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Everything you need to know about Computed Tomography (CT) & CT Scanning

Pancreas: Tumors: Islet Cell Tumors of the Pancreas: Typical and Atypical Manifestations at Single and Dual Phase Helical CT

Sheila Sheth, Ralph K. Hruban and Elliot K Fishman


Islet cell tumors (ICT) are uncommon neoplasms of neuroendocrine origin arising in the pancreas or the periampullary region . Despite their rarity, an incidence of five cases per million persons per year is reported in the literature they present a special challenge for the radiologist. The diagnosis of functioning ICT is almost always established biochemically, when the lesion is of small size. Successful curative surgical resection is greatly facilitated by preoperative imaging depicting the precise location and number of lesions . Patients harboring non-functioning ICT often present at an advanced stage. Imaging plays a pivotal role is to differentiate them from adenocarcinomas of the pancreas and identify signs of malignancy.

There has been a continuing debate in the literature about the ideal imaging modality for patients with a suspected ICT. Although invasive imaging techniques such as selective celiac and mesenteric arteriography, venography and venous sampling are progressively being abandoned, gadolinium enhanced MRI, somatostatin receptor imaging and endoscopic ultrasound have emerged as potentially competing or complementary techniques to CT . The difficulty in assessing the accuracy of these different modalities is compounded by the rarity of ICT and the small size of individual series. However, thanks to its wide spread availability and continuing technical improvements that allow for constant improvement in image quality, dual phase helical CT remains the dominant imaging modality for the diagnosis of all pancreatic neoplasms, including ICT in many centers.

The objectives of this review are to familiarize the radiologist with the imaging features of ICT on dual phase CT, to emphasize CT techniques to optimize detections of these tumors and to discuss potential pitfalls.


Clinical Presentation


Islet cell tumors are classified as functioning (FICT) if they produce symptoms related to excessive hormone production, or non functioning (NFICT). In one large series of 125 patients who underwent surgical resection in a tertiary referral center, slightly over half ICT were functioning and 52% of tumors were malignant . These neoplasms tend to affect younger age groups and, even when malignant, have a better prognosis then the more common adenocarcinoma of the exocrine pancreas.

Functioning ICT

Functioning ICT are subdivided according to the hormone they produce. Among the functioning ICT, insulinomas are the most common, are usually benign and often quite small at diagnosis. Patients experience symptomatic intractable hypoglycemia, low blood levels of glucose and high circulating plasma insulin. Gastrinomas are the second most common functioning ICT and present with signs of peptic ulcer disease or diarrhea. About 60 % are malignant. The demonstration of gastric hypersecretions and an elevated serum gastrin level confirm the diagnosis of Zollinger Ellison. Other functioning ICT such as VIPomas, glucagonomas, stomatostatinomas and ACTHoma are quite rare, representing 5% or less of all ICT .

Non functioning ICT

Non functioning ICT usually reach a large size before the patient experiences symptoms of abdominal pain, weight loss or jaundice. Signs related to extensive hepatic or nodal metastases may dominate the clinical picture when the tumors are malignant. However, with the proliferation of high quality cross-sectional imaging studies, an increasing number of small asymptomatic ICT are being discovered serendipitously .

Although the majority of ICT are sporadic, an increase prevalence of these tumors is seen in patients with Von Hippel Lindau syndrome and those affected by Multiple Endocrine Neoplasia type I

Treatment and oucome

Complete surgical removal of the tumor offers the only hope for definitive cure. Depending on the location and size of the lesion, surgical options available include enucleation of small ICT, distal pancreatectomy or pancreaticoduodenectomy for large or malignant tumors involving the pancreatic head or periampullary region

Even when malignant, ICT are slow growing and relatively indolent with reported 5 year survival of 49% to 56%, justifying aggressive management even when the tumor has spread beyond the pancreas. . In patients with liver metastases, surgical removal of the primary tumor combined with resection or transcatheter embolization of hepatic metastases of the hepatic lesions prolongs survival .



CT Technique

The introduction of helical technology has led to dramatic improvement in the imaging of pancreatic neoplasms, including ICTs. Its capacity for thin section volumetric imaging eliminates respiratory misregistration and allows arbitrary image reconstruction centered on subtle abnormalities in the pancreas as well as multiplanar reconstruction. Furthermore, rapid acquisition of the data set allows imaging of the pancreas during multiple phases of enhancement following the intravenous administration of a single bolus of contrast material.

Dual phase CT of the pancreas

The optimal temporal window to maximize conspicuity of small pancreatic tumors has been the subject of considerable investigation in the past few years. Because the pancreas has an exclusive arterial supply, it has been postulated that the portal venous phase used to maximize hepatic parenchymal enhancement is less favorable for pancreatic imaging. Some investigators have shown that maximum enhancement of the normal pancreatic gland occurs during the arterial phase, using a scan delay of 20s following the initiation of intravenous contrast injection . Others have advocated a specific pancreatic parenchymal phase, occurring after a delay of 35 to 40s . Because many of these studies use different rates of injection, and as scanning time to cover a similar anatomic area varies depending on the collimation and the equipment available (single versus multidetector technology), there may be an overlap between the different phases of pancreatic enhancement in various series, explaining most of the apparent discrepancies. There is however convincing evidence that there is a small window of opportunity to achieve maximal tumor to pancreas attenuation differences and that dual phase scanning is necessary to adequately evaluate pancreatic lesions and achieve optimal enhancement of the surrounding vascular structures .

Our CT protocol for suspected ICT

The entire pancreas is imaged using a 4 X 1.0 mm collimator setting to obtain 1.25mm slices reconstructed at 1 mm intervals. Using a power injector, 120cc of iohexol (Omnipaque 350; Nycomed Amersham, Princeton, NJ) is injected intravenously at a rate of 3ml/sec. For the arterial phase, scanning is initiated following a 25 second delay from the time of initiation of contrast material injection. The liver and pancreas are imaged from the diaphragm to the inferior edge of the liver. This technique is used to maximize the detection of potential hypervascular hepatic metastases from ICT. At the same time, the pancreas is imaged in the late arterial/early parenchymal phase to optimize the detection of the primary pancreatic mass. Subsequently, venous phase imaging of the entire liver and pancreas is initiated after a scan delay of 50seconds from the time of initiation of contrast material injection. We use water as an oral contrast agent to optimize visualization of potential small peri-ampullary masses and perform CT angiographic reconstructions for surgical planning.


CT Appearance

Because of their rich vascular supply, ICT classically are hyperattenuating compared to the surrounding pancreatic parenchyma on contrast enhanced CT.

Enhancement pattern of ICT at dual phase helical CT

Capturing the vascular blush is essential for the diagnosis of small tumors, which often do not distort the contour of the pancreas . This is particularly true in the investigation of functioning insulinomas, since these are often very small, with 50% measuring less then 1.3 cm . Non functioning ICT often reach a large size before they become symptomatic and thus easily detected by the mass effect they produce . However, some NFICT are also small at diagnosis, either because they are strategically located and obstruct the biliary tree or the pancreatic duct , or if they are found incidentally. In our series, 6 of 14 NFICT measured 2 cm or less, including two tumors smaller then 1 cm.

Several studies have emphasized the value of dual phase helical CT for the detection of small ICT. Appropriate timing of image acquisition is critical, but it may be difficult to predict which phase of enhancement will best depict a particular lesion. Because ICT are hypervascular, tumor conspicuity is expected to be greater in the arterial phase. The mean attenuation difference between the lesion and the normal parenchyma is often greater during this phase then in the venous phase . However the attenuation of ICT relative to the surrounding pancreas changes on different phase acquisitions. Several patterns of enhancement have been described in the literature and confirmed by our own observations.

The classic and most common enhancement pattern of ICT is that of a hyper attenuating lesion in the arterial and venous phase. Many small lesions enhance more prominently and thus are easier to detect in the arterial phase (figure 3). In a series of 11 cases of FICT reported by Van Hoe and colleagues, most lesions were hyperattenuating and 2 were more conspicuous on arterial phase imaging . King and co-authors reported similar results . Five of seven small ICT reported by Chung et al were only depicted in the arterial phase. However, in their protocol, the delayed phase was initiated particularly late after 180s. . In our series, 2 of the 3 insulinomas depicted at CT were small, less then 1.5cm, markedly hypervascular, one was more conspicuous on the arterial phase and one would have been missed on venous phase images .Non functioning ICT have similar enhancement characteristics with tumor conspicuity also reported to be better on the arterial phase . Among our cases of NFICT, 7 lesions exhibited greater enhancement in the arterial phase .

Careful evaluation of venous phase images is essential because some lesions, particularly if they have a cystic component, exhibit delayed enhancement and are best seen or only apparent in the portal venous phase (

Two of our cases had an unusual pattern, perhaps caused by slow enhancement within the mass over time: the lesions appeared hypoattenuating to the normal pancreas on the arterial phase and became nearly isoattenuating and imperceptible on the portal venous phase.

Unlike small ICT which appear homogeneous, larger lesions often demonstrate heterogeneous enhancement in a ring like pattern ( or central areas of necrosis or cystic degeneration .

Staging of malignant ICT at dual phase CT

Large tumors, with diameter over 5 cm are frequently malignant As portions of the tumor may become isoattenuating on the venous phase, lesion size is often larger on the arterial phase . In addition to local extension and encasement of the major peripancreatic arteries and veins, the liver and regional lymph nodes are the most common sites for metastases.

Like the primary tumor, liver metastases are hypervascular. Arterial phase imaging demonstrates the number and size of the hepatic lesions better then images acquired in the venous phase, particularly for small metastases: in the series reported by Stafford Johnson and al 17 hepatic metastases were identified in the arterial phase, but only 9 were seen in the venous phase (figure 10 Sandoe tif 54 ap and 59vp). Spread to regional lymph nodes also appears more conspicuous in the arterial phase .

As expected, arterial encasement is best depicted on the arterial phase and venous involvement is more readily appreciated on the venous phase . Both are exquisitely demonstrated on three- dimensional CT angiographic mapping, which is essential for preoperative planning.


Pitfalls and Differential Diagnosis

Sensitivity of dual phase CT in the diagnosis of ICT

The reported sensitivity of CT in localizing FICT varies from71% to 82% . The difficulty in interpreting sometimes conflicting data is compounded by the small size of individual series, the variety of CT equipment used, including older conventional CT scanners, as well as variation in scanning protocols.

As expected, small tumors are more frequently missed . In one of our cases, the tumor was not visible, even in retrospect but was diagnosed on endoscopic ultrasound and its exact location was confirmed on intra-operative ultrasound (figure 12) In addition, small hyperattenuating ICT located in the pancreatic neck or body can be confused with adjacent vascular structures. Multiplanar reconstruction may be helpful in separating the lesion from surrounding vessels thus improving diagnostic confidence .

Differential diagnosis

The characteristic tumor blush of ICT allows their differentiation from other pancreatic neoplasms, particularly adenocarcinomas, which are hypovascular lesions and almost invariably of lower attenuation then the normal gland regardless of the phase of enhancement used for image acquisition.

Pancreatic metastases from hypervascular primary tumors, particularly renal cell carcinoma display enhancement characteristics similar to ICT . Patients with previously diagnosed renal cell carcinoma may present a diagnostic dilemma because metastases can occur as late as 22 years after the initial diagnosis and because of the association of renal cell carcinoma and ICT in patients with Von Hippel Lindau disease .



Accurate localization of ICT is critical for successful surgical resection. Dual phase helical CT is a very effective imaging modality to evaluate patients with suspected ICT. Image acquisition in the arterial as well as venous phase of enhancement and careful analysis of enhancement patterns is necessary to improve the detection and localization of these tumors.



© 1999-2019 Elliot K. Fishman, MD, FACR. All rights reserved.