AJR 2002; 179:725-730
© American Roentgen Ray Society
Helical CT of Islet Cell Tumors of the Pancreas: Typical and Atypical Manifestations
Sheila Sheth1,
Ralph K. Hruban2 and
Elliot K. Fishman1
1 Russell H. Morgan Department of Radiology and Radiological Science, Johns
Hopkins University, 600 N. Wolfe St., Nelson B176D, Baltimore, MD 21287.
2 Department of Pathology, Johns Hopkins University, 401 N. Broadway St.,
Weinberg 2242, Baltimore, MD 21231.
Received January 17, 2002;
accepted after revision February 22, 2002.
Address correspondence to S. Sheth.
Introduction
Islet cell tumors are uncommon neoplasms of neuroendocrine origin arising
in the pancreas or the periampullary region. Despite their rarity, with a
reported incidence of five cases per million persons per year
[1], they present a special
challenge for the radiologist. The diagnosis of functioning islet cell tumors
is almost always established biochemically when the lesion is of small size.
Successful curative surgical resection is facilitated by preoperative imaging
depicting the precise location and number of lesions. Patients with
nonfunctioning islet cell tumors often present with the disease at an advanced
stage. Imaging plays a pivotal role in differentiating these tumors from
adenocarcinomas of the pancreas and in identifying signs of malignancy.
Although in recent years gadolinium-enhanced MR imaging,
somatostatin-receptor imaging, and endosonography have emerged as potentially
competing or complementary techniques to CT, dual-phase helical CT,
particularly with technical improvements afforded by multidetector CT, remains
the dominant imaging modality for the diagnosis of all pancreatic neoplasms,
including, in many centers, islet cell tumors. The objectives of our pictorial
essay are to illustrate the various imaging features of islet cell tumors on
dual-phase CT and to discuss potential pitfalls.
Clinical Presentation
Islet cell tumors are classified as functioning if they produce symptoms
related to excessive hormone production, or as nonfunctioning
[1]. These neoplasms tend to
affect younger age groups and, even when malignant, have a better prognosis
than the more common adenocarcinoma of the exocrine pancreas. Although most
islet cell tumors appear sporadically, an increased prevalence of these tumors
is seen in patients with von Hippel-Lindau syndrome and in those affected by
multiple endocrine neoplasia type I.
Functioning Islet Cell Tumors
Functioning islet cell tumors are subdivided according to the hormone they
produce. Insulinomas, the most common functioning islet cell tumors, are
usually benign. Patients experience symptomatic intractable hypoglycemia, low
blood levels of glucose, and high circulating plasma insulin. Gastrinomas are
the second most common functioning islet cell tumor and about 60% are
malignant [1]. Patients present
with peptic ulcer disease, diarrhea, or abdominal pain. The presence of
gastric hypersecretions and an elevated serum gastrin level confirm the
diagnosis of Zollinger-Ellison syndrome. Other functioning islet cell tumors
such as VIPomas, glucagonomas, stomatostatinomas, and ACTHoma are rare
[1].
Nonfunctioning Islet Cell Tumors
Nonfunctioning islet cell tumors usually become large before diagnosis.
However, with the proliferation of high-quality cross-sectional imaging, an
increasing number of small asymptomatic islet cell tumors are being discovered
serendipitously.
CT Technique
Because of their rich vascular supply, islet cell tumors classically are
hyperattenuating compared with the surrounding pancreatic parenchyma on
contrast-enhanced 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 because these are often small, with 50% measuring less than 1.3 cm
[1].
Nonfunctioning islet cell tumors are more easily detected by the mass
effect they produce. However, some nonfunctioning islet cell tumors are also
small at diagnosis, either because they are strategically
located—obstructing the biliary tree or the pancreatic duct—or are
found incidentally [2] (Fig.
1A,1B).
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Fig. 1A. —Malignant stomatinoma in 61-year-old woman with history of
recurrent abdominal pain. Findings illustrate benefit of using water as oral
contrast agent. This subtle mass would have been obscured if positive oral
contrast material had been administered. Patient was treated with
pylorus-preserving pancreaticoduodenectomy. Axial CT image of periampullar
region obtained in arterial phase of enhancement shows 8-mm hyperattenuating
mass (arrow) obstructing pancreatic duct.
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Fig. 1B. —Malignant stomatinoma in 61-year-old woman with history of
recurrent abdominal pain. Findings illustrate benefit of using water as oral
contrast agent. This subtle mass would have been obscured if positive oral
contrast material had been administered. Patient was treated with
pylorus-preserving pancreaticoduodenectomy. Axial CT image obtained at same
level as A in venous phase shows mass (arrow) exhibiting more
intense enhancement.
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Multidetector CT Protocol
The entire pancreas is imaged using a 4 x 1.0-mm collimator setting
to obtain 1.25-mm slices reconstructed at 1-mm intervals. Using a power
injector, we inject 120 mL of iohexol (Omnipaque 350; Nycomed Amersham,
Princeton, NJ) IV at a rate of 3 mL/sec. For the arterial phase, scanning is
initiated after a 25-sec delay from the time of initiation of contrast
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 islet cell tumors.
Subsequently, venous phase imaging of the entire liver and pancreas is
initiated after a scanning delay of 50 sec. We use water as an oral contrast
agent to optimize visualization of potential small periampullary masses and to
perform CT angiographic reconstructions for surgical planning.
CT Appearance
The classic and most common enhancement pattern of islet cell tumors is
that of a hyperattenuating lesion in the arterial and venous phases
[3,4,5].
Many small lesions enhance more prominently and thus are easier to detect in
the arterial phase (Fig.
2A,2B)
or become inconspicuous in the venous phase (Fig.
3A,3B,3C).
In a series of 11 cases of functioning islet cell tumors reported by Van Hoe
et al. [3], most lesions were
hyperattenuating and two were more conspicuous on arterial phase imaging.
Non-functioning islet cell tumors have similar enhancement characteristics
[6] (Fig.
4A,4B,4C).
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Fig. 2A. —83-year-old man with life-threatening hypoglycemia and 1.2-cm
insulinoma. Patient underwent distal pancreatectomy because enucleation of
this lesion was not possible as a result of lack of sufficient bridging
pancreatic tissue. Axial CT image of pancreas obtained in arterial phase of
enhancement shows small homogeneous hyperattenuating mass (arrow) in
neck of pancreas.
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Fig. 2B. —83-year-old man with life-threatening hypoglycemia and 1.2-cm
insulinoma. Patient underwent distal pancreatectomy because enucleation of
this lesion was not possible as a result of lack of sufficient bridging
pancreatic tissue. Axial CT image obtained at same level as A in venous
phase of enhancement shows mass (arrow) to be less conspicuous than
in arterial phase.
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Fig. 3A. —61-year-old woman with severe hypoglycemia and 1-cm
insulinoma. Axial CT image of pancreas obtained in arterial phase of
enhancement shows 1-cm homogeneous hyperattenuating mass (arrow) in
neck of pancreas.
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Fig. 3B. —61-year-old woman with severe hypoglycemia and 1-cm
insulinoma. Axial CT image of pancreas obtained in arterial phase of
enhancement at narrow window settings shows lesion (arrow) better
than A.
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Fig. 3C. —61-year-old woman with severe hypoglycemia and 1-cm
insulinoma. Axial CT image obtained at same level as A in venous phase
of enhancement shows that lesion (arrow) has become almost
inconspicuous.
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Fig. 4A. —56-year-old woman with history of pancreatic mass
incidentally detected on MR imaging at outside institution. Middle segment
pancreatectomy confirmed presence of nonfunctioning islet cell tumor and
unusual atrophy of body and tail of pancreas. Axial CT image of pancreas
obtained in arterial phase of enhancement shows subtle 2-cm hyperattenuating
mass (arrow) in body of pancreas.
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Fig. 4B. —56-year-old woman with history of pancreatic mass
incidentally detected on MR imaging at outside institution. Middle segment
pancreatectomy confirmed presence of nonfunctioning islet cell tumor and
unusual atrophy of body and tail of pancreas. Axial CT image obtained at same
level as A in venous phase of enhancement shows mass (arrow)
is nearly isoattenuating to superior mesenteric vein.
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Fig. 4C. —56-year-old woman with history of pancreatic mass
incidentally detected on MR imaging at outside institution. Middle segment
pancreatectomy confirmed presence of nonfunctioning islet cell tumor and
unusual atrophy of body and tail of pancreas. Axial CT image obtained 15 mm
below level of A shows gland distal to lesion is completely replaced
with fatty tissue (arrowheads).
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Careful evaluation of venous phase images is essential because some
lesions, particularly if they have a cystic component (Fig.
5A,5B),
exhibit delayed enhancement and are best seen or only apparent in the portal
venous phase [3,
5,
6]. Two of our patients had an
unusual pattern, perhaps caused by slow enhancement in the mass over time: the
lesions appeared hypoattenuating compared with the normal pancreas on the
arterial phase and became nearly isoattenuating and imperceptible on the
portal venous phase (Fig.
6A,6B).
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Fig. 5A. —43-year-old man with history of multiple endocrine neoplasia
type 1 and 3-cm nonfunctioning islet cell tumor. Surgical enucleation of mass
confirmed diagnosis. Axial CT image of pancreas obtained in arterial phase of
enhancement shows 3-cm exophytic and partially cystic mass (arrow)
arising from tail of pancreas.
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Fig. 5B. —43-year-old man with history of multiple endocrine neoplasia
type 1 and 3-cm nonfunctioning islet cell tumor. Surgical enucleation of mass
confirmed diagnosis. Axial CT image obtained at same level as A in
venous phase of enhancement shows heterogeneous bright enhancement in lesion
(arrow).
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Fig. 6A. —Nonfunctioning islet cell tumor in 45-year-old woman with
history of abdominal pain. Diagnosis of benign nonfunctioning islet cell tumor
was established at pancreaticoduodenectomy. Axial CT image of pancreas
obtained in arterial phase of enhancement shows 2-cm mass (arrow) in
uncinate process of pancreas. Lesion is hypoattenuating compared with normal
parenchyma. Note unopacified inferior vena cava (arrowhead) posterior
to mass.
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Fig. 6B. —Nonfunctioning islet cell tumor in 45-year-old woman with
history of abdominal pain. Diagnosis of benign nonfunctioning islet cell tumor
was established at pancreaticoduodenectomy. Axial CT image obtained at same
level as A in venous phase of enhancement shows that mass
(arrow) has become nearly isoattenuating relative to pancreas and is
nearly inconspicuous except for subtle ring enhancement. This enhancement
pattern is unusual for adenocarcinoma and islet cell tumors.
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Unlike small islet cell tumors, which appear homogeneous, larger lesions
often show heterogeneous enhancement in a ringlike pattern or with central
areas of necrosis or cystic degeneration
[7] (Figs.
7A,7B
and
8A,8B).
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Fig. 7A. —Malignant nonfunctioning islet cell tumors in 39-year-old
woman with history of von Hippel-Lindau syndrome. Patient underwent
pancreaticoduodenectomy. Axial CT image of pancreas obtained in arterial phase
of enhancement shows 3.5-cm hypervascular mass (arrow) with
hypoattenuating center and ring enhancement in uncinate process of pancreas.
Note small left renal cyst (arrowhead).
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Fig. 7B. —Malignant nonfunctioning islet cell tumors in 39-year-old
woman with history of von Hippel-Lindau syndrome. Patient underwent
pancreaticoduodenectomy. Axial CT image obtained at same level as A in
venous phase of enhancement shows that enhancement in lesion (arrow)
is more evident in this phase.
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Fig. 8A. —Malignant nonfunctioning islet cell tumor in 46-year-old man
with abdominal pain. No vascular invasion was noted at time of
pancreaticoduodenectomy. Axial CT image of pancreas obtained in arterial phase
of enhancement shows 6-cm hypervascular mass (arrow) in head of
pancreas. Note central low-attenuation area of necrosis
(arrowhead).
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Fig. 8B. —Malignant nonfunctioning islet cell tumor in 46-year-old man
with abdominal pain. No vascular invasion was noted at time of
pancreaticoduodenectomy. Axial CT image obtained at same level as A in
venous phase of enhancement shows that superior mesenteric vein (curved
arrow) is well opacified and does not appear invaded. Straight arrow
shows hypervascular mass.
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Staging of Malignant Islet Cell Tumors on Dual-Phase CT
Large tumors with diameters greater than 5 cm are frequently malignant
[7]. Three-dimensional CT
reconstructions exquisitely show local extension and encasement of the major
peripancreatic arteries and veins for surgical planning (Fig.
9A,9B,9C,9D).
The liver and regional lymph nodes are the most common sites for metastases.
Like the primary tumor, liver metastases are hypervascular. Arterial phase
images show the number and size of the hepatic lesions better than images
acquired in the venous phase, particularly for small metastases (Fig.
10A,10B,10C).
Spread to regional lymph nodes also is more conspicuous in the arterial
phase.
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Fig. 9A. —Malignant nonfunctioning islet cell tumor in 45-year-old man
with abdominal pain. Extended pancreaticoduodenectomy was required to remove
entire tumor, and peripancreatic spread was confirmed at pathology. Axial CT
image of pancreas obtained in arterial phase shows 6-cm heterogeneously
enhancing hypervascular mass (arrow) in head of pancreas. Tumor
appears to extend into peripancreatic fat.
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Fig. 9B. —Malignant nonfunctioning islet cell tumor in 45-year-old man
with abdominal pain. Extended pancreaticoduodenectomy was required to remove
entire tumor, and peripancreatic spread was confirmed at pathology. Axial CT
image obtained at same level as A in venous phase of enhancement shows
portal confluence (arrow) to be markedly narrowed.
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Fig. 9C. —Malignant nonfunctioning islet cell tumor in 45-year-old man
with abdominal pain. Extended pancreaticoduodenectomy was required to remove
entire tumor, and peripancreatic spread was confirmed at pathology. Coronal
reconstruction image obtained in arterial phase of enhancement shows tumor
abutting gastroduodenal artery (arrow).
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Fig. 9D. —Malignant nonfunctioning islet cell tumor in 45-year-old man
with abdominal pain. Extended pancreaticoduodenectomy was required to remove
entire tumor, and peripancreatic spread was confirmed at pathology. Coronal
reconstruction image obtained in venous phase of enhancement confirms severe
narrowing of portal confluence (arrow).
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Fig. 10A. —Malignant nonfunctioning islet cell tumors with liver
metastases in 58-year-old woman referred from outside institution for therapy.
Patient underwent distal pancreatectomy and splenectomy as well as wedge
resection and ablation of hepatic metastases. Axial CT image of pancreas
obtained in arterial phase of enhancement shows 5-cm heterogeneously enhancing
mass (arrow) in body and tail of pancreas. Portions of mass are
hyperattenuating. Note at least two small enhancing liver metastases
(arrowheads).
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Fig. 10B. —Malignant nonfunctioning islet cell tumors with liver
metastases in 58-year-old woman referred from outside institution for therapy.
Patient underwent distal pancreatectomy and splenectomy as well as wedge
resection and ablation of hepatic metastases. Axial CT image obtained at same
level as A in venous phase of enhancement shows that liver lesions have
become isoattenuating compared with normal liver parenchyma and are
inconspicuous. Splenic vein is invaded by mass (arrow).
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Fig. 10C. —Malignant nonfunctioning islet cell tumors with liver
metastases in 58-year-old woman referred from outside institution for therapy.
Patient underwent distal pancreatectomy and splenectomy as well as wedge
resection and ablation of hepatic metastases. Axial CT image obtained at level
of gastric fundus shows collateral veins (arrow) nicely outlined by
water-filled stomach.
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Pitfalls and Differential Diagnosis
Sensitivity of Dual-Phase CT in the Diagnosis of Islet Cell
Tumors
The reported sensitivity of CT in localizing functioning islet cell tumors
varies from 71% to 82% because small tumors are more frequently missed
[3,
5]. Small hyperattenuating
islet cell tumors located in the pancreatic neck or body can be confused with
adjacent vascular structures; multiplanar reconstruction is helpful in
separating the lesion from surrounding vessels, thus improving diagnostic
confidence (Fig.
11A,11B,11C).
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Fig. 11A. —Small insulinoma in 87-year-old man with history of severe
hypoglycemia. Tumor was easily enucleated from pancreas at surgery. Axial CT
image of pancreas obtained in arterial phase of enhancement shows 2-cm
pseudocyst (arrow) in head of pancreas. One-centimeter adjacent mass
is difficult to see.
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Fig. 11B. —Small insulinoma in 87-year-old man with history of severe
hypoglycemia. Tumor was easily enucleated from pancreas at surgery. Axial CT
image obtained at same level as A in venous phase shows lesion
(arrow) enhanced almost to same degree as adjacent portal vein.
Lesion was mistaken for vessel on preliminary review.
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Fig. 11C. —Small insulinoma in 87-year-old man with history of severe
hypoglycemia. Tumor was easily enucleated from pancreas at surgery. Sagittal
reconstruction image obtained in venous phase of enhancement clearly shows
lesion (arrow) anterior to superior mesenteric vein.
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Differential Diagnosis
The characteristic blush of islet cell tumors allows their differentiation
from other pancreatic neoplasms, particularly adenocarcinomas, which are
hypovascular lesions and almost invariably of lower attenuation than the
normal gland regardless of the phase of enhancement used for image
acquisition. Pancreatic metastases from hypervascular primary tumors,
particularly renal cell carcinomas, display enhancement characteristics
similar to those of islet cell tumors
[8] (Fig.
12A,12B).
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
islet cell tumors in patients with von Hippel-Lindau disease.
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Fig. 12A. —Hypervascular pancreatic metastasis in 69-year-old man with
history of left nephrectomy for renal cell carcinoma 10 years earlier. Axial
CT image of pancreas obtained in arterial phase of enhancement shows
hyperattenuating mass (arrow) in body and tail of pancreas. Note
small hypervascular hepatic metastasis (arrowhead).
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Fig. 12B. —Hypervascular pancreatic metastasis in 69-year-old man with
history of left nephrectomy for renal cell carcinoma 10 years earlier. Axial
CT image obtained at same level as A in venous phase of enhancement
shows that enhancement in pancreatic mass (arrow) is not as
pronounced as in A. Note that liver metastasis has become
inconspicuous, collateral veins (arrowhead) are present, and splenic
vein is occluded.
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In conclusion, accurate localization of islet cell tumors is critical for
successful surgical resection. The thinner collimation and multiple-phase
imaging afforded by multidetector CT is likely to further improve the
sensitivity of CT in detecting even small lesions in patients with suspected
islet cell tumors.
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Introduction
Clinical Presentation
