High Rate of Potentially Malignant Tumors
Guy Lahat, MD, Mendy Ben Haim, MD, Ido Nachmany, MD, Ronen Sever, MD, Arye Blachar, MD,
Richard Nakache, MD, Josef M Klausner, MD
Pancreatic incidentaloma (PI) is an increasingly common diagnosis that has received little
attention. We characterized these tumors and compared them with symptomatic pancreatic
tumors (nonincidentaloma [NI]).
STUDY DESIGN: A retrospective database of 475 consecutive pancreatectomies that were performed from January
1995 to June 2007 at our institution was analyzed. Data for PI and NI patient cohorts were
Sixty-four PIs (13.5%) and 411 NIs (86.5%) were identified; 21% of pancreatic body and tail
tumors versus 9% of tumors located in the pancreatic head were incidentally diagnosed (p ?
0.001). Twenty-two PIs (34%) versus 278 NIs (67%) were malignant (p ? 0.0001), 38 PIs
(60%) were premalignant, and the remaining 4 (6%) had little or no risk for malignant
progression. Intrapapillary mucinous cystic tumor was the most common diagnosis in the PI
group (23.4%, n ? 15). Of these, 13.3% (n ? 2) were invasive versus 40.6% (n ? 15) in the
NI group (p ? 0.02). Likewise, pathologic features for ductal adenocarcinomas were more
favorable in PI versus NI tumors. Overall, PI patients had prolonged median disease-specific
survival: 145 versus 46 months (p ? 0.001). Median disease-specific survival for PI versus NI
patients treated for adenocarcinoma were 22 versus 19 months, respectively (p ? 0.4); 5-year
disease-specific survival for PI versus NI patients treated for intrapapillary mucinous cystic
tumor/mucinous cystadenoma were 94% versus 68%, respectively (p ? 0.07).
Operation for PI is common, and a substantial proportion of these lesions might be malignant
209:313–319. © 2009 by the American College of Surgeons)
The term incidentaloma describes an asymptomatic lesion
detected incidentally by an imaging or biochemical diag-
nostic test. Incidentalomas of the adrenal gland and their
management are well characterized;1,2incidental findings
of the thyroid,3-5parathyroid,6,7pituitary,8liver,9heart,10
prostate,11and kidney12are also encountered. Although
these incidental findings have received particular attention
in the literature, data concerning pancreatic incidentaloma
(PI), an increasingly common diagnosis, are lacking. The
first case of PI was described by Kostiuk in 2001;132 series
of incidental pancreatic cysts have been reported subse-
quently.14,15Recently, Winter and colleagues16reported a
large series of pancreaticoduodenectomies performed for
pancreatic head and periampullary incidentalomas; but
these data do not include incidentalomas of body and tail,
which are expected to be more common.
In the past 2 decades, enormous advances were made in
sonographic technology, their widespread use, and in-
asymptomatic patients much more common. In addition to
abdominal CT and ultrasonography, liver function tests, tu-
mor markers, and even upper gastrointestinal endoscopy can
also detect asymptomatic findings within the pancreas.
In order to expand the current knowledge about this
rising diagnosis and its management, we reviewed a rela-
tively large database of pancreatectomies performed at a
single institution. We sought to characterize PIs and com-
pare them with symptomatic tumors. Although the major-
ity of pancreatic tumors are malignant or premalignant,
Disclosure Information: Nothing to disclose.
Received November 21, 2008; Revised April 26, 2009; Accepted May 4,
From the Departments of Surgery (Lahat, Ben Haim, Nachmany, Nakache,
Klausner) and Radiology (Blachar), Tel Aviv Sourasky Medical Center and
Nakache, Klausner), Tel Aviv University, Tel Aviv, Israel.
Correspondence address: Guy Lahat, MD, Department of Surgical Oncol-
77030. email: firstname.lastname@example.org
© 2009 by the American College of Surgeons
Published by Elsevier Inc.
our hypothesis was that most incidentalomas are not
overtly malignant, and early incidental detection might
The study was approved by our institutional review board,
and a waiver of consent was granted for the proposed re-
view of patient records. From January 1995 to June 2007,
475 consecutive patients who had pancreatic resection at
our institution were included in the study population. All
patients included in the study cohort remained in active
clinical or telephone followup. Medical records of all pa-
tients were reviewed and clinical, imaging, and pathologic
data were evaluated retrospectively.
Based on Winter and colleagues’ article,16patients were
categorized into two groups: patients with symptomatic
disease attributable to their pancreatic finding (noninci-
dentaloma group [NI]) and asymptomatic patients diag-
nosed with a pancreatic incidental lesion (PI). All patients
included in the PI group were asymptomatic for their pan-
creatic lesion at the time of diagnosis. Imaging incidenta-
lomas were identified by CT scan or other high-resolution
cross-sectional imaging technique; biochemical incidenta-
lomas were detected by elevated tumor markers and serum
liver or pancreatic enzymes. Demographic characteristics,
past medical history, intraoperative data, pathologic data,
perioperative morbidity and mortality (30-day), and long-
term disease-specific survival (DSS) were compared be-
tween the PI and the NI groups.
Time of DSS was calculated as the elapsed time from
operation at our institution to death from disease or last
Patients who died from other or unknown causes were
not included in the DSS analysis. Kaplan-Meier curves
to compare DSS between subgroups of patients.
Comparison between patient groups was performed us-
as applicable; chi-square test was used for comparison of
for parametric and median for nonparametric variables.
Statistical significance level was set at 0.05, and SPSS soft-
ware for Windows, version 12.0 (SPSS, Inc) was used for
Patient demographics and tumor location
Four hundred seventy-five pancreatic resections were per-
formed; these included 304 pancreaticoduodenectomies
(64%), 155 distal pancreatectomies (32.6%), 12 total pan-
createctomies (2.5%), and 4 enucleations (0.9%). Patients
were divided into 2 groups: 64 patients (13.5%) had oper-
ations for PI; 411 (86.5%) were clustered in the NI group.
As presented in Table 1, patient demographics and past
medical history of both PI and NI groups did not differ.
Thirty-six of 64 PIs (56%) were located in the distal
head. Looking at the proportion of PIs in each location,
21% (n ? 33) of tumors located in the body or tail were
PIs, and only 9% (n ? 28) of pancreatic head tumors were
incidentally diagnosed (p ? 0.001).
PIs were identified by tomography (n ? 27, 42%), sonog-
raphy (n ? 25, 39%), serum biochemistry (n ? 9, 14%),
and endoscopy (n ? 3, 5%). Twenty-nine incidentalomas
(45%) were diagnosed during workup for nonpancreatic
symptoms, including gynecological symptoms (n ? 6),
unspecified complaints (n ? 6), respiratory symptoms
(n ? 5), dysphagia (n ? 2), kidney stones (n ? 3), divertic-
ular disease (n ? 2), small bowel obstruction (n ? 1),
after an enema (n ? 1), and dysuria (n ? 1). Figure 1
illustrates an incidentally diagnosed solid and cystic papil-
lary tumor of the pancreas; the patient was admitted to the
emergency room after an assault, and CT was performed
Abbreviations and Acronyms
? disease-specific survival
IPMT ? intrapapillary mucinous cystic tumor
MCT ? mucinous cystic tumor
? pancreatic incidentaloma
Table 1. Patient Demographics and Medical History
Age (y), mean (range)
Coronary artery disease
PI (n ? 64)
NI (n ? 411)
There were no statistically significant differences between PI and NI groups.
NI, nonincidentaloma; NIDDM, noninsulin-dependent diabetes mellitus;
PI, pancreatic incidentaloma; PVD/CVA, peripheral vascular disease/
Lahat et al
Pancreatic IncidentalomasJ Am Coll Surg
because of severe abdominal pain shortly after the blunt
Twelve incidentalomas (18%) were detected during a
routine/executive evaluation (physical examination, labo-
ratory tests, or sonography). Ten patients (15.5%) were
followed for other malignancy or chronic disease: prostate
cancer (n ? 3), colorectal cancer (n ? 2), renal cell carci-
noma (n ? 1), ovarian cancer (n ? 1), family history of
pancreatic cancer (n ? 1), chronic back pain (n ? 1), and
familial polyposis (n ? 1). Figure 2 depicts a pancreatic
neuroendocrine tumor detected during followup for colo-
rectal cancer. Four incidentalomas (6%) were diagnosed
during routine workup before a planned operation: pros-
tatectomy (n ? 2), cataract (n ? 1) and hernia repair (n ?
1). Reasons were not specified in the remaining 10 cases
Surgical outcomes of PI versus NI patients who had pan-
pared separately (19 patients who had total pancreatec-
tomy or enucleation were excluded for the purpose of
this analysis). Twenty-eight PI (43.8%) versus 276 NI
patients (67.2%) underwent pancreaticoduodenectomy
(p ? 0.0001); perioperative mortality rates were 3.6%
(n ? 1) and 2.8% (n ? 8) in the PI and NI groups,
respectively (p ? 0.58). Major postoperative complica-
tion rates were also comparable between PI and NI pa-
tients who had pancreaticoduodenectomy, 15 (53.5%)
and 131 (47.4%), respectively (p ? 0.53). Pancreatic
fistula occurred in 25% (n ? 7) of PI versus 10.5% (n ?
29) of NI patients (p ? 0.03). Twenty-two NI patients
(7.9%) were reoperated, and no PI patient required re-
operation (p ? 0.04); mean hospitalization time did not
differ significantly between PI versus NI groups, 22.7
days (SD ? 12.1) versus 24.3 days (SD ? 15.6), respec-
tively (p ? 0.14).
Thirty-four PI patients (53.1%) versus 118 NI patients
(28.7%) underwent distal pancreatectomy; comparing both
subcohorts of patients for all surgical outcomes mentioned
here, there were no statistically significant differences.
The main pathologic diagnoses in the PI group were as
follows: pancreatic ductal or ampullary adenocarcinoma
(25%, n ? 16), intrapapillary mucinous cystic tumor
(IPMT; 23.4%, n ? 15), mucinous cystic tumor (MCT;
15.6%, n ? 10), and neuroendocrine tumor (15.6%, n ?
Figure 1. Axial CT scan of the upper abdomen demonstrates a round,
well-defined, slightly heterogeneous mass with a well-defined hyper-
dense border consistent with a solid and papillary cystic neoplasm.
Figure 2. . (A) Axial CT scan image and (B) coronal maximum
intensity projection reconstruction during the pancreatic arterial
phase shows a hypervascular round and slightly heterogeneous
mass demonstrating intense enhancement consistent with an islet
Vol. 209, No. 3, September 2009
Lahat et al
10). The most common pathologies in the NI group were
pancreatic ductal adenocarcinoma (44.5%, n ? 183), am-
pullary adenocarcinoma (9.5%, n ? 39), and IPMT (9%,
n ? 37). Pathologic diagnoses are presented in Table 2.
Twenty-two PIs (34.3%) versus 278 NIs (67.6%) were
malignant (p ? 0.0001); 11 PIs (17.2%) versus 183 NIs
(44.5%) were diagnosed as pancreatic ductal adenocarci-
nomas (p ? 0.001).
IPMTs and mucinous cystadenomas were subcatego-
presented in Table 3. Fifteen PIs (23.4%) versus 37 NIs
group were invasive, compared to 15 (40.6%) in the NI
group (p ? 0.02).
Ten PIs (15.6%) compared to 43 NIs (10.4%) were
MCTs (p ? 0.28); there were 9 cystadenocarcinomas
(21%) in the NI group, compared with 0 (0%) in the PI
cohort (p ? 0.3).
Table 4 summarizes the pathologic data of all malig-
nancies; median tumor diameter was 2.5 cm (range, 0.4
to 16 cm) and 3.5 cm (range, 0.7 to 25 cm) in the PI and
NI groups, respectively (p ? 0.32). Metastatic lymph
nodes were found in 10 PIs (45.4%) and 130 NIs
(46.7%; p ? 0.43), and the mean number of metastatic
lymph nodes was 0.4, compared with 1.15 (SD ? 1.17)
in the PI and NI groups, respectively (p ? 0.001). Vas-
cular invasion was found in 4 PIs (18.2%), compared to
73 NIs (36.2%; p ? 0.002), and perineural invasion was
detected in 6 (27%) and 132 (47.4%) of the PI and NI
groups, respectively (p ? 0.0001). Analyses of 238 pan-
creatic ductal or ampullary adenocarcinomas, according
to their degree of differentiation, are presented in Table
4. Well-differentiated carcinomas were more common
in the PI group, 6 (37.5%) versus 33 (14.8%; p ? 0.04),
and poorly differentiated carcinomas were more com-
mon in the NI group, 61 (67.4%) versus 2 (12.5%; p ?
Table 4. Pathologic Data for Malignant Tumors
Tumor diameter (cm), median (range)
Positive margins, n (%)
Metastatic LN, n (%)
Mean No. of positive LN (SD ? 1.17)
Vascular invasion, n (%)
Perineural invasion, n (%)
Differentiation of ductal and ampullary carcinoma
Well, n (%)
Moderate, n (%)
Poor, n (%)
PI (n ? 22)
NI (n ? 278)
*Statistical significance versus nonincidentaloma group (p ? 0.05).
LN, lymph nodes; NI, nonincidentaloma; PI, pancreatic incidentaloma.
Table 2. Pathologic Diagnoses
Mucinous cystic tumors
Distal bile duct cancer
Solid and cystic
(n ? 64)
(n ? 411)
3 4.75 1.20.04
*Statistical significance versus NI group (p ? 0.05).
Table 3. Staging of Intrapapillary Mucinous Cystic Tumor
and Mucinous Cystadenoma
Adenoma or borderline
Intrapapillary mucinous cystic
tumor with invasive cancer
Mucinous cystic tumor
(n ? 15)
(n ? 37)
10 100 79
009 21 0.1
*Statistical significance versus NI group (p ? 0.05).
Lahat et al
Pancreatic IncidentalomasJ Am Coll Surg
Overall, longterm outcomes were better for the cohort of
PI patients (n ? 64) as compared with the cohort of NI
patients (n ? 411); 1-, 2-, and 5-year DSS rates for PI and
NI patients were 91%, 75%, and 64% versus 75%, 59%,
and 47%, respectively, with a median survival of 145
months compared to 46 months (p ? 0.001). The 1-, 2-,
and 5-year DSS rates for patients with solid and/or cystic
malignant PI (n ? 22) versus NI (n ? 278) were 75%,
46%, and 31% versus 67%, 44%, and 28%, respectively,
with a median survival of 23 months versus 20 months
(p ? 0.3; Fig. 3A). We also evaluated DSS rates when the
data were confined to pancreatic solid ductal or ampullary
adenocarcinomas; 1-, 2-, and 5-year survival rates for PI
(n ? 16) versus NI (n ? 222) patients were 78%, 44%,
and 29% versus 67%, 43%, and 26%, respectively, with a
median survival of 22 months versus 19 months (p ? 0.4;
Fig. 3B). DSS of PI versus NI patients who had operations
for IPMT and/or MCT were evaluated separately; a trend
toward significantly improved survival was demonstrated
in the PI group (n ? 25) in comparison to the NI group
(n ? 81); 5-year DSS rates were 94% versus 68%, respec-
tively; median survival was not yet reached in either group
(p ? 0.07; Fig. 3C).
PI is a rapidly increasing phenomenon, and pancreatic op-
erations for asymptomatic patients are likely to become
common. The proportion of PIs operated on in our series
of 475 pancreatectomies is 13.5%, ? 90% of them after
the year 2000. Since that year, the rate of pancreatic oper-
ations for PI is 17.3%!
Most commonly, PIs are detected on abdominal CT
performed for various other clinical manifestations. As
cited by Winter and colleagues,16since the advent of mul-
tislice CT in 1998, the number of CT scans performed in
US perform ? 50 million CT scans annually.19In our
institution, 3 multidetector CT scanners are installed (2
Philips Brilliance 16 and 1 Philips Brilliance 64 scanners)
and perform approximately 40,000 scans per year. The
Figure 3. (A) Kaplan-Meier disease-specific survival curves for pa-
tients with malignant tumors who underwent pancreatectomy for
pancreatic incidentaloma (PI) versus nonincidentaloma (NI). (B)
Kaplan-Meier disease-specific survival curves for patients with ade-
nocarcinoma who underwent pancreatectomy for PI versus NI. (C)
Kaplan-Meier disease-specific survival curves for patients with intra-
papillary mucinous cystic tumor or mucinous cystic tumor who un-
derwent pancreatectomy for PI versus NI.
Vol. 209, No. 3, September 2009
Lahat et al
number of CT studies per 1,000 emergency department
total number of emergency room visits during the decade
between 1995 and 2004 increased by 17%, and the num-
ber of CT scans increased by 255%. This demonstrates a
disproportionate use of CT in the emergency room. In
addition, the total number of CT scans performed at our
institution has increased by ? 30% since 2004. In our
institution, as in other high-volume centers, there is an
increased use of CT, and this likely explains the rising rate
of pancreatectomies performed for PI by our group.
mass are yet to be studied. There is a clear paucity of data
for PI. Winter and colleagues16reported the experience of
Johns Hopkins with pancreaticoduodenectomies performed
for PI, and Fernandez-del Castillo and colleagues14reported
the Massachusetts General Hospital experience with opera-
tions for pancreatic cystic incidentalomas.
As mentioned previously, most incidentalomas are usu-
ally detected during workup or followup for other medical
conditions.20,21In our series, approximately two-thirds of
PIs were diagnosed during workup for nonpancreatic
symptoms or during surveillance for other malignancy or
chronic disease; the remaining PIs were diagnosed in
asymptomatic healthy individuals.The anatomic distribu-
tion of PI was not equal. Not surprisingly, there was a
considerably higher proportion of PIs in the distal pan-
creas, where mass-induced symptoms are less likely to oc-
cur. Most notable in this series is the high rate of malig-
nancy or malignant potential of PI, ie, 94%. This rate is
higher than reported previously14,16and includes all carci-
nomas, IPMT, MCT, and neuroendocrine tumor cases.
The likely explanation for this high rate is routine use of
preoperative multislice CT and endoscopic ultrasound
with fine needle aspiration/biopsy, which enables careful
patient selection for pancreatic operation.22All patients in
this series had a preoperative abdominal CT, endoscopic
ultrasound was performed in 65% of them (n ? 308), and
endoscopic ultrasound-guided fine needle aspiration/
biopsy was performed in 33% (n ? 153). Solid tumors
were considered potentially malignant, as were cystic le-
sions with solid areas, mucin, other characteristic features
of IPMT, high CEA levels, or atypical cells in cystic fluid.
Forty percent of PIs were ultimately diagnosed as IPMT
or MCT.These cystic tumors are likely to progress to inva-
sive cancer with time.The point of malignant transforma-
tion cannot be anticipated from time of detection, and
once invasive cancer occurs, the prognosis is considerably
13% of incidental IPMTs, were invasive, considerably less
where cancer was diagnosed in 21% of the symptomatic
MCTs and almost half of the symptomatic IPMTs. Higher
incidence of invasive cancer among the NI patients treated
for cystic tumors explains the worse prognosis demon-
strated in our separate survival analysis for this cohort of
patients. Apparently, development of invasive cancer is
time dependent in both tumors, and it is expected that
Several recent reports recommend a selective approach
toward resection of IPMT;23-25but adequate data and tech-
nology are still lacking in order to establish proper patient
or invasive cancer. Until then, we support an aggressive
approach if the patient is not a poor surgical candidate.
Rates of malignant PI versus malignant NI were 34.3%
versus 67.6% respectively, p ? 0.0001; this significant dif-
ference correlates with previous data showing that symp-
tomatic tumors are more likely to be malignant.14,16This
better 5-year DSS rate of all PI as compared with all NI pa-
tients, as well as the better prognosis of patients who had
PI is much higher in comparison with resected adrenal inci-
dentalomas, supporting a thorough diagnostic approach to-
ward incidentally diagnosed pancreatic lesions.16,26
Almost half (45.4%) of malignant PIs had metastasized to
lymph nodes, similar to the rate of lymph node involvement
in the NI group; but the mean number of involved lymph
nodes was lower in the PI group.These results are difficult to
interpret, because both groups are composed of differently
of lymphatic spread, using larger cohorts of patients, might
enable similar analysis for specific pathologies.
Analyzing the pathologic data of the pancreatic adenocar-
cinomas only, PIs had significantly favorable features: smaller
tumor diameter (2.5 versus 3.5 cm), lower rates of vascular
and perineural invasion, and a higher level of differentiation.
These characteristics can be explained by less aggressive local
behavior of PIs, which makes them more likely to be asymp-
tomatic; but early detection is also a possible explanation for
these favorable pathologic characteristics.
Interestingly, our data demonstrate higher survival rates
for patients treated for malignant PI versus NI, with me-
dian survival lengths of 23 months versus 20 months, re-
who had operations for pancreatic ductal and ampullary
adenocarcinomas: 22 months versus 19 months, respec-
Lahat et al
Pancreatic Incidentalomas J Am Coll Surg
tively. Thesedifferenceswerenotstatisticallysignificant.Bet- Download full-text
ter pathologic features observed in the malignant PI group
validated using a larger and more homogenous cohort of pa-
tion as an independent predictor of outcomes in pancreatic
Our study has two main limitations: First, it includes
surgically resected PIs only, although most pancreatic inci-
dentalomas are followed by gastroenterologists as benign
our data collection. In spite of these limitations, the large
number of patients in our study enabled us to achieve sta-
tistical power in most analyses, thereby advancing the cur-
rent knowledge concerning PIs and their management.
Results of this study show that surgical management of
PIs is an increasing phenomenon. Although PIs are asymp-
tomatic by definition, most patients who had operations
not mislead clinicians in favor of a conservative approach.
Our data demonstrate that overt malignancy, as well as
nodal involvement, are not uncommon findings in asymp-
tomatic pancreatic tumors; thus, symptomatic presenta-
tion as a marker for malignancy may be wrong. Accidental
early detection and resection of tumors with malignant
potential can prevent cancer. Interestingly, although the
incidence of malignancy in PIs was high, these lesions dis-
played more favorable pathologic features and longterm
outcomes. Future prospective clinicopathologic data col-
lection of all incidentally detected pancreatic tumors is
needed to allow a thorough understanding of their nature
and to establish an algorithm for their management.
Study conception and design: Lahat, Nakache, Klausner
Acquisition of data: Lahat, Nachmany, Sever, Blachar
Drafting of manuscript: Lahat, Blachar, Klausner
Critical revision: Klausner
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