article and taking the test, the reader will be able to:- Recognize the clinical manifestations of both syndromic and nonsyndromic islet cell tumors of the pancreas.
- Discuss the appropriate CT techniques for patients with suspected islet cell tumors.
- Describe the CT appearances of syndromic and nonsyndromic islet cell tumors.
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Introduction
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Pancreatic islet cell tumors (ICTs) are rare, well-differentiated neuroendocrine neoplasms that usually occur sporadically but can be associated with genetic syndromes such as multiple endocrine neoplasia type 1 (MEN 1), von Hippel–Lindau disease, neurofibromatosis type 1, and tuberous sclerosis (1). Unlike adenocarcinomas, ICTs rarely result in pancreatic ductal dilatation. The lesions can be located within the gland or can be exophytic. ICTs produce and secrete hormones to a variable degree. In the past, they have been categorized as either functioning or nonfunctioning (nonhyperfunctioning). However, because all of the neoplasms are hormonally active, it is more accurate to classify them as either syndromic (functioning) or nonsyndromic (non-hyperfunctioning), on the basis of clinical and laboratory findings.
Gadolinium-enhanced magnetic resonance imaging, somatostatin receptor imaging, and endoscopic ultrasonography have all been reported to be useful for the detection and staging of pancreatic ICTs (2–4). However, computed tomography (CT) remains the primary imaging modality and plays an important role in the diagnosis and staging of both syndromic and nonsyndromic ICTs. New multi–detector row CT scanners and three-dimensional (3D) imaging software have improved the detection of small lesions by allowing thin collimation and optimizing the timing of data acquisition and the intravenous administration of contrast material. In addition, evaluation of vascular encasement and liver metastases has improved with use of dual phase imaging and 3D CT angiography. CT is also important in surgical planning and subsequent patient treatment.
In this article, we review the clinical manifestations, pathophysiologic features, multi–detector row CT diagnosis, and treatment of both syndromic and nonsyndromic pancreatic ICTs.
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Clinical Manifestations
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Syndromic ICTs
Syndromic ICTs show clinical evidence of hormone production and produce a recognizable endocrinopathy. These neoplasms usually manifest at a relatively small size compared with nonsyndromic ICTs owing to the symptoms produced by the associated hormone production. Most syndromic ICTs actually produce multiple hormones, but the predominant hormone usually determines the clinical syndrome (1). There are several recognized types of syndromic ICTs, which are named according to the predominant hormone they secrete. The two most common types are insulinoma and gastrinoma. Other types include glucagonoma, vipoma, and somatostatinoma.
Insulinoma.—
Insulinoma is the most common syndromic ICT. The classic clinical triad (Whipple triad) includes fasting serum glucose levels less than 50 mg/dL, symptoms of hypoglycemia, and relief of symptoms after glucose administration. In addition, patients may report symptoms such as palpitations, sweating, and headache, all of which are related to catecholamine release (5). Ten percent of insulinomas are associated with MEN 1, 10% are malignant, and 10% of patients with the clinical syndrome will have "islet cell hyperplasia" rather than a discrete insulinoma.
Gastrinoma.—
Gastrinoma is the second most common syndromic ICT. Because of the excess production of gastrin, many patients will have Zollinger-Ellison syndrome, and gastrinoma is the most common ICT in patients with MEN 1. Most patients present with epigastric pain related to recurrent or intractable peptic ulcer disease, or with ulcers in unusual (eg, postbulbar) locations. Patients may also have diarrhea due to excessive delivery of acid to the small bowel (6). Diagnosis is made by documenting elevated serum gastrin levels. Gastrinomas are frequently malignant, with approximately 30% of patients presenting with liver metastases (1).
Glucagonoma.—
Glucagonoma is an uncommon neuroendocrine neoplasm that typically manifests in middle-aged patients and affects men and women equally. Most of these lesions are malignant. Patients present with a characteristic migratory rash called necrolytic migratory erythema, which usually affects the genitals. Patients may also experience stomatitis, diarrhea, anemia, weight loss, depression, and deep vein thrombosis. The syndrome is termed the "4D syndrome" (dermatosis, diarrhea, depression, and deep vein thrombosis) (1). Sometimes, diabetes mellitus will result due to the elevated levels of glucagon. An elevated glucagon level helps confirm the diagnosis. Levels of associated hormones such as insulin, serotonin, or gastrin may also be elevated.
Vipoma.—
Vipoma was first described in 1958 by Verner and Morrison (7). These neoplasms secrete a variety of hormones, including vasoactive intestinal peptide (VIP) (1). VIP binds to receptors on the epithelial cells in the intestine, stimulating production of cyclic adenosine monophosphate and resulting in fluid and electrolyte secretion into the lumen, causing a characteristic watery diarrhea. This peptide also inhibits gastrin production, resulting in achlorhydria. The syndrome is also referred to as WDHA (watery diarrhea, hypokalemia, and achlorhydria). Most vipomas are malignant, usually accompanied by liver metastases at the time of diagnosis (1).
Somatostatinoma.—
Somatostatinoma is very rare, with fewer than 200 cases having been reported in the literature (8). These neoplasms secrete somatostatin, resulting in diarrhea, cholelithiasis, indigestion, and hypochlorhydria. The diagnosis is made on the basis of the presence of the clinical syndrome and elevated plasma somatostatin levels. About one-half of patients have metastases at the time of diagnosis.
Nonsyndromic ICTs
Nonsyndromic ICTs typically represent one-half of all ICTs and are larger than syndromic ICTs at initial presentation. Nonsyndromic ICTs show no clinical evidence of hormone production, although the tumors are still hormonally active. Large (usually >5-cm) nonsyndromic ICTs produce symptoms related to mass effect, local invasion, or metastases. Patients typically present with abdominal pain, whereas patients with syndromic ICTs usually present with distinctive signs and symptoms related to the endocrine syndrome.
Nonsyndromic ICTs, especially small lesions, are being incidentally discovered with increasing frequency in asymptomatic patients, most likely owing to advances in imaging technology (9).
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Pathophysiologic Features
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Normal Pancreas
Less than 5% of the total mass of the pancreas consists of endocrine cells. These endocrine cells are clustered in small groups (islets of Langerhans) throughout the gland and are called pancreatic islet cells. These islet cells are of three main types: The beta cells (B cells) are the most abundant, are located in the center of the islets, and produce insulin; the alpha cells (A cells) secrete glucagon; and the delta cells (D cells) secrete somatostatin. Other cells produce minor hormones. For example, D1 cells produce VIP; enterochromaffin cells synthesize serotonin; and pancreatic polypeptide (PP) cells produce PP, which stimulates secretion of gastric and intestinal enzymes and inhibits intestinal motility. PP cells are present in the islets and are scattered throughout the exocrine pancreas. The pancreas usually lacks gastrin-producing cells, although gastrinomas are common.
Like all endocrine cells, islet cells secrete hormones into the bloodstream and are thus surrounded by a rich blood supply. Although islet cells account for only 1%–2% of the mass of the pancreas, they receive about 10%–15% of the pancreatic blood flow. In addition, they are innervated by parasympathetic and sympathetic neurons, and nerve signals clearly modulate the secretion of insulin and glucagon.
Islet Cell Tumors
Most ICTs are composed of well-differentiated endocrine cells. These cells typically form nests, trabeculae, or ribbons. The neoplastic cells are small to medium in size and characteristically contain uniform round nuclei with "salt-and-pepper" chromatin. The endocrine differentiation can be confirmed with a Grimelius silver stain or with immunohistochemical labeling for chromogranin or synaptophysin. Specific hormone production by the neoplasms can also be confirmed with immunolabeling. Predicting the clinical behavior of a well-differentiated endocrine neoplasm of the pancreas can be extremely difficult. The only unequivocal criteria for malignancy are gross invasion of adjacent organs, large vessel invasion, and metastases to lymph nodes or distant organs.
Histologic differentiation between benign and malignant tumors is difficult because tumors that metastasize are not necessarily histologically different from those that do not. Tumor size is an important factor in predicting the behavior of nonsyndromic ICTs. Larger tumors tend to behave more aggressively and are more likely to metastasize (9). In addition, local invasion, vascular invasion, and metastatic disease are more common with larger tumors (10). The presence or absence of metastases is the major predictor of survival.
It is not usually possible to distinguish syndromic from nonsyndromic tumors with immunohistochemical staining alone (11).
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Diagnosis with CT
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CT is considered to be the imaging modality of choice for tumor detection and staging, surgical planning, and follow-up in patients with pancreatic ICTs. In patients with a suspected or known pancreatic ICT, careful CT technique is important.
Contrast Material
We typically administer 500 mL of water 30 minutes prior to the study and an additional 250 mL of water immediately prior to the study to achieve adequate distention of the stomach and duodenum. In addition to water, other low-density, orally administered contrast agents have been reported to be useful for opacifying the gastrointestinal tract, including milk and polyethylene glycol–based agents (12–14). Low-density intraluminal agents may improve identification of small intraluminal tumors (gastrinomas) as well as facilitate 3D volume rendering (VR) techniques and CT angiography in the assessment of vascular involvement.
High-density oral contrast agents will interfere with the 3D imaging of vessels and require extensive editing of images. In addition, because pancreatic ICTs are often vascular, they can appear well enhanced at arterial imaging and may be either detected with difficulty or overlooked if the adjacent bowel is opacified with high-density material. However, ICTs can occasionally be cystic and exophytic. Therefore, the images must be reviewed carefully so as not to mistake a cystic ICT for a fluid-filled bowel loop.
Intravenous contrast material is essential for detection of the primary tumor, identification of vascular encasement, and detection of liver metastases. We inject 120 mL of nonionic contrast material (Omnipaque 350; GE Healthcare, Princeton, NJ) at a rate of 3–4 mL/sec. Dual phase imaging is essential. Some investigators have shown improved conspicuity of ICTs during the arterial phase of enhancement, whereas others have shown portal venous phase imaging to be more helpful (15–17). One study found improved detection with imaging performed during the arterial and parenchymal phases (18). The exact timing of the arterial, portal venous, and parenchymal phases varies widely between centers. We typically use an empiric delay of 25 seconds for arterial phase imaging and of 55–60 seconds for early portal venous phase imaging. In our experience, most ICTs (especially small ones) are better seen during the arterial phase of enhancement.
Scanning Parameters
The thin collimation and improved spatial and temporal resolution afforded by multi–detector row CT definitely improve the visualization of small lesions. We use a Siemens Sensation 64 CT scanner (Siemens Medical Solutions, Malvern, Pa) with a 64 x 0.6-mm collimator setting or a Siemens Sensation 16 scanner with a 16 x 0.75-mm collimator setting to obtain 0.75-mm sections reconstructed at 0.5-mm intervals for 3D imaging. For hard-copy review, 3-mm sections are usually adequate.
Three-dimensional Imaging
All of the data are then transferred to our 3D workstation (Leonardo, Siemens) for VR. The 16 x 0.75-mm or 64 x 0.6-mm collimation setting allows creation of isotropic data sets, so that the 3D images of the pancreas and abdominal vessels are of excellent quality. All images are reviewed with InSpace software (Siemens), which allows multiplanar reformation as well as interactive 3D VR. The brightness, opacity, and window width and level can be adjusted in real time to accentuate the wall of the gastrointestinal tract and optimize the visualization of abnormalities. The process can be simplified by creating "presets" that can be applied quickly, after which only minor adjustments are needed.
In the evaluation of the mesenteric vessels, VR is the main algorithm used. In some cases, however, maximum intensity projection can be helpful for visualizing the most distal branches of the vessels. Modern 3D software allows instant switching between VR and maximum intensity projection.
For visualization of the pancreas itself, VR is the most helpful technique. Typically, coronal or coronal oblique images are optimal, although sagittal or axial images can also be useful depending on the location of the mass. Small tumors, especially those that do not demonstrate much enhancement, may be easier to detect on 3D images than on the axial images alone. In addition, small hyperenhancing lesions may be mistaken for a vascular structure or aneurysms mistaken for pancreatic tumors (Fig 1) on the axial images, but such lesions are readily apparent on 3D images.
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Figure 1a. (a) Contrast material–enhanced axial CT scan demonstrates a 1-cm enhancing lesion (arrow) in the pancreatic body. This finding was thought to represent a possible ICT of the pancreas. (b) VR CT angiographic image reveals that the lesion (arrow) is actually a splenic artery aneurysm.
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Figure 1b. (a) Contrast material–enhanced axial CT scan demonstrates a 1-cm enhancing lesion (arrow) in the pancreatic body. This finding was thought to represent a possible ICT of the pancreas. (b) VR CT angiographic image reveals that the lesion (arrow) is actually a splenic artery aneurysm.
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CT Findings
Several studies have shown promising results in the preoperative detection of ICTs with dual phase CT, which typically demonstrates a sensitivity exceeding 80% (16,18,19). Most investigators subscribe to the necessity of obtaining images during more than one phase of enhancement. For example, in a study by King et al (16), six of six neoplasms were detected in the arterial phase, whereas only four were visible in the portal venous phase. Conversely, in a study of both syndromic and nonsyndromic ICTs by Ichikawa et al (17), more lesions were detected in the portal venous phase than in the arterial phase. More recently, more focused studies have been performed, addressing the usefulness of CT and specific protocols in the evaluation of syndromic versus nonsyndromic lesions or of specific tumor types such as insulinomas and gastrinomas.
In a study of 19 patients with 26 ICTs, dual phase CT and magnetic resonance imaging demonstrated similar effectiveness in detecting the tumors (17).
Syndromic ICTs.—
In general, syndromic ICTs are less than 3 cm in size. They are typically hyperenhancing and are usually best seen in the arterial phase. However, some neoplasms will be hypoattenuating relative to the enhancing pancreas and therefore will be seen best in the portal venous or pancreatic phase. Syndromic ICTs can be homogeneous, heterogeneous, or cystic in appearance. Cystic degeneration, calcification, and necrosis are more common in larger syndromic ICTs and in nonsyndromic ICTs.
As mentioned earlier, insulinoma is the most common syndromic ICT. In the past, preoperative imaging for detection of suspected pancreatic insulinoma has been controversial (20). First, the sensitivity of cross-sectional imaging was somewhat limited before the development of multi–detector row CT. Second, some authorities have argued that preoperative imaging is not necessary, since most insulinomas can be localized intraoperatively with palpation or ultrasonography (21). Today, however, most physicians value preoperative imaging for detection of the primary neoplasm and staging for local spread or metastasis. In addition, the CT findings may alter the surgical approach: Lesions near the surface of the gland can be treated with enucleation, which can sometimes be performed laparoscopically.
In one large retrospective series of 30 patients with benign insulinomas, multiphasic contrast-enhanced single– or multi–detector row CT with a collimation of 2.5–5 mm was performed (15). Radiologists prospectively detected 63% of insulinomas, and 83% of the lesions could be seen in retrospect (15). Most insulinomas exhibited increased enhancement in at least one phase (Figs 2–5), although hypoenhancing lesions or even cystic lesions were also seen. Most of the false-negative lesions were overlooked due to their proximity to adjacent vessels. Three-dimensional imaging would probably have improved the identification of these lesions but was not included in the study. In a study by Chung et al (22), five of seven ICTs were detected on the axial images, whereas all seven were seen on multiplanar reformatted images.
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Figure 2. Insulinoma in a 63-year-old woman with hypoglycemia. Contrast-enhanced CT scan demonstrates a 1-cm enhancing lesion (arrow) in the midbody of the pancreas. Robotic laparoscopic enucleation of the lesion was performed. At histologic analysis, a well-differentiated 1.5-cm ICT with a low mitotic rate was seen. The patient’s symptoms resolved after surgery.
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Figure 3. Insulinoma in an 87-year-old man with intractable hypoglycemia. Dual phase CT scan through the pancreas demonstrates a subtle, well-defined 1-cm enhancing lesion (arrow) in the pancreatic neck. A small cyst is also seen. A well-differentiated 1.2-cm ICT was completely excised at surgery. Histologic stains were positive for insulin. The hypoglycemia resolved after surgery.
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Figure 4. Insulinoma in an 84-year-old man who presented with life-threatening hypoglycemia. Contrast-enhanced CT scan demonstrates a 1-cm hyperenhancing lesion (arrow) in the pancreatic neck. A 1.5-cm ICT with no significant mitotic activity was removed at surgery. The lesion was of low malignant potential, being small with circumscribed borders. The patient’s symptoms resolved after surgery.
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Figure 5. Insulinoma in a 46-year-old woman with elevated insulin levels and hyperglycemia. Arterial phase contrast-enhanced CT scan demonstrates a 1.5-cm enhancing mass (arrow) in the pancreatic neck. A 1.5-cm insulinoma was resected at surgery. The lesion had low malignant potential owing to its low mitotic rate, and there was no evidence of invasion of the surrounding tissues.
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Unlike insulinomas, gastrinomas are usually multiple and are often extrapancreatic in location. Pancreatic lesions average 3–4 cm in size (Figs 6–8). Most gastrinomas occur in the gastrinoma triangle (Fig 9), which is defined as the confluence of the cystic and common bile ducts superiorly, the second and third portions of the duodenum inferiorly, and the neck and body of the pancreas medially (6).
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Figure 6. Gastrinoma in a 43-year-old patient with MEN 1 who presented with elevated gastrin levels. The patient had a history of nephrolithiasis, hypercalcemia, hyperuricemia, and peptic ulcer disease. Contrast-enhanced CT scan demonstrates a 2-cm exophytic mass (arrow) off the pancreatic tail. The lesion was enucleated laparoscopically. Histologic analysis demonstrated a 3.5-cm ICT. The gastrin levels returned to normal after surgery.
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Figure 7. Gastrinoma in a 62-year-old man with severe peptic ulcer disease and elevated gastrin levels. Contrast-enhanced CT scan demonstrates a subtle, 1-cm enhancing lesion (arrow) in the pancreatic neck. A small ICT was removed at surgery. Histologic analysis showed elevated gastrin markers.
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Figure 8a. Gastrinoma in a 50-year-old man who presented with weight loss and markedly elevated gastrin levels. The patient had MEN 1 with hyperparathyroidism and nephrolithiasis and was thought to have Zollinger-Ellison syndrome. (a) Nonenhanced CT scan shows marked gastric wall thickening. (b) Nonenhanced CT scan reveals a 3–4-cm mass (arrow) in the pancreatic neck. There was no associated pancreatic ductal dilatation. A malignant 5-cm ICT was resected at surgery. Metastatic lymph nodes were also seen.
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Figure 8b. Gastrinoma in a 50-year-old man who presented with weight loss and markedly elevated gastrin levels. The patient had MEN 1 with hyperparathyroidism and nephrolithiasis and was thought to have Zollinger-Ellison syndrome. (a) Nonenhanced CT scan shows marked gastric wall thickening. (b) Nonenhanced CT scan reveals a 3–4-cm mass (arrow) in the pancreatic neck. There was no associated pancreatic ductal dilatation. A malignant 5-cm ICT was resected at surgery. Metastatic lymph nodes were also seen.
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Glucagonomas are frequently malignant, with approximately 60% of patients presenting with liver metastases (1). Most of these lesions are relatively large. Seventy percent of patients present with masses over 5 cm in size, and most of these patients have metastases at the time of diagnosis (1). Most glucagonomas occur in the body or tail of the pancreas, although extrapancreatic glucagonoma has been reported (6). Most tumors will appear solid and enhancing at CT but may have low-attenuation areas. Cystic lesions are rare.
Most vipomas are located within the pancreas, with 75% of these pancreatic lesions being in the tail (23). Vipomas are usually over 3 cm in size, and almost one-half of patients will have liver metastases at the time of diagnosis (Fig 10) (1).
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Figure 10. Vipoma in a 74-year-old man with watery diarrhea and elevated VIP and PP hormone levels. Contrast-enhanced CT scan demonstrates a large mass with internal septa and calcification in the body and tail of the pancreas. The lesion was resected at surgery. Pathologic analysis revealed a well-differentiated 14.5-cm ICT with soft-tissue invasion and eight nodes, one of which was positive for tumoral involvement. The diarrhea resolved and the VIP and PP hormone levels returned to normal after surgery.
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Somatostatinoma can occur in the pancreas or duodenum, with malignant potential in either location. The pancreatic lesions are most commonly seen in the head of the pancreas, whereas the duodenal tumors most commonly occur at the ampulla of Vater (Fig 11). One-half of patients with pancreatic somatostatinoma present with metastatic disease, typically involving the liver or lymph nodes. These neoplasms are usually large enough to be detected at cross-sectional imaging. The duodenal tumors manifest with obstructive symptoms, since they are less likely to produce clinical symptoms and are not commonly associated with elevated plasma somatostatin levels. There is an increased prevalence of somatostatinomas in patients with neurofibromatosis type 1.
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Figure 11. Duodenal somatostatinoma in a 53-year-old woman with a history of neurofibromatosis who presented with abdominal pain and anemia. The patient had recently experienced a near syncopal episode. Coronal VR CT image demonstrates an enhancing periampullary mass (straight arrow) obstructing the distal common bile duct (curved arrow).
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Nonsyndromic ICTs.—
Nonsyndromic ICTs tend to be larger than syndromic ICTs at initial presentation. In one series of 16 nonsyndromic ICTs, the average tumor size was 5.2 cm (range, 0.8–17 cm) (Figs 12–17) (9).
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Figure 12. Nonsyndromic ICT in a 47-year-old patient who presented with abdominal pain. Contrast-enhanced CT scan demonstrates a 2-cm enhancing mass (arrow) in the pancreatic neck. A 2.5-cm ICT was resected at surgery. Minimal angiolytic invasion was noted at histologic analysis.
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Figure 13. Nonsyndromic ICT in a 61-year-old man who presented with abdominal pain. Contrast-enhanced VR CT image demonstrates a 2-cm enhancing mass (arrow) in the pancreatic head and uncinate process. The patient underwent surgery. Postoperative histologic analysis revealed a malignant, well-differentiated 2.3-cm ICT with nodal metastases.
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Figure 14. Nonsyndromic ICT in a 76-year-old man who presented with abdominal pain. Contrast-enhanced VR CT image demonstrates a 10-cm enhancing mass with central necrosis and calcification (arrows) in the pancreatic body and tail. A well-differentiated 12-cm ICT was resected at surgery. No nodal or vascular invasion was noted.
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Figure 15. Nonsyndromic ICT in a 35-year-old man who presented with abdominal pain. Contrast-enhanced CT scan demonstrates a 13 x 8-cm enhancing mass in the pancreatic body. Minimal calcification is present, and encasement of the superior mesenteric and portal veins is also noted. A large ICT was resected at surgery. Vascular invasion was noted at pathologic analysis.
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Figure 16a. Nonsyndromic ICT in a 75-year-old man who presented with abdominal pain. (a) Arterial phase contrast-enhanced CT scan demonstrates enhancing liver metastases. A large hiatal hernia is also noted. (b) Coronal VR CT image shows a 5-cm enhancing mass (arrows) arising from the tail of the pancreas and invading the spleen. A large hiatal hernia and right renal cysts are also seen. Partial pancreatectomy and splenectomy were performed and revealed a pancreatic ICT.
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Figure 16b. Nonsyndromic ICT in a 75-year-old man who presented with abdominal pain. (a) Arterial phase contrast-enhanced CT scan demonstrates enhancing liver metastases. A large hiatal hernia is also noted. (b) Coronal VR CT image shows a 5-cm enhancing mass (arrows) arising from the tail of the pancreas and invading the spleen. A large hiatal hernia and right renal cysts are also seen. Partial pancreatectomy and splenectomy were performed and revealed a pancreatic ICT.
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Figure 17. Nonsyndromic ICT in a 36-year-old man who presented with abdominal pain. Coronal slab VR CT image shows a large mass (arrow) in the left upper quadrant replacing the pancreas and invading the portal vein. Biopsy revealed a pancreatic neuroendocrine tumor.
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In a series of cases from the Armed Forces Institute of Pathology, cystic and necrotic ICTs were usually nonhyperfunctioning (nonsyndromic) (10). In that series, 56 of 133 tumors demonstrated necrosis or cystic changes, with a mean tumor diameter of 8.4 cm. Thirty-six of these 56 tumors were nonsyndromic ICTs (10). Larger size also showed good correlation with calcification and malignant behavior, including local invasion, vascular invasion, and distant metastases.
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Treatment
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The treatment for patients with syndromic ICTs and no metastasis consists of complete surgical resection. Unlike patients with adenocarcinoma of the pancreas, those with ICTs who undergo surgical resection may achieve long-term survival. Lesions in the pancreatic tail can be treated with distal pancreatectomy, whereas lesions in the pancreatic head require Whipple surgery. Small lesions, especially those that are exophytic, can be treated with enucleation, which can be performed laparoscopically.
Patients with liver metastases and a symptomatic primary tumor may still benefit from resection of the latter (24). In most patients with syndromic tumors, clinical endocrinopathies are relieved after surgery, a response that usually lasts for several months (25).
Patients with limited liver metastases may benefit from surgical resection of the metastases (26). In addition, some studies support the use of hepatic artery embolization for control of liver metastases in these patients (27). Chemoembolization effectively improves clinical symptoms and, in selected patients, may provide sustained tumor control (26). Data regarding mechanical ablation (cryotherapy or radiofrequency ablation) of metastatic ICTs are limited (27), but these methods may also be of value.
Even with complete resection of liver metastases, the recurrence rate for these neoplasms is extremely high. In practical terms, patients with metastatic, well-differentiated neuroendocrine tumors are rarely cured, but aggressive treatment can result in an extended survival period and control of endocrine symptoms (25).
Somatostatin analogues such as octreotide may benefit patients with unresectable or residual disease.
Chemotherapy may be used for palliation when ablative techniques have failed or when significant extrahepatic disease is present. Chemotherapeutic agents such as cisplatin, 5-fluorouracil, and streptozotocin have been used with variable success (28,29). Irradiation does not play a major role in treatment.
More recent clinical trials have been conducted to evaluate newer antineoplastic agents and treatment strategies.
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Conclusions
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Multi–detector row CT is valuable in the diagnosis and staging of both syndromic and nonsyndromic ICTs. These neoplasms can present a diagnostic challenge, both clinically and radiologically. It is important for the radiologist to be familiar with appropriate CT protocol for imaging patients with suspected pancreatic ICT and to understand the variable CT appearances of these neoplasms.
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Footnotes
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Abbreviations: ICT = islet cell tumor, MEN 1 = multiple endocrine neoplasia type 1, PP = pancreatic polypeptide, 3D = three-dimensional, VIP = vasoactive intestinal peptide, VR = volume rendered
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References
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- Hoff A, Cote G, Gagel R. Management of neuroendocrine cancers of the gastrointestinal tract: islet cell carcinoma of the pancreas and other neuroendocrine carcinomas. In: Abbruzzese J, Evans D, Willett C, Fenoglio-Preiser C, eds. Gastrointestinal oncology. New York, NY: Oxford University Press, 2004; 780–800.
- Anderson CJ, Dehdashti F, Cutler PD, et al. 64Cu-TETA-octreotide as PET imaging agent for patients with neuroendocrine tumors. J Nucl Med 2001;42:213–221.[Abstract/Free Full Text]
- Thoeni RF, Mueller-Lisse UG, Chan R, Do NK, Shyn PB. Detection of small functional islet cell tumors in the pancreas: selection of MR imaging sequences for optimal sensitivity. Radiology 2000; 214:483–490.[Abstract/Free Full Text]
- Gouya H, Vignaux O, Augui J, et al. CT, endoscopic sonography, and a combined protocol for preoperative evaluation of pancreatic insulinomas. AJR Am J Roentgenol 2003;181:987–992.[Abstract/Free Full Text]
- Demos TC, Posniak HV, Harmath C, Olson MC, Aranha G. Cystic lesions of the pancreas. AJR Am J Roentgenol 2002;179:1375–1388.[Free Full Text]
- Roggli VL, Judge DM, McGavran MH. Duodenal glucagonoma: a case report. Hum Pathol 1979;10: 350–353.[Medline]
- Verner JV, Morrison AB. Islet cell tumor and a syndrome of refractory watery diarrhea and hypokalemia. Am J Med 1958;25:374–380.[CrossRef][Medline]
- Soga J, Yakuwa Y. Somatostatinoma/inhibitory syndrome: a statistical evaluation of 173 reported cases as compared to other pancreatic endocrinomas. J Exp Clin Cancer Res 1999;18:13–22.[Medline]
- Furukawa H, Mukai K, Kosuge T, et al. Nonfunctioning islet cell tumors of the pancreas: clinical, imaging and pathological aspects in 16 patients. Jpn J Clin Oncol 1998;28:255–261.[Abstract/Free Full Text]
- Buetow PC, Parrino TV, Buck JL, et al. Islet cell tumors of the pancreas: pathologic-imaging correlation among size, necrosis and cysts, calcification, malignant behavior, and functional status. AJR Am J Roentgenol 1995;165:1175–1179.[Abstract/Free Full Text]
- Buetow PC, Miller DL, Parrino TV, Buck JL. Islet cell tumors of the pancreas: clinical, radiologic, and pathologic correlation in diagnosis and localization. RadioGraphics 1997;17:453–472.[Abstract]
- Baert AL, Roex L, Marchal G, Hermans P, Dewilde D, Wilms G. Computed tomography of the stomach with water as an oral contrast agent: technique and preliminary results. J Comput Assist Tomogr 1989;13:633–636.[Medline]
- Mazzeo S, Caramella D, Belcari A, et al. Multidetector CT of the small bowel: evaluation after oral hyperhydration with isotonic solution. Radiol Med (Torino) 2005;109:516–526.
- Horton KM, Eng J, Fishman EK. Normal enhancement of the small bowel: evaluation with spiral CT. J Comput Assist Tomogr 2000;24:67–71.[CrossRef][Medline]
- Fidler JL, Fletcher JG, Reading CC, et al. Preoperative detection of pancreatic insulinomas on multiphasic helical CT. AJR Am J Roentgenol 2003;181:775–780.[Abstract/Free Full Text]
- King AD, Ko GT, Yeung VT, Chow CC, Griffith J, Cockram CS. Dual phase spiral CT in the detection of small insulinomas of the pancreas. Br J Radiol 1998;71:20–23.[Abstract]
- Ichikawa T, Peterson MS, Federle MP, et al. Islet cell tumor of the pancreas: biphasic CT versus MR imaging in tumor detection. Radiology 2000; 216:163–171.[Abstract/Free Full Text]
- Van Hoe L, Gryspeerdt S, Marchal G, Baert AL, Mertens L. Helical CT for the preoperative localization of islet cell tumors of the pancreas: value of arterial and parenchymal phase images. AJR Am J Roentgenol 1995;165:1437–1439.[Abstract/Free Full Text]
- Keogan MT, McDermott VG, Paulson EK, et al. Pancreatic malignancy: effect of dual-phase helical CT in tumor detection and vascular opacification. Radiology 1997;205:513–518.[Abstract/Free Full Text]
- Hashimoto LA, Walsh RM. Preoperative localization of insulinomas is not necessary. J Am Coll Surg 1999;189:368–373.[CrossRef][Medline]
- Norton JA, Cromack DT, Shawker TH, et al. Intraoperative ultrasonographic localization of islet cell tumors: a prospective comparison to palpation. Ann Surg 1988;207:160–168.[Medline]
- Chung MJ, Choi BI, Han JK, Chung JW, Han MC, Bae SH. Functioning islet cell tumor of the pancreas: localization with dynamic spiral CT. Acta Radiol 1997;38:135–138.[Medline]
- Perry RR, Vinik AI. Clinical review 72: diagnosis and management of functioning islet cell tumors. J Clin Endocrinol Metab 1995;80:2273–2278.[Abstract]
- Evans DB, Skibber JM, Lee JE, et al. Nonfunctioning islet cell carcinoma of the pancreas. Surgery 1993;114:1175–1182.[Medline]
- Sarmiento JM, Que FG. Hepatic surgery for metastases from neuroendocrine tumors. Surg Oncol Clin N Am 2003;12:231–242.[CrossRef][Medline]
- Yao KA, Talamonti MS, Nemcek A, et al. Indications and results of liver resection and hepatic chemoembolization for metastatic gastrointestinal neuroendocrine tumors. Surgery 2001;130:677–682.[CrossRef][Medline]
- Brentjens R, Saltz L. islet cell tumors of the pancreas: the medical oncologist’s perspective. Surg Clin North Am 2001;81:527–542.[CrossRef][Medline]
- Rothman H, Cantrell JE Jr, Lokich J, et al. Continuous infusion 5-fluorouracil plus weekly cisplatin for pancreatic carcinoma: a Mid-Atlantic Oncology Program study. Cancer 1991;68:264–268.[CrossRef][Medline]
- Moertel CG, Lefkopoulo M, Lipsitz S, Hahn RG, Klaassen D. Streptozocin-doxorubicin, streptozocin-fluorouracil or chlorozotocin in the treatment of advanced islet-cell carcinoma. N Engl J Med 1992;326:519–523.[Abstract]
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Abstract
LEARNING OBJECTIVES
