Multi–Detector Row CT of Pancreatic Islet Cell Tumors1

Article (PDF Available)inRadiographics 26(2):453-64 · March 2006with9 Reads
DOI: 10.1148/rg.262055056 · Source: PubMed
Abstract
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.

Full-text (PDF)

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EDUCATION EXHIBIT
453
Multi–Detector Row
CT of Pancreatic Islet
Cell Tumors
1
ONLINE-ONLY
CME
See www.rsna
.org/education
/rg_cme.html.
LEARNING
OBJECTIVES
After reading this
article and taking
the test, the reader
will be able to:
Recognize the clini-
cal manifestations of
both syndromic and
nonsyndromic islet
cell tumors of the
pancreas.
Discuss the appro-
priate CT techniques
for patients with sus-
pected islet cell tu-
mors.
Describe the CT
appearances of syn-
dromic and nonsyn-
dromic islet cell tu-
mors.
Karen M. Horton, MD
Ralph H. Hruban, MD
Charles Yeo, MD
Elliot K. Fishman, MD
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 presen-
tation 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 under-
stand the variable CT appearances of these neoplasms.
©
RSNA, 2006
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
RadioGraphics 2006; 26:453– 464
Published online 10.1148/rg.262055056
Content Codes:
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 educa-
tion exhibit at the 2004 RSNA Annual Meeting. Received March 18, 2005; revision requested May 9 and received July 14; accepted July 20. All au-
thors have no financial relationships to disclose. Address correspondence to K.M.H. (e-mail: kmhorton@ jhmi.edu).
©
RSNA, 2006
RadioGraphics
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Introduction
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 endo-
crine 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 hor-
mones to a variable degree. In the past, they have
been categorized as either functioning or non-
functioning (nonhyperfunctioning). However,
because all of the neoplasms are hormonally ac-
tive, 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 en-
doscopic ultrasonography have all been reported
to be useful for the detection and staging of pan-
creatic ICTs (2– 4). However, computed tomog-
raphy (CT) remains the primary imaging modal-
ity 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 allow-
ing thin collimation and optimizing the timing of
data acquisition and the intravenous administra-
tion 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 manifesta-
tions, pathophysiologic features, multi– detector
row CT diagnosis, and treatment of both syn-
dromic and nonsyndromic pancreatic ICTs.
Clinical Manifestations
Syndromic ICTs
Syndromic ICTs show clinical evidence of hor-
mone production and produce a recognizable en-
docrinopathy. These neoplasms usually manifest
at a relatively small size compared with nonsyn-
dromic ICTs owing to the symptoms produced
by the associated hormone production.
Most syn-
dromic ICTs actually produce multiple hor-
mones, 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 somatostati-
noma.
Insulinoma.—Insulinoma is the most common
syndromic ICT. The classic clinical triad (Whip-
ple triad) includes fasting serum glucose levels
less than 50 mg/dL, symptoms of hypoglycemia,
and relief of symptoms after glucose administra-
tion. 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 hy-
perplasia” 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 uncom-
mon neuroendocrine neoplasm that typically
manifests in middle-aged patients and affects men
and women equally. Most of these lesions are ma-
lignant. Patients present with a characteristic mi-
gratory rash called necrolytic migratory erythema,
which usually affects the genitals. Patients may
also experience stomatitis, diarrhea, anemia,
weight loss, depression, and deep vein thrombo-
sis. The syndrome is termed the “4D syndrome”
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(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 se-
crete a variety of hormones, including vasoactive
intestinal peptide (VIP) (1). VIP binds to recep-
tors on the epithelial cells in the intestine, stimu-
lating production of cyclic adenosine monophos-
phate and resulting in fluid and electrolyte secre-
tion into the lumen, causing a characteristic
watery diarrhea. This peptide also inhibits gastrin
production, resulting in achlorhydria. The syn-
drome is also referred to as WDHA (watery diar-
rhea, hypokalemia, and achlorhydria). Most vipo-
mas 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 re-
ported in the literature (8). These neoplasms se-
crete somatostatin, resulting in diarrhea, choleli-
thiasis, indigestion, and hypochlorhydria. The
diagnosis is made on the basis of the presence of
the clinical syndrome and elevated plasma soma-
tostatin 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, al-
though the tumors are still hormonally active.
Large (usually 5-cm) nonsyndromic ICTs pro-
duce symptoms related to mass effect, local inva-
sion, 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).
Pathophysiologic Features
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 Langer-
hans) throughout the gland and are called pancre-
atic islet cells. These islet cells are of three main
types: The beta cells (B cells) are the most abun-
dant, 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 so-
matostatin. Other cells produce minor hormones.
For example, D1 cells produce VIP; enterochro-
maffin cells synthesize serotonin; and pancreatic
polypeptide (PP) cells produce PP, which stimu-
lates 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 hor-
mones into the bloodstream and are thus sur-
rounded 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 inner-
vated by parasympathetic and sympathetic neu-
rons, and nerve signals clearly modulate the se-
cretion 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-pep-
per” chromatin. The endocrine differentiation
can be confirmed with a Grimelius silver stain or
with immunohistochemical labeling for chromo-
granin or synaptophysin. Specific hormone pro-
duction by the neoplasms can also be confirmed
with immunolabeling. Predicting the clinical be-
havior of a well-differentiated endocrine neo-
plasm of the pancreas can be extremely difficult.
The only unequivocal criteria for malignancy are
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gross invasion of adjacent organs, large vessel in-
vasion, 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 dif-
ferent from those that do not. Tumor size is an
important factor in predicting the behavior of
nonsyndromic ICTs. Larger tumors tend to be-
have more aggressively and are more likely to me-
tastasize (9). In addition, local invasion, vascular
invasion, and metastatic disease are more com-
mon with larger tumors (10). The presence or
absence of metastases is the major predictor of
survival.
It is not usually possible to distinguish syn-
dromic from nonsyndromic tumors with immu-
nohistochemical staining alone (11).
Diagnosis with CT
CT is considered to be the imaging modality of
choice for tumor detection and staging, surgical
planning, and follow-up in patients with pancre-
atic ICTs. In patients with a suspected or known
pancreatic ICT, careful CT technique is impor-
tant.
Contrast Material
We typically administer 500 mL of water 30 min-
utes prior to the study and an additional 250 mL
of water immediately prior to the study to achieve
adequate distention of the stomach and duode-
num. In addition to water, other low-density,
orally administered contrast agents have been
reported to be useful for opacifying the gastroin-
testinal tract, including milk and polyethylene
glycol– based agents (12–14). Low-density in-
traluminal agents may improve identification of
small intraluminal tumors (gastrinomas) as well
as facilitate 3D volume rendering (VR) tech-
niques and CT angiography in the assessment of
vascular involvement.
High-density oral contrast agents will interfere
with the 3D imaging of vessels and require exten-
sive editing of images. In addition, because pan-
creatic ICTs are often vascular, they can appear
well enhanced at arterial imaging and may be ei-
ther detected with difficulty or overlooked if the
adjacent bowel is opacified with high-density ma-
terial. 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 me-
tastases. 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 ar-
terial and parenchymal phases (18). The exact
timing of the arterial, portal venous, and paren-
chymal 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 experi-
ence, 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 0.6-mm collimator setting or
a Siemens Sensation 16 scanner with a 16
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 0.75-mm or 64 0.6-mm collimation set-
ting allows creation of isotropic data sets, so that
the 3D images of the pancreas and abdominal
vessels are of excellent quality. All images are re-
viewed with InSpace software (Siemens), which
allows multiplanar reformation as well as interac-
tive 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 “pre-
sets” 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, how-
ever, maximum intensity projection can be help-
ful for visualizing the most distal branches of the
vessels. Modern 3D software allows instant
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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 sag-
ittal or axial images can also be useful depending
on the location of the mass. Small tumors, espe-
cially those that do not demonstrate much en-
hancement, 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 pan-
creatic tumors (Fig 1) on the axial images, but
such lesions are readily apparent on 3D images.
CT Findings
Several studies have shown promising results in
the preoperative detection of ICTs with dual
phase CT, which typically demonstrates a sensi-
tivity exceeding 80% (16,18,19). Most investiga-
tors 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 ve-
nous phase. Conversely, in a study of both syn-
dromic and nonsyndromic ICTs by Ichikawa et al
(17), more lesions were detected in the portal ve-
nous phase than in the arterial phase. More re-
cently, more focused studies have been per-
formed, addressing the usefulness of CT and spe-
cific 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 dem-
onstrated similar effectiveness in detecting the
tumors (17).
Syndromic ICTs.—In general, syndromic ICTs
are less than 3 cm in size. They are typically hy-
perenhancing and are usually best seen in the ar-
terial phase. However, some neoplasms will be
hypoattenuating relative to the enhancing pan-
creas and therefore will be seen best in the portal
venous or pancreatic phase. Syndromic ICTs can
be homogeneous, heterogeneous, or cystic in ap-
pearance. 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, preopera-
tive imaging for detection of suspected pancreatic
insulinoma has been controversial (20). First, the
sensitivity of cross-sectional imaging was some-
what 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 intraop-
eratively with palpation or ultrasonography (21).
Today, however, most physicians value preopera-
tive imaging for detection of the primary neo-
plasm and staging for local spread or metastasis.
In addition, the CT findings may alter the surgi-
cal approach: Lesions near the surface of the
Figure 1. (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 im-
age reveals that the lesion (arrow) is actually a splenic artery aneurysm.
RG f Volume 26
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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 insuli-
nomas, and 83% of the lesions could be seen in
retrospect (15). Most insulinomas exhibited in-
creased 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
Figures 2–5. (2) Insulinoma in a 63-year-old woman with hypoglycemia. Contrast-enhanced CT scan demon-
strates a 1-cm enhancing lesion (arrow) in the midbody of the pancreas. Robotic laparoscopic enucleation of the le-
sion 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. (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 pan-
creatic 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. (4) Insulinoma in an 84-year-old man who
presented with life-threatening hypoglycemia. Contrast-enhanced CT scan demonstrates a 1-cm hyperenhancing le-
sion (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. (5) Insulinoma in a 46-year-old woman with elevated insulin levels and hyperglycemia. Arterial phase con-
trast-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 evi-
dence of invasion of the surrounding tissues.
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proximity to adjacent vessels. Three-dimensional
imaging would probably have improved the iden-
tification 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 refor-
matted images.
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
Figures 6, 7. (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 laparoscopi-
cally. Histologic analysis demonstrated a 3.5-cm ICT. The gastrin levels returned to normal after surgery. (7) Gastri-
noma 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.
Figure 8. Gastrinoma in a 50-year-old man who presented with weight loss and markedly elevated gas-
trin 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 associ-
ated pancreatic ductal dilatation. A malignant 5-cm ICT was resected at surgery. Metastatic lymph
nodes were also seen.
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triangle (Fig 9), which is defined as the conflu-
ence of the cystic and common bile ducts superi-
orly, the second and third portions of the duode-
num inferiorly, and the neck and body of the pan-
creas medially (6).
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 extrapan-
creatic 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 me-
tastases at the time of diagnosis (Fig 10) (1).
Somatostatinoma can occur in the pancreas or
duodenum, with malignant potential in either
location. The pancreatic lesions are most com-
monly 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
Figure 9. Drawing illustrates the gastrinoma triangle,
the area in which gastrinomas most commonly occur.
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.
Figure 11. Duodenal somatostatinoma in a 53-year-
old woman with a history of neurofibromatosis who
presented with abdominal pain and anemia. The pa-
tient 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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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 associ-
ated with elevated plasma somatostatin levels.
There is an increased prevalence of somatostati-
nomas in patients with neurofibromatosis type 1.
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).
Figure 12. Nonsyndromic ICT in a 47-year-old pa-
tient 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.
Figure 13. Nonsyndromic ICT in a 61-year-old man
who presented with abdominal pain. Contrast-en-
hanced VR CT image demonstrates a 2-cm enhancing
mass (arrow) in the pancreatic head and uncinate pro-
cess. The patient underwent surgery. Postoperative
histologic analysis revealed a malignant, well-differenti-
ated 2.3-cm ICT with nodal metastases.
Figure 14. Nonsyndromic ICT in a 76-year-old man
who presented with abdominal pain. Contrast-en-
hanced 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 vascu-
lar invasion was noted.
Figure 15. Nonsyndromic ICT in a 35-year-old man
who presented with abdominal pain. Contrast-en-
hanced CT scan demonstrates a 13 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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In a series of cases from the Armed Forces In-
stitute of Pathology, cystic and necrotic ICTs
were usually nonhyperfunctioning (nonsyn-
dromic) (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 me-
tastases.
Treatment
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 pan-
creatic head require Whipple surgery. Small le-
sions, especially those that are exophytic, can be
treated with enucleation, which can be performed
laparoscopically.
Patients with liver metastases and a symptom-
atic primary tumor may still benefit from resec-
tion of the latter (24). In most patients with syn-
dromic tumors, clinical endocrinopathies are re-
lieved after surgery, a response that usually lasts
for several months (25).
Figure 16. Nonsyndromic ICT in a 75-year-old man who presented with abdominal pain. (a) Arterial phase con-
trast-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.
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 por-
tal vein. Biopsy revealed a pancreatic neuroendocrine
tumor.
462 March-April 2006
RG f Volume 26
Number 2
RadioGraphics
Patients with limited liver metastases may ben-
efit from surgical resection of the metastases (26).
In addition, some studies support the use of he-
patic artery embolization for control of liver me-
tastases in these patients (27). Chemoemboliza-
tion effectively improves clinical symptoms and,
in selected patients, may provide sustained tumor
control (26). Data regarding mechanical ablation
(cryotherapy or radiofrequency ablation) of meta-
static ICTs are limited (27), but these methods
may also be of value.
Even with complete resection of liver metasta-
ses, the recurrence rate for these neoplasms is ex-
tremely 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 con-
trol of endocrine symptoms (25).
Somatostatin analogues such as octreotide may
benefit patients with unresectable or residual dis-
ease.
Chemotherapy may be used for palliation
when ablative techniques have failed or when sig-
nificant extrahepatic disease is present. Chemo-
therapeutic agents such as cisplatin, 5-fluoroura-
cil, and streptozotocin have been used with vari-
able success (28,29). Irradiation does not play a
major role in treatment.
More recent clinical trials have been con-
ducted to evaluate newer antineoplastic agents
and treatment strategies.
Conclusions
Multi– detector row CT is valuable in the diagno-
sis and staging of both syndromic and nonsyn-
dromic ICTs. These neoplasms can present a di-
agnostic challenge, both clinically and radiologi-
cally. 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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This article meets the criteria for 1.0 category 1 credit toward the AMA Physician’s Recognition Award. To obtain
credit, see www.rsna.org/education/rg_cme.html.
464 March-April 2006 RG f Volume 26
Number 2
RadioGraphics
RG Volume 26 Volume 2 March-April 2006 Horton et al
Teaching Points for Multi–Detector Row CT of Pancreatic Islet
Cell Tumors
Karen M. Horton, MD, et al
Page 454
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.
Page 454
Insulinoma is the most common syndromic ICT.
Page 455
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.
Page 456
Intravenous contrast material is essential for detection of the primary tumor, identification of vascular
encasement, and detection of liver metastases.
Page 456
The thin collimation and improved spatial and temporal resolution afforded by multi–detector row
CT definitely improve the visualization of small lesions.
RadioGraphics 2006; 26:453– 464
Published online 10.1148/rg.262055056
Content Codes:
    • "This technique is usually performed as a multiphase dynamic study, and the pancreatic parenchymal or portal venous phase can facilitate the detection of PanNETs [2,3]. Many studies have reported the radiologic findings of PanNETs456 . Typical PanNETs show hyperattenuation during the pancreatic parenchymal and portal venous phases because of their rich blood capillary networks [5]. "
    [Show abstract] [Hide abstract] ABSTRACT: To determine whether CT features can predict the pathological tumor grades of pancreatic neuroendocrine tumors (PanNETs) according to the recent WHO classification. In all, 28 patients with histologically confirmed PanNETs underwent preoperative contrast CT examinations. Thirteen tumors were classified as G1 and 15 as G2. Two radiologists independently evaluated the CT features (tumor delineation, peripancreatic vascular involvement, upstream pancreatic duct dilatation, N (regional lymph node metastasis) and M (distant metastasis) grades, tumor homogeneity, cystic or necrotic change, and tumor conspicuity). The tumor sizes and Hounsfield unit values of all PanNETs during each phase on CT were measured by one radiologist. We compared the CT features between pathological tumor grades using Fisher's exact test for nominal scales and Mann-Whitney U test for ordinal scales or continuous variables. Additionally, we evaluated the performances of the CT findings and their combinations to diagnose G2 tumors. G2 tumors showed significantly larger in tumor size than G1 tumors (p=0.029). All 4 tumors with hepatic metastases were G2. Non-hyperattenuation compared with pancreatic parenchyma during portal venous phase (PVP) was significantly associated with G2 (p=0.016). The accuracy for G2 diagnosis of tumor size (≥20mm), M grade (M1), and tumor conspicuity (non-hyperattenuation during PVP) were 71%, 61%, and 71%, respectively, while the accuracy of their combination was 82%. Contrast-enhanced CT features (tumor size, M grade, and tumor conspicuity during PVP) can predict the pathological tumor grades of PanNETs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Full-text · Article · May 2015
    • "small size (i.e., <3 cm) and often located in the tail. The majority of the lesions show homogeneous unilocular, thick wall lesion with wall enhancement on arterial phase (Fig. 13) and are less frequently associated with lymph nodes and liver metastases [114][115][116]. In about 25% of patients, cystic endocrine tumors are associated with a multiple neuroendocrine syndrome [117]. "
    [Show abstract] [Hide abstract] ABSTRACT: Magnetic resonance (MR) imaging has become a widespread diagnostic solving tool for the detection and characterization of a large range of pancreatic cystic lesions. Benign and malignant cystic lesions of the pancreas including serous microcystic adenoma, mucinous cystic tumor, intraductal papillary mucinous tumor, solid pseudopapillary tumor, and also the less common lesions such as cystic endocrine tumors, cystic metastases, and lymphangiomas have suggestive MR imaging presentation that allows them to be differentiated from each other. Knowledge of MR imaging findings of cystic pancreatic lesions is critical to help suggest the diagnosis and chose the best therapeutic approach. The purpose of this review is to discuss and illustrate MR imaging features that are helpful for pancreatic cystic lesion detection and characterization and to provide an update in current MR imaging diagnostic features and management.
    Full-text · Article · Nov 2013
    • "The atten�at�on �eve�s o� �ancreat�c �arench���a �a�� d���er ��th d���erent t���es o� MDCT �enerat�ons or scanners. B�rnba�� et al [11] assessed �ntra-and �nterscanner var�ab���t�� �s�n� an anthro�o�or�h�c bod�� CT �hanto��� sho�ing that there are significant differences of CT attenuation �eve�s bet�een d���erent MDCT scanner �enerat�ons as �e�� as bet�een d���erent �an��act�rers' scanners. F�rther studies should investigate the influence of scan delays for �ancreat�c ��a��n� ��th d���erent �an��act�rer's scanners. "
    [Show abstract] [Hide abstract] ABSTRACT: To compare different multidetector computed tomography (MDCT) protocols to optimize pancreatic contrast enhancement. Forty consecutive patients underwent contrast-enhanced biphasic MDCT (arterial and portal-venous phase) using a 64-slice MDCT. In 20 patients, the scan protocol was adapted from a previously used 40-channel MDCT scanner with arterial phase scanning initiated 11.1 s after a threshold of 150 HU was reached in the descending aorta, using automatic bolus tracking (Protocol 1). The 11.1-s delay was changed to 15 s in the other 20 patients to reflect the shorter scanning times on the 64-channel MDCT compared to the previous 40-channel system (Protocol 2). HU values were measured in the head and tail of the pancreas in the arterial and portal-venous phase. Using an 11.1-s delay, 74.2 HU (head) were measured on average in the arterial phase and 111.2 HU (head) were measured using a 15-s delay (P < 0.0001). For the pancreatic tail, the average attenuation level was 76.73 HU (11.1 s) and 99.89 HU (15 s) respectively (P = 0.0002). HU values were also significantly higher in the portal-venous phase [pancreatic head: 70.5 HU (11.1 s) vs 84.0 HU (15 s) (P = 0.0014); pancreatic tail: 67.45 HU (11.1 s) and 77.18 HU (15 s) using Protocol 2 (P = 0.0071)]. Sixty-four MDCT may yield a higher contrast in pancreatic study with (appropriate) optimization of scan delay time.
    Full-text · Article · Jul 2012
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