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GASTROINTESTINAL IMAGING E283

Cystic Lesions of the

ONLINE-ONLY
CME
See www.rsna
.org/education
/search/RG
LEARNING
OBJECTIVES
After completing this
journal-based CME
activity, participants
will be able to:
■■Listthe different
types of cystic le-
sions of the pancre-
as and describe their
epidemiology.
■■Identify key imag-
ing features that
distinguish the dif-
ferent types of cystic
pancreatic lesions.
■■Discuss general
management of pa-
tients with cystic
pancreatic lesions.
Pancreas: Radiologic-
Endosonographic
Correlation1
Jennifer N. Kucera, MD, MS • Stephen Kucera, MD • Scott D. Perrin, MD
Jamie T. Caracciolo, MD, MBA • Nathan Schmulewitz, MD • Rajendra P.
Kedar, MD
Cystic lesions of the pancreas are relatively common findings at cross-
sectional imaging; however, classification of these lesions on the basis
of imaging features alone can sometimes be difficult. Complementary
evaluation with endoscopic ultrasonography and fine-needle aspira-
tion may be helpful in the diagnosis of these lesions. Cystic lesions of
the pancreas may range from benign to malignant and include both
primary cystic lesions of the pancreas (including intraductal papil-
lary mucinous neoplasms, mucinous cystic neoplasms, serous cystad-
enomas, pseudocysts, and true epithelial cysts) and solid neoplasms
undergoing cystic degeneration (including neuroendocrine tumors,
solid pseudopapillary neoplasms, and, rarely, adenocarcinoma and its
variants). Familiarity with the imaging features of these lesions and the
basic treatment algorithms is essential for radiologists, as collaboration
with gastroenterologists and surgeons is often necessary to obtain an
early and accurate diagnosis. Supplemental material available at http://
radiographics.rsna.org/lookup/suppl/doi:10.1148/rg.327125019/-/DC1.

Scan this code for
access to supple-
mental material
on our website.
Introduction
The prevalence of cystic lesions of the pancreas has been estimated to range from
2.4% to 24% in imaging and autopsy studies (1–5). Separating cystic pancreatic le-
sions with malignant potential from those typically associated with a benign clinical
course is an important clinical distinction with respect to treatment, as curative sur-
gery can be offered in most instances. Decisions regarding surgical treatment of cystic
lesions of the pancreas are based on the projected risk of malignancy or the presence
of symptoms relatable to the cyst or both. Studies have shown that computed tomog-
raphy (CT) and magnetic resonance (MR) imaging are only 40%–60% accurate in

Abbreviations: CEA = carcinoembryonic antigen, EUS = endoscopic US, FNA = fine-needle aspiration, IPMN = intraductal papillary mucinous
neoplasm, MRCP = MR cholangiopancreatography

RadioGraphics 2012; 32:E283–E301 • Published online 10.1148/rg.327125019 • Content Codes:

1
From the Department of Radiology, University of South Florida College of Medicine,12901 Bruce B. Downs Blvd, Box 17, Tampa, FL 33612 (J.N.K.,
S.D.P., R.P.K.); Department of Diagnostic Imaging, Moffitt Cancer Center, Tampa, Fla (J.T.C.); and Department of Internal Medicine, Division of Di-
gestive Diseases, University of Cincinnati, Cincinnati, Ohio (S.K., N.S.) Presented as an education exhibit at the 2011 RSNA Annual Meeting. Received
February 23, 2012; revision requested March 22 and received April 16; accepted May 10. For this journal-based CME activity the authors, editor, and
reviewers have no relevant relationships to disclose. Address correspondence to J.N.K. (e-mail: jennifer.kucera@hotmail.com).
See discussion on this article by Levy and Haddad (pp E301–E303).
©
RSNA, 2012 • radiographics.rsna.org
E284  November-December 2012 radiographics.rsna.org
determining the correct histologic diagnosis of
cystic lesions of the pancreas (6–8); however, im-
aging can help differentiate aggressive from nonag-
gressive lesions in 75%–90% of cases (7,9).
In general, dedicated multidetector CT evalua-
tion of pancreatic lesions is best performed with a
multiphasic technique consisting of a precontrast
scan, an early arterial angiographic phase, a pan-
creatic parenchymal phase, and a portal venous
phase. Optimal parenchymal enhancement of the
pancreas is achieved at 35–45 seconds after ini-
tiation of injection of contrast agent. The useful-
ness of CT for the evaluation of cystic pancreatic
lesions remains an understudied topic primarily
because of the multiple advantages of MR imag-
ing relative to CT in the characterization of these
lesions; however, recently published data suggest
that the role of CT can be comparable and some-
times complementary to that of MR imaging for
characterization of these lesions (8,10).
Because of its superior fluid and soft-tissue
contrast, MR imaging affords the best nonin-
vasive means for the morphologic evaluation of
cystic lesions of the pancreas. The helpful dis-
tinguishing characteristics of cystic pancreatic
lesions (specifically their internal septal enhance-
ment patterns and whether they communicate
with the pancreatic ductal system) are empirically
easier to elucidate at MR imaging and MR chol-
angiopancreatography (MRCP) than at CT, thus
allowing a more narrowed list of differential di-
agnoses. MR imaging of cystic pancreatic lesions
can be performed adequately at either 1.5-T or
3-T field strength (11). Standard sequences in-
clude T1-weighted gradient echo; T2-weighted
axial and coronal (usually multishot turbo spin
echo or single-shot fast spin echo), including fat
saturation to help elucidate acute inflammation;
two-dimensional and three-dimensional MRCP;
and three-dimensional T1-weighted gradient
echo before and after administration of a gado-
linium contrast agent (12). Patients are given a
negative oral contrast agent a few minutes before
imaging. Recent publications have highlighted
the usefulness of secretin-enhanced MRCP for
improved evaluation of ductal disease (13). The
emerging use of diffusion-weighted imaging may
provide even more diagnostic information in the
future, although the current utility of diffusion-
weighted imaging for cystic pancreatic lesions has
been less than originally hoped (14).
Endoscopic ultrasonography (EUS) combines
both endoscopic and US examinations into a
single modality. Because an inverse relationship
exists between the ultrasound frequency and the
depth of penetration (15), internal positioning al-
lows close high-resolution imaging of organs and
surrounding structures adjacent to the gut lumen.
Frequencies of 6–10 MHz are typically used dur-
ing EUS. Linear echoendoscopes contain biopsy
channels that allow for fine-needle aspiration
(FNA). FNA has transformed EUS from a purely
imaging modality into a diagnostic and thera-
peutic modality whereby cyst fluid sampling and
tissue acquisition can be performed safely and
efficiently. With respect to cystic lesions of the
pancreas, EUS permits high-resolution imaging
of morphology that might not be visualized with
CT or MR imaging, while FNA allows for collec-
tion of cyst fluid for analysis.
In a large prospective multicenter study, mor-
phologic features seen at EUS alone were shown
to be accurate for differentiating mucinous from
nonmucinous lesions in only 51% of cases (16).
The addition of cyst fluid cytology increased the
accuracy to 59%, while a concentration of tumor
marker carcinoembryonic antigen (CEA) at a level
of >192 ng/mL allowed accurate characterization
in 79% of cases (16). This distinction is clinically
important, as the malignant potential of mucinous
lesions necessitates surgical resection in most
cases, while nonmucinous lesions generally have
an extremely low malignant potential and are usu-
ally treated conservatively. EUS with FNA and
cyst fluid analysis is an effective method of clas-
sifying cystic lesions of the pancreas, the specificity
of which has exceeded 90% in most studies (17).
Common cystic lesions of the pancreas are
intraductal papillary mucinous neoplasms
(IPMNs), mucinous cystic neoplasms, serous
cystadenomas, pseudocysts, and true epithelial
cysts. Several solid tumors may contain cystic
components related to degeneration, including
neuroendocrine tumors, solid pseudopapillary
tumors, and, rarely, adenocarcinoma and its vari-
ants. The key features of these lesions at CT, MR
imaging, and EUS are discussed.
Intraductal
Papillary Mucinous Neoplasm
IPMNs of the pancreas originate from the muci-
nous epithelium of the pancreatic ductal system
and are characterized by intraductal papillary
growth and abundant mucin production, leading
RG  •  Volume 32  Number 7 Kucera et al  E285

Figure 1.  Main-duct IPMN in a 75-year-old woman. (a) Axial contrast-enhanced CT image demon-
strates diffuse irregular dilatation of the main pancreatic duct with heterogeneous intraductal densities
(arrow). (b) EUS scan demonstrates diffuse dilatation of the main pancreatic duct beginning at the level of
the ampulla and extending to the tail of the pancreas. (See Movie 1 for real-time evaluation.)

Figure 2.  Main-duct IPMN in a 77-year-old woman. (a) MRCP demonstrates a dilated main pan-
creatic duct with areas of irregular stenosis (arrows). (b) Direct endoscopic visualization shows a clas-
sic “fish mouth” papilla extruding mucin.

to ductal dilatation (18). IPMNs account for ap-
proximately 20% of cystic lesions of the pancreas
(19) and are classified on the basis of site of origin
of the pancreatic ductal system: main-duct IPMN,
which can be diffuse or segmental; side-branch
IPMN; and mixed IPMN involving both the main
duct and side branches (20). IPMNs occur slightly
more commonly in men, with a mean age of oc-
currence of 65 years (21). Most lesions are identi-
fied incidentally at cross-sectional imaging, but
when they are symptomatic, presentations include
abdominal pain, weight loss, pancreatitis, and pan-
creatic insufficiency.
The imaging features of IPMN depend
on the subtype of tumor. At CT, a main-duct
IPMN may demonstrate diffuse or segmental
dilatation of the main pancreatic duct (Fig 1).
At MR imaging, a main-duct IPMN may dem-
onstrate diffuse or segmental ductal dilatation,
with hypointense T1 and hyperintense T2 signal
(Fig 2). Mural nodules, mucin globules, or a
dilatated major or minor papilla bulging into the
duodenal lumen may be seen. Parenchymal atro-
phy may also be present.
E286  November-December 2012 radiographics.rsna.org

Figure 3.  Macrocystic side-branch IPMN in a 79-year-old woman. (a) Axial contrast-enhanced CT im-
age demonstrates a solitary cystic focus in the body of the pancreas. (b) EUS scan shows a mural nodule
within the cyst that was not discernible at CT. FNA with cyst fluid analysis helped confirm the presence of
a side-branch IPMN. (See Movie 2 for real-time evaluation.)

Figure 4.  Microcystic side-branch IPMN in a 67-year-old woman. (a) Axial contrast-enhanced CT
image demonstrates multiple small, clustered cystic foci involving the pancreatic head and uncinate pro-
cess that were originally interpreted as serous cystadenoma. FNA with cyst fluid analysis helped confirm
the presence of a side-branch IPMN. (b) The lesion shows similar morphology on the EUS scan.

Main-duct IPMN is classically characterized EUS as isoechoic to hyperechoic frondlike pro-

endoscopically by a gaping papilla that extrudes
mucin (“fish-mouth papilla”) (Fig 2); however,
this abnormality is seen in only 25%–50% of
main-duct IPMNs (22). The morphologic fea-
tures of main-duct IPMN seen with EUS include
diffuse or segmental ectasia of the main pancre-
atic duct, often with cystic side-branch dilatation
as a result of secondary mucin obstruction in side
branches (23) (Fig 1, Movie 1). Mural nodules
may be seen. Intraductal papillary growth, a dis-
tinguishing feature of IPMN, can be identified at
jections from the duct wall (17).
Side-branch IPMNs can have two different
imaging appearances: a macrocystic pattern, in
which there is a unilocular or multilocular cyst
with few septa (Fig 3), and a microcystic pattern,
in which multiple thin septa separate numer-
ous fluid-filled spaces (Fig 4) (20). Side-branch
IPMNs usually appear as hypoattenuating het-
erogeneous lesions at CT and are classically
located in the uncinate process (24), but they
can be found anywhere in the pancreas (Figs 3,
4). At MR imaging, side-branch IPMNs usually
appear as small round or oval lobulated masses.
RG  •  Volume 32  Number 7 Kucera et al  E287
Figure 5.  Multifocal side-branch IPMN in an 80-year-old man. (a) Axial T2-weighted MR image
demonstrates multiple cystic foci (arrows) in the pancreatic body and tail that communicate with the
main pancreatic duct. (b) EUS with FNA of the cystic lesion in the pancreatic tail helped confirm the
diagnosis of IPMN.
A connection to the pancreatic duct is often
demonstrated on cross-sectional images (20).
Approximately 30% of side-branch IPMNs are
multifocal (25) (Fig 5). Mixed IPMNs can have a
combination of features and can be encountered
in the main duct and side branches.
The morphology of side-branch IPMNs at
EUS can vary from a simple unilocular anechoic
lesion to a complex multiseptated multilocular le-
sion (Figs 3–5, Movie 2). A normal-caliber main
pancreatic duct is present, and often the com-
munication between the side-branch cystic lesion
itself and the main duct can be appreciated with
EUS. Morphology alone is generally insufficient to
distinguish side-branch IPMNs from other cystic
neoplasms such as mucinous cystic neoplasms or
macrocystic variants of serous cystadenoma.
EUS-guided FNA with cyst fluid analysis can
be clinically useful for differentiating IPMNs from
other cystic neoplasms. Aspiration of viscous col-
orless fluid is typical. Cytologic findings may be
acellular fluid or fluid with mucinous papillary
epithelial cells (17). Classically, cyst fluid analysis
reveals an elevated CEA concentration (>192 ng/
dL), with normal to high amylase levels (16,17).
According to the World Health Organization,
IPMNs can be divided into three subgroups:
(a) benign neoplasms without dysplasia, (b) bor-
derline neoplasms (mild to moderate dysplasia),
and (c) carcinoma (either noninvasive or invasive)
(26). Carcinoma is found in approximately 70%
of IPMNs that involve the main duct and in ap-
proximately 25% of neoplasms that involve only
side branches (25). Varying degrees of atypia are
often seen within the same tumor, which reflects
the current concept of stepwise progression of
a benign IPMN to invasive cancer (27). Mural
nodules, focal solid components, large unilocular
cystic components, enhancement of the main pan-
creatic duct wall, and main pancreatic duct diam-
eter greater than 18 mm are features suggestive of
malignant degeneration within main-duct IPMNs
(28,29). Similarly, predictors of malignant degen-
eration in side-branch IPMNs include the pres-
ence of mural nodules and focal solid components
(28). The absolute size of side-branch IPMNs has
also been shown to be an important predictor of
malignant potential: Side-branch IPMNs less than
3 cm in diameter without mural nodules are con-
sidered to have low malignant potential (30,31).
Interestingly, several authors report an increased
(27%–29%) prevalence of synchronous or meta-
chronous malignant neoplasms of other organs
in patients with IPMNs, including tumors of the
stomach, colon, rectum, lung, breast, and liver
(32–34).
An unusual clinical complication of main-duct
IPMNs is fistulization into adjacent organs, the
prevalence of which was reported to be 6.6% in
one series (35). Although fistulization can occur
after frank malignant degeneration and secondary
direct extension, it can also occur before malig-
nant degeneration as a result of mechanical pen-
etration due to high pressure within the mucin-
filled duct (35). When main-duct IPMN fistuliza-
tion occurs, the duodenum is the most frequently
affected organ, followed by the common bile duct
and stomach (35) (Fig 6, Movies 3, 4).
E288  November-December 2012 radiographics.rsna.org

Figure 6.  Main-duct IPMN with multiorgan fistulization in

an 86-year-old man. (a) Axial CT image demonstrates massive
dilatation of the main pancreatic duct (***). (b, c) Coronal CT
images demonstrate a pancreaticoduodenal fistula (arrow in b)
and a pancreaticojejunal fistula (arrowhead in b; a pancreati-
cogastric fistula (dashed arrow in c) is also seen. (d, e) Direct
pancreatoscopy shows intraductal mucin (d) and papillary
fronds projecting into the main pancreatic duct (e). (f ) EUS
scan demonstrates papillary fronds and mucin, with a con-
firmed pancreaticoduodenal fistula measuring more than 2 cm
in diameter. (See Movie 3 for real-time evaluation.) (g) ERCP
radiograph shows an irregular filling defect (arrow) involving
the mid to distal common bile duct, with dilatation of the
biliary tree. Endoscopic sphincterotomy and balloon sweep
demonstrated expression of a large amount of mucin from the
common bile duct. (See Movie 4 for real-time evaluation.)
RG  •  Volume 32  Number 7 Kucera et al  E289

Figure 7.  Benign mucinous cystic neoplasm

in a 44-year-old woman. (a) Axial CT image
demonstrates a simple-appearing cystic lesion
in the head of the pancreas. (b) T2-weighted
MR image shows minimal internal septa (ar-
row). (c) EUS scan shows a few thin septa
(arrows) in the cyst, with collapsibility at FNA.
Surgical excision helped confirm the presence of
a benign mucinous cystic neoplasm. (See Movie
5 for real-time evaluation.)

Clinical treatment decisions regarding surgi- Mucinous Cystic Neoplasm

cal resection of IPMNs are based on symptoms
and the malignant potential of the lesion. All
symptomatic IPMNs should be resected. Con-
sensus guidelines recommend surgical resection
for all main-duct and mixed-type IPMNs and
for all side-branch IPMNs greater than 3 cm
in diameter (25). Surgical resection of asymp-
tomatic side-branch IPMNs smaller than 3 cm
is recommended in the presence of high-risk
features (mural nodules, positive cytologic find-
ings) or rapid cyst growth (>2 mm per year)
(25,36). Small side-branch IPMNs without
high-risk features can be followed with serial
imaging (EUS, CT, or MR imaging). Annual
imaging is recommended for lesions smaller than
1 cm; 6–12-month follow-up is recommended
for lesions between 1 and 2 cm; and 3–6-month
follow-up is recommended for lesions larger than
2 cm (25). Because of the risk of recurrence, sur-
veillance imaging after resection of an IPMN is
recommended; a 6-month interval has been pro-
posed for malignant IPMNs, and annual imaging
is recommended for benign IPMNs (25).
Mucinous cystic neoplasms have malignant po-
tential and are associated with mucin production
(17). The distinguishing histopathologic feature
of mucinous cystic neoplasms is the presence of
ovarian stroma underlying the mucinous colum-
nar epithelium (37). Mucinous cystic neoplasms
occur almost exclusively in females, with a mean
age of 47 years (38), and account for approxi-
mately 10% of cystic lesions of the pancreas (19).
The patient may be asymptomatic or present
with nonspecific abdominal pain, nausea, weight
loss, and back pain (39).
CT may demonstrate a unilocular or septated
hypoattenuating cystic lesion, often with a thick
wall that enhances at delayed imaging. Although
the cyst is filled with mucin, the most common
MR signal characteristics are those of simple fluid
(40) (Fig 7). These lesions usually do not commu-
nicate with the pancreatic duct, and approximately
95% are located in the pancreatic body or tail
E290  November-December 2012 radiographics.rsna.org
Figure 8.  Malignant mucinous cystic neoplasm
in a 54-year-old woman. (a) Axial CT image
demonstrates a large complicated cystic lesion.
(b, c) T2-weighted MR image (b) shows fluid-
fluid level, and postcontrast T1-weighted MR
image (c) shows enhancing mural nodules (ar-
rows). Surgical excision helped confirm the pres-
ence of malignant mucinous cystic neoplasm.
(38). Peripheral calcifications may be present in as
many as 15% of cases (39), and nodules with soft-
tissue enhancement may be seen (Fig 8).
The morphologic features of mucinous cystic
neoplasms at EUS typically include a thick-
rimmed macrocystic (>2 cm) unilocular lesion
with few internal septa of variable thickness (Fig
7). Communication with the main pancreatic duct
is rarely observed (41); if additional cystic lesions
within the pancreas are noted, an alternative di-
agnosis (primarily IPMN) should be considered.
Mucinous cystic neoplasms may also contain
hyperechoic internal debris and wall-adherent
echogenic solid papillary projections or nodules
(23,42) (Fig 7, Movie 5). EUS-guided FNA with
cyst fluid analysis can contribute to the diagnosis.
The cyst fluid is viscous, containing mucin and
columnar epithelial cells. Typically, cyst fluid CEA
levels are elevated (>192 ng/dL), and amylase lev-
els are low (indicating no communication with the
main pancreatic duct) (16,17).
Approximately 17.5% of mucinous cystic
neoplasms contain carcinoma. Because patients
with invasive carcinoma are significantly older
than those with noninvasive neoplasms, there is
the suggestion of a progression of benign muci-
nous cystic neoplasms to malignant neoplasms
(43). Imaging features suggestive of malignancy
include the presence of nodules or a tumor diam-
eter greater than 6.0 cm (43). Eggshell calcifica-
tion (44), increased wall thickness or irregularity,
and obstruction or displacement of the main
pancreatic duct also suggest malignant transfor-
mation (45).
Because of their malignant potential, mu-
cinous cystic neoplasms should be resected in
all cases in which the patient is fit for surgery
(17,25). There is no risk of recurrence after
complete resection of a benign mucinous cystic
neoplasm when negative margins are seen at pa-
thology; therefore, future surveillance is unneces-
sary (43). However, surveillance is required for
resected malignant mucinous cystic neoplasms,
as the risk of recurrence is substantial; cross-
RG  •  Volume 32  Number 7 Kucera et al  E291

Figure 9.  Serous cystadenoma of the pancreas in a 78-year-old woman. (a) Axial contrast-enhanced
CT image demonstrates numerous small cysts conjoined in a honeycomb pattern in the pancreatic head
and neck. (b) EUS scan shows innumerable tiny cysts separated by thin septa. (See Movie 6 for real-
time evaluation.)

Figure 10.  Serous cystadenoma of the pancreas with calcification of the central scar in a 59-year-old
woman. (a) Axial contrast-enhanced CT image shows calcification (arrowhead) centrally within the le-
sion. (b) Axial postcontrast T1-weighted MR image demonstrates innumerable tiny cysts with enhanc-
ing septa.

sectional imaging at 6-month intervals is recom-
mended in consensus guidelines (25).
Serous Cystadenoma
Serous cystadenomas are generally benign neo-
plasms of the pancreas that comprise approxi-
mately 20% of cystic lesions of the pancreas (19).
Approximately 75% of these occur in females,
with a mean age of 61.5 years (46). More than
80% of these lesions are identified in the body
or tail of the pancreas (47). Patients with von
Hippel-Lindau disease may have multiple serous
cystadenomas (48). Patients may present with
abdominal pain, nausea, vomiting, or weight loss;
however, patients are typically asymptomatic, and
these lesions are identified incidentally (47).
The typical microcystic form of serous cystad-
enoma consists of a cluster of several (more than
six) small cysts (49), each typically less than 1
cm in diameter. The cysts may be arranged in a
honeycomb configuration, separated by fibrous
septa (23) (Fig 9). CT may demonstrate sunburst
calcification of the central scar, which is seen in
approximately 30% of cases (50) (Fig 10). MR
imaging may demonstrate a cluster of tiny cysts
with high T2 signal intensity, with intervening
E292  November-December 2012 radiographics.rsna.org

Figure 11.  Serous cystadenoma of the pancreas in a 63-year-old woman with von Hippel-Lindau
disease. T2-weighted axial MR image (a) and postcontrast T1-weighted axial MR image (b) dem-
onstrate thin enhancing internal septa (arrow in b) radiating from a central scar (* in b). Numerous
renal cysts are also seen.

septa and a central scar that may enhance on
delayed imaging (Fig 11). There is no communi-
cation with the pancreatic ductal system (51). A
rare macrocystic oligocystic form of serous cyst-
adenoma, which cannot be reliably distinguished
from mucinous cystic neoplasm with imaging
alone, has been reported (52) (Fig 12).
Contrary to other cystic pancreatic neoplasms,
the morphologic characteristics seen at EUS are
highly suggestive and often considered diagnostic
for microcystic serous cystadenoma. Microcystic
serous cystadenomas are well-delineated lesions
composed of numerous (more than six) small
(typically <5 mm in diameter) anechoic cystic
areas separated by thin septa, giving the lesion a
honeycomb appearance (17,53) (Fig 9, Movie 6).
The rare macrocystic variant of serous cystade-
noma is composed of multiple anechoic cystic ar-
eas separated by fibrous septa, with one or more
of the cystic components being large (>2 cm)
(54,55) (Fig 12). Morphologically, macrocystic
serous cystadenomas cannot be readily differenti-
ated from side-branch IPMNs or mucinous cystic
neoplasms; EUS-guided FNA with cyst fluid
analysis of one of the large components should be
considered. Because of the small size of the cystic
compartments and the vascular intercystic septa,
it is often difficult to obtain a sufficient fluid
sample from microcystic serous cystadenomas for
analysis; however, macrocystic serous cystadeno-
mas often yield adequate material when one of
the larger components of the cyst is sampled. The
fluid is typically colorless (except when contami-
nated with blood), and the cytologic appearance
is small glycogen-staining cuboidal cells (17).
Cyst fluid amylase and CEA concentrations are
low to undetectable, and a cyst fluid CEA con-
centration of less than 5 ng/mL virtually excludes
a mucinous lesion and lends support to the diag-
nosis of serous cystadenoma (17,56,57).
Classically, it has been thought that malignant
transformation from serous cystadenoma is rare;
therefore, nonoperative management has been
recommended in the absence of symptoms (17).
A recent cross-sectional review of 257 surgically
resected serous cystadenomas during a 20-year
time period has suggested, however, that more
aggressive subtypes exist (58). In this series, 5.1%
of serous cystadenomas were locally aggressive
(defined as invasion of surrounding structures
or vasculature or direct extension into peripan-
creatic lymph nodes), and 0.8% were malignant
(defined by the presence of metastasis) (58).
Multivariate analysis showed that tumor diameter
and location of the tumor in the pancreatic head
were independently associated with aggressive be-
havior, leading the authors to conclude that these
factors should merit special consideration when
considering clinical management (58).
RG  •  Volume 32  Number 7 Kucera et al  E293

Figure 12.  Macrocystic variant of serous cyst-

adenoma in a 69-year-old woman who presented
with upper abdominal pain. (a) Axial contrast-
enhanced CT image demonstrates a cystic mass
in the tail of the pancreas, with nearly impercep-
tible thin internal septa (arrow) and multiple
cystic foci larger than 1 cm in diameter. (b) Axial
T2-weighted MR image better demonstrates the
multiple thin internal septa (arrow). (c) EUS
scan helps confirm the multiseptate morphology
(arrow), which is nonspecific and could represent
macrocystic serous cystadenoma or mucinous
cystic neoplasm. Surgical excision yielded a final
pathologic diagnosis of serous cystadenoma.

Until further research leads to a better un-
derstanding of the behavior of serous cystad-
enomas, current clinical practice is to assume
that these lesions will follow a benign course.
Imaging surveillance at 6–12-month intervals is
recommended until size stability over a 2-year
period is achieved (17,58). For serous cystad-
enomas that are surgically resected with negative
margins, imaging surveillance is considered un-
necessary (17,58).
Pseudocyst
A pancreatic pseudocyst is a nonneoplastic
cystic lesion of the pancreas associated with
pancreatitis or trauma. Overall, pseudocysts are
the most common cystic lesion of the pancreas
and can occur at any age and in either sex (59).
They result from hemorrhagic fat necrosis and
encapsulation of pancreatic secretions by granu-
lation tissue and a fibrous capsule that does not
contain epithelium. Pseudocysts occur in ap-
proximately 20%–40% of patients with chronic
pancreatitis and in 2%–3% of those with acute
pancreatitis (60).
Pseudocysts can occur adjacent to any portion
of the pancreas. Imaging characteristics may vary
depending on the age and contents of the pseu-
docyst. CT may demonstrate a usually unilocular
round or oval fluid collection with a wall that can
range in thickness from barely perceptible early
in its formation to thick and enhancing after time
(61). Although the wall may enhance, no enhanc-
ing soft-tissue components are present within
pseudocysts. Pseudocysts may contain simple fluid
that may be hyperintense on T2-weighted images,
or blood products and proteinaceous fluid may
be present within the lesion and can demonstrate
increased signal on T1-weighted images (40). As-
E294  November-December 2012 radiographics.rsna.org

Figure 13.  Large pancreatic pseudocyst in a

56-year-old man. (a) Axial CT image demon-
strates a large cystic lesion arising from the head
of the pancreas. The pancreas is atrophic, with a
dilated main pancreatic duct (arrow) and coarse
calcifications (arrowhead). Note multiple gallstones
within the gallbladder. (b) EUS scan shows a
unilocular anechoic collection without solid com-
ponents, wall abnormalities, or septa. (c) Endo-
scopic view of the posterior gastric body shows a
bulging contour abnormality (dashed line) second-
ary to extrinsic compression of this portion of the
stomach by the pancreatic pseudocyst.

sociated findings of acute or chronic pancreatitis or intraductal papillary mucinous neoplasms. In

may be present, including peripancreatic inflam-
mation, parenchymal calcifications, ductal dilata-
tion, and atrophy of the gland (61) (Fig 13).
The endoscopic appearance of pancreatic pseu-
docysts can vary. Large pseudocysts can cause a
compressive effect on the stomach or duodenum,
which can be observed under standard white
light endoscopy as a subepithelial “bulge.” At
EUS, pseudocysts typically appear as thin-walled
unilocular anechoic cystic lesions (Fig 13). Intra-
cystic septa are rare but can occur. The presence
of debris (irregular hyperechoic material) within
the cyst or thickening of the cyst wall can confuse
the endosonographer, as these features make the
EUS appearance alone difficult to distinguish from
the appearance of mucinous cystic neoplasms
situations in which the diagnosis is unclear, EUS-
guided FNA with cyst fluid analysis can be help-
ful in distinguishing pancreatic pseudocysts from
primary cystic neoplasms. Aspirated cyst fluid of
low viscosity and dark color that contains inflam-
matory cells and occasional blood is characteristic
of pseudocysts (56). Additionally, pseudocyst fluid
CEA concentrations are typically low; however,
amylase and lipase concentrations are characteristi-
cally elevated, with amylase levels often exceeding
5,000 U/mL and lipase levels greater than 2,000
U/mL (42).
Indications for drainage of pseudocysts include
the presence of symptoms, gastric outlet obstruc-
tion, obstruction of the extrahepatic biliary tree,
and infection (42). In the absence of these clinical
features, large pseudocysts can be treated conser-
vatively; absolute size itself is not considered an
indication for drainage. Pseudocyst drainage can
be achieved surgically, endoscopically, or percuta-
RG  •  Volume 32  Number 7 Kucera et al  E295

Figure 14.  True epithelial cysts in two differ-

ent patients with von Hippel-Lindau disease.
(a) T2-weighted axial MR image demonstrates
multiple T2 hyperintense foci in the body and tail
of the pancreas, the largest of which (arrow) is
exophytic from the tail of the pancreas. (b) EUS
scan in the same patient demonstrates multiple
unilocular simple cysts. (c) Axial CT image in
another patient with von Hippel-Lindau dis-
ease shows complete cystic replacement of the
pancreas.

neously. Percutaneous drainage under radiologic
guidance is limited by the risk of puncture of
adjacent viscera, infection, prolonged periods of
external drainage, and the potential development
of a pancreaticocutaneous fistula (62). Compared
with surgical cystogastrostomy, EUS-guided cys-
togastrostomy of uncomplicated pseudocysts has
been shown to be technically equivalent, with no
difference in pseudocyst recurrence or reinterven-
tion rates, and with shorter postprocedure hospital
stays and substantialy lower costs (63–65). For
these reasons, EUS-guided cystogastrostomy can
be considered the first-line procedure for uncom-
plicated pseudocyst drainage.
True Epithelial Cyst
True epithelial cysts are associated with von
Hippel-Lindau disease, autosomal-dominant
polycystic kidney disease, and cystic fibrosis (63).
Isolated true pancreatic cysts are rare (64) and
generally should not be included in the differen-
tial diagnosis of a cystic lesion of the pancreas in
the absence of associated disease.
CT demonstrates a unilocular cyst with no per-
ceptible wall and no internal septa. No enhance-
ment is seen after administration of contrast mate-
rial. MR imaging demonstrates a simple cyst that
is hypointense on T1-weighted images and hyper-
intense on T2-weighted images, without internal
complexity. Multiple cysts may be present in von
Hippel-Lindau disease (24) (Fig 14).
At EUS, true epithelial cysts are unilocular an-
echoic homogeneous lesions with thin walls and no
internal septa (Fig 14). Epithelial cysts are typi-
cally small (<1–2 cm in diameter). EUS-guided
FNA with cyst fluid analysis yields relatively bland
cytologic findings (hypocellular with mixed inflam-
matory cells). Cyst fluid CEA and amylase concen-
trations are low. These lesions are managed conser-
vatively, and imaging surveillance is unnecessary.
E296  November-December 2012 radiographics.rsna.org

Figure 15.  Cystic pancreatic neuroendocrine tumor in a 33-year-old man with known multiple endo-
crine neoplasia type 1 syndrome. (a) Axial CT image demonstrates avid peripheral arterial enhancement
(arrow) of a cystic lesion within the pancreatic head. (b) T2-weighted axial MR image shows a septation
within the cyst (arrow). (c) Coronal octreoscan single photon emission CT/CT demonstrates mild uptake
(arrowhead) within the cystic lesion. (d) EUS scan of the lesion shows a round cystic lesion with mixed
solid and cystic features. EUS-guided FNA with cyst fluid analysis yielded a diagnosis of neuroendocrine
tumor. (See Movie 7 for real-time evaluation.)

Cystic Neuroendocrine Tumor
Cystic neuroendocrine tumors represent a small
subset of neuroendocrine tumors, accounting
for approximately 17% of all neuroendocrine tu-
mors. Cystic neuroendocrine tumors, like their
solid counterparts, have an overall equal gender
predilection, with a mean patient age of 53 years.
However, cystic neuroendocrine tumors are larger
(49 mm vs 23.5 mm), more often symptomatic
(73% vs 45%), and more likely to be nonfunc-
tional (80% vs 50%) than solid neuroendocrine
tumors. Cyst formation is thought to be secondary
to tumor degeneration. Patients with cystic neuro-
endocrine tumors are 3.5 times more likely to have
multiple endocrine neoplasia type 1 than patients
with solid neuroendocrine tumors. The propensity
for metastasis is the same in patients with cystic
tumors as in those with solid tumors (65).
Cystic neuroendocrine tumors most com-
monly occur in the body and tail of the pancreas.
In keeping with the hypervascular nature of neu-
roendocrine tumors, imaging of cystic neuroen-
docrine tumors typically demonstrates a septated
cyst with at least a rim of arterially enhancing
tissue (65). These tumors are generally well-
circumscribed (40), and they may demonstrate
variable levels of uptake on an indium 111 (111In)
pentetreotide scan (Fig 15).
RG  •  Volume 32  Number 7 Kucera et al  E297

Figure 16.  Solid pseudopapillary tumor of the

pancreas in a 27-year-old woman. Noncontrast
(a), early arterial phase (b), and late arterial
phase (c) axial CT images demonstrate pro-
gressive enhancement of a large encapsulated
solid and cystic mass in the pancreatic head.

Morphology at EUS is nonspecific: Cystic dopapillary neoplasms can be located anywhere

neuroendocrine tumors are well-circumscribed
heterogeneous lesions that can appear either
completely cystic or contain solid and cystic
components (Fig 15, Movie 7). FNA can be
diagnostic when small homogeneous cells with
round nuclei that stain positive for chromogranin
and synaptophysin are identified (17). Cyst fluid
CEA concentrations are noted to be low to un-
detectable, and amylase concentrations are also
low (17). Given their varying malignant potential,
complete resection is the treatment choice for
cystic neuroendocrine tumors (66).
Solid Pseudopapillary Neoplasm
Solid pseudopapillary neoplasms are rare tumors
with low-grade malignant potential that typically
affect young women. Approximately 91% of these
tumors occur in females, with a mean age of 22
years. The most common clinical presentation
is pain, followed by a palpable mass. Solid pseu-
in the pancreas, with a slight predilection for the
pancreatic tail. These tumors are generally large
at the time of presentation, with an average di-
ameter of 6 cm, and approximately 20% demon-
strate metastasis at the time of presentation (67).
Tumors may be solid or cystic, which can lead
to variable imaging characteristics. Tumors are
well-circumscribed and may demonstrate areas
of T2 hyperintensity that correlate with cystic
components. Areas of increased T1 signal inten-
sity are commonly seen within the tumor and are
related to hemorrhagic degeneration. The soft-
tissue components of these lesions demonstrate
a gradual enhancement pattern after administra-
tion of contrast material (40) (Figs 16, 17). Pe-
ripheral calcifications may be present in approxi-
mately 31% of cases (68).
E298  November-December 2012 radiographics.rsna.org
Figure 17.  (a, b) Precontrast (a) and postcon-
trast (b) T1-weighted MR images in a 24-year-
old woman demonstrate a heterogeneous mass in
the head of the pancreas. Internal high T1 signal
intensity suggests hemorrhage (arrow in a) is
present. (c) Correlative EUS scan shows a het-
erogeneous hypoechoic mass with compression
of the superior mesenteric vein (arrow).
The EUS appearance of a solid pseudopapil-
lary neoplasm is a hypoechoic heterogeneous
well-demarcated lesion that appears predomi-
nantly solid and contains cystic components
of various sizes (69,70) (Fig 17). The hallmark
of these lesions is central hemorrhagic cystic
degeneration; thus, the FNA sample is often a
low-viscosity bloody fluid (42). Cytology reveals
branching eosinophilic papillary cells in a back-
ground of blood and necrosis; cyst fluid CEA
concentrations vary, and amylase levels are low
(42). Surgical resection is considered the main-
stay of treatment.
Pancreatic Adenocarcinoma
Pancreatic adenocarcinoma is the most com-
mon and most fatal malignancy of the pancreas.
The frequency of pancreatic adenocarcinoma
increases with age and is slightly more common
in men. Approximately 60% occur in the pancre-
atic head, with the classic clinical presentation of
painless jaundice (51). Although it is predomi-
nantly a solid lesion, as many as 8% of adenocar-
cinomas have been reported to demonstrate some
element of cystic change (71). Cystic changes
are more commonly observed in large poorly dif-
ferentiated adenocarcinomas (66) and their rare
variants, including undifferentiated pleomorphic
carcinoma, adenosquamous carcinoma, and mu-
cinous noncystic carcinoma (71).
Imaging features of adenocarcinoma are gen-
erally distinct from those of other cystic lesions
of the pancreas and include a hypovascular infil-
trative pancreatic mass, often with resultant ob-
struction of the pancreatic or common bile duct.
Vascular invasion is common (24). Rarely cystic
change can be present, which may be related to a
cystic neoplastic component, necrosis, retention
cysts from pancreatic ductal obstruction, or pseu-
docysts from pancreatitis (71).
RG  •  Volume 32  Number 7 Kucera et al  E299
The morphology of an adenocarcinoma at
EUS is that of a predominantly solid hetero-
geneous mass, occasionally with hypoechoic to
anechoic cystic components. FNA of the cystic
component can yield diagnostic cytologic mate-
rial; however, typically the solid component of the
lesion is targeted for FNA. Cyst fluid CEA and
amylase levels vary.
Treatment of adenocarcinoma of the pancreas
depends on the stage at diagnosis and patient co-
morbidities but could include surgical resection
and chemotherapy or radiation or both.
Conclusions
Detection of cystic lesions of the pancreas is
becoming more common because of the wide-
spread use of cross-sectional imaging. Histologic
classification of these lesions can sometimes be
difficult at CT and MR imaging and may require
additional evaluation with EUS and FNA. It is
important for radiologists to be familiar with
treatment and imaging surveillance guidelines for
the various cystic lesions of the pancreas. Use of
a multidisciplinary approach, early diagnosis, and
accurate classification of cystic lesions of the pan-
creas will lead to improved patient outcomes.
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TM
Teaching Points November-December Issue 2012

Cystic Lesions of the Pancreas: Radiologic-Endosonographic Correlation

Jennifer N. Kucera, MD, MS • Stephen Kucera, MD • Scott D. Perrin, MD • Jamie T. Caracciolo, MD, MBA •
Nathan Schmulewitz, MD • Rajendra P. Kedar, MD
RadioGraphics 2012; 32:E283–E301 • Published online 10.1148/rg.327125019 • Content Codes:

Page E284
EUS with FNA and cyst fluid analysis is an effective method of classifying cystic lesions of the pancreas, the
specificity of which has exceeded 90% in most studies (17).

Page E287
Mural nodules, focal solid components, large unilocular cystic components, enhancement of the main
pancreatic duct wall, and main pancreatic duct diameter greater than 18 mm are features suggestive of ma-
lignant degeneration within main-duct IPMNs (28,29). Similarly, predictors of malignant degeneration in
side-branch IPMNs include the presence of mural nodules and focal solid components (28). The absolute
size of side-branch IPMNs has also been shown to be an important predictor of malignant potential: Side-
branch IPMNs less than 3 cm in diameter without mural nodules are considered to have low malignant
potential (30,31).

Page E291
The typical microcystic form of serous cystadenoma consists of a cluster of several (more than six) small
cysts (49), each typically less than 1 cm in diameter. The cysts may be arranged in a honeycomb configu-
ration, separated by fibrous septa (23) (Fig 9).

Page E293
CT may demonstrate a usually unilocular round or oval fluid collection with a wall that can range in thick-
ness from barely perceptible early in its formation to thick and enhancing after time (61). Although the
wall may enhance, no enhancing soft-tissue components are present within pseudocysts. Pseudocysts may
contain simple fluid that may be hyperintense on T2-weighted images, or blood products and proteinaceous
fluid may be present within the lesion and can demonstrate increased signal on T1-weighted images (40).

Page E295
Isolated true pancreatic cysts are rare (64) and generally should not be included in the differential diag-
nosis of a cystic lesion of the pancreas in the absence of associated disease.